Transcriptomic behavior of genes associated with chromosome 21 aneuploidies in early embryo development
Fertil Steril. 2019 May;111(5):991-1001.e2. doi: 10.1016/j.fertnstert.2019.01.023. Epub 2019 Mar 25.
Sanchez-Ribas I1, Diaz-Gimeno P2, Sebastián-León P3, Mercader A4, Quiñonero A5, Ballesteros A6, Pellicer A7, Domínguez F3.
OBJECTIVE: To analyze how chromosome 21 (HSA21) ploidy affects global gene expression of early human blastocysts.
DESIGN: Prospective study.
SETTING: University-affiliated in vitro fertilization clinic.
PATIENT(S): A total of 26 high-quality donated embryos from in vitro fertilization (IVF) patients: trisomy 21 (n = 8), monosomy 21 (n = 10), and euploid (n = 8) blastocysts.
MAIN OUTCOME MEASURE(S): Blastocyst transcriptome changes and its associated functions.
RESULT(S): Trisomy 21, monosomy 21, and euploid blastocysts were classified by comparative genomic hybridization. The global transcriptome of whole blastocysts was analyzed with small cell number RNA sequencing, and they were compared to understand the gene expression behavior at early development and its implications for embryo implantation. We identified 1,232 differentially expressed genes (false discovery rate <0.05) in monosomy 21 compared with euploid blastocysts associated with dysregulated functions in embryo development as the Rap1 signaling pathway. Curiously, Down syndrome in early development revealed fewer transcriptomic changes than expected. In addition, Down syndrome gene expression in neonates, children, and adults revealed that the number of deregulated genes increases across life stages from blastocysts to adults, suggesting a potential dosage-compensation mechanism for human chromosome 21.
CONCLUSION(S): At the transcriptomic level, early development in Down syndrome is mainly dosage compensated. However, monosomy 21 is strongly transcriptionally affected because early development involving main functions is associated with embryo implantation.
Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
KEYWORDS: Blastocyst transcriptome; Down Syndrome in early development; HSA21 gene expression; chromosome 21 abnormalities; trisomy and monosomy 21 PMID: 30922649 DOI: 10.1016/j.fertnstert.2019.01.023
National screening guidelines and developments in prenatal diagnoses and live births of Down syndrome in 1973-2016 in Denmark
Acta Obstet Gynecol Scand. 2018 Feb;97(2):195-203. doi: 10.1111/aogs.13273.
Lou S1,2, Petersen OB1,3, Jørgensen FS4, Lund ICB1,5, Kjaergaard S6; Danish Cytogenetic Central Registry Study Group, Vogel I1,5. Collaborators (4)
INTRODUCTION: Denmark was the first country in the world to implement a national, free-for-all offer of prenatal screening for Down syndrome to all pregnant women. It has a high uptake (>90%) compared to other countries. Thus, Denmark offers an interesting case for investigating the consequences of implementing comprehensive, national prenatal screening guidelines. The aim of this study was to describe the historical developments in invasive procedures, pre-/postnatal diagnoses of Down syndrome and Down syndrome live births in the period 1973-2016 in Denmark. MATERIAL AND METHODS: Data on invasive procedures, pre- and postnatal Down syndrome diagnoses were retrieved from the Danish Cytogenetic Central Registry. RESULTS: From 1973 to 1993, screening based on maternal age and high-risk indications resulted in a constant increase in invasive procedures. After the introduction of the triple test in 1994, invasive procedures decreased for the first time in 20 years. Following the introduction of an offer of combined screening to all pregnant women in 2004, the number of invasive procedures decreased markedly, while there was a concurrent increase in prenatal diagnoses of Down syndrome. Additionally, the number of Down syndrome live births decreased suddenly and significantly, but subsequently stabilized at 23-35 annual live births. Of these, the majority were diagnosed postnatally. CONCLUSION: Though prenatal screening technologies constantly improve, it was the introduction of and adherence to national guidelines that resulted in marked shifts in screening procedures and outcome in Denmark. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology. KEYWORDS: Denmark; Prenatal screening; amniocentesis; chorionic villus sampling; combined first trimester screening; diagnosis; down syndrome PMID: 29194566 DOI: 10.1111/aogs.13273
Widespread domain-like perturbations of DNA methylation in whole blood of Down syndrome neonates
PLoS One. 2018 Mar 30;13(3):e0194938. doi: 10.1371/journal.pone.0194938. eCollection 2018.
Henneman P1, Bouman A1, Mul A1, Knegt L1, van der Kevie-Kersemaekers AM1, Zwaveling-Soonawala N2, Meijers-Heijboer HEJ1, van Trotsenburg ASP3, Mannens MM1.
INTRODUCTION: Down syndrome (DS) is the most frequent genetic cause of intellectual disability. Despite the fact that more than 50 years have passed since the discovery of its genetic aberrations, the exact pathogenesis of the DS phenotype has remained largely unexplained. It was recently hypothesized that the DS pathogenesis involves complex (epi)genetic, molecular and cellular determinants. To date, many reports have addressed epigenetic aberrations associated with DS at different developmental stages/ages and tissue types, but to our best knowledge not in DS newborns. This study aimed to investigate genome-wide methylation patterns in DS newborns compared to non-trisomic newborns. METHOD: We analyzed blood samples obtained from ten newborns with DS and five age-matched non-trisomic newborns. Epigenetic profiles were obtained from extracted DNA using the Illumina Infinium 450K array. Since aberrant blood cell distribution is known to be present in DS, we applied two distinct models: with and without correction for estimated blood cell distribution. RESULTS: Differentially methylated position (DMP) analysis of the uncorrected model detected 19525 significant hits (51,2% hypomethylated). In the corrected model, we found 121953 significant DMPs (49,8% hypomethylated). Independent of the used model we observed a chromosome 21 dosage effect. Moreover, we detected 46 and 145 differentially methylated regions in the uncorrected and corrected model respectively, both showing hypomethylation overrepresentation. Replication analyses of DMPs and DMRs found by Bacalini et al. (2015) showed a large overlap. CONCLUSION: In this study, we found methylation profile differences between DS newborns and controls reflecting a systematically affected epigenetic profile. The observed chromosome 21 dosage effect suggests the involvement of affected essential regulatory factors/regions or altered expression of chromatin modeling enzymes located on chromosome 21. Additional research is necessary to substantiate these hypotheses.
PMID: 29601581 DOI: 10.1371/journal.pone.0194938
Transcriptome analysis of genetically matched human induced pluripotent stem cells disomic or trisomic for chromosome 21
PLoS One. 2018 Mar 27;13(3):e0194581. doi: 10.1371/journal.pone.0194581. eCollection 2018.
Gonzales PK1,2, Roberts CM1,2, Fonte V1,2, Jacobsen C2, Stein GH1,3, Link CD1,2.
Abstract Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. These cells were originally derived by Li et al, who genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell pairs maintained as iPSCs or differentiated into cortical neuronal cultures. In addition to characterization of gene expression levels, we have also investigated patterns of RNA adenosine-to-inosine editing, alternative splicing, and repetitive element expression, aspects of the transcriptome that have not been significantly characterized in the context of Down syndrome. We identified significant changes in transcript accumulation associated with chromosome 21 trisomy, as well as changes in alternative splicing and repetitive element transcripts. Unexpectedly, the trisomic iPSCs we characterized expressed higher levels of neuronal transcripts than control disomic iPSCs, and readily differentiated into cortical neurons, in contrast to another reported study. Comparison of our transcriptome data with similar studies of trisomic iPSCs suggests that trisomy of chromosome 21 may not intrinsically limit neuronal differentiation, but instead may interfere with the maintenance of pluripotency. PMID: 29584757 DOI: 10.1371/journal.pone.0194581
Early human embryos are naturally aneuploid-can that be corrected?
J Assist Reprod Genet. 2017 Jan;34(1):15-21. doi: 10.1007/s10815-016-0845-7. Epub 2016 Nov 29.
Lee A1, Kiessling AA2.
Abstract Aneuploidy is common and may be a natural occurrence in early human embryos. Selecting against embryos containing aneuploid cells for embryo transfer has been reported to increase clinical pregnancies per transfer in some studies, but not others. Some aneuploidy is due to misallocation of chromosomes during meiosis, in either the egg or sperm, but most aneuploidy is due to misallocation of chromosomes during mitoses after fertilization. Big questions are as follows: Why does this happen? How much aneuploidy in a preimplantation embryo is compatible with normal fetal development? Is aneuploidy increased by in vitro culture, and/or could it be prevented or corrected in the IVF lab? KEYWORDS: Aneuploid; Chromosome; Egg donor; Euploid; Human embryo; In vitro fertilization; Preimplantation genetic screening PMID: 27900612 PMCID: PMC5330987 DOI: 10.1007/s10815-016-0845-7
Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal-dominant Alzheimer's disease
Alzheimers Dement. 2017 Apr 29. pii: S1552-5260(17)30146-2. doi: 10.1016/j.jalz.2017.03.007. [Epub ahead of print]
Carmona-Iragui M1, Balasa M2, Benejam B3, Alcolea D4, Fernández S3, Videla L3, Sala I4, Sánchez-Saudinos MB4, Morenas-Rodriguez E4, Ribosa-Nogué R4, Illán-Gala I4, Gonzalez-Ortiz S5, Clarimón J4, Schmitt F6, Powell DK6, Bosch B7, Lladó A7, Rafii M8, Head E6, Molinuevo JL9, Blesa R4, Videla S10, Lleó A4, Sánchez-Valle R7, Fortea J11.
INTRODUCTION: We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]). METHODS: Neuroimaging features of CAA, apolipoprotein (APOE), and cerebrospinal fluid amyloid-β (Aβ) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68). RESULTS: CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. APOE ε4 genotype was borderline significantly associated with CAA in sporadic EOAD (P = .06) but not with DS or ADAD. There were no differences in Aβ040 levels between groups or between subjects with and without CAA. DISCUSSION: CAA is more frequently found in genetically determined AD than in sporadic EOAD. Cerebrospinal fluid Aβ40 levels are not a useful biomarker for CAA in AD. Copyright © 2017. Published by Elsevier Inc. KEYWORDS: Autosomal-dominant Alzheimer's disease; Cerebral amyloid angiopathy; Cerebrospinal fluid biomarkers; Down syndrome; Neuroimaging; Sporadic early-onset Alzheimer's disease
PMID 28463681 DOI: 10.1016/j.jalz.2017.03.007
Trisomy 21 consistently activates the interferon response
Elife. 2016 Jul 29;5. pii: e16220. doi: 10.7554/eLife.16220.
Sullivan KD1,2,3,4, Lewis HC1,2, Hill AA1,2, Pandey A1,2,3,4, Jackson LP1,3,4, Cabral JM1,3,4, Smith KP1, Liggett LA1,5, Gomez EB1,3,4, Galbraith MD1,2,3,4, DeGregori J1,5,6,7,8,9, Espinosa JM1,2,3,4.
Although it is clear that trisomy 21 causes Down syndrome, the molecular events acting downstream of the trisomy remain ill defined. Using complementary genomics analyses, we identified the interferon pathway as the major signaling cascade consistently activated by trisomy 21 in human cells. Transcriptome analysis revealed that trisomy 21 activates the interferon transcriptional response in fibroblast and lymphoblastoid cell lines, as well as circulating monocytes and T cells. Trisomy 21 cells show increased induction of interferon-stimulated genes and decreased expression of ribosomal proteins and translation factors. An shRNA screen determined that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts, and this defect is rescued by pharmacological JAK inhibition. Therefore, we propose that interferon activation, likely via increased gene dosage of the four interferon receptors encoded on chromosome 21, contributes to many of the clinical impacts of trisomy 21, and that interferon antagonists could have therapeutic benefits. KEYWORDS: JAK inhibitors; chromosomes; down syndrome; genes; human; human biology; interferon; medicine; mouse; ruxolitinib; trisomy 21
PMID 27472900 PMCID: PMC5012864 DOI: 10.7554/eLife.16220
Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome
Nat Med. 2015 Apr;21(4):318-26. doi: 10.1038/nm.3827. Epub 2015 Mar 16.
Deidda G1, Parrini M1, Naskar S1, Bozarth IF1, Contestabile A1, Cancedda L1.
Down syndrome (DS) is the most frequent genetic cause of intellectual disability, and altered GABAergic transmission through Cl(-)-permeable GABAA receptors (GABAARs) contributes considerably to learning and memory deficits in DS mouse models. However, the efficacy of GABAergic transmission has never been directly assessed in DS. Here GABAAR signaling was found to be excitatory rather than inhibitory, and the reversal potential for GABAAR-driven Cl(-) currents (ECl) was shifted toward more positive potentials in the hippocampi of adult DS mice. Accordingly, hippocampal expression of the cation Cl(-) cotransporter NKCC1 was increased in both trisomic mice and individuals with DS. Notably, NKCC1 inhibition by the FDA-approved drug bumetanide restored ECl, synaptic plasticity and hippocampus-dependent memory in adult DS mice. Our findings demonstrate that GABA is excitatory in adult DS mice and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS.
Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos
McCoy RC1, Demko Z2, Ryan A2, Banjevic M2, Hill M2, Sigurjonsson S2, Rabinowitz M2, Fraser HB1, Petrov DA1.
Aneuploidy, the inheritance of an atypical chromosome complement, is common in early human development and is the primary cause of pregnancy loss. By screening day-3 embryos during in vitro fertilization cycles, we identified an association between aneuploidy of putative mitotic origin and linked genetic variants on chromosome 4 of maternal genomes. This associated region contains a candidate gene, Polo-like kinase 4 (PLK4), that plays a well-characterized role in centriole duplication and has the ability to alter mitotic fidelity upon minor dysregulation. Mothers with the high-risk genotypes contributed fewer embryos for testing at day 5, suggesting that their embryos are less likely to survive to blastocyst formation. The associated region coincides with a signature of a selective sweep in ancient humans, suggesting that the causal variant was either the target of selection or hitchhiked to substantial frequency. Copyright © 2015, American Association for the Advancement of Science. Comment in Development. Aneuploidy and mother's genes. [Science. 2015] PMID 25859044
Science. 2015 Apr 10;348(6231):235-8. doi: 10.1126/science.aaa3337.
Prevalence of congenital heart defects associated with Down syndrome in Korea
J Korean Med Sci. 2014 Nov;29(11):1544-9. doi: 10.3346/jkms.2014.29.11.1544. Epub 2014 Nov 4.
Kim MA1, Lee YS1, Yee NH2, Choi JS2, Choi JY3, Seo K1.
Congenital heart defect (CHD) is common in infants with Down syndrome (DS), which is the principle cause of mortality. However, there is no data available for the frequency and types of CHD in infants with DS in Korea. We investigated the frequency of CHD in infants with DS in Korea. After the survey on birth defects was conducted throughout the country, the prevalence of CHD in DS in 2005-2006 was calculated. This study was conducted based on the medical insurance claims database of the National Health Insurance Corporation. The number of total births in Korea was 888,263 in 2005-2006; of them, 25,975 cases of birth defects were identified. The prevalence of DS was 4.4 per 10,000 total births, accounting for 1.5% of all birth defects. Of the 394 infants with DS, 224 (56.9%) had a CHD. Atrial septal defect was the most common defect accounting for 30.5% of DS followed by ventricular septal defect (19.3%), patent duct arteriosus (17.5%), and atrioventricular septal defect (9.4%). Our study will be helpful to demonstrate the current status of DS and to identify the distribution of CHD in infants with DS in Korea. KEYWORDS: Down Syndrome; Heart Defects, Congenital; Prevalence, Korea
Influence of second-trimester ultrasound markers for down syndrome in pregnant women of advanced maternal age
J Pregnancy. 2014;2014:785730. doi: 10.1155/2014/785730. Epub 2014 Mar 25.
Rumi Kataguiri M, Araujo Júnior E, Silva Bussamra LC, Nardozza LM, Fernandes Moron A.
The objective of the present study was to evaluate the influence of second-trimester ultrasound markers on the incidence of Down syndrome among pregnant women of advanced maternal age. This was a retrospective cohort study on 889 singleton pregnancies between the 14th and 30th weeks, with maternal age ≥ 35 years, which would undergo genetic amniocentesis. The second-trimester ultrasound assessed the following markers: increased nuchal fold thickness, cardiac hyperechogenic focus, mild ventriculomegaly, choroid plexus cysts, uni- or bilateral renal pyelectasis, intestinal hyperechogenicity, single umbilical artery, short femur and humerus length, hand/foot alterations, structural fetal malformation, and congenital heart disease. To investigate differences between the groups with and without markers, nonparametric tests consisting of the chi-square test or Fisher's exact test were used. Moreover, odds ratios with their respective 95% confidence intervals were calculated. Out of the 889 pregnant women, 131 (17.3%) presented markers and 758 (82.7%) did not present markers on the second-trimester ultrasound. Increased nuchal fold (P < 0.001) and structural malformation (P < 0.001) were the markers most associated with Down syndrome. The presence of one marker increased the relative risk 10.5-fold, while the presence of two or more markers increased the risk 13.5-fold. The presence of markers on the second-trimester ultrasound, especially thickened nuchal fold and structural malformation, increased the risk of Down syndrome among pregnant women with advanced maternal age.
Noninvasive prenatal testing: a replacement for chorionic villus sampling and amniocentesis for advanced maternal age?
Obstet Gynecol. 2014 May;123 Suppl 1:165S-6S. doi: 10.1097/01.AOG.0000447169.52898.80.
Pettit KE1, Hull AD, Korty L, Jones MC, Pretorius DH.
INTRODUCTION: Our objective was to assess the effect of the availability of noninvasive prenatal testing using circulating cell-free fetal DNA on the uptake of routine chorionic villus sampling (CVS) or genetic amniocentesis for advanced maternal age greater than or equal to 35 years. METHODS: Retrospective cohort study of all women who chose noninvasive prenatal testing from May to December 2012 at the University of California San Diego Fetal Care and Genetics Center. Indications for noninvasive prenatal testing were advanced maternal age, high-risk aneuploidy screening, abnormal ultrasound findings, and a family history of aneuploidy. Data were collected by chart review. The numbers of CVS and amniocenteses performed from May to December 2012 were recorded. RESULTS: Two hundred six patients chose noninvasive prenatal testing and 155 (75%) had advanced maternal age. The remaining 51 had abnormal aneuploidy screening, ultrasound findings, or both suggestive of aneuploidy. For 70 women (34%), advanced maternal age alone was the indication for noninvasive prenatal testing. The mean age of this group was 37.7±2.5 years (range 35-44 years). One of the tests done for advanced maternal age alone was positive for trisomy 21, which was confirmed by CVS. The remaining 69 women (98.6%) declined invasive testing. None of these 69 neonates had abnormal karyotypes. CONCLUSIONS: In our practice, women are choosing noninvasive prenatal testing rather than undergoing invasive testing for the sole indication of advanced maternal age. Although detection of aneuploidy with noninvasive prenatal testing is not 100%, patients with reassuring serum aneuploidy screening and normal ultrasound findings appear to favor a small risk of missing a diagnosis of aneuploidy over the risk of procedure-related pregnancy loss. PMID 24770069
Maternal plasma fetal DNA fractions in pregnancies with low and high risks for fetal chromosomal aneuploidies
PLoS One. 2014 Feb 28;9(2):e88484. doi: 10.1371/journal.pone.0088484. eCollection 2014.
Hudecova I1, Sahota D2, Heung MM1, Jin Y1, Lee WS1, Leung TY2, Lo YM1, Chiu RW1. Author information
Recently published international guidelines recommend the clinical use of noninvasive prenatal test (NIPT) for aneuploidy screening only among pregnant women whose fetuses are deemed at high risk. The applicability of NIPT to aneuploidy screening among average risk pregnancies requires additional supportive evidence. A key determinant of the reliability of aneuploidy NIPT is the fetal DNA fraction in maternal plasma. In this report, we investigated if differences in fetal DNA fractions existed between different pregnancy risk groups. One hundred and ninety-five singleton pregnancies with male fetuses divided into 3 groups according to first trimester screening parameters were examined for fetal DNA percentage by counting Y chromosome DNA sequences using massively parallel sequencing. Fetal DNA fractions were compared between risk groups and assessed for correlations with first trimester screening parameters. There was no statistically significant difference in fetal DNA fractions across the high, intermediate and low risk groups. Fetal DNA fraction showed a strong negative correlation with maternal weight. Fetal DNA fraction also showed weak but significant correlations with gestational age, crown-rump length, multiple of medians of free β-subunit of human chorionic gonadotropin and pregnancy-associated plasma protein A. Similar fetal DNA fractions in maternal plasma between high, intermediate and low risk pregnant women is a precondition for uniform performance of the aneuploidy NIPTs for the general population. This study thus shows that the aneuploidy screening by NIPT is likely to offer similar analytical reliability without respect to the a priori fetal aneuploidy risk.
DNA sequencing versus standard prenatal aneuploidy screening
N Engl J Med. 2014 Feb 27;370(9):799-808. doi: 10.1056/NEJMoa1311037.
Bianchi DW1, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, Craig JA, Chudova DI, Devers PL, Jones KW, Oliver K, Rava RP, Sehnert AJ; CARE Study Group. Collaborators (21)
Abstract BACKGROUND: In high-risk pregnant women, noninvasive prenatal testing with the use of massively parallel sequencing of maternal plasma cell-free DNA (cfDNA testing) accurately detects fetal autosomal aneuploidy. Its performance in low-risk women is unclear. METHODS: At 21 centers in the United States, we collected blood samples from women with singleton pregnancies who were undergoing standard aneuploidy screening (serum biochemical assays with or without nuchal translucency measurement). We performed massively parallel sequencing in a blinded fashion to determine the chromosome dosage for each sample. The primary end point was a comparison of the false positive rates of detection of fetal trisomies 21 and 18 with the use of standard screening and cfDNA testing. Birth outcomes or karyotypes were the reference standard. RESULTS: The primary series included 1914 women (mean age, 29.6 years) with an eligible sample, a singleton fetus without aneuploidy, results from cfDNA testing, and a risk classification based on standard screening. For trisomies 21 and 18, the false positive rates with cfDNA testing were significantly lower than those with standard screening (0.3% vs. 3.6% for trisomy 21, P<0.001; and 0.2% vs. 0.6% for trisomy 18, P=0.03). The use of cfDNA testing detected all cases of aneuploidy (5 for trisomy 21, 2 for trisomy 18, and 1 for trisomy 13; negative predictive value, 100% [95% confidence interval, 99.8 to 100]). The positive predictive values for cfDNA testing versus standard screening were 45.5% versus 4.2% for trisomy 21 and 40.0% versus 8.3% for trisomy 18. CONCLUSIONS: In a general obstetrical population, prenatal testing with the use of cfDNA had significantly lower false positive rates and higher positive predictive values for detection of trisomies 21 and 18 than standard screening. (Funded by Illumina; ClinicalTrials.gov number, NCT01663350.). Comment in Screening for trisomies in circulating DNA. [N Engl J Med. 2014]
Detection of triploidy at 11-14 weeks of gestation: a cohort study of 198,000 pregnant women
Ultrasound Obstet Gynecol. 2013 Mar 14. doi: 10.1002/uog.12460. [Epub ahead of print]
Engelbrechtsen L, Brøndum-Nielsen K, Ekelund C, Tabor A, Skibsted L; the Danish Fetal Medicine study group. Source Department of Obstetrics and Gynecology, University Hospital Roskilde, Roskilde, Denmark.
OBJECTIVES: To assess the detection rate of triploidy at first-trimester screening for trisomy 21 and evaluate outcome in triploid pregnancies. METHODS: From 2008-2011, 198,427 patients women with singleton pregnancies underwent first-trimester screening (FTS) at 11+2 - 14+0 weeks of gestation. FTS included: Nuchal translucency (NT), maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein-A (PAPP-A). In all triploid fetuses FTS parameters were re-evaluated. Karyotypes were established by invasive testing (CVS or AC) or post abortem and obtained from the Danish Cytogenetic Central Register and the Danish Fetal Medicine Database. RESULTS: A total of 30 triploid fetuses attended FTS. Twenty-five triploid fetuses were diagnosed as a result of abnormal FTS, a detection rate of 83%.Twenty-three fetuses were identified due to a high risk of trisomy 13, 18 or 21 and two fetuses due to structural abnormalities at FTS. The incidence of triploidy at FTS was 1:6614. A smaller CRL than estimated by last menstrual period was found in 95 % of the fetuses with the data available for evaluation. Eight fetuses had larger BPD than expected by gestational age. 69, XXX fetuses had significantly lower β-hCG MoM and PAPP-A MoM than 69, XXY fetuses (p=0.045 and p=0.02). No infants with triploidy were born in the study period. Among the triploid gestations, 80% of the women chose termination of pregnancy, 16 % had spontaneous miscarriages, and one was stillborn. CONCLUSION: First trimester screening for trisomy 21 also provides a high detection rate for triploidy. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.
Reliability of fetal nasal bone length measurement at 11-14 weeks of gestation
BMC Pregnancy Childbirth. 2013 Jan 16;13(1):7. [Epub ahead of print]
Suwanrath C, Pruksanusak N, Kor-Anantakul O, Suntharasaj T, Hanprasertpong T, Pranpanus S. Abstract ABSTRACT: BACKGROUND: Nasal bone assessment has been incorporated into Down syndrome screening in first trimester. Several studies have established the normal reference values for fetal nasal bone length in the first trimester, which were found to be varied by population. However, the study on reliability of nasal bone length measurement was limited with contradictory results. This study aimed to investigate the reliability of fetal nasal bone length measurement at 11--14 weeks of gestation in the Thai population. METHODS: A total of 111 pregnant women at 11--14 weeks of gestation attending for the routine first-trimester ultrasound examination were recruited. Each case was measured separately by two examiners. Examiner 1 performed the first measurement in all cases; any of the other 5 examiners consecutively performed the second measurement. Three independent measurements were performed by each examiner and they were blinded to the results of the others. Intraobserver and interobserver variabilities were evaluated with the intraclass correlation coefficient (ICC). RESULTS: Nasal bone measurement was successfully performed in 106/111 cases (95.5%) by at least one examiner; 89 cases were performed by two examiners. The intraobserver variability was excellent for all examiners (ICC, 0.840-0.939). The interobserver variability between different pairs of examiners varied from moderate to excellent (ICC, 0.467-0.962). The interobserver variability between examiner 1 and any other examiner was good (ICC, 0.749). The Bland-Altman plot of the interobserver differences of nasal bone length measurements between examiner 1 and any other examiner showed good agreement. CONCLUSIONS: The reliability of the fetal nasal bone length measurement at 11--14 weeks of gestation was good. The nasal bone length measurement was reproducible. Ethnicity has an effect on fetal nasal bone length, but reliability of nasal bone length measurement is critical to accuracy of screening and should be audited on an ongoing basis.
Prenatal diagnosis of Down syndrome: a systematic review of termination rates (1995-2011)
Prenat Diagn. 2012 Feb;32(2):142-53. doi: 10.1002/pd.2910.
Natoli JL, Ackerman DL, McDermott S, Edwards JG. Source University of South Carolina, Columbia, South Carolina, USA. email@example.com
OBJECTIVE: The objective of this study was to review the published literature on pregnancy termination following a prenatal diagnosis of Down syndrome in the United States. METHOD: A systematic search of US English-language articles (1995-2011) was conducted to identify primary research studies that reported data for pregnancies with definitive prenatal diagnosis of Down syndrome with subsequent pregnancy termination. Studies that provided indirect estimates of pregnancy termination, such as mathematical models, were excluded. The weighted mean termination rate was calculated across studies. RESULTS: Twenty-four studies were accepted. The weighted mean termination rate was 67% (range: 61%-93%) among seven population-based studies, 85% (range: 60%-90%) among nine hospital-based studies, and 50% (range: 0%-100%) among eight anomaly-based studies. Evidence suggests that termination rates have decreased in recent years. Termination rates also varied with maternal age, gestational age, and maternal race/ethnicity. CONCLUSION: This systematic review presents the largest synthesis of United States data on termination rates following a prenatal diagnosis of Down syndrome. Evidence suggests that termination rates are lower than noted in a previous review that was based on less contemporary studies and had an international focus. Heterogeneity across studies suggests that a summary termination rate may not be applicable to the entire US population. © 2012 John Wiley & Sons, Ltd.
Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11 105 pregnancies with mixed risk factors
Prenat Diagn. 2012 Nov 9:1-8. doi: 10.1002/pd.4002. [Epub ahead of print]
Dan S, Wang W, Ren J, Li Y, Hu H, Xu Z, Lau TK, Xie J, Zhao W, Huang H, Xie J, Sun L, Zhang X, Wang W, Liao S, Qiang R, Cao J, Zhang Q, Zhou Y, Zhu H, Zhong M, Guo Y, Lin L, Gao Z, Yao H, Zhang H, Zhao L, Jiang F, Chen F, Jiang H, Li S, Li Y, Wang J, Wang J, Duan T, Su Y, Zhang X. Source BGI-Shenzhen, Shenzhen, China; Department of Perinatology, Beijing Obstetrics and Gynecology Hospital, Capital University of Medical Sciences, Beijing, China.
Abstract OBJECTIVE: To report the performance of massively parallel sequencing (MPS) based prenatal noninvasive fetal trisomy test based on cell-free DNA sequencing from maternal plasma in a routine clinical setting in China. METHOD: The MPS-based test was offered as a prenatal screening test for trisomies 21 and 18 to pregnant women in 49 medical centers over 2 years. A total of 11 263 participants were recruited and the MPS-based test was performed in 11 105 pregnancies. Fetal outcome data were obtained after the expected date of confinement. RESULTS: One hundred ninety cases were classified as positive, including 143 cases of trisomy 21 and 47 cases of trisomy 18. With the karyotyping results and the feedback of fetal outcome data, we observed one false positive case of trisomy 21, one false positive case of trisomy 18 and no false negative cases, indicating 100% sensitivity and 99.96% specificity for the detection of trisomies 21 and 18. CONCLUSION: Our large-scale multicenter study proved that the MPS-based test is of high sensitivity and specificity in detecting fetal trisomies 21 and 18. The introduction of this screening test into a routine clinical setting could avoid about 98% of invasive prenatal diagnostic procedures. © 2012 John Wiley & Sons, Ltd.
Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation
Eur J Hum Genet. 2012 Jul;20(7):742-7. doi: 10.1038/ejhg.2011.272. Epub 2012 Feb 8.
Handyside AH, Montag M, Magli MC, Repping S, Harper J, Schmutzler A, Vesela K, Gianaroli L, Geraedts J. Source London Bridge Fertility, Gynaecology and Genetics Centre, London, UK. firstname.lastname@example.org
Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis following natural conception and spontaneous miscarriage demonstrates that trisomies arise mainly in female meiosis and particularly in the first meiotic division. Here, we studied copy number gains and losses for all chromosomes in the two by-products of female meiosis, the first and second polar bodies, and the corresponding zygotes in women of advanced maternal age undergoing IVF, using microarray comparative genomic hybridisation (array CGH). Analysis of the segregation patterns underlying the copy number changes reveals that premature predivision of chromatids rather than non-disjunction of whole chromosomes causes almost all errors in the first meiotic division and unlike natural conception, over half of aneuploidies result from errors in the second meiotic division. Furthermore, most abnormal zygotes had multiple aneuploidies. These differences in the aetiology of aneuploidy in IVF compared with natural conception may indicate a role for ovarian stimulation in perturbing meiosis in ageing oocytes.
Prenatal blood test for Down's syndrome is to be introduced in Germany despite ethical and legal concerns
BMJ. 2012 Jul 18;345:e4836. doi: 10.1136/bmj.e4836.
BMJ 2012; 345 doi: 10.1136/bmj.e4836 (Published 18 July 2012)
A new prenatal test that can detect Down’s syndrome from a mother’s blood sample is expected to be introduced soon in Germany, despite a legal expert saying that the test does not comply with Germany’s law on genetic diagnostic tests.
Currently, about 50 000 people in Germany have Down’s syndrome, which is detected in one in 800 pregnancies.
Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma
PLoS One. 2011;6(11):e27709. Epub 2011 Nov 23.
Lim JH, Kim SY, Park SY, Lee SY, Kim MJ, Han YJ, Lee SW, Chung JH, Kim MY, Yang JH, Ryu HM. Source Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Seoul, Korea. Abstract BACKGROUND: Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A. METHODOLOGY/PRINCIPAL FINDINGS: A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively. CONCLUSIONS: Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.
Prenatal screening for fetal aneuploidy in singleton pregnancies
J Obstet Gynaecol Can. 2011 Jul;33(7):736-50.
Chitayat D, Langlois S, Wilson RD; Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada; Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists. Source Toronto ON. Abstract OBJECTIVE: To develop a Canadian consensus document on maternal screening for fetal aneuploidy (e.g., Down syndrome and trisomy 18) in singleton pregnancies. OPTIONS: Pregnancy screening for fetal aneuploidy started in the mid 1960s, using maternal age as the screening test. New developments in maternal serum and ultrasound screening have made it possible to offer all pregnant patients a non-invasive screening test to assess their risk of having a fetus with aneuploidy to determine whether invasive prenatal diagnostic testing is necessary. This document reviews the options available for non-invasive screening and makes recommendations for Canadian patients and health care workers. OUTCOMES: To offer non-invasive screening for fetal aneuploidy (trisomy 13, 18, 21) to all pregnant women. Invasive prenatal diagnosis would be offered to women who screen above a set risk cut-off level on non-invasive screening or to pregnant women whose personal, obstetrical, or family history places them at increased risk. Currently available non-invasive screening options include maternal age combined with one of the following: (1) first trimester screening (nuchal translucency, maternal age, and maternal serum biochemical markers), (2) second trimester serum screening (maternal age and maternal serum biochemical markers), or (3) 2-step integrated screening, which includes first and second trimester serum screening with or without nuchal translucency (integrated prenatal screen, serum integrated prenatal screening, contingent, and sequential). These options are reviewed, and recommendations are made. EVIDENCE: Studies published between 1982 and 2009 were retrieved through searches of PubMed or Medline and CINAHL and the Cochrane Library, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. BENEFITS, HARMS, AND COSTS: This guideline is intended to reduce the number of prenatal invasive procedures done when maternal age is the only indication. This will have the benefit of reducing the numbers of normal pregnancies lost because of complications of invasive procedures. Any screening test has an inherent false-positive rate, which may result in undue anxiety. It is not possible at this time to undertake a detailed cost-benefit analysis of the implementation of this guideline, since this would require health surveillance and research and health resources not presently available; however, these factors need to be evaluated in a prospective approach by provincial and territorial initiatives. RECOMMENDATIONS 1. All pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies in addition to a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A) 2. Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A) 3. Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available. (II-2A) 4. Invasive prenatal diagnosis for cytogenetic analysis should not be performed without multiple marker screening results except for women who are at increased risk of fetal aneuploidy (a) because of ultrasound findings, (b) because the pregnancy was conceived by in vitro fertilization with intracytoplasmic sperm injection, or (c) because the woman or her partner has a history of a previous child or fetus with a chromosomal abnormality or is a carrier of a chromosome rearrangement that increases the risk of having a fetus with a chromosomal abnormality. (II-2E) 5. At minimum, any prenatal screen offered to Canadian women who present for care in the first trimester should have a detection rate of 75% with no more than a 3% false-positive rate. The performance of the screen should be substantiated by annual audit. (III-B) 6. The minimum standard for women presenting in the second trimester should be a screen that has a detection rate of 75% with no more than a 5% false-positive rate. The performance of the screen should be substantiated by annual audit. (III-B) 7. First trimester nuchal translucency should be interpreted for risk assessment only when measured by sonographers or sonologists trained and accredited for this service and when there is ongoing quality assurance (II-2A), and it should not be offered as a screen without biochemical markers in singleton pregnancies. (I-E) 8. Evaluation of the fetal nasal bone in the first trimester should not be incorporated as a screen unless it is performed by sonographers or sonologists trained and accredited for this service and there is ongoing quality assurance. (II-2E) 9. For women who undertake first trimester screening, second trimester serum alpha fetoprotein screening and/or ultrasound examination is recommended to screen for open neural tube defects. (II-1A) 10. Timely referral and access is critical for women and should be facilitated to ensure women are able to undergo the type of screening test they have chosen as first trimester screening. The first steps of integrated screening (with or without nuchal translucency), contingent, or sequential screening are performed in an early and relatively narrow time window. (II-1A) 11. Ultrasound dating should be performed if menstrual or conception dating is unreliable. For any abnormal serum screen calculated on the basis of menstrual dating, an ultrasound should be done to confirm gestational age. (II-1A) 12. The presence or absence of soft markers or anomalies in the 18- to 20-week ultrasound can be used to modify the a priori risk of aneuploidy established by age or prior screening. (II-2B) 13. Information such as gestational dating, maternal weight, ethnicity, insulin-dependent diabetes mellitus, and use of assisted reproduction technologies should be provided to the laboratory to improve accuracy of testing. (II-2A) 14. Health care providers should be aware of the screening modalities available in their province or territory. (III-B) 15. A reliable system needs to be in place ensuring timely reporting of results. (III-C) 16. Screening programs should be implemented with resources that support audited screening and diagnostic laboratory services, ultrasound, genetic counselling services, patient and health care provider education, and high quality diagnostic testing, as well as resources for administration, annual clinical audit, and data management. In addition, there must be the flexibility and funding to adjust the program to new technology and protocols. (II-3B). Comment in Prenatal screening for fetal aneuploidy. [J Obstet Gynaecol Can. 2011] Prenatal screening for fetal aneuploidy. [J Obstet Gynaecol Can. 2011]
Introduction of first trimester combined test increases uptake of Down's syndrome screening
Eur J Obstet Gynecol Reprod Biol. 2011 Aug 10.
Tringham GM, Nawaz TS, Holding S, McFarlane J, Lindow SW. Source Hull York Medical School, Hertford Building, University of Hull, Kingston upon Hull, UK.
OBJECTIVE: To describe any trends in the uptake of antenatal screening for Down's syndrome since the addition of the earlier first trimester combined test.
STUDY DESIGN: All antenatal screening tests for Down's syndrome were carried out and their results were recorded by the Clinical Biochemistry Department at the Hull Royal Infirmary (HRI) and reviewed against the antenatal booking data held at the Women and Children's Hospital at HRI. The uptake of antenatal Down's syndrome screening for 5 different age groups of women across a four-year-period from 2007 to 2010 was analysed.
RESULTS: There was a significant increase in uptake of antenatal screening for Down's syndrome from 43.9% to 56.5% after the introduction of the combined test in 2010. This increase was apparent in all age groups. There was no change in the proportion of women opting for an invasive test following a positive screening test.
CONCLUSION: Addition of the earlier first trimester combined test has increased uptake of antenatal screening for Down's syndrome in women of all ages. This is most likely due to the advantages this test gives women such as earlier decision making, earlier further invasive diagnostic testing and earlier termination, if necessary.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Learning curve in measurement of fetal frontomaxillary facial angle at 11-13 weeks of gestation
Ultrasound Obstet Gynecol. 2010 May;35(5):530-4.
Yang X, Chen M, Wang HF, Leung TY, Borenstein M, Nicolaides K, Sahota DS, Lau TK. Source Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
OBJECTIVE: To determine the number of ultrasound examinations required to train sonographers to accurately measure the fetal frontomaxillary facial (FMF) angle at 11-13 weeks of gestation.
METHODS: Eight sonographers accredited for nuchal translucency thickness (NT) measurement (and with different levels of experience) were trained to measure the fetal FMF angle using specially acquired three-dimensional (3D) volumes. Training was provided in cycles, and each cycle consisted of a training period on 20 randomly selected cases followed by an examination using 10 randomly selected cases. During training, the sonographer was informed of the true FMF angle value after each FMF angle measurement on a case-by-case basis. During examination, the difference between the measured and the true values of the FMF angle (i.e. the delta angle) was calculated. A measurement was considered accurate if the delta angle was less than 5 degrees . The sonographer was considered to be competent and the training finished if all 10 examination cases satisfied this criterion. Otherwise, the sonographer would undergo further cycles of training-examination, until he/she became competent.
RESULTS: The number of training cases required for a sonographer to become competent was 40 for two sonographers, 60 for one, 80 for one, 100 for two, 120 for one and 140 for one, with a median of 90. The median number of failed cases reduced from 2.5 (out of 10) at the first cycle to 0 by the 7(th) cycle. As training cycles increased, the mean angle deviation and measurement time required both reduced significantly. The average delta angle of the passing examination cycle was 2.06 +/- 1.40 degrees . The number of training cases required to become competent in FMF angle measurement was 40 for the two most experienced trainees and 80, 120 and 140 for the three least experienced ones.
CONCLUSIONS: We have demonstrated that competence in FMF angle measurement was achieved after a median number of 90 cases, with a range of up to 140. The number required was substantially lower, at 40 cases, among those with extensive experience of NT measurement.
Copyright 2010 ISUOG. Published by John Wiley & Sons, Ltd.
Maternal antimullerian hormone levels do not predict fetal aneuploidy
J Assist Reprod Genet. 2010 Jul;27(7):409-14. Epub 2010 May 20.
Plante BJ, Beamon C, Schmitt CL, Moldenhauer JS, Steiner AZ. Source The University of North Carolina School of Medicine, Department of Obstetrics and Gynecology, Chapel Hill, 27599-7570, USA. email@example.com
PURPOSE: To determine if diminished ovarian reserve (measured by maternal antimullerian hormone (AMH) levels), is associated with fetal aneuploidy (determined by prenatal karyotype).
METHODS: This case-control study included 213 women with singleton pregnancies who underwent both serum aneuploidy screening and invasive prenatal diagnosis. 18 patients carrying an aneuploid fetus served as cases and the remaining 195 women with a euploid fetus were controls. Serum AMH was measured using two assays: AMHbc (Beckman-Coulter) and AMHdsl (Diagnostic Systems Laboratories). Karyotypes were determined by chorionic villus sampling or amniocentesis.
RESULTS: AMHbc levels did not differ between women with an aneuploid fetus and women with a euploid fetus (p = 0.46) and did not predict aneuploidy (ROC Area = 0.57). Additionally, AMHbc values declined significantly with advancing gestational age.
CONCLUSIONS: Maternal AMH does not appear to be a marker of fetal aneuploidy in ongoing pregnancies. Contrary to previous reports, we found a significant decline in maternal AMH levels with advancing gestational age.
First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker
Reprod Biol Endocrinol. 2010 Oct 29;8:129.
Tørring N, Ball S, Wright D, Sarkissian G, Guitton M, Darbouret B. Department of Clinical Biochemistry, Aarhus University Hospital-Skejby, Aarhus, Denmark. firstname.lastname@example.org
BACKGROUND: A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model.
METHOD: In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model.
RESULTS: The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP-A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free β-hCG with or without nuchal translucency.
CONCLUSION: The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.
PMID: 21034452 http://www.ncbi.nlm.nih.gov/pubmed/21034452
Prenatal sonographic features of fetuses in trisomy 13 pregnancies. IV
Taiwan J Obstet Gynecol. 2010 Mar;49(1):3-12.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. email@example.com Abstract Prenatal ultrasound is a powerful tool to detect structural abnormalities associated with the fetuses in trisomy 13 pregnancies. This article provides a comprehensive review of the prenatal sonographic markers of trisomy 13 in the first trimester, including fetal nuchal translucency thickness, fetal heart rate, fetal nasal bone, fetal tricuspid regurgitation, ductus venous flow, fetal crown-rump length, fetal trunk and head volume, fetal frontomaxillary facial angle, gestational sac volume and umbilical cord diameter, along with biochemical markers such as maternal serum free beta-human chorionic gonadotropin, maternal serum pregnancy-associated plasma protein-A, maternal serum placental growth factor, and the fetal and total cell-free DNA concentration in the maternal circulation.
Novel Screening Strategies
There are several additional suggested screeening stratagies currently at various stages of development. These techniques should be seen as at the research stage olny until data, a clinical concensus and a recommendation has been made.
- Odibo AO, Sehdev H, Stamilio DM, Macones GA. OC053: The efficiency of second-trimester nasal bone (NB) hypoplasia as a Down syndrome marker in low versus high-risk groups. Ultrasound Obstet Gynecol. 2008 Aug 11;32(3):259-260. PMID: 18697081
- van Heesch PN, Struijk PC, Brandenburg H, Steegers EA, Wildschut HI. Jugular lymphatic sacs in the first trimester of pregnancy: the prevalence and the potential value in screening for chromosomal abnormalities. J Perinat Med. 2008 Aug 6. PMID: 18681837
- Calda P, Belosovicova-Viskova H, Valtrova H, Svabik K, Manasova S, Zizka Z, Brestak M, Nekovarova K. OC052: Ultrasound at 20-22 weeks of pregnancy increases the rate of detection of Down syndrome above that of combined first-trimester screening alone. Ultrasound Obstet Gynecol. 2008 Aug 11;32(3):259. PMID: 18697054
- Kirkegaard I, Petersen OB, Uldbjerg N, Turring N. Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks. Prenat Diagn. 2008 Aug 1. PMID: 18677711
Novel Screening Strategies
There are several additional suggested screeening stratagies currently at various stages of development. These techniques should be seen as at the research stage only until data, a clinical concensus and a recommendation has been made.
- Jugular lymphatic sacs in the first trimester of pregnancy 
- First-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks 
- The National Down Syndrome Project: Design and Implementation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1802119/
Increased prevalence of renal and urinary tract anomalies in children with Down syndrome
Pediatrics. 2009 Oct;124(4):e615-21. Epub 2009 Sep 14.
Kupferman JC, Druschel CM, Kupchik GS. Source Divisions of Pediatric Nephrology and Hypertension, Maimonides Infants and Children's Hospital, Brooklyn, New York 11219, USA. firstname.lastname@example.org Abstract OBJECTIVE: The goal was to investigate the prevalence of renal and urinary tract anomalies (RUTAs) in a Down syndrome (DS) population.
METHODS: Data were obtained from the New York State Congenital Malformation Registry (NYS-CMR) in this retrospective cohort study. The occurrence of RUTAs was assessed for children with and without DS who were born in NYS between 1992 and 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each malformation.
RESULTS: Between 1992 and 2004, 3832 children with DS and 3 411 833 without DS were born in NYS. The prevalence of RUTAs in the DS population was 3.2%, compared with 0.7% in the NYS population (OR: 4.5 [95% CI: 3.8 -5.4]). Children with DS had significantly increased risks of anterior urethral obstruction (OR: 29.7 [95% CI: 4.0 -217.7]), cystic dysplastic kidney (OR: 4.5 [95% CI: 1.5-14.1]), hydronephrosis (OR: 8.7 [95% CI: 6.8 -11.0]), hydroureter (OR: 8.5 [95% CI: 3.5-20.4]), hypospadias (OR: 2.0 [95% CI: 1.4 -2.9]), posterior urethral valves (OR: 7.1 [95% CI: 1.8 -28.8]), prune belly syndrome (OR: 11.9 [95% CI: 1.6 - 85.4]), and renal agenesis (OR: 5.4 [95% CI: 2.8 -10.4]). There was no significantly increased risk of ectopic kidney (OR: 1.6 [95% CI: 0.2-11.2]) or ureteropelvic junction obstruction (OR: 1.4 [95% CI: 0.2-9.9]) in the DS population.
CONCLUSION: Children with DS have significantly increased risks of RUTAs.
PMID: 19752083 http://www.ncbi.nlm.nih.gov/pubmed/19752083
Discovery of novel serum biomarkers for prenatal Down syndrome screening by integrative data mining
"To facilitate the experimental search for novel maternal serum biomarkers in prenatal Down Syndrome screening, we aimed to create a set of candidate biomarkers using a data mining approach."
Down syndrome—recent progress and future prospects
Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice
"Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here, we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice and that the effect increases with advancing maternal age."
Down syndrome—recent progress and future prospects
Frances K. Wiseman, Kate A. Alford, Victor L.J. Tybulewicz, and Elizabeth M.C. Fisher Hum Mol Genet. 2009 April 15; 18(R1): R75–R83. doi: 10.1093/hmg/ddp010.
Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice
Leland S, Nagarajan P, Polyzos A, Thomas S, Samaan G, Donnell R, Marchetti F, Venkatachalam S. Proc Natl Acad Sci U S A. 2009 Jul 17. PMID: 19617567
- "Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here, we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice and that the effect increases with advancing maternal age."
Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free beta-hCG and pregnancy-associated plasma protein-A
Kagan KO, Wright D, Valencia C, Maiz N, Nicolaides KH. Hum Reprod. 2008 Sep;23(9):1968-75. Epub 2008 Jun 10. PMID: 18544579
Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age
Hum Reprod Update. 2008 Mar-Apr;14(2):143-58. Epub 2007 Dec 14.
Jones KT. Source Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Framlington Place, Newcastle, NE2 4HH, UK. email@example.com Abstract Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV), dictyate stage of prophase I and at metaphase II. These arrests are spanned by three key events, the focus of this review: (i) passage from mitosis to GV arrest during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and (iii) completion of meiosis II following fertilization, both meiotic divisions being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human oocytes is associated with an age-related high rate of chromosomal mis-segregation, such as trisomy 21 (Down's syndrome), resulting in aneuploid conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a consequence of an age-long decline in the cohesive ties holding chromosomes together. Such loss goes undetected by the oocyte during meiosis I either because its ability to respond and block division also deteriorates with age, or as a consequence of being inherently unable to respond to the types of segregation defects induced by cohesion loss.
Frequency and distribution of chromosome abnormalities in human oocytes
Cytogenet Genome Res. 2005;111(3-4):193-8.
Kuliev A, Cieslak J, Verlinsky Y.
Reproductive Genetics Institute, Chicago, IL 60614, USA. firstname.lastname@example.org Abstract It was previously shown that more than half of the human oocytes obtained from IVF patients of advanced reproductive age are aneuploid, due to meiosis I and meiosis II errors. The present paper further confirms that 61.8% of the oocytes tested by fluorescent probes specific for chromosomes 13, 16, 18, 21 and 22 are abnormal, representing predominantly chromatid errors, which are the major source of aneuploidy in the resulting embryos. Almost half of the oocytes with meiosis I errors (49.3%) are prone to sequential meiosis II errors, which may lead to aneuploidy rescue in 30.8% of the cases. Half of the detected aneuploidies (49.8%) are of complex nature with involvement of two or more chromosomes, or the same chromosome in both meiotic divisions. The aneuploidy rates for individual chromosomes are different, with a higher prevalence of chromosome 21 and 22 errors. The origin of aneuploidy for the individual chromosomes is also not random, with chromosome 16 and 22 errors originating more frequently in meiosis II, and chromosome 18, 13 and 21 errors in meiosis I. There is an age dependence not only for the overall frequency of aneuploidies, but also for each chromosome error, aneuploidies originating from meiosis I, meiosis II, and both meiosis I and meiosis II errors, as well as for different types of aneuploidies. The data further suggest the practical relevance of oocyte aneuploidy testing for detection and avoidance from transfer of the embryos deriving from aneuploid oocytes, which should contribute significantly to the pregnancy outcomes of IVF patients of advanced reproduction age.
Impact of trisomy on fertility and meiosis in male mice
Hum Reprod. 2007 Feb;22(2):468-76. Epub 2006 Oct 17. Davisson M, Akeson E, Schmidt C, Harris B, Farley J, Handel MA.
The Jackson Laboratory, Bar Harbor, ME 04609, USA. email@example.com Abstract BACKGROUND: Chromosomal abnormalities frequently are associated with impairment or arrest of spermatogenesis in mammals but are compatible with fertility in female carriers of the same anomaly. In the case of trisomy, mice have extra genomic DNA as well as the chromosomal abnormality, usually present as an extra, unpaired chromosome. Thus, impairment of spermatogenesis in trisomic males could be due to the presence of extra genomic material (i.e. triplicated genes) or due to the chromosomal abnormality and presence of an unpaired chromosome in meiosis.
METHODS: In this study, fertility and chromosomal pairing configurations during meiotic prophase were analysed in male mice trisomic for different segments of the genome. Four have an extra segmental or tertiary trisomic chromosome--Ts(17(16))65Dn, Ts(10(16))232Dn, Ts(12(17))4Rk and Ts(4(17))2Lws--and one has the triplicated segment attached to another chromosome--Ts(16C-tel)1Cje. Ts(17(16))65Dn and Ts(16C-tel)1Cje have similar gene content triplication and differ primarily in whether the extra DNA is in an extra chromosome or not.
RESULTS: The presence of an intact extra chromosome, rather than trisomy per se, is associated with male sterility. Additionally, sterility is correlated with a high frequency of association of the unpaired chromosome with the XY body, which contains the largely unpaired X and Y chromosomes.
CONCLUSIONS: Intact extra chromosomes disrupt spermatogenesis, and unpaired chromosomes establish a unique chromatin territory within meiotic nuclei.
Trisomy 21 enhances human fetal erythro-megakaryocytic development
Chou ST, Opalinska JB, Yao Y, Fernandes MA, Kalota A, Brooks JS, Choi JK, Gewirtz AM, Danet-Desnoyers GA, Nemiroff RL, Weiss MJ. Blood. 2008 Dec 1;112(12):4503-6. PMID: 18812473
"Children with Down syndrome exhibit 2 related hematopoietic diseases: transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia (AMKL). Both exhibit clonal expansion of blasts with biphenotypic erythroid and megakaryocytic features and contain somatic GATA1 mutations. ...Our findings indicate that trisomy 21 itself is associated with cell-autonomous expansion of erythro-megakaryocytic progenitors. This may predispose to TMD and AMKL by increasing the pool of cells susceptible to malignant transformation through acquired mutations in GATA1 and other cooperating genes."
Kirkegaard I, Petersen OB, Uldbjerg N, T√∏rring N. Abstract Improved performance of first-trimester combined screening for trisomy 21 with the double test taken before a gestational age of 10 weeks.Prenat Diagn. 2008 Aug 1. [Epub ahead of print]
Breathnach FM, Malone FD. Screening for aneuploidy in first and second trimesters: is there an optimal paradigm? Curr Opin Obstet Gynecol. 2007 Apr;19(2):176-82.
"Screening strategies for aneuploidy continue to evolve, with the most recent evidence favouring a contingent sequential approach."
American College of Obstetricians and Gynecologists New Recommendations for Down Syndrome Call for Screening of All Pregnant Women (January 2, 2007) (More? [#ACOGrecommendations ACOG Screening Recommendations])
"This new recommendation says that the maternal age of 35 should no longer be used by itself as a cut-off to determine who is offered screening versus who is offered invasive diagnostic testing"
Akiyama T, Nagata M, Aoki F. Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice. Proc Natl Acad Sci U S A. 2006 May 1;
"It was recently reported that histones are globally deacetylated in mammalian oocytes during meiosis but not mitosis. ... The high incidence of aneuploidy in the embryos of older females may be due to inadequate meiotic histone deacetylation."
Chitty LS, Kagan KO, Molina FS, Waters JJ, Nicolaides KH. Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study. BMJ. 2006 Feb 13
2011 ANAT2341 Student - Page Assessments
--Mark Hill 09:50, 22 September 2011 (EST) Lab 7 Online Assessment I would like each student to now also look at the following online page before the next Lab and write a comment based upon the group project assessment criteria. http://php.med.unsw.edu.au/embryology/index.php?title=Trisomy_21 Paste your comment on the Trisomy 21 discussion page and also on your own student page.
Trisomy 21 Comments:
The page seems to have a numerous amount of information and effort.
- Introduction seems short for such a big topic. It would be great if it incorporates to what is actually in the page.
- The Definition of Down Sydndrom and Aneuploidy can be possibly moved to the Terms.
- The Location of the Links could be shifted to the External link sub heading, because the reader might find it disturbing to have plenty of links from the start.
- The two sections “ Heart Defects” and “ Limb Defects” need more elaboration, rather than links. It is great to see other links in the middle that would lead you to another source, however, a couple of paragraphs would make the section more engaging.
- In the Section “ Associated Congenital Abnormalities, the Image seems to miss a description!
- The Prevalence can be shifted to the top of the page as the information is related to the introduction. Also the size of the image needs to be minimized because the section is not that large. In addition, the Limit of two countries can be expanded to a worldwide range.
- “Screening by Country” seems to be limited to one country, it would look more professional if other countries were involved.
- I liked how the diagram of “screening” shows the analysis process.
- References can be moved towards the end of the page
- Generally, a great deal of research has been put into this project, but with some alteration of the project structure, modify some minor mistakes ,and addition to global information could make it more superb. --z3284061 12:54, 22 September 2011 (EST)
Review: -The flow of contents within the whole page- (with respect to headings) seems rather disjointed. For instance, prevalence could have come below the introduction section- as it would give readers a sense of how common this disease is.
-Within the introduction section, it would have been better if it portrayed more generic information that gave the reader a top down view of the topic. Also, the picture of Down J.L.H would have been better included in this section, instead of further down.
- The pictures attached fail to have copyright information included.
- The placement of links to genetics and diagnosis links seems misplaced and messy in the introduction.
- Under the "some recent findings" section- which could have been better placed at the end of the page, before the conclusion- it would have been better if the papers were described in text, instead of simply listing the title and the abstract.
-There is excessive use of dot points in this site. More text and descriptions is needed.
-Under prevalence- whilst it is stated that data from different world regions is described, only data from atlanta (US) and Galway (Ireland) are included
-There is good use of charts and tables to highlight data.
-Under "Screening by country"- only data from Spain is included.
-There are irrelevant sections included in the wiki- such as Aneuploidy- which merely states definitions.
-The inclusion of relevant journals and books in the reference section is a good idea, that enables the reader to engage in further research on the topic if required. --Rahul Mohan 12:09, 22 September 2011 (EST)
Trisomy 21 page evaluation:
Good brief and concise introduction. The use of the links at the end of the introduction is very helpful as the reader doesn't have to go back and fort if a section for external links was just made, but I believe there are too many links to put in one section, especially the introduction, it makes the section too cluttered and busy. I believe some of the links could be reevaluated and see if they should be incorporated in the page/section.
The recent findings section was an amazing idea, as it allows the reader to see that there are current progress on the disease, and it also gives credibility to the page as being up-to-date with the information.
I believe the karyotyping, aneuploidy, and Meiosis 1 & 2 section can be combined together as 1 subheading talking about the genetics/aetiology of the disease, which is not really explored in the page. It would have been much more informative if the page discussed about the current theories as to how the aneuploidy occurred, and use the Meiosis 1 & 2 section as back up evidence for it. Basically some of the sections are informative but not really necessary, like the Aneuploidy section, and it would have been better if the genetics side of things have been further explored.
The associated congenital abnormalities, heart defect and limb defect could have been synthesised together and presented in a much more conducive way, where the information is organised in a more orderly fashion, like the use of subheadings. The information contained in each of the 3 sections mentioned above have enough detail to get an idea about the defects in the disorder.
The section American College of Obstetricians and Gynecologists Recommendations and Trisomy growth charts could be interchanged, as it may allow the page to flow better than how it is.
The section of Prevalence and Diagnosis are done very well and are very informative.
The images and diagrams are used effectively throughout the whole page, there are no diagrams that should not be found in a section that it should not be in.
Overall it is a good page, not outstanding. It could still use some more information in it and the structuring could still be modified. --z3290841 11:59, 22 September 2011 (EST)
Trisomy 21 comments:
• The key points relating to the topic that your group allocated are clearly described.
This is generally well done, except that the introduction relies a lot on the external links that are provided. Perhaps there should be more elaboration of the history of Downs syndrome, and specific sections on etiology and epidemiology; these sections require more written on their specific section given the importance of this disease.
• The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
It is well covered, and there is a large number of diagrams tables and graphs which make the information easily accessible. However, at times it seems that the content relies on dot points and diagrams; there are no sections of text that have bodies of text and this makes the information feel artificial; there is not much flow in the information and seems to skip from point to point. Otherwise, the selected images are appropriate; perhaps graphs for each specific section (such as a graph for epidemiology) might be appropriate as well.
• Content is correctly cited and referenced.
Unfortunately the first diagram present on the page isn’t correctly cited or referenced, and there are a few sections which lack references altogether, such as the Heart Defects section. The picture of John Langdon Down also lacks a proper reference.
• The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
The information is highly information and quite interesting, but I feel lacks a written paragraph to link all of the information together. There is a severe lack of information on treatment and future research directions, as well as the physiological mechanisms that underlie the disease process.
• Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
There is extensive research past the formal teaching activities as can be seen by the content provided by the external links; however, it still seems like these links are relied on as opposed to having the critical information presented within the project itself.
• Relates the topic and content of the Wiki entry to learning aims of embryology.
It would be nice to see that the sections are a little better explained, such as the basic mechanisms of growth and development been outlined, followed by a discussion of how the disease process of Downs syndrome alters and changes these basic growth processes. Whilst this information is provided as external links it would be nice to see it elaborated on the actual page, keeping the relevant information specific to the project. --Z3288827 11:30, 22 September 2011 (EST)
Trisomy 21 review:
Introduction: It is quite disjointed and doesnt flow very well, there are no references as to where the statstics came from. There is a qoute in the intro with no reference either. Also, the picture used has no description and also no reference to the original picture/article it was obtained from.
Some recent finding: Why is this after introduction!?! this should be like towards the end! in anyway the part looks good, has good references and the picture's image source is well done.
Trisomy 21 karyotypes: whilst what you have said is good, i just dont understand what this has to do with the process please link it in properly.
Associated Congenital Abnormalities: good listing, but describe more? whats the picture have to do with it? please link!
Heart Defects:Love the idea of links being incorporated for further reading, but where do these percentages come from? references?
Limb defects: I think you need to state a description and introduction into the actual heading! its very fast and doesnt allow a person to comprehend it properly.
Prevalence: Why is this in between screening and recomendations!?! also, world regions? and then only listing ireland and US? be mroe specific about where the data was obtained from!
Screening: Describe the actual processes? it would be great to get some idea of how the screening process occurs?!No image source for John Langdon. Terms should be in a all in one glossary list.
Meosis 1 and 11: what does thsi section have to do with your project page? please relate the two.
Aneuploidy: You didnt need a second heading for this, it could have been incorporated elsewhere.
Overall much work needs to be done in making this page come upto scratch. :) --z3291423 11:11, 22 September 2011 (EST)
- The linking of words to the glossary is good.
- Some pictures are formatted in a way that the page doesn't flow very well.
- Formatting is ok. Some areas where there is large empty spaces.
- Good amount of pictures and text.
- Informative content.
--z3217043 10:54, 22 September 2011 (EST)
Overall, the page looks good, however there are a few formatting issues. The pictures are not aligned properly to the text and many of them are not referenced properly. There are no copyright statements stating the picture was of free access or any permission to use the images. These images should be removed or the copyright statement added to the content. There is also no student image as required by the assessment. Although there is a long list of references, there is a lack of information on the page. There is a lack of detail in all the sections. There is a good balance between the (inappropriate) use of images and information. The images do not relate to the imformation and some of the text lack a reference. The overall flow of the headings and subheadings needs more work. The heading " American College of Obstetricians and Gynecologists Recommendations" should be under the subheading diagnosis as it refers to diagnosis techniques recomended by the association. Although the page looked good, there is still a lot of work to be done.
--Z3332178 10:52, 22 September 2011 (EST)
Trisomy 21 Peer Review
- Introduction does not seem to flow. Maybe restructure paragraphs?
- Good links, could be placed somewhere else other than introduction?
- Some heading were too specific eg. Heart defects
- The order of headings should be revised so that it is in a logical order that builds on the previous heading
- Some pictures did not have correct referencing eg. Associated congenital abnormalities. Is this picture relevant?
- Understandable-language not too technical
- No student drawn diagrams or figures
- Adequate research-lots of references
- Overall, good level of content
- Good balance of text and pictures
--Z3308965 10:29, 22 September 2011 (EST)
- the layout of the graphs and images were not consistent
- overall an okay wiki page
--z3060621 19:57, 28 September 2011 (EST)
- Lacks structure. Some of the detail included could belong in a separate sub-heading such as ‘Epidemiology’ or ‘Genetic Characteristics’.
- Definition of ‘Aneuploidy’ belongs in the glossary, not in the introduction sub-heading.
- Link to increased genetic risk with maternal age belongs in a subheading of its own such as ‘Associated Factors’ or ‘Contributing Factors’
The image provided to the right of the introduction has no copyright statement and also has no description provided.
Some Recent Findings
- This sub-heading could be worded a bit better, ‘Recent Findings’ would be more suitable
- The explanations of the studies are not directly addressing the audience. Explanations are just quotes from the abstracts of the various studies mentioned. There is no element of explaining the studies in order to teach at a peer level.
Trisomy 21 Karyotypes
- No explanation of image and no copyright statement provided.
Associated Congenital Abnormalities
- This is a good start to the section but each dot point needs further depth and explanation. Further referencing is required and formatting must be attended to.
Heart Defects/Limb Defects
- Links provided here are helpful, although I think it would be suitable to have some form of description of each of the defects on this page.
American College of Obstetricians and Gynecologists Recommendations
- This should not be a sub-heading, the information found here should be under headings such as ‘Diagnosis’, ‘Management’ or ‘Screening’
Meiosis I and Meiosis II
- This should not be a sub-heading, it might better be suited to a headings such as ‘Recent Findings’ or ‘Associated Research’
- Again, this belongs in the glossary and should not be a sub-heading
- Further description and explanation required.
--z3331469 08:21, 22 September 2011 (EST)
Trisomy 21 Peer Assessment
- To begin with, the way you have arranged the order of the headings doesn’t flow very nicely
- Although the intro is concise, it doesn’t introduce the topic as much as it could- a little more detail could help. The historical reference would also be better suited elsewhere.
- Recent findings would be better suited towards the end of the page, and a short summary of the actual paper would be better than a direct quote.
- Where are your historical references? (besides the one point in the introduction)
- How does karyotyping work? This is not explained very well- expand on this.
- Associated Congenital abnormalities would be better under one heading rather than having a separate one for each defect (i.e. heart defect, limb defect)
- Heart defects should be explained in more detail and an image would help back this up
- A list of signs and symptoms would fit nicely with congenital abnormalities.
- Copyright info is missing for the John Langdon Down image- and what is its purpose here?
- Prevalence: only Ireland and the USA are listed- this shows that not much research has been done. You need a more worldwide distribution.
- The meiosis section is a little confusing, and does not exaplin how meiosis actually occurs- this section would also be better under ‘recent findings’
- Growth charts are interesting
- Your ‘terms’ list should not be placed under your references- they would be better suited above the references to make them easier to find.
- No student drawn image here?
- Overall, interesting information that has potential for a good project
--Z3290379 08:14, 22 September 2011 (EST)
Trisomy 21 Page Judgment Comment
Some areas were quite lacking in content, such as ‘Trisomy 21 Karotypes’. More detail needs to be included so that the audience is more informed. Most images have no copyright clearance statement this leaving UNSW Embryology open to legal issues. Something to consider. We are not told how Karyotype works and what it is clearly at all. Screening by country needs to have more than one country listed. Spain is only one country, not many. All the images on the page were not explained very clearly. An example of this is the Trisomy 21 graphs, which are poorly explained. It appears as if the project was rushed. All areas of the project need to be expanded upon. Otherwise, the students cannot grasp what they need to know about Down Syndrome. The section on Prevalence needs to have more than the two countries of Ireland and the USA listed. It needs to have at least 6 or 7 for a somewhat valid comparison. The section entitled meiosis 1 and 2 with aneuploidy did not link in with the rest of the project. Where was its relevance? The introduction needs more information. It is too fluffy and wordy. Wordiness is not equivalent to extra information. The research conducted needs to be explained more clearly and be linking in with the rest of the page. There is still a long way to go yet before the page is suitable for the site. As well, the glossary needs more terms. There are not enough of them at the moment. --Robert Klein 07:24, 22 September 2011 (EST)
Critique of Trisomy 21
General Structure: The sub-heading structure is a little out of order, for example ‘Recent Findings’ should be placed at a later stage, whilst a ‘history’ subheading and/or ‘Epidemiology’ would have been more competent at the top. Also, of the sub-headings aren’t worded well, for example ‘some recent findings’, would read better as just ‘Recent findings’. Content is poor in areas such as ‘Trisomy 21 Karotypes’, more detail could have been included in explaining each one. ‘Heart defects’ and ‘limb defects’ also lacked a substantial amount of detail.Most of your images do not have a copyright clearance statement. No student drawn image should have at least 1 or 2.
Introduction: The introduction is very wordy and I don’t feel it gives a good opening to the disease. It reads poorly in structure. The introduction is the first thing that is read, so this needs to be improved. Also, the history of the disease is not explained well, if there is not going to be subheading for it, the origin of the disease should be outlined in the introduction. The image included is good, however the copyright clearance statement is not clearly supplied. The external links prove to be very helpful, however I think they are ‘overwhelming’ to have at the start, a better position for these links may possibly be the bottom of the page.
Some recent findings: The name of this sub-heading is not proficient. The quotes from the readings clash with points 1 and 5 of the Group Assessment Criteria, because you have not gone to the effort of explaining it in your own words, remember that the reader’s are your peers.
Trisomy 21 Karotypes: Good use of images, however the detail is lacking here. How does karotyping actually work? Maybe the descriptions in each image can be incorporated under the sub-heading.
Heart Defects and Limb defects: Only 1 image. No images for heart defects, a visual aid is necessary for this section. Also, where are all the references?
Prevalence: Nothing from Australia? I’m also not quite sure why the picture of John Langdon Down is under this sub-heading, should be under “history’ or introduction.
Down ’s syndrome screening: Nice use of the table. I think this is the best explained sub-heading, with plenty of descriptions and detail. The image is uploaded in the correct manner. Could have put the ‘terms’ with the glossary below.
Meiosis I and II + Aneuploidy: Relevance? Information should probably have been included in ‘Recent findings’.
Trisomy growth charts: You should use your own words to explain the charts. --z3289829 01:02, 22 September 2011 (EST)
Trisomy 21 Peer assessment --z3331556 00:17, 22 September 2011 (EST)
- hyper-link words to glossary is useful, this should be done for Aneuploidy instead of listing it in the intro
- Down Syndrome is the historic name used for this condition identified by Down, J.L.H. in a 1866 paper where he described the "phenotypic features that includes mental retardation and characteristic facies". --this sentence could be incorporated in the opening paragraph so intro can flow better
- Maybe recent findings could go toward the end, just so we get more of an idea of what the features of Trisomy 21 are first, also quotes directly from the article shouldn't be the main focus of this section, it would be better to summarise the findings in your own words
- Some of the images need to be referenced properly, some contain no copyright clearance statement
- More info needed for Associated Congenital Abnormalities section, not just a list
- heart defects section has not been referenced, where have the figures come from?, more description of these conditions are needed not just the definition, maybe include what how this abnormality is manifested, also percentages could be better displayed in a table, the same could be done for the limb defects section
- Image of John Langdon Down appears to be in an odd place, should go around intro when he is mentioned
- Prevalence could appear toward the beginning, the definition of prevalence could also be a hyper-link to glossary instead of including it in the body of project, might want to include the prevalence of down syndrome in Australia, this may be better formatted in a table
- American College of Obstetricians and Gynecologists Recommendations section has some good information, however, it may be better to put this under a broader subheading (e.g. management/or diagnosis) maybe a good idea to combine it with Down syndrome screening
- Screening could also be better formatted in a table with a little more description about how these screenings are conducted
- Miosis I and II shouldn't really be a heading on its own, maybe better to incorporate it with recent findings.
- Aneuploidy also should not be a heading on its own this can be included as a glossary term
- Again a whole section dedicated to growth charts doesn't seem right, good info but could be incorporated into a broader heading
- I also feel there's info missing from the page, like maybe some the physical characteristics of Trisomy 21 i.e facial abnormalities
- reference list: i like the idea of splitting up the different kinds of sources used, however this needs to be refined as it is a bit confusing
Trisomy 21 Peer Assessment --z3290808 23:03, 21 September 2011 (EST)
- The introduction is not very well structured. It does not give an overview of what is to come and does not initially evoke the reader.
- I like the internal links used on this page such as “nondisjunction” which takes you directly to the glossary section. This saves the reader time and effort instead of having to look up the meaning of the unfamiliar words.
- “Aneuploidy is the term used to describe any abnormal number of chromosomes either an increase or decrease in total number.” This sentence seems out of place. Perhaps an internal link to the glossary (like that of the word “nondisjunction” used earlier) should have been provided as it does not link in with the rest of the introduction- the word was not even mentioned anywhere else in this introduction.
- I like the extra links provided at the end of the introduction which allow the reader to read up on some extra information, however, some links are repeated in both “genetic links” and “diagnosis links” such as “prenatal diagnosis.” Also, some links are not very related to Trisomy 21- these may confuse the reader and we don’t want them to completely deviate away from the subject at hand.
- I like the image – it helps to visualise the genetic abnormality of Trisomy 21. The image, however, is lacking a name at the bottom. Also the image does not contain a copyright notice!
- There is only one reference in this whole introduction- not good enough. 1st, 3rd and 4th paragraphs are not even cited!
Some Recent Findings:
- Firstly, I don’t think this section should be placed here. I think it should appear later on the page, possibly towards the end?
- I like how this section is arranged structurally, however there are some issues. Firstly, it is not sufficient to merely quote the information as a whole. If a quote is required, it should not make up the bulk of the information. This information should have been put into your own words. Also, the references should be placed directly after the quote (not as done here).
- This is a good image; however I don’t think it belongs under this heading as it does not display any recent findings. I think it more shows some of the facial phenotypic characteristics of the disease. I think it should be in the signs and symptoms section of this page – however the dilemma I found is that this page actually lacks a specific “signs and symptoms” subheading which I think is imperative, especially for this specific genetic disorder which shows many phenotypic characteristics. From the looks of it the image has been referenced appropriately with the inclusion of the copyright notice.
Trisomy 21 (Down Syndrome) Karyotypes:
- The two images are good and referenced adequately. Do they need a copyright notice however? They help to visualise the genetic abnormality of chromosome 21 associated with this disorder in both males and females which is good.
- The description below could be more targeted at the images above. An explanation of the difference between the male and female karyotype would have also been good.
- It just seems like this section is slightly too brief, although it does get the message across.
- Lack of references of the text in this section!
Associated Congenital Abnormalities:
- To make it look more professional, the first letter after the bullet point should be a capital.
- Only one reference for this whole list?
- I like the “(More? Hearing Abnormalities)” section for readers who are interested in reading further.
- The image in this section is too small as a thumbnail. It also has no title so the reader does not know what they are obtaining from the image before they click onto it. The image is not referenced appropriately. I think the image does not need to be there- it does not seem to complement the adjacent text of this section.
- Links are good, however same issue as above – would look more professional with the bullet point starting with a capital letter.
- No references in this section which is worrying considering you have provided percentages that need to be justified with an appropriate citation.
- Quite a brief section but is okay in structure.
- Only one reference for this section?
- Image is appropriate and complements the writing of this section. It also has a title, thus the reader knows before even clicking onto it what it encompasses. Image reference seems adequate.
American College of Obstetricians and Gynecologists Recommendations:
- This section is overall good, however I am not too sure if it is appropriate to dedicate an entire section to this?
- Interesting section- it says “Listed below are some sample data from different world regions” although the reader is only provided with data based on Ireland and USA. If it’s possible to obtain, more data on many other countries would be good to allow the reader to gain insight into the prevalence of the disorder worldwide.
- References have been included which is good.
Down's syndrome Screening:
- This section is possibly too long and dense with information – you may lose the reader!
- I don’t think the image of “John Langdon Down” is appropriate for this section on screening of down’s syndrome. Maybe this could go in the introduction? Also this image has not been properly referenced and no copyright notice has been displayed.
- The image of the “Tandem SNP Analysis Process” seems appropriate for this section and is satisfactory referenced.
- Parts of this section are not referenced.
Meiosis I and Meiosis II:
- “A recent study has analysed two large USA studies…” I do not think this should be a section on its own. It could very well be added into the “Some recent findings” section.
- Firstly, no references in this section!
- Secondly, as with the previous section, I do not believe this information should be dedicated an entire subheading. It could easily be incorporated into the glossary via an internal link such as the one used in the introduction.
Trisomy 21 Growth Charts:
- “Data from this paper…” Which paper? Please reference exactly which paper and include authors of paper as well as year published.
- Once again I do not think this should be dedicated to an entire sub heading. It does not seem directly relevant.
- Nevertheless, graph charts are good with appropriate references and titles.
- As I have mentioned in a previous comment, it is not very good to quote a whole paragraph. Try to put this in your own words and maybe only quote a vital piece of information.
References + Glossary:
- References seem to be formatted correctly. However, I think 20 references is insufficient for this amount of information and data.
- Too many subheadings for individual forms of references. This may overwhelm the reader!
- Glossary is good and in alphabetical order so it is made easier for the reader to locate the word.
- The Glossary links section at the bottom is good.
- Structure needs refining and referencing was a consistent issue. Creator needs to read over the page and edit where appropriate. Also, it would have been good to see a self-drawn image to engage the reader, which has not been done on this page. Otherwise, sound and interesting information on Trisomy 21 has been provided for the reader.--z3290808 23:03, 21 September 2011 (EST)
Group Assessment Criteria
- The key points relating to the topic that your group allocated are clearly described.
- Good and concise explanation of the subheadings,however, I would've liked to see some attempt to further explain how the associated congenital abnormalities occur.
- The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
- Lots of images, graphs and table used effectively to help reader better understand the disease. They also gave the project page some colour to make it more pleasing to the eye. Unfortunately, some images were placed (eg. John Langdon Down)in the wrong sections and interrupted the flow of the project page.
- In addition, some of the images were not referred to within the project page.
- Furthermore, the overall structure and layout of the page could be improved, such as putting the Diagnostic Links under diagnosis instead of the introduction
- I also felt American College of Obstetricians and Gynecologists Recommendations could've been a subheading under 'screening'
- Content is correctly cited and referenced.
- The very first image does not provide any information on the permissions to reuse the image (open access).
- The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
- Would've been better to include more self drawn diagrams and tables to further illustrate the group's knowledge of this disease
- Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
- Lots of Pubmed articles have been used to make this page more credible and reliable
- Relates the topic and content of the Wiki entry to learning aims of embryology.
- Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback.
- Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
- Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
- The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
- More words need to be explained in the glossary, such as 'tandem single nucleotide polymorphisms'
- Develops and edits the wiki entries in accordance with the above guidelines
--Z3291643 22:55, 21 September 2011 (EST)
Peer Assessment: Trisomy 21
- Great balance of text, pictures and tables.
- The links under introduction is distracting, might look better under the ‘links’ subsection.
- The introduction sounds incomplete and the small paragraphs are non coherent.
- "Some Recent Findings" fits better towards the end of the page; once the topic has been discussed in detail.
- Under Some Recent Findings all the points are direct quotes from research papers. It would be more informative if clear and precise summaries were included instead.
- The section "associated abnormalities" have not been discussed adequately. A brief discussion on why they are related would be much more constructive to the reader.
- The figure "Human Idiogram - Chromosome 21" has no copyright information and the resolution is too small
- The sections "limb defects" and "heart defects" should not claim their own sections. Again instead of bullet points with links attached to them a brief discussion would look better.
- The picture of "John Langdon Down" has no copyright information attached. Also the picture might fir better next to a section where the discovery has been discussed.
- A timeline or history subsection should be added as this gives the reader a perspective of how the condition has been discovered and the developments made over time.
- The section "prevalence" should look at a broader perspective rather than just touching on two regions.
- Although the table in "screening" looks neat it needs more discussion at the end, eg. What time period the data is from etc
- "Screening by country" is too short and does not have a broad view.
- "Detection using Tandem Single Nucleotide Polymorphisms" uses an "easy to follow" flowchart with adequate information without being too verbose, well done!
- The "Australian Support" section is a useful one and it is a nice touch to add!
--Z3308968 22:30, 21 September 2011 (EST)
Peer Assessment: Trisomy 21
- Within the Introduction there are definition of terms such as "Aneuploidy" which should be added to the glossary not the introduction, sudden change of subject cause confusion and not enough information within the introduction only so key features.
- heart defects was not expanded only presenting statistics no detain explaining statistics
- heading of recent findings would be placed further down instead at the beginning to create sense of flow and building of the subject
- heart and hand defects should be placed under same sub heading "defects"
- The sub heading "American College of Obstetricians and Gynecologists Recommendations" should be placed as recent findings
- terms should be placed under heading of glossary and joined together with all the definitions instead of seperated
- referencing link to paper "PLoS One" is not correct method of referencing only a link
- Picture found in the introduction contains no verification of allowing usage due to incorrect referencing
- images within the "Associated Congenital Abnormalities" and the "Introduction" contain no description of the image and the what is being conveyed.
z3332250 20:42, 21 September 2011 (EST)
- Introduction is brief and paragraphs do not flow
- Good use of external links.
- Appropiate images are used and but arent correctly cited e.g. for the image of 'John Langdon Down'
- Subheadings are a bit confusing and lack flow. Perhaps the defects could be combined. Meiosis 1 and 2 does not seem like an appropriate heading for that particular section.
- Contents of the prevalence section would have benefited from a table format and a bit more information about other regions involved.
- Screening by country looks incomplete with only reference to spain
- There is no mention of treatment or management
- Needs more terms added to the glossary
- References: very extensive and reliable sources used. Shows great understanding and research of the topic
- The page would benefit from a timeline or a section on the history of trisomy 21
--Z3332327 23:59, 21 September 2011 (EST)
Peer Review for Trisomy 21
- Growth curves for trisomy- Although the graph was easy to understand, there was no description that explained the significance of the results, and punctuation was not used correctly in the one sentence used to describe the image.
- References: The fact that the references had so many subheadings, specifically in the opening page, led me to believe that it was merely there to give a false impression of comprehensive research. Even though there were some aspects of the writings that were all-inclusive.
- Lack of a glossary –This page would be available to a broad range of readers, and it might be worthwhile and of value to invest some time in developing a glossary describing the terminology used. For example atrioventricualr canal in the abnormalities segment.
- Definitions as in depth research: For example: “Prevalence is measure of the proportion of a population that are disease cases at a point in time. Generally used to measure only relatively stable conditions, not suitable for acute disorders.” And “Aneuploidy is the term used to describe any abnormal number of chromosomes either an increase or decrease in total number.” These should all be moved to the glossary segment. The fact that the definitions are taking up almost 1/3rd of the space dedicated to the specific section shows lack of research and dedication.
- Associated congenital abnormalities – Some of these can well be represented by pictures – either hand drawn or photographs would make the page more pleasing to look at and would encourage readers to understand to read on. The detail given to explain the abnormalities is very poor. They have not shown any link between the defect and the abnormalities (even if they haven’t been well understood, you can still mention any current or past research trying to discover these links), nor have they explained what these abnormalities are. For example: "leukemia - Acute lymphocytic (lymphoblastic) leukemia (ALL) and Acute megakaryocytic leukemia (AML). AML occurs 200 to 400 times more frequently in Down syndrome." This is a very interesting point, but there is no explanation of why AML is more frequent in Down Syndrome or any information given on what ALL/AML actually are.
- Structure of writing: Most of the writings were in dot-point format. This may be an efficient way to make a draft of what will be discussed, but inappropriate as the final copy. It looked very rushed and “last-minute”.
--z3290270 20:27, 21 September 2011 (EST)
Peer Review for Trisomy 21
As there is some history in the introduction but nowhere else in the paper, there should be a bit more history to Trisomy 21 portrayed in the introduction. Although the introduction does portray some interesting facts, it felt that the flow was disconnected and that effort should be made to make the introduction flow better and that the information presented connects with each other. The image found in the introduction is not referenced in accordance to the referencing requirements for any uploaded image (e.g. copyright clearance statement is not provided). The image could have been reduced in size or put in a thumb so it can be presented better so that the picture doesn’t overly into the next section.’ Links at the bottom of the introduction is a good idea, but it seems too overcrowded with links at the start of the page, and thus it should have been at the bottom of the page in the external links section.
Some Recent Findings:
The information presented in this section is appropriate, however it should be moved to the end of the page before the glossary section as it will fit well when the reader reads this information once they understand the disease. Image is referenced well. Trisomy 21 (Down Syndrome) Karyotypes: This section provides relevant information about the karyotypes found in trisomy 21 patients. However an image which portrays normal male and female Karyotype images should be posted so people with amateur understanding of genetics could understand the problem between the two situations.
Associated Congenital Abnormalities:
The abnormalities found in this section have many words that don’t have links to their meanings, nor are they found in the glossary section below. The image on the right in the thumb should have a caption below it to describe what is being shown. Also, when it was being referenced, there is no image url source.
Good choice of providing links to pages that provide more information of the cardiac problems. Hwoever, none of the information presented in this section is referenced, possibly making the information being presented not credible. Explanations on how each defect should be described.
Only listed the Defects, if how these defects arise could be described it would be better. No evidence of copyright clearance on the hand image used.
This section which contains epidemiology should be included at the start of the page as it introduces the reader into the world of the disease being discussed on the page. Also image of John Langdon Down is not properly referenced and it should be included at the start of the page where the introduction is.
The information presented is very well done as it provides extensive information within an easy to read table. Links to the components of the tests is well done aswell The novel screening strategies section could have been expanded upon slightly as it should have described how those novel strategies actually work in detecting the trisomy. The ‘detection using tandem single nucleotide polymorphisms has a diagram which is well referenced. However the information contained within this subsection is too detailed and alot of technical jargon is used which can throw the reader off from reading. Even though there is terms underneath the paragraph, no attempt is made to try to simplify that section so it can be more reader friendly. The screening by country subsection does not contain enough information to be put under its own subsection.
Meiosis I and II
This subheading should not have existed, instead the information found here should have been written down in the ‘recent findings’ section as it is more relevant there and it doesn’t require its own subheading all the way at the bottom of the page.
This section shouldn’t even exist, instead the terms described here should be shifted to the glossary section.
Trisomy 21 growth charts:
The Paragraph found in this section is one direct text over 4 sentences. Effort should be made to summarise the paper’s findings instead of quoting 4 lines from the paper. However the diagrams are relevant to the information trying to be presented and they are properly referenced.
I like how everything is referenced and after that it is put into subsections so the readers could decide what type of reference they could use in their inquiry. Also, this section should come after the ‘Terms’ subheading as references should be the last feature of the page
This section is well done as it guides readers for further information in regards to trisomy 21--Z3291317 19:27, 21 September 2011 (EST)
Regards --Z3291317 19:27, 21 September 2011 (EST)
Peer review for trisomy 21
INTRODUCTION: An introduction is a brief summary of the content of the page, should only contain information that will be discussed in more detail below and not be confusing. Furthermore it should raise the interest to keep on reading. This introduction did not have this effect for me. Try to explain what trisomy 21 is about, what the characteristics are and quickly introduce the sections that will be talked about on this page. Trisomy 21 is a very common condition and we have all seen people with it on the street, it would be nice to have a picture of a person with trisomy 21 for recognition. They are lovely people and it would engage the reader. The image "Chromosome- trisomy" is a repetition of the image "Trisomy 21 (Down Syndrome) Karyotypes" and fits much better in an "etiology/pathogenesis" section, which I am hoping to find below. Links to websites with further information or to a glossary are great when they are actually directly related to the section and relevant to it. However, the introduction is rather an invitation to read more on the actual page, where the content will be discussed in detail and where links to external pages and to the glossary can be used for further information. The text itself needs proper referencing (1st and 3rd paragraph).
SOME RECENT FINDINGS: The title "recent findings" would be more appropriate under the assumption that the most recent and most relevant research is discussed here. Recent findings should rather be placed in the end of the project. The image "Trisomy 21 newborn" has no copyright information and has also no relation to this section. It neither has to do with the recent findings discussed nor is it mentioned or referred to in the text.
TRISOMY 21 (DONW SYNDROME) KARYOTYPES: The image a good illustration of what the genetic difference of an individual with trisomy 21 and a normal person is. However it could be explained more in detail. First of all if "Karyotypes" appears in the title, it should as well be explained directly in the section and not via a link to an external glossary. Secondly it would be nice to see an etiology/pathogenesis section on the page. Some one who is interested in finding out more about trisomy 21 would want to know how it is caused, what the risk factors are (eg.: the age of the mother plays and important role), and how it happens, that the genes do not separate. A suggestion would be to make an etiology/pathogenesis section and to discuss the "Trisomy 21 karyotypes" and "Meiosis I and Meiosis II" in this section. Additioinally, in the introduction it has been explained that trisomy 21 and Down's syndrome are two names for the same abnormality. Hence from that point on chose one of the names and stick with it rather that mixing them up or having the both in the same heading. The spelling in the heading is wrong (Down Syndrome, should be Down's Syndrome).
ASSOCIATED CONGENITAL ABNORMALITIES: The associated congenital abnormalities are important because they have an impact on the life of individuals with trisomy 21. Hence the section could be a little more complex. It might be worth writing an introducing paragraph, in which the most common associated abnormalities and the prevalence is mentioned. Not to forget, that the clinical picture of trisomy 21 individuals varies highly. For example there is a person that even made it into university while in more severe cases individuals only speak a few words lifelong - some individuals present with congenital heart defects some have perfectly normal hearts and no problems lifelong, etc. May be each of the relevant abnormalities could be explained in a table as under "limb defects".
AMERICAN COLLEGE: Instead of this section it would be nice to see a "diagnostic test" section. In this the "ACOG" could be incorporated as external link. The tests mentioned here for example: measuring features of the back of the neck and ultrasound are not diagnostic test for trisomy 21. Trisomy 21 is detected by sampling the amniotic fluid and by genetic testing. Abnormalities of the back of the neck and ultrasound are techniques to detect other abnormalities. Hence these are not directly relevant to trisomy 21. I have noticed that there is a complex section about screening - which discusses the detection of trisomy 21 somewhat. However I find it a little confusing. A table is a good idea but maternal age is not a procedure and what are all the tests for? Trisomy 21? How do they work? A diagram is as well and excellent idea but what does it all mean? How is a buccal swap done? And again is that all relevant to trisomy 21? If I was for example a pregnant woman with the concern that my baby has trisomy 21, I would like to know what the commonly used test is, how it is done, what the risk factors are and how accurate it is.
PREVALENCE these section would be more appropriate after the introduction, may be as "epidemiology" section. Furthermore it would be interesting the see some figures that are more recent and worldwide.
SCREENING: See comment under AMERICAN COLLEGE. Also about "SCREENING BY COUNTRY" One sentence does not need and extra heading. Either this information is not important or there could perhaps be some more information about other countries as well and about the difference such an screening makes.
MEIOSIS I AND MEIOSIS II: See comment under TRISOMY 21 (DONW SYNDROME) KARYOTYPES ANEUPLOIDY: Aneuploidy has been explained before and this section has as such no relevance to the topic.
GROWTH CHARTS: May be this information could be presented under "Clinical presentation". From this section on its own I cannot derive weather children with trisomy 21 show abnormalities in growth or not and why it should be relevant. --z3279511 15:18, 21 September 2011 (EST)
Peer review “Trisomy 21”
- The introduction appears not quite complete.
- The “some recent findings” section would fit better at the end of the page.
- Adding some historic background to the page would be interesting.
- The key points relating to the topic were well described and illustrated.
- The choice of content shows a good understanding of the topic area.
- Some images (e.g Human ideogram- chromosome or Chromosome trisomy) lack a reference and or copyright notice.
- No student drawing included.
- The term descriptions tear the page apart, they would fit better in the glossary.
- Relates the topic and content of the Wiki entry to learning aims of embryology.
- Use of a broad variety of reliable resources.
--Z3387190 21:41, 20 September 2011 (EST)
- I quite like the incorporated links that take you directly to the glossary, nice effect.
- The list of links at the end of the introduction doesn’t flow very nicely. I like the idea, but maybe if you move them to the top of the page or even the bottom it would fit better.
- The introduction could do with a bit more information and correspondence to the rest of the project.
- The section “Some Recent Findings” would probably be better just titled “Recent Findings”, it sounds more professional. This section would also fit better at the end of the page after we know all the details of the disorder. It is too difficult to jump straight into these specifics. Also, it is a good idea, but instead of using direct quotes from the paper, a succinct summary of the research would be better. That way you could refer back to the entire page.
- How does karyotyping work?
- Can you elaborate on the section “associated abnormalities”? The setting is a little confusing, what disorders are you referring to? Why are they similar? Or are these a list of signs and symptoms? If so, why are they associated with the addition of an extra chromosome 21?
- Instead of linking to the glossary, why not try to incorporate some of this information into the text?
- Interesting information, but some of these topics can be incorporated together, ie “limb defects” and “heart defects”. Or else, add more information in each, it looks a little sparse.
- There is no copyright information on the picture of ‘John Langdon Down’.
- I like the idea of prevalence, this is important to give perspective to the disorder, but a more worldwide distribution would be good instead of just Ireland and USA.
- The table in “screening” looks really good, but another column or something describing the screening techniques and details involved would be really good. The information in “novel screening strategies” sounds interesting but there needs to be more.
- Interesting diagram for SNP screening.
- “Screening by country” really should reference a few more countries than just spain.
- A glossary situated directly on the page would be good, as opposed to some links to an outside glossary, and other terms defined in text ie in the “aneuploidy” section.
- The topic and a lot of the work sounds very interesting and has the potential for a fantastic project, just a bit more content and better structured sub-headings needs to added and revised.
--Z3289066 21:40, 18 September 2011 (EST)
Trisomy 21 assessment
- Although it is nice that the 'nondisjunction' definition is linked to a medical dictionary, it was confusing having to scroll down to find it. It would have been easier if the link was to a page that only had the nondisjunction definition on it.
- The introduction is very vague and does not indicate much as to what the project is about. It gives one historical reference, a definition that seems out of place and a few extra links to other genetic conditions. It would have been better to have a little more information on the actual condition rather than a definition, a few statistics and a date. Also, while the image does represent the cause of the problem, I believe it would be much more effective to have an image of a child with Trisomy 21 so that the reader is able to gauge the severity of the condition. Genetic details will (hopefully) be discussed later and this image will fit in later.
- "recent finsings" would be better placed at the end of the project. It is difficult to understand their significance without understanding the topic
- No historical findings are noted (other than the one date in the introduction). This should be elaborated on.
- In the kayrotypes section, there should be an image of the normal set of chromosomes so that the reader can see the difference between that and the trisomy karyotype
- It would also be interesting to note HOW trisomy 21 develops.
- The list of congenital abnormalities could be expanded on to say why they are associated with trisomy 21.
- The image in the congenital abnormalities section is not at all useful. Also, the list does not explain what the actual problems are and their significance.
- Human idiogram-chromosome 21.jpg is not referenced
- Heart defects need to be explained- what are they?
- Limb abnormalities = interesting with a useful image
- prevalence should be earlier in the project and Australia should be included in these statistics
- The Image of Down is out of place, it has no significance here and is halfway between two sections
- terms should be put in a glossary at the end (which is non existent)
- the Aneuploidy section could be removed, and these terms put into a glossary instead
- Meiosis I and Meiosis II is not a suitable heading as it does not actually explain how meiosis occurs. This information needs to be included and would be better at the top of the project
- Overall, most of the information is present, it just needs to be rearranged into the right order.
--Z3288729 09:33, 18 September 2011 (EST)
Comments on Trisomy 21
- The frequency of trisomy 21 in the population is approximately 1 in 650 to 1,000 live births, in Australia between 1991-97 there were 2,358 Trisomy 21 (Down) infants.: it would be better to put this statement under the heading "Prevalence".
- It would be clearer to put the data under "Prevalence" in the form of a table.
- The caption for the table on detection rate of various procedures, "Table data from United Kingdom" is too vague.
- Choice of headings/sub-headings can be improved. For example, the headings, "Heart Defects" & "Limb Defects" can be sub-headings under "Associated Congenital Abnormalities".
- The sequence of the headings can also be improved. For example, the heading "Recent Findings" should probably be one of the last few headings and should not be just after the introduction as it gives a disjointed feel to the page.
- Reference No. 20 was not formatted properly.
--Z3389806 15:56, 18 September 2011 (EST)
Peer assessment of Trisomy 21:
- This page covered a broad scope of information
- Lots of relevant links if more information was wanted
- Not sure of the set out of headings, it seemed like there could have been a better order of topics
- Formatting gaps tended to disrupt the flow of the page
- The “some recent findings” was an interesting topic, however I think that instead of quotes being used, that maybe a more concise summary for each could have been formulated.
- Sounds silly, but grammatically errors were noticed such as lower case letters beginning dot points.
- Prevalence of more than 2 countries probably could have been used.
- Good use of a broad range of references
--Z3332629 08:37, 20 September 2011 (EST)
Peer Assessment: Trisomy 21
- The uncommon words linked straight to the glossary, for example nondisjunction, make the article more accessible and easier to read for the general population.
- The sentence explaining aneuploidy in the introduction is unnecessary and/or wrongly placed. Either the definition should be given in the first sentence that you use aneuploidy, in the section on aneuploidy or the uncommon word linked to glossary formatting should be used again.
- The word screening is probably common enough that you do not need to link it to the glossary.
- The last two sentences of the introduction do not flow very well - the first sentence regarding recent literature would probably be better used as an introductory sentence in the some recent findings section.
- The some recent findings section might be better placed towards the end of the page with the meiosis I and II and growth chart sections. Instead background information could be placed at the beginning.
- The articles in the some recent findings section are informative and well referenced. They could be summarised in your own words.
- There is a lack of referencing for some of the information in sections: associated congenital abnormalities, heart defects, detection using tandem single nucleotide polymorphisms and aneuploidy.
- Citation number 6 and 9 are not properly referenced. More information should be given - see the UNSW referencing webpage.
- It is good that a number of sections include external links where more information can be found.
- There is a good amount of images, however some of them could be placed more appropriately. For example the photograph of John Down could be placed adjacent to the introduction section as he is mentioned there.
- For all images and figures copyright information should be given on the image file page - this has not been completed for the first image and a number of other ones.
--z3217345 12:39, 20 September 2011 (EST)
Peer Review Trisomy 21
- Good use of headings, structure seems to be a little mixed. Maybe start with board heading the subdheadings to beak up the writing and make it easy to understand.
- Illustration and text ratio was nice not to heavy on either. No student drawing.
- Would have been nice to add a genetics heading rather then just linking to different pages. This looks strange at the top.. maybe rethink position. Trisomy Karyotypes could have been added here.
- Some words are not included in glossary eg AMH acronyms must be explained
- some pictures seem to be muddle eg the picture of Down himself would have fit nicely in the intro..
- many aspects of the page are not cited. This would give you page more credibility.
- Detection using Tandem Single Nucleotide Polymorphisms image. Consider resizing as it is very large.
- The first sentence is a little to wordy, as introduction should be punchy and to the point. Maybe try and re-word
Down syndrome or trisomy 21 is caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal and is one of the most common chromosomal abnormalities in liveborn children. Maybe.. The most common chromosomal abnormality occurring in live births is Down syndrome, otherwise known as Trisomy 21. This syndrome is caused by the nondisjustion of the 21st chromosome, in which there is the partial or whole presence of an extra chromosome.
- The history of Down syndrome would be a nice extra such as when the chromosome was identified.
Also rewording of the sentence Down Syndrome is the historic name used for this condition identified by Down, J.L.H. in a 1866 paper where he described the "phenotypic features that includes mental retardation and characteristic facies". Such as, In 1866 John Langdon Down identified and described some of his patients who he said to have "phenotypic features that includes mental retardation and characteristic facies". Due to his historic findings this syndrome now bares Downs’ name. Reference?
• In recent findings it might be nice to summaries the paper rather then quote directly from it. Some things are difficult to understand and I don’t quite get the gist of what is actually being done. • I like the link to PubMed- great thinking.
Associated Congenital Abnormalities • good use of bullet point maybe have been nice to illustrate abnormalities with pictures.
- I like the of percentages but where were these numbers generated from? No reference??
- Good use of links here.
Limb Defects could have had major head “defects” then use subheading to differentiate limb and heart. The use of references should accompany statistics.
American College of Obstetricians and Gynecologists Recommendations
- interesting choice, would have been nice to see in own words not just copy and pasted.
Prevalence • May fit in nicer near the intro, as readers are generally very interested in this part. • Good to see the use of references
Down's syndrome Screening
- Great use of table and stats.
--z3294943 14:51, 20 September 2011 (EST)
Peer review Trisomy 21
- The introduction could be a little bit longer, and maybe include a little bit of a historic timeline?
- Having the recent findings follow the introduction immediately is confusing as the reader hasn't had a chance to learn anything about the condition yet, so can't really relate the recent findings to anything.
- A broad range of topics is covered which is good, but there doesn't seem to be a logical structure to it - things don't lead on from each other.
- The links to further external resources are a very good idea, and there are a lot of them, which is good and makes it easy to find out more and get a deeper understanding. Including these links also makes the page itself less crowded and helps keep a good overview.
- The mere use of bullet points in most parts does keep things simple and clear, but also partly gives an impression of lack of depth. Certain points could be explained in a little bit more detail.
- The table that is used for Screening Strategies is an efficient way of showing the data, though I don't quite understand what the "maternal age" screening procedure is, and how that can have a detection rate? I assume it relates to the fact that older mothers have a higher risk of bearing Down Syndrome children, but what exactly is the screening procedure?
- Though the terms are explained in "detection using tandem nucleotide repeats", the section is still too technical. It doesn't explain why this technique allows the detection of the trisomy 21. For somebody who isn't familiar with genetics, it is very hard to understand. I am familiar with genetics, but the sentence "Tandem SNP sequences identified as heterozygous on maternal buccal swab are amplified on maternal plasma by ..." doesn't quite make sense to me - how can the sequences be amplified ON the maternal plasma?
- Listing the screening by country is a good idea, but then should contain more than just information for 1 country.
- Generally, there is a curious mix of very well explained terms and sections, and sections that still seem incomplete.
--z3389343 19:56, 20 September 2011 (EST)
- The introduction is good
- There are a lot of subheadings, maybe some of them could be combined
- Recent findings might be better towards the end of the page
- The links at the end of the subheadings are good
- The "Screening by Country" section should contain more than one country
- The Prevalence section could also use more examples
- Some of the images need to be properly referenced
- It may have been good to include some backgorund information
- Some of the images, especially the John Down one, didnt seem to fit in the section where they were placed and would be bettter used somewhere more relevent.
--z3292953 12:15, 21 September 2011 (EST)
Introduction: The image here is lacking an appropriate title and is not properly cited. The text should give a brief overview of Trisomy 21 without overwhelming the audience with statistics. The definitions of “Down Syndrome” and “aneuploidy” would fit better under the glossary heading or made to fit into the text so that it does not disrupt the flow of reading.
Some recent findings: This subheading would be better suited towards the end of the page to allow the reader to obtain a good understanding of what Trisomy 21 actually is before jumping into recent findings. The content here though is very thorough and easy to read due to the bolded headings and the use of an image here is a great way to break up a big chunk of text.
Associated congenital abnormalities: This section could benefit by increasing the image size and including a title.
Heart defects and Limb defects: These sections could be merged under one subheading such as “defects” to continue the flow of reading.
Overall the content is there, just some rearranging of text and a punchier introduction will improve this page. The ratio of text to images is especially impressive but make sure that each image relates to its section and has proper titles and citing.
--z3290815 21:42, 21 September 2011 (EST)
- I found the introduction rather brief and disjunctive. More elaboration on the history and the nature of the condition would be more informative and possibly allow for a more flowing intro.
- Recent findings subheading is a great idea. However it seems to make more sense that this would be better placed towards the end of the page, as very little information is given about Trisomy 21 prior to this, it might be better understood by the layperson once they have read a little more about the disorder. Also thought the articles could be explained, rather than just using direct quotations from the text. Would be more informative to include the general direction of future research in this subheading as well.
- Karyotype is not explained, only images provided. Greater detail here would make it clearer as to what “Trisomy 21” actually means i.e extra chromosome.
- Associated Abnormalities subheading is extremely brief. I feel that a little more detail here would help.
- The subheading Aneuploidy seems unnecessary, as this has already been explained.
- The screening subheading gives a clear picture of the detection rate of various test, however maybe some more information as to what these tests actually are and how they work could be important.
- Screening by Country subheading seems incomplete.
- The overall flow of the presentation could be improved.
--Z3288196 21:45, 21 September 2011 (EST)
Peer Review - trisomy 21
* The key points relating to the topic that your group allocated are clearly described.
Key points are poorly described, some information is out of place (Eg: explaination of aneuploidy in the introduction with nothing linking it to information in context). Links to other pages on the wiki barrages the reader with too much information too quickly. Explanation and summary of each linked section should be made on the page to provide adequate basic information before directing the reader to deeper information. Quotes in recent findings are not explained. Congenital defects are not explained well with only listing and no link to further information (how and why the main defects forms would be good). Novel screening technology only lists things, does not explain why the screening is done and how it determines trisomy 21. Termination information should be provided even if it is a short summary in the screening section. Tandem Single Nucleotide Polymorphisms describes the process well but does not explain how it determines trisomy 21 (does it determine trisomy 21 by some kind of genetic or molecular marker in maternal DNA?), terminology is also poorly explained. Terms in Tandem Single Nucleotide Polymorphisms should be put into glossary. Short section titled 'screening by country' should be expanded or removed. Terms in aneuploidy section should be put into glossary - and information on why aneuploidy causes trisomy 21 should be put there instead and moved into same sub-heading as karyotypes, and meiosis I and meiosis II as they relate to each other. Trisomy Growth charts do not demonstrate relevance and quoted text has no meaning without further explaination (Ie: Why is the reader looking at the trisomy growth chart).
* The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
The headings and subheadings are all over the place. Heart and Limb defects should appear as subheadings to Associated Congenital Abnormalities, recent findings should be at the bottom of the page titled 'current research'. Introduction can include the prevalence, more historical information would be good as well. Karyotypes, Meiosis I and Meiosis II, and Aneuploidy should be put in the same heading with each of them as a sub-heading. Recommendations should be put at the end of of the article before current research. Screening should be put after introduction. Text extract in recommendations show poor understanding - summary or paraphrasing would show more understanding. See above for more problems relating to content.
* Content is correctly cited and referenced.
Poor citation through out. Citation not given after any sentence in the Tandem Single Nucleotide Polymorphisms section (how does the reader confirm the techniques with no references). Referencing section is poor - many references are not directly referenced to a particular section or sentence in the article. References not referenced in article should instead go into 'external links' or 'further reading'.
* The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
Diagrams used, table in screening strategies is informative and well set out. No individual diagrams used. Poor element of peer teaching as information is poorly set out with little explanation for lists.
* Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
There is significant research provided but information on page is limited with any technical information poorly summarised/explained and use of large quotations does not explain technical information well.
* Relates the topic and content of the Wiki entry to learning aims of embryology.
Relates well as it is a congenital defect and demonstrates abnormalities arising from abnormal embryological development. However, normal development without trisomy 21 should also be briefly explored to show the reader the differences in development.
* Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
Comments cannot be made at this time as no comments on the page has been made.
* Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
Comments cannot be made at this time.
* The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
Research is broad but depth of knowledge can be further demonstrated with more explanations and less quotation. Poor connection to other aspects of trisomy 21 makes it difficult to inform peers.
* Develops and edits the wiki entries in accordance with the above guidelines.
Did not develop and edit the wiki well based on the above guidelines. See above comments for improvements.
--z3329495 22:02, 21 September 2011 (EST)
Trisomy 21 Peer Assessment
1.The different headings seem a bit much… ie: The defects could be somehow joined into one category with abnormalities and Meiosis discussion combined with aneuploidy. The flow would just seem better with more subheadings instead of headings.
2.In the introduction, there seems to be some disorganization. Instead of having aneuploidy defined, how about have a hyperlink on it to take you to the glossary and have it defined there, or describe it within the first paragraph where it is first mentioned?
3.Human_idiogram-chromosome_21.jpg This image seems to not be formatted correctly. I couldn’t find any reference for it, and it didn’t have a caption under it to help describe the picture properly.
4.Chromosome-_trisomy.jpg This image also is missing a caption from under it.
5.Under prevalence, the numbers need editing; currently it is trying to show the years as a telephone number.
6.The image “Tandem SNP Analysis Process” just looks a bit awkward… Maybe it’s too big, or maybe the text can be formatted to fit around it and make it more aesthetically appeasing.
7.The aneuploidy section seems a bit out of order. Should be combined with Meiosis I and Meiosis II to help offer a more holistic explanation of what happens to cause the disease.
8.More information needs to be cited. For example, neither defects section has much, if any, citations for the facts that are given.
9.For the references section, is it really necessary to separate the sources based on Journals, Reviews, etc? If you think so, the formatting should at least be kept consistent throughout, including the first section which is formatted numerically instead of with dots.
10.The information given is helpful in allowing us to follow along and understand the copious amounts of information that goes along with this topic. Lots of hyperlinks are available for further descriptions of things also, which is helpful.
--Z3391078 02:06, 22 September 2011 (EST)
Peer Assessment of the Trisomy 21 Page
•The links in the introduction to further information regarding genetic and diagnostic links were useful, and they are in a good position on the page.
•In terms of the subheadings, the order does not have a very good flow about it. I think that the recent findings subheading should be further down towards the end of the page, not straight under the introduction before any elaboration on the causes or characteristics of Trisomy 21 have been provided.
•There is a good balance between pictures and information, though some of the pictures, in particular the graphs are not incorporated into the written information or explained very well in any detail.
•There also seems to be information missing in terms of important areas that should be explored in greater detail throughout the page. This includes information regarding aspects such as symptoms and characteristics of the abnormality, maybe a bit more on the history and discovery of the abnormality and some future research or directions regarding the disorder.
•Do not all have captions underneath them – for instance the first picture in the introduction section
•They do not all have the copyright information relating to free access included – regarding the image of John Langdon Down. Also this image does not relate to the information that it is placed near. It would be more relevant to have it in a section such as history of the abnormality. The image is also in the middle of 2 subheadings, and looks as it is not placed in the correct position.
•The terms or glossary list is below the references, where it should be just above them
•Reference number 6 is not formatted correctly – there is just a link with no other information
--z3332183 10:41, 22 September 2011 (EST)
Trisomy 21--z3330313 00:23, 22 September 2011 (EST)
-Introduction: Does cover details of the disorder briefly however the format did not flow because for some of the information written it looked as though it belonged to the glossary section of the page. But there was a good use of external links
-Some recent findings: Regarding the flow of the page the next sub heading did not fit. It would be more appealing if the "some recent findings" heading were to be loacted near the end of the page. However, the information was written very well and easy to read/condensed.
-Trisomy 21 (Down Syndrome) Karyotypes : The use of images is to be congratulated, it is a helpful visual aid. However, the use of good image was not taken advantage of in written form. The information written was limited and too brief, the writer relied on the image too much.
-Associated Congenital Abnormalities: This section had a list of the abnormalities however that was just it. There was no explanation of what type of disorder it is or any description what so ever. This section is somewhat of an important sub heading as it deals with abnormal changes to the embryo or fetus during development but the writer only left a brief note which only shows laziness.
-Heart Defect: Very good use of statistics and external links to help the reader understand the information laid out. Most words were hyperlinked to the glossary section, maybe instead of doing that the writer could just incorpate the information into the main text because it is not just one word but a few thus it would be easier to read it in one go also these words are bulletpointed anyways.
-Limb Defects: Good use of external links again and a nice image but why not conbine the previous subheading into one heading as, "DEFECTS" because they were both short pieces of information and they both relate to the same topic so it would thus look more appealing and less spaced.
-It would be a suggestion to have a subheading as "epidemiology" so not only information on prevalence will be covered but also statistics on rate of incidence etc.. and why it is occurring at that rate. Furthermore, if Australian statistics were to be used than that would be fantastic as it would be more relevant to us.
-The reference list was good. It was categorised into the different types of sources used. A good job!
--z3330313 00:23, 22 September 2011 (EST)