Abnormal Development - Genetic

Embryology - 5 Dec 2023        Expand to Translate
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Introduction

Chromosomes in trisomy 21

This page gives a general introduction to information about genetic abnormalities their relationship to age, ethnicity and prenatal testing. Use the listed links for more information about specific abnormalities. In developed countries with increasing maternal age comes the increased risk of age related genetic abnormalities, such as trisomy 21.

In order to detect some genetic abnormalities many countries offer genetic screening programs that include maternal serum screening (MSS, for detection of Down's syndrome and neural tube defects), embryonic and newborn screening (for phenylketonuria (PKU), hypothyroidism, cystic fibrosis and metabolic disorders).

In terms of maternal/paternal family history, some ethnic backgrounds have been shown to have disease-associated genetic variants, though most common genetic diseases are consistent across ethnic boundaries. For example: Caucasians of northern European ancestry and cystic fibrosis (CTFR gene), Mediterranean, Asian and Far Eastern ancestry with beta-thalassaemia.

Note that the development of in vitro fertilization techniques now allows cells from early stage blastocysts to be removed and genetically analysed prior to implantation. This has raised some ethical issues relating to what parameters will be in future used in blastocyst selection.

Some Recent Findings

Human idiogram

A graph theory approach to analyze birth defect associations "Birth defects are prenatal morphological or functional anomalies. Associations among them are studied to identify their etiopathogenesis. The graph theory methods allow analyzing relationships among a complete set of anomalies. A graph consists of nodes which represent the entities (birth defects in the present work), and edges that join nodes indicating the relationships among them. The aim of the present study was to validate the graph theory methods to study birth defect associations. All birth defects monitoring records from the Estudio Colaborativo Latino Americano de Malformaciones Congénitas gathered between 1967 and 2017 were used. From around 5 million live and stillborn infants, 170,430 had one or more birth defects. Volume-adjusted Chi-Square was used to determine the association strength between two birth defects and to weight the graph edges. The complete birth defect graph showed a Log-Normal degree distribution and its characteristics differed from random, scale-free and small-world graphs. The graph comprised 118 nodes and 550 edges. Birth defects with the highest centrality values were nonspecific codes such as Other upper limb anomalies. After partition, the graph yielded 12 groups; most of them were recognizable and included conditions such as VATER and OEIS associations, and Patau syndrome. Our findings validate the graph theory methods to study birth defect associations. This method may contribute to identify underlying etiopathogeneses as well as to improve coding systems." The BabySeq Project "The BabySeq Project is a first-of-its-kind randomized clinical trial designed to examine how best to use genomics in clinical pediatric medicine by creating and safely testing methods for integrating sequencing into the care of newborns." Clinical Trials The Impact of Sperm and Egg Donation on the Risk of Pregnancy Complications "The aim of this study was to evaluate obstetric outcomes in relation to the extent of donor sperm exposure with and without egg donation.  This is a retrospective cohort study in a single tertiary care center. All women with a singleton pregnancy who conceived following sperm donation (SD) were included. Obstetrics and neonatal outcomes for pregnancies following single SD were compared with pregnancies following repeat SD from the same donor. In a secondary analysis, we compared pregnancy outcomes among three modes of assisted reproductive technology (intrauterine insemination [IUI-SD], in vitro fertilization [IVF-SD], and IVF sperm + egg donation [IVF-SD + ED]). A total of 706 pregnant women met the inclusion criteria, 243 (34.4%) following the first SD and 463 (65.6%) following repeat donations. Compared with repeat SDs, single donation was not associated with higher rates of preterm delivery (12.8 vs. 12.7%, respectively, p = 0.99), preeclampsia (7.0 vs. 6.9%, p = 0.999), and intrauterine growth restriction (4.1 vs. 3.9%, p = 0.88). Pregnancies following IVF-SD + ED had increased risk for preeclampsia (adjusted odds ratio [AOR], 3.1; 95% confidence interval [CI], 1.5-6.6), preterm labor (AOR, 2.4; 95% CI, 1.1-5.4), and cesarean section (AOR, 2.1; 95% CI, 1.0-4.3) compared with IUI-SD and IVF-SD.  The extent of donor sperm exposure did not correlate with obstetrics complications, but double gamete donation was associated with increased risk for preeclampsia, preterm labor, and cesarean section." (More? ART | spermatozoa | oocyte}

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Genetic Abnormal Development | Developmental Genetic Abnormalities | Trisomy | Uniparental+disomy

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Outcomes of Women Delivering at Very Advanced Maternal Age "Retrospective cohort study using the Texas Public Use Data File, years 2013-2014 (96,879 deliveries). Maternal age was a three-level variable: 35-39 (referent), 40-44, and 45-59 years (VAMA). Adjusted risk ratios (aRRs) for the two older age groups for various obstetrical and nonobstetrical complications were calculated from log-binomial regression models. The sample consisted of 96,879 deliveries. In univariate analyses, a higher frequency (p < 0.05) of gestational diabetes, pregestational diabetes, chronic hypertension, pregnancy related hypertensive disorders, multiple gestation, oligohydramnios, polyhydramnios, placenta previa, postpartum hemorrhage, small for gestational age, intrauterine fetal death, and length of stay were noted in the two older maternal age groups compared to the youngest maternal age group. Multiple gestations were noted to be more frequent in the two older groups. The risk of the following outcomes was approximately doubled in VAMA women compared to the referent (all statistically significant): small for gestational age (aRR = 1.92), stillbirth (aRR = 2.12), and intrauterine fetal death (aRR = 1.96). This population-based study detected a dose-response association between maternal age and the risk of multiple maternal and fetal complications." (More? maternal age) Inefficient Crossover Maturation Underlies Elevated Aneuploidy in Human Female meiosis "Meiosis is the cellular program that underlies gamete formation. For this program, crossovers between homologous chromosomes play an essential mechanical role to ensure regular segregation. We present a detailed study of crossover formation in human male and female meiosis, enabled by modeling analysis. Results suggest that recombination in the two sexes proceeds analogously and efficiently through most stages. However, specifically in female (but not male), ∼25% of the intermediates that should mature into crossover products actually fail to do so. Further, this "female-specific crossover maturation inefficiency" is inferred to make major contributions to the high level of chromosome mis-segregation and resultant aneuploidy that uniquely afflicts human female oocytes (e.g., giving Down syndrome). Additionally, crossover levels on different chromosomes in the same nucleus tend to co-vary, an effect attributable to global per-nucleus modulation of chromatin loop size. Maturation inefficiency could potentially reflect an evolutionary advantage of increased aneuploidy for human females." (More? meiosis) Maternal Age-Specific Rates for Trisomy 21 and Common Autosomal Trisomies in Fetuses from a Single Diagnostic Center in Thailand "We retrospectively reviewed prenatal cytogenetic results obtained between 1990 and 2009 in Songklanagarind Hospital, a university teaching hospital, in southern Thailand. Maternal age-specific rates of T21 and common autosomal trisomies were established using different regression models, from which only the fittest models were used for the study. A total of 17,819 records were included in the statistical analysis. The fittest models for predicting rates of T21 and common autosomal trisomies were regression models with 2 parameters (Age and Age2). The rate of T21 ranged between 2.67 per 1,000 fetuses at the age of 34 and 71.06 per 1,000 at the age of 48. The rate of common autosomal trisomies ranged between 4.54 per 1,000 and 99.65 per 1,000 at the same ages. This report provides the first maternal age-specific rates for T21 and common autosomal trisomies fetuses in a Southeast Asian population and the largest case number of fetuses have ever been reported in Asians." (More? maternal age) Responsible innovation in human germline gene editing: Background document to the recommendations of ESHG and ESHRE "Technological developments in gene editing raise high expectations for clinical applications, including editing of the germline. The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. This document provides the background to the Recommendations. Germline gene editing is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if germline gene editing would become safe and effective. What were the arguments behind this legislation, and are they still convincing?" (More? Human germline gene editing: Recommendations PMID 29326428) Sex ratios among infants with birth defects, National Birth Defects Prevention Study, 1997-2009 "A small number of population-based studies have examined sex differences among infants with birth defects. The highest elevations in sex ratios (i.e., male preponderance) among isolated non-cardiac defects were for craniosynostosis (2.12), cleft lip with cleft palate (2.01), and cleft lip without cleft palate (1.78); the lowest sex ratios (female preponderance) were for choanal atresia (0.45), cloacal exstrophy (0.46), and holoprosencephaly (0.64). Among isolated cardiac defects, the highest sex ratios were for aortic stenosis (2.88), coarctation of the aorta (2.51), and d-transposition of the great arteries (2.34); the lowest were multiple ventricular septal defects (0.52), truncus arteriosus (0.63), and heterotaxia with congenital heart defect (0.64)." Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies "Available evidence strongly supports the use of chromosomal microarray (CMA) in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages." Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia "Except for FLNB, HIC1 and ZNF189, maternal genes did not appear to influence the risk of clefting in our data. This is consistent with recent epidemiological findings showing no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefts in these two populations. It is likely that fetal genes make the major genetic contribution to clefting risk in these populations, but we cannot rule out the possibility that maternal genes can affect risk through interactions with specific teratogens or fetal genes." Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome "The ICF syndrome is a rare autosomal recessive disorder, the most common symptoms of which are immunodeficiency, facial anomalies and cytogenetic defects involving decondensation and instability of chromosome 1, 9 and 16 centromeric regions. ...DNA hypomethylation, previously reported to correlate with the decondensation of centromeric regions in metaphase described in these patients, appears also to correlate with the heterochromatin spatial configuration in interphase. "

ICD-11 Chromosomal Anomalies

The International Classification of Diseases (ICD) World Health Organization's classification used worldwide as the standard diagnostic tool for epidemiology, health management and clinical purposes.

ICD-11 Chromosomal anomalies excluding gene mutations
LD40 Complete trisomies of the autosomes LD41 Duplications of the autosomes LD42 Polyploidies LD43 Complete monosomies of the autosomes LD44 Deletions of the autosomes LD45 Uniparental disomies LD46 Imprinting errors LD47 Balanced rearrangements or structural markers
Sex chromosome anomalies LD50 Number anomalies of chromosome X   LD51 Structural anomalies of chromosome X, excluding Turner syndrome LD52 Number anomalies of chromosome Y LD53 Structural anomalies of chromosome Y LD54 Male with sex chromosome mosaicism LD55 Fragile X chromosome LD56 Chimaera 46, XX, 46, XY
LD5Y Other specified sex chromosome anomalies   LD5Z Sex chromosome anomalies, unspecified
LD7Y Other specified chromosomal anomalies, excluding gene mutations LD7Z Chromosomal anomalies, excluding gene mutations, unspecified
genetic abnormalities ICD-11 Links:  ICD-11 | Anomalies one body system | Multiple anomalies or syndromes | Chromosomal anomalies | Intellectual development | Abnormal Development | Prenatal Diagnosis | Birth | Neonatal Diagnosis | ICD-10 | Reports | | Category:ICD-11

Human Chromosomes

Human Chromosomes: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | X | Y

Idiogram Chromosome Banding - The term refers to the light and dark pattern, seen after staining with a dye, of individual chromosomes identified in metaphase. It is only in meiosis and mitosis during metaphase that chromosomes can be easily identified, during the normal cell life (interphase) the chromosomes are unravelled and distributed within the nucleus in chromosome territories. A band is that part of a chromosome which is clearly distinguishable from nearby regions by appearing darker or brighter with one or more banding techniques.

Genetic abnormality locations: 1-4 | 5-8 | 9-12 | 13-16 | 17-20 | 21-XY | sSMC

Inheritance Pattern images: Genetic Abnormalities | autosomal dominant | autosomal recessive | X-linked dominant (affected father) | X-Linked dominant (affected mother) | X-Linked recessive (affected father) | X-Linked recessive (carrier mother) | mitochondrial inheritance | Codominant inheritance | Genogram symbols | Genetics

Links: Genetics | Abnormal Development - Genetic

Human Oocyte Aneuploidy

• Frequency and distribution of chromosome abnormalities in human oocytes "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."

Links: Genetic risk maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Oocyte Development

Embryonic Aneuploidy

Embryonic aneuploidy model based on fragmentation. (See also Fragmentation Model and Monosomic Embryo Movie)

Some Human Disease Gene Locations

Sex Bias

Some developmental abnormalities show a difference in distribution related to embryo sex, Male and Female. While other genetic abnormalities are related to the maternal mitochondrial inheritance sex chromosomes {{ChrX)} and {{ChrY).

Some examples of some abnormalities sex related statistics are shown below.

USA Abnormalities Sex Ratio (1997-2009)

Male preponderance	Female preponderance
craniosynostosis (2.12) cleft lip and palate (2.01) cleft lip without cleft palate (1.78)	choanal atresia (0.45) cloacal exstrophy (0.46) holoprosencephaly (0.64)
Cardiac defects
aortic stenosis (2.88) coarctation of the aorta (2.51) transposition of the great vessels (2.34)	multiple ventricular septal defects (0.52) truncus arteriosus (0.63) heterotaxia with congenital heart defect (0.64)
Table data   Links: abnormal development | cardiovascular abnormalities | USA | Male | Female | cleft lip and palate

Some neural abnormalities, such as autism and intellectual disability, have a Male sex bias. This can be affected by the presence of specific comorbidities, specific copy number variants, mutational burden, and pre-existing family history of neurodevelopmental phenotypes.

Neural tube defects: Sex ratio changes after fortification with folic acid "Historically, neural tube defects (NTDs) have predominated in Female infants but the reasons remain unclear. In South America, the pre- folic acid fortification (FAF) rates of NTDs were around 18/10,000 births for females and 12/10,000 births for males, with an estimated sex ratio (male/female) of 0.67.

More than 80% of autoimmune disease predominantly affects Females. A possible contribution was suggested in part due to a preponderance of immune system-related genes (ISRG) on the X chromosome, but a recent study has shown these genes are no more abundant on the X chromosome as compared to autosomal chromosomes.

Thyroid pyramidal lobe

Other abnormalities of development are considered "anatomical variations" as they do not have any serious impacts. For example, the thyroid has a common anatomical variation of a pyramidal lobe seen more frequently in Male than in Female.

Genetic Inheritance

The figures below show the pattern of inheritance of a range of genetic disorders. In addition to these patterns are the known effects of increased maternal age and the effects of genetic mutations in the embryo and newborn.

• 

  Autosomal dominant inheritance

• 

  Autosomal recessive inheritance

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  X-Linked dominant (affected father)

• 

  X-Linked dominant (affected mother)

• 

  X-Linked recessive (affected father)

• 

  X-Linked recessive (carrier mother)

• 

  Mitochondrial genome inheritance

• 

  Codominant inheritance

Inheritance Pattern images: Genetic Abnormalities | autosomal dominant | autosomal recessive | X-linked dominant (affected father) | X-Linked dominant (affected mother) | X-Linked recessive (affected father) | X-Linked recessive (carrier mother) | mitochondrial inheritance | Codominant inheritance | Genogram symbols | Genetics

An example of autosomal recessive traits are the majority of 50 or so lysosomal diseases, with two X-linked exceptions, that of Fabry disease and Mucopolysaccharidosis II.

Carrier Testing

Preconception carrier tests are available for some autosomal recessive (AR) diseases. These were initially developed for autosomal recessive diseases that were frequent in specific ethnic groups:

• Tay–Sachs disease - Ashkenazi Jews
• hemoglobinopathies - Mediterranean and African populations
• cystic fibrosis - European-derived populations

Genome-wide association study

The National Human Genome Research Institute (USA) lists publications as part of the genome-wide association study (GWAS) in an attempt to assay at least 100,000 single nucleotide polymorphisms (SNPs) in the initial stage.

Links: Genome-wide association study | National Human Genome Research Institute

Fertility

Male Infertility Genes

Selected genes in Male Infertility

Gene abbreviation	Name	Gene Location	Online Mendelian Inheritance in Man (OMIM)	HUGO Gene Nomenclature Committee (HGNC)	GeneCards (GCID)	Diagnosis
AURKC	Aurora kinase C	19q13.43	603495	11391	GC19P057230	Macrozoospermia
CATSPER1	Cation channel sperm-associated 1	11q13.1	606389	17116	GC11M066034	Asthenozoospermia
CFTR	Cystic fibrosis transmembrane conductance regulator	7q31.2	602421	1884	GC07P117465	Obstructive azoospermia
DNAH1	Dynein axonemal heavy chain 1	3p21.1	603332	2940	GC03P052350	Asthenozoospermia
DPY19L2	Dpy-19-like 2 gene	12q14.2	613893	19414	GC12M063558	Globozoospermia
GALNTL5	Polypeptide N-acetylgalactosaminyltransferase-like 5	7q36.1	615133	21725	GC07P151956	Asthenozoospermia
MAGEB4	MAGE family member B4	Xp21.2	300153	6811	GC0XP030260	Azoospermia
NANOS1	Nanos C2HC-type zinc finger 1	10q26.11	608226	23044	GC10P119029	Azoospermia
NR0B1	Nuclear receptor subfamily 0 group B member 1	Xp21.2	300473	7960	GC0XM030322	Azoospermia
NR5A1	Nuclear receptor subfamily 5 group A member 1	9q33.3	184757	7983	GC09M124481	Azoospermia
SOHLH1	Spermatogenesis and oogenesis-specific basic helix–loop–helix 1	9q34.3	610224	27845	C09M135693	Azoospermia
vSPATA16	Spermatogenesis-associated 16	3q26.31	609856	29935	GC03M172889	Globozoospermia
SYCE1	Synaptonemal complex central element protein 1	10q26.3	611486	28852	GC10M133553	Azoospermia
TAF4B	TATA-box binding protein-associated factor 4b	18q11.2	601689	11538	GC18P026225	Azoospermia
TEX11	Testis expressed 11	Xq13.1	300311	11733	GC0XM070528	Azoospermia
TEX15	Testis expressed 15, meiosis and synapsis associated	8p12	605795	11738	GC08M030808	Azoospermia
WT1	Wilms tumour 1	8p12	607102	12796	GC11M032365	Azoospermia
ZMYND15	Zinc-finger MYND-type containing 15	17p13.2	614312	20997	GC17P004740	Azoospermia
Table data source (table 1)    Links: fertilization | spermatozoa | testis | Male Infertility Genes | Female Infertility Genes | oocyte | ovary | Genetic Abnormalities | ART   Asthenozoospermia - (asthenospermia) term for reduced spermatozoa motility. Azoospermia - term for no spermatozoa located in the ejaculate. Globozoospermia - term for spermatozoa with a round head and no acrosome.

Female Infertility Genes

Selected Female Infertility Genes

Gene abbreviation	Name	Gene Location	Online Mendelian Inheritance in Man (OMIM)	HUGO Gene Nomenclature Committee (HGNC)	GeneCards (GCID)	Diagnosis
BMP15	Bone morphogenetic protein 15	Xp11.22	300247	1068	GC0XP050910	Primary ovarian insufficiency
CLPP	Caseinolytic mitochondrial matrix peptidase proteolytic subunit	19p13.3	601119	2084	GC19P006369	Primary ovarian insufficiency
EIF2B2	Eukaryotic translation initiation factor 2B subunit beta	14q24.3	606454	3258	GC14P075002	Primary ovarian insufficiency
FIGLA	Folliculogenesis-specific BHLH transcription factor	2p13.3	608697	24669	GC02M070741	Primary ovarian insufficiency
FMR1	Fragile X mental retardation 1	Xq27.3	309550	3775	GC0XP147912	Primary ovarian insufficiency
FOXL2	Forkhead box L2	3q22.3	605597	1092	GC03M138944	Primary ovarian insufficiency
FSHR	Follicle stimulating hormone receptor	2p16.3	136435	3969	GC02M048866	Primary ovarian insufficiency
GALT	Galactose-1-phosphate uridylyltransferase	9p13.3	606999	4135	GC09P034636	Primary ovarian insufficiency
GFD9	Growth differentiation factor 9	5q31.1	601918	4224	GC05M132861	Primary ovarian insufficiency
HARS2	Histidyl-TRNA synthetase 2, mitochondrial	5q31.3	600783	4817	GC05P141975	Primary ovarian insufficiency
HFM1	HFM1, ATP-dependent DNA helicase homolog	1p22.2	615684	20193	GC01M091260	Primary ovarian insufficiency
HSD17B4	Hydroxysteroid 17-beta dehydrogenase 4	5q23.1	601860	5213	GC05P119452	Primary ovarian insufficiency
LARS2	Leucyl-TRNA synthetase 2, mitochondrial	3p21.31	604544	17095	GC03P045405	Primary ovarian insufficiency
LHCGR	Luteinizing hormone/choriogonadotropin receptor	2p16.3	152790	6585	GC02M048647	Primary ovarian insufficiency
LHX8	LIM homeobox 8	1p31.1	604425	28838	GC01P075128	Primary ovarian insufficiency
MCM8	Minichromosome maintenance 8 homologous recombination repair factor	20p12.3	608187	16147	GC20P005926	Primary ovarian insufficiency
MCM9	Minichromosome maintenance 9 homologous recombination repair factor	6q22.31	610098	21484	GC06M118813	Primary ovarian insufficiency
NOBOX	NOBOX oogenesis homeobox	7q35	610934	22448	GC07M144397	Primary ovarian insufficiency
NOG	Noggin	17q22	602991	7866	GC17P056593	Primary ovarian insufficiency
PMM2	Phosphomannomutase 2	16p13.2	601785	9115	GC16P008788	Primary ovarian insufficiency
POLG	DNA polymerase gamma, catalytic subunit	15q26.1	174763	9179	GC15M089316	Primary ovarian insufficiency
REC8	REC8 meiotic recombination protein	14q12	608193	16879	GC14P024171	Primary ovarian insufficiency
SMC1B	Structural maintenance of chromosomes 1B	22q13.31	608685	11112	GC22M045344	Primary ovarian insufficiency
SOHLH1	Spermatogenesis and oogenesis-specific basic helix–loop–helix 1	9q34.3	610224	27845	GC09M135693	Primary ovarian insufficiency
STAG3	Stromal antigen 3	7q22.1	{{Chr 608489	11356	GC07P100177	Primary ovarian insufficiency
SYCE1	Synaptonemal Complex Central Element Protein 1	10q26.3	611486	28852	GC10M133553	Primary ovarian insufficiency
TLE6	Transducin-like enhancer of split 6	19p13.3	612399	30788	GC19P002976	Embryonic lethalithy
TUBB8	Tubulin beta 8 Class VIII	10p15.3	616768	20773	GC10M000048	Oocyte maturation arrest
TWNK	Twinkle MtDNA helicase	10q24.31	606075	1160	GC10P100991	Primary ovarian insufficiency
Table data source (table 1)    Links: fertilization | oocyte | ovary | | Female Infertility Genes | spermatozoa | testis | Male Infertility Genes | Genetic Abnormalities | ART  Primary ovarian insufficiency - depletion or dysfunction of ovarian follicles with cessation of menses before age 40 years.  Oocyte maturation arrest - arrest of human oocytes may occur at different stages of meiosis.

Genetic Risk Maternal Age

Genetic Risk Maternal Age

Age of Mother	Risk of Trisomy 21	Risk of Any Chromosomal Abnormality
20	1 in 1667	1 in 526
21	1 in 1667	1 in 526
22	1 in 1429	1 in 500
23	1 in 1429	1 in 500
24	1 in 1250	1 in 476
25	1 in 1250	1 in 476
26	1 in 1176	1 in 476
27	1 in 1111	1 in 455
28	1 in 1053	1 in 435
29	1 in 1000	1 in 417
30	1 in 952	1 in 384
31	1 in 909	1 in 384
32	1 in 769	1 in 323
33	1 in 625	1 in 286
34	1 in 500	1 in 238
35	1 in 385	1 in 192
36	1 in 294	1 in 156
37	1 in 227	1 in 127
38	1 in 175	1 in 102
39	1 in 137	1 in 83
40	1 in 106	1 in 66
41	1 in 82	1 in 53
42	1 in 64	1 in 42
43	1 in 50	1 in 33
44	1 in 38	1 in 26
45	1 in 30	1 in 21
46	1 in 23	1 in 16
47	1 in 18	1 in 13
48	1 in 14	1 in 10
49	1 in 11	1 in 8
Table Data Genetic Links: genetic abnormalities | maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | trisomy mosaicism | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | VACTERL | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics

Uniparental Disomy

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. This can occur as a random event during the formation of the germ cells (oocyte or spermatozoa) or can also occur in early fetal development.

Trisomy

The term trisomy refers to the abnormal copy number of a specific chromosome, that is 3 copies instead of 2. The abnormality is identified by the chromosome that is present as 3 copies within the cell.

In humans, the most common trisomy is Trisomy 21 or Down syndrome. Other identified human trisomies include Trisomy 13, Trisomy 18 and Trisomy X. Trisomies for other chromosomes are mainly placental in origin and can be associated with miscarriage and growth restriction, or with true fetal mosaicism.

• 

  Trisomy 21 (male)

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  Trisomy 21 (female)

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  Trisomy 18

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  Trisomy 13

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  Trisomy X

Trisomy Mosaicisms

There have also been a number of trisomy mosaicisms identified for the above and other chromosomes. A "mosaicism" is a rare chromosome disorder characterized by having an extra copy of a chromosome in a proportion, but not all, of a person’s cells.

Identified human examples of this disorder include: Trisomy 22 mosaicism, Trisomy 18 mosaicism, Trisomy 17 mosaicism, Trisomy 14 mosaicism, Trisomy 12 mosaicism, Trisomy 9 mosaicism, Trisomy 8 mosaicism, and Trisomy 2 mosaicism.

Links: trisomy mosaicism

Ring Chromosome

Ring chromosomal 15

Triploidy

Triploidy

Cells with one additional set of chromosomes, for a total of 69 chromosomes, are called triploid.

ICD-11 LD42.0 Triploidy - A disease caused by one additional set of chromosomes, for a total of 69 chromosomes. Triploidy can present with albuminuria, edema, or hypertension in the mother. The fetus may present with microcephaly and a placenta that is enlarged and filled with cysts in the case of extra maternally inherited chromosomes, while extra paternally inherited chromosomes cause severe growth problems, an enlarged head, and a small placenta that does not have cysts. Non-mosaic triploidy is highly lethal, and is rarely observed in live births. Confirmation is through observation of an additional set of chromosomes by karyotyping.

Tetraploidy

Cells with two additional sets of chromosomes, for a total of 92 chromosomes, are called tetraploid. A condition in which every cell in the body has an extra set of chromosomes and is not compatible with life. Until 1990 there had been been seven reported total number of liveborn infants with a 92,XXYY karyotype. Postnatally, tetraploidy can also occur prior to tumorigenesis through nondisjunction of chromosomes in mitosis.

ICD-111705084192 LD42.1 Tetraploidy] - A disease caused by two additional sets of chromosomes, for a total of 92 chromosomes. This disease commonly results in spontaneous abortion during the first trimester. Live births of tetraploidy individuals are very rare. These cases are characterized by facial dysmorphism, severely delayed growth and developmental delay. Confirmation is through observation of two additional set of chromosomes by karyotyping.

Selected Topics

• Williams Syndrome
• Hutchinson-Gilford Progeria Syndrome

Mutagen

A chemical or agent that can cause permanent damage to the genetic material, DeoxyriboNucleic Acid (DNA) in a cell. DNA damage in the human oocyte or spermatozoa may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases. DNA damage postnatally can lead to a variety of tumours.

There are a large number of known mutagenic agents including those that are physical, chemical or biological in origin.

Neonatal Testing

The main neonatal genetic test is the Bloodspot Test also known as the Guthrie Test.

Bloodspot Test or Guthrie Test

Guthrie card

A blood screening test developed by Dr Robert Guthrie (1916-95) at University of Buffalo. The test is carried out on neonatal (newborn) blood detecting markers for a variety of known disorders (phenylketonuria (PKU), hypothyroidism and cystic fibrosis).

Links: Guthrie test | neonatal diagnosis

Australia - NSW Newborn Screening Programme

Each year test more than 90,000 babies and detects about 90 who need urgent assessment and treatment. In NSW and Victoria, the bloodspot cards are currently stored indefinitely.

• Phenylketonuria (PKU) - 1 in 10,000 live births (about 10 babies per year). PKU causes high blood levels of phenylalanine and severe intellectual disability. A diet low in phenylalanine, started in the first two to three weeks results in normal development.
• Primary congenital hypothyroidism - 1 in 3,500 live births (about 26 babies per year). It is caused by the absence or abnormal formation or function of the thyroid gland. This causes growth and intellectual disability if not treated. Medication with thyroid hormone started early, results in normal growth and development.
• Cystic Fibrosis (CF) - 1 in 2,500 live births (about 34 babies per year). Without treatment babies develop chest infections and often have very serious failure to thrive. Early institution of treatment greatly improves the health of babies with CF. Newborn bloodspot screening detects about 95% of babies with CF but also detects a few babies who may only be healthy carriers. For these babies a sweat test at about six weeks of age determines whether the baby has CF or is a healthy carrier.
• Galactosaemia - 1 in 40,000 births (about 1-3 cases per year). Babies cannot process galactose, a component of lactose. Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first week is life saving.
• Rarer metabolic disorders - Some fatty acid, organic acid and other amino acid defects can now be detected using Tandem Mass Spectrometry. These much rarer metabolic disorders affect about 15 – 18 babies per year. Early detection is important as diet and medications can treat most of these disorders. Without appropriate management they can cause severe disability or death.

Genetics services in NSW - coordinated by the NSW Genetics Service Advisory Committee, which is supported by the Statewide Services Development Branch of the Strategic Development Division, NSW Department of Health. (Information from NSW Health - Newborn Bloodspot Screening Policy 13-Nov-2006)

neonatal diagnosis | NSW Genetics Health

Science Student Projects 2011

The links below are to pages prepared as part of an undergraduate science student projects carried out in the Embryology course. Please note these are student submissions and may include inaccuracies in either description or understanding.

2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip

International Classification of Diseases

Some examples of genetic abnormalities from the  ICD-11 classification system.

ICD-11

ICD-11 - LD40.0 Complete trisomy 21 - a chromosomal abnormality, characterised by the presence of a third (partial or total) copy of chromosome 21, which clinical manifestations include variable intellectual deficiency, muscular hypotonia and joint laxity, often associated with facial dysmorphism and variable malformations (essentially heart and digestive) and a risk of complications (epilepsy, leukemia, auto-immune and endocrine pathologies, earlier aging and Alzheimer disease. LD40.1 Complete trisomy 13 - a chromosomal anomaly caused by the presence of an extra chromosome 13 and is characterized by brain malformations (holoprosencephaly), facial dysmorphism, ocular anomalies, postaxial polydactyly, visceral malformations (cardiopathy) and severe psychomotor retardation. LD40.2 Complete trisomy 18 - a chromosomal abnormality associated with the presence of an extra chromosome 18 and characterized by growth delay, dolichocephaly, a characteristic facies, limb anomalies and visceral malformations. LD42.0 Triploidy - A disease caused by one additional set of chromosomes, for a total of 69 chromosomes. Triploidy can present with albuminuria, edema, or hypertension in the mother. The fetus may present with microcephaly and a placenta that is enlarged and filled with cysts in the case of extra maternally inherited chromosomes, while extra paternally inherited chromosomes cause severe growth problems, an enlarged head, and a small placenta that does not have cysts. Non-mosaic triploidy is highly lethal, and is rarely observed in live births. Confirmation is through observation of an additional set of chromosomes by karyotyping. LD42.1 Tetraploidy - A disease caused by two additional sets of chromosomes, for a total of 92 chromosomes. This disease commonly results in spontaneous abortion during the first trimester. Live births of tetraploidy individuals are very rare. These cases are characterized by facial dysmorphism, severely delayed growth and developmental delay. Confirmation is through observation of two additional set of chromosomes by karyotyping. LD45 Uniparental disomies - Any disease caused by the inheritance of two homologous copies of a chromosome from one parent, and none from the other parent. Confirmation is by observation of identical chromosomes pairs by genetic testing. LD50.0 Turner syndrome - Karyotype missing one X chromosome (45, X0 or 45,XO/46,XX mosaicism) ; gonads: ovaries (streak); phenotype female with short stature, amenorrhea (hypergonadotrophic hypogonadism), absence of sexual development, webbed neck, low set ears, posterior hairline, widely-spaced nipples, short fourth metacarpals, and increased carrying angle at the elbow (cubitus valgus). Often associated with renal, cardiac and ocular abnormalities. LD50.1 Karyotype 47,XXX - Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). Most individuals are only mildly affected or asymptomatic, the most common physical features including tall stature, epicanthal folds, hypotonia and clinodactyly, with seizures, renal and genitourinary abnormalities, and premature ovarian failure being also associated findings. LD50.3 Klinefelter syndrome - Klinefelter syndrome defines a group of chromosomal disorders in which there is at least one extra X chromosome compared with the normal 46,XY male karyotype. The effects on physical features and on physical and cognitive development increase with the number of extra X's, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15-16 points, with language most affected, particularly expressive language skills. LD50.30 Klinefelter syndrome with karyotype 47,XXY, regular - Karyotype 47 XXY; gonads: testes (hypogonadism) small and firm with decreased spermatogenesis ; phenotype male with associated congenital abnormalities (decreased virilization due to decreased testosterone production, long arms and legs, short trunk, psychosocial problems) LD50.31 Klinefelter syndrome, male with more than two X chromosomes - A disease affecting males, caused by the presence of more than two X chromosomes in each cell. This disease is characterized by impaired sexual development, intellectual disability, distinctive facial features, skeletal abnormalities, poor coordination, and severe problems with speech. This disease may be differentiated from classic Klinefelter syndrome by increased severity of symptoms. Confirmation is through observation of more than two X chromosomes by karyotyping. LD55 Fragile X chromosome - Fragile X syndrome is a rare genetic disease associated with mild to severe intellectual deficit that may be associated with behavioral disorders and characteristic physical features. Prevalence is estimated at approximately 1/ 2,500 (prevalence of the full mutation allele) to 1/ 4,000 (prevalence of symptomatic cases) for both genders. JA02.0 Complete hydatidiform mole - A condition caused by the over-production of cells arising into the placenta during pregnancy. This condition is characterized by a pregnancy with abnormal placental growth in which the chorionic villi become hydropic, slight to severe trophoblast proliferation and invasion of the uterine tissue within 10-16 weeks after conception, a placental mass, 25-30% theca lutein cysts, 15-20% persistent trophoblastic disease, 50% uterine size for dates, and vaginal bleeding, nausea, or vomiting. This condition leads to an absent fetus. JA02.1 Incomplete or partial hydatidiform mole - A condition caused by the over-production of cells arising into the placenta during pregnancy. This condition is characterized by a pregnancy with abnormal placental growth in which the chorionic villi become hydropic, slight to moderate trophoblast proliferation and invasion of the uterine tissue within 10-16 weeks after conception, a placental mass, theca lutein cysts, 1-5% persistent trophoblastic disease, small uterine size for dates, and vaginal bleeding, nausea, or vomiting. This condition leads to some fetal development and a missed abortion.

References

Reviews

Webster A & Schuh M. (2017). Mechanisms of Aneuploidy in Human Eggs. Trends Cell Biol. , 27, 55-68. PMID: 27773484 DOI.

Search Pubmed

Search Pubmed: genetic developmental abnormality

Terms

Genetic Terms (expand to view)
genetic abnormalities | Molecular Development | meiosis | mitosis Alpha-Fetoprotein test (APF test) A prenatal test to measure the amount of a fetal protein in the mother's blood (or amniotic fluid). Abnormal amounts of the protein may indicate genetic or developmental problems in the fetus. Serum alpha-fetoprotein (AFP) is a fetal glycoprotein produced by the yolk sac and fetal liver. Low levels of AFP normally occur in the blood of a pregnant woman, high levels may indicate neural tube defects (spina bifida, anencephaly). (More? Alpha-Fetoprotein) anaphase B - Cell division term referring to the part of anaphase during which the poles of the mitotic spindle move apart. (More? mitosis) antisense - a sequence of DNA that is complementary usually to coding sequence of DNA or mRNA. Has been used experimentally to perturb or block gene expression. Also a mechanism that has been found to occur naturally as a regulatory mechanism. aneuploidy - Genetic term used to describe an abnormal number of chromosomes mainly (90%) due to chromosome malsegregation mechanisms in maternal meiosis I. autosomal inheritance - some hereditary diseases are described as autosomal which means that the disease is due to a DNA error in one of the 22 pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked. base - another term for nucleotide (usually a t c g). base pair - Double stranded DNA has nucleotides A-T, C-G, paired by hydrogen bonds (2 for AT, 3 for GC). Note this means that GC is harder to separate that AT. cis-acting elements - DNA sequences that through transcription factors or other trans-acting elements or factors, regulate the expression of genes on the same chromosome. cohesin - a multi-protein subunit complex required to keep the sister chromatids together until their separation at anaphase (both in mitosis and meiosis), can also form rings that connect two DNA segments. copy number variation - (copy number variants,CNVs) a DNA segment of one kilobase (kb) or larger that is present at a variable copy number in comparison with a reference genome. (More? Nature) disomy - Genetic term referring to the presence of two chromosomes of a homologous pair in a cell, as in diploid. See chromosomal number genetic disorders uniparental disomy and aneuploidy. Humans have pairs usually formed by one chromosome from each parent. DNMT - DNA methyltransferase. DNA - DeoxyriboNucleic Acid. The genetic material found in mammalian chromosomes and mitochondria. Consisting of 4 nucleic acids (ATCG) that combine in a triptych (3 nucleotide codon) code for protein amino acids (3nt = 1aa). DNA duplex - double stranded base-paired DNA forming a helix. dominant inheritance - With autosomal dominant inheritance, there is an error in one of the 22 chromosome pairs. But the damaged gene dominates over the normal gene received from the other parent. If one of the parents has a disease caused by an autosomal dominant gene, all the children will have a 50 per cent risk of inheriting the dominant gene and a 50 per cent chance of not inheriting it. The children who do not inherit the damaged dominant gene will not themselves suffer from the disease, nor will they be able to pass the gene on to future children. This type of inheritance is present for example in Huntington's disease. Down Syndrome - The historic name used for Trisomy 21, named after the original identifier Down, J.L.H. in a 1866 paper (cited above). enhancer - A cis-regulatory sequence that can regulate levels of transcription from an adjacent promoter. Many tissue-specific enhancers can determine spatial patterns of gene expression in higher eukaryotes. Enhancers can act on promoters over many tens of kilobases of DNA and can be 5' or 3' to the promoter they regulate. exon - a block of protein encoding sequence of DNA in a gene. Many proteins are made of several exons "stitched" or spliced together by editing out non-coding (intron) sequences. fasta - a format for listing DNA sequence, where the first line has descritive information followed on the next line by the sequence without numbering. GC repeat - a string of GC sequence repeated several times. Also associated with GC expansion, a mutational process that may lead eventually to serious gene expression effects. gene - a sequence of DNA that encodes an individual protein. genetic code - the 3 nucleotide sequence that forms a codon for a single amino acid or stop. See the gene code. genome - the complete genetic information in the form of DNA available to a specific species. hairpin loop - a folding of RNA generated by base pairing making a "===()" structure, the end loop and or stem of this structure can then interact with proteins or other RNA. heteroplasmy - within a cell when more than one type of mitochondrial DNA (mtDNA) genome exists within the mitochondrion, or between mitochondria. Heteroplasmy can generate a pathogenic mutation, for example transfer RNA leucine (tRNALeu(UUR)) 3243A > G mutant can result in diabetes. HyperD - hypermethylated domain has a role in regulating gene expression and epigenomics. The early embryo has large alterations in methylation patterns and DNA modification. (More? PMID 1943996) HypoD - hypomethylated domain has a role in regulating gene expression and epigenomics. The early embryo has large alterations in methylation patterns and DNA modification. (More? PMID 1943996) igDMR - imprinted germline differentially methylated regions intron - a block of DNA within a gene not encoding a protein. Edited, spliced, out during transcription into mRNA. Originally thought not to contain any information, but more and more this appears not to be the case. Some intron sequences have been shown to regulate gene expression during development (eg c elegans, Lin 14) karyotype - [Greek, karyon = kernel or nucleus + typos= stamp] The chromosomal makeup of a cell. Karyotyping describes the clinical genetic test. meiosis I (MI) The first part of meiosis resulting in separation of homologous chromosomes, in humans producing two haploid cells (N chromosomes, 23), a reductional division. Meiosis I: Prophase I - Metaphase I - Anaphase I - Telophase I meiosis II - (MII) The second part of meiosis. In male human spermatogenesis, producing of four haploid cells (23 chromosomes, 1N) from the two haploid cells (23 chromosomes, 1N), each of the chromosomes consisting of two sister chromatids produced in meiosis I. In female human oogenesis, only a single haploid cell (23 chromosomes, 1N) is produced. Meiosis II: Prophase II - Metaphase II - Anaphase II - Telophase II mosaic autosome monosomy - genetic abnormality caused by embryonic fusion or loss of an autosome early in embryonic development, resulting in a subset of cells in the body having only one of a pair of autosomes.  ICD-11 LD43.1 Mosaic monosomy of autosome mRNA - messenger, transcribed from DNA in the nucleus and in mitochondria. Is translated by the ribosome in the cytoplasm (or mitochondrial matrix). Intermediate step in gene expression. (DNA-> mRNA-> protein). mutation - any process which results in the alteration of the DNA sequence. Some conservative mutations may have no effect on the final amino acid encoded. ncRNA - non-coding RNA. nuchal translucency - (fetal nuchal-translucency thickness) An initial Trisomy 21 diagnostic ultrasound measurement in the fetal neck region carried out by trans-abdominal ultrasound at gestational age GA 10–14 weeks. Fetal sagittal section scan at a magnification that the fetus occupied at least 75% of the image. Measured is the maximum thickness of the subcutaneous translucency between the skin and the soft tissue overlying the cervical spine. Philadelphia chromosome - (Philadelphia translocation) Genetic term referring to a chromosomal abnormality resulting from a reciprocal translocation between chromosome 9 and 22 (t(9;22)(q34;q11)). This is associated with the disease chronic myelogenous leukemia (CML). ploidy - refers to the chromosomal genetic content of cells. promoter - A regulatory region a short distance upstream from the 5' end of a transcription start site that acts as the binding site for RNA polymerase II. A region of DNA to which RNA polymerase IIbinds in order to initiate transcription. point mutation - a change in a single nucleotide. recessive inheritance - With autosomal recessive inheritance, the diseased individual has inherited the same gene damage from both father and mother. The damage is found on both chromosomes in the pair. But as this is not ´dominant gene damageª, neither father nor mother show any sign of disease, they are healthy carriers of the gene. We are all carriers of about five recessive genes of this type, but as spouses are seldom carriers of exactly the same damaged gene(s), all will probably go well in the next generation. regulatory sequence - (regulatory region, regulatory area) is a segment of DNA where regulatory proteins such as transcription factors bind preferentially. ribosome - complex of rRNA and ribosomal proteins, bind mRNA and translate it into protein. RNA - RiboNucleic Acid. The intermediate nucleic acid involved in gene expression. It comes in 3 forms: tRNA, mRNA, rRNA. rRNA - ribosomal, translates mRNA into protein. rRNA provides the "scaffolding" on which many ribosomal proteins are assembled as 2 subunits that themselves assemble to form a ribosome. rRNA genes are localized to the nucleolus in the nucleus, a sometimes visible region of DNA usually constantly being transcribed. segmental aneuploidies - generated when a small piece of a chromosome is gained or lost during cell division, resulting in subchromosomal copy number (CN) changes. single umbilical artery - (SUA) Placental cord with only a single placental artery (normally paired). This abnormality can be detected by ultrasound (colour flow imaging of the fetal pelvis) and is used as an indicator for further prenatal diagnostic testing for chromosomal abnormalities and other systemic defects. (More? Prenatal Diagnosis | Ultrasound) telophase - Cell division term referring to the fifth mitotic stage, where the vesicles of the nuclear envelope reform around the daughter cells, the nucleoli reappear and the chromosomes unfold to allow gene expression to begin. This phase overlaps with cytokinesis, the division of the cell cytoplasm. telomere - regions at the end of chromosomes. Shortening of the telomeres is thought to be associated with cellular aging. The enzyme that maintains the telomere is called telomerase. Introducing this gene into a cell can extend the cells lifespan. topologically associating domain - (TAD) a self-interacting genomic region, DNA sequences within a TAD physically interact with each other more frequently than with sequences outside the TAD. transcription factor - a protein which binds to DNA activating (usually) gene expression. There are many different ways and forms that this activation can take place, but most transcription factors fall into specific classes (eg zinc fingers, helix loop helix). triple markers - alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol. ))trisomy 21}} triploidy - genetic abnormality caused by one additional set of chromosomes, for a total of 69 chromosomes. Maternally present with albuminuria, edema, or hypertension. Extra maternally inherited chromosomes, microcephaly and an enlarged placenta that is enlarged and filled with cysts. Extra paternally inherited chromosomes, severe growth problems, enlarged head, and a small placenta. Non-mosaic triploidy is highly lethal, and is rarely observed in live births.  ICD-11 LD42.0 Triploidy trisomy mosaicism - a rare chromosome disorder characterized by having an extra copy of a chromosome in a proportion, but not all, of a person’s cells. tRNA - transfer, binds single amino acids acts as a "donor' for protein synthesis. uniparental disomy - Genetic term referring to cells containing both copies of a homologous pair of chromosomes from one parent and none from the other parent.
Other Terms Lists   Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Endocrine | Gastrointestinal | Genital | Genetic | Head | Hearing | Heart | Immune | Integumentary | Neonatal | Neural | Oocyte | Palate | Placenta | Radiation | Renal | Respiratory | Spermatozoa | Statistics | Tooth | Ultrasound | Vision | Historic | Drugs | Glossary

Cell Division Terms (expand to view)
meiosis | mitosis anaphase - (Greek, ana = up, again) Mitosis term referring to the fourth stage, where the paired chromatids now separate and migrate to spindle poles. This is followed by telophase. anaphase A - Mitosis term referring to the part of anaphase during which the chromosomes move. anaphase B - Mitosis term referring to the part of anaphase during which the poles of the mitotic spindle move apart. aneuploidy - (aneuploid) term used to describe an abnormal number of chromosomes mainly (90%) due to chromosome malsegregation mechanisms in maternal meiosis I. aster - (Latin, aster = star) star-like object visible in most dividing eukaryotic cells contains the microtubule organizing center. astral microtubule - spindle apparatus microtubule (MT) originating from the centrosome which does not connect to a kinetochore. These microtubules only exist during mitosis, the other spindle types are polar and kinetochore microtubules. autosomal inheritance - term used in hereditary diseases which means that the disease is due to a DNA error in one of the 22 chromosome pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked. bivalent - (tetrad) a pair of homologous chromosomes physically held together by at least one DNA crossover. bouquet stage - meiosis term for when in prophase transition to the zygotene stage, the chromosome telomeres attachment to the inner nuclear envelope and form a cluster. This occurs before the onset of homologous pairing and synapsis. The name comes from the chromosomes resembling a "bouquet of flowers". diploid - (Greek, di = double + ploion = vessel) having two sets of chromosomes (2n), this is the normal euploidy state for all human cells, other than gametes that are haploid (n, a single set of chromosomes). diplotene stage- (diplotene phase, diplonema; Greek, diplonema = "two threads") meiotic stage seen during prophase I, the chromosomes separate from one another a small amount giving this appearance. In the developing human ovary, oocytes remain at the diplotene stage from fetal life through postnatal childhood, until puberty when the lutenizing hormone (LH) surges stimulate the resumption of meiosis. Prophase I, is divided into 5 stages (leptotene, zygotene, pachytene, diplotene, diakinesis) based upon changes associated with the synaptonemal complex structure that forms between two pairs of homologous chromosomes. euploidy - the normal genome chromosomal set (n, 2n, 3n) or complement for a species, in humans this is diploid (2n). The other classes of numerical chromosomal abnormalities include aneuploidy, polyploidy and mixoploidy. FUCCI - Acronym for Fluorescence Ubiquitination Cell Cycle Indicator a molecular tool for identifying the stage in the cell cycle. In G0/G1 cells express a red fluorescent protein and S/G2/M cells express a green fluorescent protein. (More? Tooth Development Movie) haploid - (Greek, haploos = single) Having a single set of chromosomes (n) as in mature germ/sex cells (oocyte, spermatozoa) following reductive cell division by meiosis. Normally cells are diploid, containing 2 sets of chromosomes. Ploidy refers to the number of sets of chromosomes in the nucleus of a cell. heteroplasmy - presence of more than one type of organellar genome. In humans this can refer to variations in the mitochondrial DNA (mtDNA). (More? PMID 26281784) homologous chromosomes - meiosis term for the two matching (maternal and one paternal) chromosomes that align during meiosis I. homologous recombination - meiosis term when DNA of homologous chromosomes is covalently exchanged to produce chromosomes with new allele combinations, and also links homologous chromosomes with each other to form a bivalent human genome - DNA within the 23 nucleus chromosome pairs and the cytoplasmic mitochondrial DNA. kinetochore - the protein structure formed on chromatids where the spindle kinetochore microtubules attach during cell division. kinetochore microtubule - spindle apparatus microtubule (MT) that attaches to the chromosome kinetochore by its plus end, the other spindle types are astral and polar microtubules. kinesin - a microtubule (MT) motor protein that exists in many isoforms and most move towards the MT positive end. Different isoforms have different functions within the spindle apparatus. PMID 20109570 meiosis - reductive cell division required to produce germ cells (oocyte, spermatozoa) and for sexual reproduction. Note that only spermatozoa complete meiosis before fertilisation. Chromosome number is reduced from diploid to haploid, during this process maternal and paternal genetic material are exchanged. All other non-germ cells in the body divide by mitosis. (More? Meiosis | Spermatozoa Development | Oocyte Development | Week 1) meiosis I - (MI) the first part of meiosis resulting in separation of homologous chromosomes, in humans producing two haploid cells (N chromosomes, 23), a reductional division. meiosis II - (MII) the second part of meiosis. In male human spermatogenesis, producing of four haploid cells (23 chromosomes, 1N) from the two haploid cells (23 chromosomes, 1N), each of the chromosomes consisting of two sister chromatids produced in meiosis I. In female human oogenesis, only a single haploid cell (23 chromosomes, 1N) is produced. Meiosis II: Prophase II - Metaphase II - Anaphase II - Telophase II. meiotic silencing of unsynapsed chromatin - (MSUC) an aneuploidy protective mechanism for subsequent generations, during meiosis where chromosomes are silenced that fail to pair with their homologous partners. merotelic kinetochore - cell division abnormality in chromosomal attachment that occurs when a single kinetochore is attached to microtubules arising from both spindle poles. Normal chromosomal attachment in early mitosis, is by only one of the two sister kinetochores attached to spindle microtubules (monotelic attachment) later sister kinetochores attach to microtubules arising from opposite spindle poles (amphitelic attachment). metaphase - mitosis term referring to the third stage where mitotic spindle kinetochore microtubules align chromosomes in one midpoint plane. Metaphase ends when sister kinetochores separate. Originally based on light microscopy of living cells and electron microscopy of fixed and stained cells. A light microscope analysis called a "metaphase spread" was originally used to detect chromosomal abnormalities in cells. Mitosis Phases: prophase - prometaphase - metaphase - anaphase - telophase metaphase spread - In mitosis using light microscope analysis originally used to detect chromosomal abnormalities in cells, as chromosomes are only visible during cell division. microfilament - (MF) cytoskeleton filament normally required for cytoplasmic intracellular transport, motility and cell shape. Named by the actin monomers assembling into the smallest in cross-section of the three filament systems (microtubules and intermediate filaments). This system is disassembled and reassembled as the contractile ring for cytokinesis (cytoplasm division) following cell division mitosis and meiosis. microtubule - (MT) cytoskeleton filament normally required for cytoplasmic intracellular transport and motility. Named by the tubulin monomers assembling into "tubes", and are the largest in cross-section of the three filament systems (microfilaments and intermediate filaments). This system is disassembled and reassembled as the spindle apparatus during cell division. mitochondrial DNA - (mtDNA) multiple copies of a small circular DNA molecule located within the mitochondria matrix. In humans 16,568 bp in length containing 37 genes, originally inherited only from the oocyte (maternal inheritance). mitosis - (M phase) The normal division of all cells, except germ cells, where chromosome number is maintained (diploid). In germ cell division (oocyte, spermatozoa) meiosis is a modified form of this division resulting in reduction in genetic content (haploid). Mitosis, division of the nucleus, is followed by cytokinesis the division of the cell cytoplasm and the cytoplasmic contents. cytokinesis overlaps with telophase. p - chromosome short arm (possibly French, petit) and used along with chromosome and band number to indicate genes located on this arm of the chromosome. The chromosome long arm is identified as q (possibly French, tall) chosen as next letter in alphabet after p. These chromosomal arms are only seen when the chromosome is folded for cell division. polar body - a small cytoplasmic exclusion body containing the excess DNA formed during the oocyte meiosis cycle and following spermatozoa fertilization. polar microtubule - spindle apparatus microtubule (MT) that can arise from either pole and overlap at the spindle midzone. This interdigitating structure consisting of antiparallel microtubules is responsible for pushing the poles of the spindle apart. The other spindle types are astral and kinetochore microtubules. prometaphase - (Greek, pro = before) mitosis term referring to the second stage, when the nuclear envelope breaks down into vesicles. Microtubules then extend from the centrosomes at the spindle poles (ends) and reach the chromosomes. This is followed by metaphase. pronuclear fusion - (Greek, pro = before) the process of the fusion of the two haploid nuclear structures (pronuclei) contributed from the spermatazoa and oocyte to form the first diploid nucleus cell. Can also be called "fusion of pronuclei". pronucleus - (Greek, pro = before; plural, pronuclei) the two haploid nuclei or nuclear structures containing the genetic material from the spermatozoa and the oocyte. These two haploid nuclei will fuse together to form the first diploid nucleus cell, the zygote. Therefore the nuclear structures that exist "before the nucleus", the plural term is pronuclei. prophase - (Greek, pro = before) - mitosis term referring to the first stage, when the diffusely stained chromatin resolves into discrete chromosomes, each consisting of two chromatids joined together at the centromere. prophase I - meiosis term refers to the first phase of meiosis I, which together with meiosis II results in the reductive cell division only occurring gametes. Prophase can be further divided into a number of stages: leptotene zygotene, pachytene, diplotene, diakinesis. q - chromosome long arm (possibly French, tall), the next letter in alphabet after p, and used along with chromosome and band number to indicate genes located on this arm of the chromosome. The chromosome short arm is identified as p (possibly French, petit). These chromosomal arms are only seen when the chromosome is folded for cell division. S phase - during interphase of cell cycle where DNA is duplicated prior to second growth period (G2 phase) that is followed by mitosis (M phase). synapsis - (syndesis) meiosis term for the pairing of two homologous chromosomes that occurs during prophase I. synaptonemal complex - meiosis term for a protein structure essential for synapsis of homologous chromosomes. (proteins SCP3 and SCP1). telomere - region found at each end of the chromosome and involved in cellular ageing and the capacity for division. The regions consist of repeated sequences protecting the ends of chromosomes and harbour DNA repair proteins. In the absence of the enzyme telomerase, these regions shorten during each cell division and becoming critically short, cell senescence occurs. telophase - mitosis term referring to the fifth stage, where the vesicles of the nuclear envelope reform around the daughter cells, the nucleoli reappear and the chromosomes unfold to allow gene expression to begin. This phase overlaps with cytokinesis, the division of the cell cytoplasm. telomerase - the enzyme that maintains the chromosome end length, the telomeres, involved in cellular ageing and the capacity for division. Absence of telomerase activity leads to the chromosome ends shorten during each cell division, becoming critically short and cell senescence then occurs. tetrad - (bivalent) a pair of homologous chromosomes physically held together by at least one DNA crossover.
Other Terms Lists   Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Endocrine | Gastrointestinal | Genital | Genetic | Head | Hearing | Heart | Immune | Integumentary | Neonatal | Neural | Oocyte | Palate | Placenta | Radiation | Renal | Respiratory | Spermatozoa | Statistics | Tooth | Ultrasound | Vision | Historic | Drugs | Glossary

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

• Australia NHMRC - Genetics in Family Medicine: The Australian Handbook for General Practitioners Testing and pregnancy PDF (2007)
• Online Mendelian Inheritance in Man
• NHGRI Catalog of Published Genome-Wide Association Studies | PDF
• Genome-Wide Associations (GWA) Karyogram
• Idiogram Album David Adler
• NSW Centre for Genetics Education - Fact Sheets
• The BabySeq Project | Clinical Trials - "The BabySeq Project is a first-of-its-kind randomized clinical trial designed to examine how best to use genomics in clinical pediatric medicine by creating and safely testing methods for integrating sequencing into the care of newborns."

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Cite this page: Hill, M.A. (2023, December 5) Embryology Abnormal Development - Genetic. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Genetic

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G