Genome Sequencing

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Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.

Introduction

Chromosome- trisomy.jpg
This Embryology site is a developmental educational resource, it does not provide specific clinical details, you should always refer to a health professional.

Draft Page.


Diagnosis Links: Prenatal Diagnosis | Pregnancy Test | Amniocentesis | Chorionic villus sampling | Ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis
| In Vitro Fertilization

Some Recent Findings

  • DNA sequencing versus standard prenatal aneuploidy screening[1] "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. ...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.)."
  • 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[2] "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. 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. 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."

Genetic Testing

Trisomy

Trisomy 21 karyotype cartoon

There are clinically more and more tests becoming available as we learn more about the genetic basis of some diseases. The most common diagnostic test relates to the current trend in an increasing maternal age, which has long been associated with an increase in genetic abnormalities, the most frequent of these is trisomy 21 or Down syndrome.

Links: Genetic risk maternal age | Trisomy 21

Single Gene Disorders

  • Cystic fibrosis
  • beta-thalassaemia
  • Spinal muscular atrophy
  • Sickle-cell anaemia
  • Huntington disease
  • Myotonic dystrophy type 1
  • Duchenne or Becker muscular dystrophy
  • Haemophilia
  • Fragile-X syndrome

Australia

A recent publication from NHMRC Medical Genetic Testing: information for health professionals (2010). This paper covers background information on all types of genetic tests, not just those associated with prenatal diagnosis.

Types of genetic tests

  • Somatic cell genetic testing involves testing tissue (usually cancer) for non-heritable mutations. This may be for diagnostic purposes, or to assist in selecting treatment for a known cancer.
  • Diagnostic testing for heritable mutations involves testing an affected person to identify the underlying mutation(s) responsible for the disease. This typically involves testing one or more genes for a heritable mutation.
  • Predictive testing for heritable mutations involves testing an unaffected person for a germline mutation identified in genetic relatives. The risk of disease will vary according to the gene, the mutation and the family history.
  • Carrier testing for heritable mutations involves testing for the presence of a mutation that does not place the person at increased risk of developing the disease, but does increase the risk of having an affected child developing the disease.
  • Pharmacogenetic testing for a genetic variant that alters the way a drug is metabolised. These variants can involve somatic cells or germline changes. Even if these variants are heritable (that is germline changes), the tests are usually of relevance to genetic relatives only if they are being treated with the same type of medication.


Links: NHMRC - Medical Genetic Testing: information for health professionals

USA

A new site developed by NIH "GeneTests" provides medical genetics information resources available at no cost to all interested persons. It contains educational information, a directory of genetic testing laboratories and links to other databases such as OMIM.


Links: GeneTests | Medline Plus - Genetic Testing

Ethics of Testing

Major developmental abnormalities detected early enough can be resolved far more easily than those discovered late in a pregnancy.

What are the ethical questions that are raised by prenatal testing? Future individual rights or parents rights? But what about diseases, like Huntington's, where a diagnostic test can be made but there are no current treatments for the postnatal (95% of cases adult onset) disease?

Huntington's disease

Guidelines for the molecular genetics predictive test

Recommendation 2.1 "the test is available only to individuals who have reached the age of majority."
Recommendation 7.2 "the couple requesting antenatal testing must be clearly informed that if they intend to complete the pregnancy if the fetus is a carrier of the gene defect, there is no valid reason for performing the test."

(excerpt from: IHA and the World Federation of Neurology Research Group on Huntington's Chorea. Guidelines for the molecular genetics predictive test in Huntington's disease.)

References

  1. Diana W Bianchi, R Lamar Parker, Jeffrey Wentworth, Rajeevi Madankumar, Craig Saffer, Anita F Das, Joseph A Craig, Darya I Chudova, Patricia L Devers, Keith W Jones, Kelly Oliver, Richard P Rava, Amy J Sehnert, CARE Study Group DNA sequencing versus standard prenatal aneuploidy screening. N. Engl. J. Med.: 2014, 370(9);799-808 PubMed 24571752 | N Engl J Med.
  2. Shan Dan, Wei Wang, Jinghui Ren, Yali Li, Hua Hu, Zhengfeng Xu, Tze Kin Lau, Jianhong Xie, Weihua Zhao, Hefeng Huang, Jiansheng Xie, Luming Sun, Xiaohong Zhang, Weipeng Wang, Shixiu Liao, Rong Qiang, Jiangxia Cao, Qiufang Zhang, Yulin Zhou, Haiyan Zhu, Mei Zhong, Yi Guo, Linhua Lin, Zhiying Gao, Hong Yao, Hongyun Zhang, Lijian Zhao, Fuman Jiang, Fang Chen, Hui Jiang, Songgang Li, Yingrui Li, Jun Wang, Jian Wang, Tao Duan, Yue Su, Xiuqing Zhang 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, 32(13);1225-32 PubMed 23138752

Reviews


Articles


Journals

Search PubMed

Search Pubmed: Preimplantation Genetic Screening | Preimplantation Genetic Diagnosis



Prenatal Diagnosis Terms

  • ART - Assisted Reproductive Technology a general term to describe all the clinical techniques used to aid fertility.
  • blastomere biopsy - An ART preimplantation genetic diagnosis technique carried out at cleavage stage (day 3), excluding poor quality embryos, detects chromosomal abnormalities of both maternal and paternal origin. May not detect cellular mosaicism in the embryo.
  • blastocyst biopsy - An ART preimplantation genetic diagnosis technique carried out at blastocyst stage (day 4-5), removes several trophoblast (trophoderm) cells, detects chromosomal abnormalities of both maternal and paternal origin and may detect cellular mosaicism.
  • cell-free fetal deoxyribonucleic acid - (cffDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood.
  • false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
  • false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
  • negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
  • Non-Invasive Prenatal Testing - (NIPT) could refer to ultrasound or other imaging techniques, but more frequently used to describe analysis of cell-free fetal DNA circulating in maternal blood.
  • polar body biopsy - (PB biopsy) An ART preimplantation genetic diagnosis technique that removes either the first or second polar body from the zygote. As these are generated by oocyte meiosis they detects chromosomal abnormalities only on the female genetics.
  • positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
  • pre-implantation genetic diagnosis - (PGD, pre-implantation genetic screening) a diagnostic procedure for embryos produced through Assisted Reproductive Technology (ART, in vitro fertilisation, IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.
  • prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
  • prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.
  • single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
Other Terms Lists  
Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Gastrointestinal | Genetic | Hearing | Heart | Immune | Integumentary | Neural | Oocyte | Palate | Placenta | Renal | Respiratory | Spermatozoa | Ultrasound | Vision | Historic | Glossary

External Links

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Cite this page: Hill, M.A. 2017 Embryology Genome Sequencing. Retrieved October 21, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Genome_Sequencing

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G