Genome Sequencing

Embryology - 11 Dec 2023        Expand to Translate
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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

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.

| In Vitro Fertilization

Some Recent Findings

DNA sequencing versus standard prenatal aneuploidy screening "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 "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."

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: Prenatal% Genome Sequencing <pubmed limit=5>Prenatal Genome Sequencing</pubmed>

Older papers

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.)

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.

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  Autosomal dominant inheritance

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  Autosomal recessive inheritance

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  X-Linked dominant (affected father)

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  X-Linked dominant (affected mother)

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  X-Linked recessive (affected father)

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  X-Linked recessive (carrier mother)

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  Mitochondrial genome inheritance

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  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

References

Journals

• Journal - Prenatal diagnosis

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 - (cfDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood. Can be performed from GA 10 weeks as a first-tier test or as a second-tier test, with women with increased probability on combined first trimester screening offered cfDNA or diagnostic testing.

• 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.

• free β human chorionic gonadotrophin - beta-hCG subunit of hCG used as a diagnostic marker for: early detection of pregnancy, Trisomy 21, spontaneous abortion, ectopic pregnancy, hydatidiform mole or choriocarcinoma.

• multiples of the median - (MoM) A multiple of the median is a measure of how far an individual test result deviates from the median and is used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.

• 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.

• quadruple test (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, unconjugated estriol, and inhibin A) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).

• single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.

• triple test - (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, and unconjugated estriol) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).

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 Medical Genetic Testing Information for health professionals - April 2010

Glossary Links

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Cite this page: Hill, M.A. (2023, December 11) Embryology Genome Sequencing. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Genome_Sequencing

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