Prenatal Genetic Diagnosis
These resources give a general introduction to some of the many new prenatal genetic diagnostic techniques available at different stages of pregnancy. These diagnostic techniques now include Preimplantation Genetic Screening (PGS) in association with the many Assisted Reproductive Technologies, more commonly known as In Vitro Fertilization (IVF).
- 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 | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Category:Neonatal Diagnosis
Some Recent Findings
Preimplantation Genetic Screening
A range of techniques including fluorescence in situ hybridization (FISH)-based testing, PCR amplification-based testing and both polar body and embryo biopsy for PGD/preimplantation genetic screening (PGS).
- Links: In Vitro Fertilization
Biological Collection Techniques
Percutaneous umbilical blood sampling (PUBS, fetal blood sampling, umbilical vein sampling) This chromosome analysis test is done at in the 18th week or later of high-risk pregnancies. The technique may be used when either alternative tests (amniocentesis, CVS, ultrasound) are either inconclusive or not achievable (severe oligohydramnios).
The risk of a miscarriage related to the test is about 3 per cent (occurring in 3 in 100 pregnancies).
Is a technique of sampling of extracoelomic fluid usually for an early prenatal diagnostic technique.
As a prenatal diagnostic test, a positive fetal fibronectin test result can indicate a higher risk of preterm delivery, but may also has false positive results. The negative result is more reliable as an indicator of reduced risk of preterm birth.
(fFN) is an extracellular matrix glycoprotein produced by fetal cells. Fetal fibronectin appears to act as an adhesive between the interface of the chorion and the decidua (fetal membrane and uterine lining).
Fluorescence In Situ Hybridization (FISH)
This technique has several diagnostic and screening applications including:
- embryo sexing for X-linked diseases
- embryo sexing for social reasons (gender selection/family balancing)
- inherited chromosome rearrangements
- aneuploidy screening (PGS)
The following information for probe selection is based upon the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium set of Guidelines for Best Practice PGD. The guidelines were first published in 2005 and recently updated in 2010.
A probe set containing at least probes specific for the centromere regions of the X and Y chromosomes, and one autosome.
A probe set should at least contain sufficient probes to detect all expected unbalanced forms of the chromosomal rearrangement.
Comparative Genomic Hybridization
This new test under development is based upon microarray-based comparative genomic hybridization (array CGH).
All fetal cells should have complete copies of maternal and paternal genomes. The test compares regions of fetal DNA that deviate from this "pattern" due to either too much or too little DNA, alterations reflect regions of the genome that are either copied or deleted. These genetic changes may therefore cause disease. (More? Prenatal Diagnosis - Comparative Genomic Hybridization)
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.
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?
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."
Prenatal Diagnosis Terms
- 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.
- positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
- pre-implantation genetic diagnosis - (PGD) a screening procedure for embryos produced through 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.
- ↑ G L Harton, M C Magli, K Lundin, M Montag, J Lemmen, J C Harper, European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium/Embryology Special Interest Group ESHRE PGD Consortium/Embryology Special Interest Group--best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS). Hum. Reprod.: 2011, 26(1);41-6 PMID:20966459
- ↑ G L Harton, M De Rycke, F Fiorentino, C Moutou, S SenGupta, J Traeger-Synodinos, J C Harper, European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium ESHRE PGD consortium best practice guidelines for amplification-based PGD. Hum. Reprod.: 2011, 26(1);33-40 PMID:20966462
- ↑ G L Harton, J C Harper, E Coonen, T Pehlivan, K Vesela, L Wilton, European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium ESHRE PGD consortium best practice guidelines for fluorescence in situ hybridization-based PGD. Hum. Reprod.: 2011, 26(1);25-32 PMID:20966461
- ↑ G Harton, P Braude, A Lashwood, A Schmutzler, J Traeger-Synodinos, L Wilton, J C Harper, European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium ESHRE PGD consortium best practice guidelines for organization of a PGD centre for PGD/preimplantation genetic screening. Hum. Reprod.: 2011, 26(1);14-24 PMID:20966460
- ↑ Ji Hyeon Park, Jung Hoon Woo, Sung Han Shim, Song-Ju Yang, Young Min Choi, Kap-Seok Yang, Dong Hyun Cha Application of a target array comparative genomic hybridization to prenatal diagnosis. BMC Med. Genet.: 2010, 11();102 PMID:20576126 | BMC Med Genet.
Gary Fruhman, Ignatia B Van den Veyver Applications of array comparative genomic hybridization in obstetrics. Obstet. Gynecol. Clin. North Am.: 2010, 37(1);71-85, Table of Contents PMID:20494259
Justine Coppinger, Sarah Alliman, Allen N Lamb, Beth S Torchia, Bassem A Bejjani, Lisa G Shaffer Whole-genome microarray analysis in prenatal specimens identifies clinically significant chromosome alterations without increase in results of unclear significance compared to targeted microarray. Prenat. Diagn.: 2009, 29(12);1156-66 PMID:19795450
Anthony J Schaeffer, June Chung, Konstantina Heretis, Andrew Wong, David H Ledbetter, Christa Lese Martin Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am. J. Hum. Genet.: 2004, 74(6);1168-74 PMID:15127362