Abstract:
:In vitro fertilization (IVF), blastomere biopsy of the 6-8 cell embryo, and single cell DNA diagnosis allows couples at risk of transmitting an X-linked or autosomal disease to start a pregnancy knowing their child will not be affected. We present a quick and reliable nested PCR strategy for sex determination at the single cell level by simultaneous amplification and subsequent restriction fragment analysis of the homologous but non-allelic ZFX and ZFY genes present on the X and Y chromosomes respectively. Amplified ZFX and ZFY sequences are of equal size and produce distinguishable HaeIII digestion products. In a randomized, blinded study of 194 individually isolated lymphoblasts, amniocytes, chorion villus cells, and blastomeres, 191 amplified successfully (98.4% sensitivity). None of the sample blanks showed any PCR product, all 90 of the karyotypically XY cells were correctly genotyped as ZFX/ZFY, all 83 of the 84 XX cells that amplified were correctly genotyped as ZFX only, and analyses of all same-embryo blastomeres were completely concordant (100% specificity). This strategy avoids a source of misdiagnosis observed in methods which detect only Y-specific sequences, where amplification failure in an XY cell results in an erroneous XX diagnosis. This rapid (6 hr) and simple method of analysis, when applied to preimplantation embryo diagnosis, allows the avoidance of offspring affected with an X-linked recessive disorder by transferring only female embryos for implantation and ensuing pregnancy.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Chong SS,Kristjansson K,Cota J,Handyside AH,Hughes MRdoi
10.1093/hmg/2.8.1187subject
Has Abstractpub_date
1993-08-01 00:00:00pages
1187-91issue
8eissn
0964-6906issn
1460-2083journal_volume
2pub_type
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