Differential expression of parental alleles of BRCA1 in human preimplantation embryos.
Gene expression from both parental genomes is required for completion of embryogenesis. Differential methylation of each parental genome has been observed in mouse and human preimplantation embryos. It is possible that these differences in methylation affect the level of gene transcripts from each parental genome in early developing embryos. The aim of this study was to investigate if there is a parent-specific pattern of BRCA1 expression in human embryos and to examine if this affects embryo development when the embryo carries a BRCA1 or BRCA2 pathogenic mutation. Differential parental expression of ACTB, SNRPN, H19 and BRCA1 was semi-quantitatively analysed by minisequencing in 95 human preimplantation embryos obtained from 15 couples undergoing preimplantation genetic diagnosis. BRCA1 was shown to be differentially expressed favouring the paternal transcript in early developing embryos. Methylation-specific PCR showed a variable methylation profile of BRCA1 promoter region at different stages of embryonic development. Embryos carrying paternally inherited BRCA1 or 2 pathogenic variants were shown to develop more slowly compared with the embryos with maternally inherited BRCA1 or 2 pathogenic mutations. This study suggests that differential demethylation of the parental genomes can influence the early development of preimplantation embryos. Expression of maternal and paternal genes is required for the completion of embryogenesis.
Department of Medical Genetics, Near East University, Faculty of Medicine, Yakin Dogu Bulvari, Nicosia, Cyprus. pinar.tulay@ucl.ac.uk.|UCL Preimplantation Genetics Group, Institute for Women's Health, University College London, London, UK. pinar.tulay@ucl.ac.uk.|4Current address: Near East University, Faculty of Medicine, Department of Medical Genetics, Yakin Dogu Bulvari, Nicosia, Cyprus., . pinar.tulay@ucl.ac.uk.
Pinar
P
Tulay
The Centre for Reproductive and Genetic Health, The New Wing Eastman Dental Hospital, London, UK.
Alpesh
A
Doshi
The Centre for Reproductive and Genetic Health, The New Wing Eastman Dental Hospital, London, UK.
Paul
P
Serhal
Department of Medical Genetics, Near East University, Faculty of Medicine, Yakin Dogu Bulvari, Nicosia, Cyprus.|UCL Preimplantation Genetics Group, Institute for Women's Health, University College London, London, UK.
Sioban B
SB
SenGupta
D000483:Alleles; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001755:Blastocyst / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D000072741:Maternal Inheritance / Q000235:genetics; D051379:Mice; D009154:Mutation; D010290:Parents; D011247:Pregnancy
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
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