Embryonic loss of human females with partial trisomy 19 identifies region critical for the single active X

• Published in: PloS one 2017-04, Vol.12 (4), p.e0170403
• Main Authors: Migeon, Barbara R, Beer, Michael A, Bjornsson, Hans T
• Format: Article
• Language: English
• Subjects: Ablation; Abortion, Spontaneous - genetics; Animal models; Attachment; Biological evolution; Biology and Life Sciences; Biomedical engineering; Cell death; Cells (biology); Chromatin; Chromosome 19; Chromosomes; Chromosomes, Human, Pair 19 - genetics; Chromosomes, Human, X - genetics; Compensation; CpG islands; Cytogenetics; Defects; Defensive behavior; Degradation; Demethylation; Deoxyribonucleic acid; DNA; DNA methylation; Dosage; Dosage compensation; Embryo cells; Embryogenesis; Embryonic growth stage; Embryos; Engineering; Epigenesis, Genetic; Epigenetics; Female; Females; Fetuses; Gene Deletion; Gene expression; Gene silencing; Genes; Genetics; Humans; Inactivation; Male; Males; Mammals; Mathematical models; Medicine; Medicine and Health Sciences; Mice; Mosaics; Multigene Family; Mutagenesis; Mutation; Nucleic acids; Nucleotide sequence; Placenta; Probability theory; Proteins; Sex differences (Biology); Sex Factors; Sex ratio; Statistical analysis; Stem cells; Survival; Transcription; Trend analysis; Trisomy; Vital statistics; X chromosome; X Chromosome Inactivation; X chromosomes; Zinc; Zinc Fingers - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0170403

To compensate for the sex difference in the number of X chromosomes, human females, like human males have only one active X. The other X chromosomes in cells of both sexes are silenced in utero by XIST, the Inactive X Specific Transcript gene, that is present on all X chromosomes. To investigate the means by which the human active X is protected from silencing by XIST, we updated the search for a key dosage sensitive XIST repressor using new cytogenetic data with more precise resolution. Here, based on a previously unknown sex bias in copy number variations, we identify a unique region in our genome, and propose candidate genes that lie within, as they could inactivate XIST. Unlike males, the females who duplicate this region of chromosome 19 (partial 19 trisomy) do not survive embryogenesis; this preimplantation loss of females may be one reason that more human males are born than females.