title: Embryonic loss of human females with partial trisomy 19 identifies region critical for the single active X.
abstract: 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.
authors.affiliation: McKusick Nathans Institute of Genetic Medicine, Baltimore, MD, United States of America.|Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, MD, United States of America.
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Migeon
authors.affiliation: McKusick Nathans Institute of Genetic Medicine, Baltimore, MD, United States of America.|Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beer
authors.affiliation: McKusick Nathans Institute of Genetic Medicine, Baltimore, MD, United States of America.|Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, MD, United States of America.
authors.forename: Hans T
authors.identifier: http://orcid.org/0000-0001-6635-6753
authors.initials: HT
authors.lastname: Bjornsson
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D005810:Multigene Family; D012737:Sex Factors; D014314:Trisomy; D049951:X Chromosome Inactivation; D016335:Zinc Fingers / Q000235:genetics