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 silencedin uterobyXIST, theInactive 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 byXIST, we updated the search for a key dosage sensitiveXISTrepressor 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 inactivateXIST. 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.