TY - JOUR
T1 - Embryonic loss of human females with partial trisomy 19 identifies region critical for the single active X
AU - Migeon, Barbara R.
AU - Beer, Michael A.
AU - Bjornsson, Hans T.
N1 - Funding Information:
We are grateful to many. We thank Patricia A Jacobs for her contributions to, and support of, the single active X hypothesis. Thanks to David Valle for directing us to the DECIPHER database. We also thank Andrew McCallion, Haig Kazazian, Kirby Smith, Hal Dietz, Dimitrios Avramopoulos and Geraldine Seydoux for their helpful comments about the paper, Cate Kiefe for her rendering of and Giovanni Carosso for help with formatting. This study makes use of data generated by the DECIPHER community. A full list of centres that contributed to the generation of the data is available from http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk . Funding for the DECIPHER project was provided by the Wellcome Trust.
Publisher Copyright:
© 2017 Migeon et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0170403
DO - 10.1371/journal.pone.0170403
M3 - Article
C2 - 28403217
AN - SCOPUS:85017559519
SN - 1932-6203
VL - 12
JO - PLoS One
JF - PLoS One
IS - 4
M1 - e0170403
ER -