TY - JOUR
T1 - Chromosomal localization of ZFX-A human gene that escapes X inactivation-and its murine homologs
AU - Page, David C.
AU - Disteche, Christine M.
AU - Simpson, Elizabeth M.
AU - de la Chapelle, Albert
AU - Andersson, Mea
AU - Alitalo, Tiina
AU - Brown, Laura G.
AU - Green, Phil
AU - Akots, Gita
N1 - Funding Information:
We thank David Adler for computer-generated chromosome idiograms and Rebecca Mosher and Douglas Vollratb for comments on the manuscript. We thank Louis Kunkel, Sam Latt (deceased), Jean-Louis Mandel, and Teresa Wang for DNA probes. We are especially grateful to Giovanni Romeo and Stefania Fadda for allowing us to analyze their unpublished pERT87-15 genotype data. This work was supported by grants from the National Institutes of Health (HD22532 to D.C.P., GM40543 to Helen Donis-Keller, GM30476 to C.M.D.), the Lucille P. Markey Charitable Trust, the March of Dimes, the American Cancer Society, the Sigrid Juselius Foundation, the Folk-h&an Institute of Genetics, and the Academy of Finland.
PY - 1990/5
Y1 - 1990/5
N2 - The ZFY gene, found in the sex-determining region of the human Y chromosome, encodes a zinc-finger protein that may be the pivotal sex-determining signal. A closely related gene, ZFX, is found on the human X chromosome, and it may also function in sex determination. ZFX is one of a few genes on the human X chromosome that are known to escape X inactivation. We report the localization of ZFX, by meiotic linkage analysis and physical mapping, distal to POLA but proximal to DXS41 (p99-6), near the boundary of bands Xp21.3 and Xp22.1. (Our results suggest the following order of loci in Xp21-p22: cen-DMD-[GK, AHC]-DXS67 (pB24)-POLA-ZFX-[DXS41 (p99-6), DXS274 (CRI-L1391)]-DXS43 (pD2)-pter.) These findings contradict the model that escape from X inactivation is limited to genes near the short-arm telomere (i.e., in Xp22.3). Instead, escape from X inactivation is likely a property of several noncontiguous segments of the X chromosome. Curiously, in mouse, the homologous Zfx gene maps to X chromosome band D, near the center from which an X-inactivating signal is thought to spread. As judged by comparative mapping, it appears that an X-chromosomal segment that spans the ZFX and DMD genes has remained grossly intact during the divergence of mouse and human from a common ancestor. Conservation of this chromosomal segment may extend to marsupials, where homologs of the ZFX and DMD genes have been observed in proximity, but on an autosome. While autosomal homologs of ZFX have not been observed in other placental mammals, a locus derived from a processed Zfx transcript is found on mouse chromosome 10 band B3 or B4.
AB - The ZFY gene, found in the sex-determining region of the human Y chromosome, encodes a zinc-finger protein that may be the pivotal sex-determining signal. A closely related gene, ZFX, is found on the human X chromosome, and it may also function in sex determination. ZFX is one of a few genes on the human X chromosome that are known to escape X inactivation. We report the localization of ZFX, by meiotic linkage analysis and physical mapping, distal to POLA but proximal to DXS41 (p99-6), near the boundary of bands Xp21.3 and Xp22.1. (Our results suggest the following order of loci in Xp21-p22: cen-DMD-[GK, AHC]-DXS67 (pB24)-POLA-ZFX-[DXS41 (p99-6), DXS274 (CRI-L1391)]-DXS43 (pD2)-pter.) These findings contradict the model that escape from X inactivation is limited to genes near the short-arm telomere (i.e., in Xp22.3). Instead, escape from X inactivation is likely a property of several noncontiguous segments of the X chromosome. Curiously, in mouse, the homologous Zfx gene maps to X chromosome band D, near the center from which an X-inactivating signal is thought to spread. As judged by comparative mapping, it appears that an X-chromosomal segment that spans the ZFX and DMD genes has remained grossly intact during the divergence of mouse and human from a common ancestor. Conservation of this chromosomal segment may extend to marsupials, where homologs of the ZFX and DMD genes have been observed in proximity, but on an autosome. While autosomal homologs of ZFX have not been observed in other placental mammals, a locus derived from a processed Zfx transcript is found on mouse chromosome 10 band B3 or B4.
UR - https://www.scopus.com/pages/publications/0025002570
U2 - 10.1016/0888-7543(90)90516-W
DO - 10.1016/0888-7543(90)90516-W
M3 - Article
C2 - 1970799
AN - SCOPUS:0025002570
SN - 0888-7543
VL - 7
SP - 37
EP - 46
JO - Genomics
JF - Genomics
IS - 1
ER -