title: Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene.
abstract: Women with balanced translocations between the long arm of the X chromosome (Xq) and an autosome frequently suffer premature ovarian failure (POF). Two "critical regions" for POF which extend from Xq13-->q22 and from Xq22-->q26 have been identified using cytogenetics. To gain insight into the mechanism(s) responsible for ovarian failure in women with X;autosome translocations, we have molecularly characterized the translocation breakpoints of nine X chromosomes. We mapped the breakpoints using somatic cell hybrids retaining the derivative autosome and densely spaced markers from the X-chromosome physical map. One of the POF-associated breakpoints in a critical region (Xq25) mapped to a sequenced PAC clone. The translocation disrupts XPNPEP2, which encodes an Xaa-Pro aminopeptidase that hydrolyzes N-terminal Xaa-Pro bonds. XPNPEP2 mRNA was detected in fibroblasts that carry the translocation, suggesting that this gene at least partially escapes X inactivation. Although the physiologic substrates for the enzyme are not known, XPNPEP2 is a candidate gene for POF. Our breakpoint mapping data will help to identify additional candidate POF genes and to delineate the Xq POF critical region(s).
authors.affiliation: Eugene McDermott Center for Human Growth and Development and Department of Internal Medicine, The University of Texas Southwestern Medical School, Dallas, TX, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Prueitt
authors.forename: J L
authors.initials: JL
authors.lastname: Ross
authors.forename: A R
authors.initials: AR
authors.lastname: Zinn
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002648:Child; D019457:Chromosome Breakage / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D016649:Primary Ovarian Insufficiency / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D016324:Sequence Tagged Sites; D014178:Translocation, Genetic / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase