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. 1989 Apr;86(7):2296–2300. doi: 10.1073/pnas.86.7.2296

Exchange of terminal portions of X- and Y-chromosomal short arms in human XY females.

J Levilliers 1, B Quack 1, J Weissenbach 1, C Petit 1
PMCID: PMC286899  PMID: 2928333

Abstract

Human Y(+) XX maleness has been shown to result from an abnormal terminal Xp-Yp interchange that can occur during paternal meiosis. To test whether human XY females are produced by the same mechanism, we followed the inheritance of paternal pseudoautosomal loci and Xp22.3-specific loci in two XY female patients. Y-specific sequences and the whole pseudoautosomal region of the Y chromosome of their fathers were absent in these patients. However, the entire pseudoautosomal region and the X-specific part of Xp22.3 distal to the STS locus had been inherited from the X chromosome of the respective father. This Xp transfer to Yp was established by in situ hybridization experiments showing an Xp22.3-specific locus on Yp in both cases. Such results demonstrate that an abnormal and terminal X-Y interchange generated the rearranged Y chromosome of these two XY females; they appear to be the true countertype of Y(+) XX males. In these patients, who also display some Turner stigmata, the Y gene(s) involved in this phenotype is (are) localized to interval 1 or 2. If the loss of such gene(s) affects fetal viability, their proximity to TDF would account for the underrepresentation of interchange 46,XY females compared with Y(+) XX males.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Affara N. A., Ferguson-Smith M. A., Magenis R. E., Tolmie J. L., Boyd E., Cooke A., Jamieson D., Kwok K., Mitchell M., Snadden L. Mapping the testis determinants by an analysis of Y-specific sequences in males with apparent XX and XO karyotypes and females with XY karyotypes. Nucleic Acids Res. 1987 Sep 25;15(18):7325–7342. doi: 10.1093/nar/15.18.7325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Affara N. A., Ferguson-Smith M. A., Tolmie J., Kwok K., Mitchell M., Jamieson D., Cooke A., Florentin L. Variable transfer of Y-specific sequences in XX males. Nucleic Acids Res. 1986 Jul 11;14(13):5375–5387. doi: 10.1093/nar/14.13.5375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ballabio A., Parenti G., Carrozzo R., Sebastio G., Andria G., Buckle V., Fraser N., Craig I., Rocchi M., Romeo G. Isolation and characterization of a steroid sulfatase cDNA clone: genomic deletions in patients with X-chromosome-linked ichthyosis. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4519–4523. doi: 10.1073/pnas.84.13.4519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cooke H. J., Brown W. R., Rappold G. A. Hypervariable telomeric sequences from the human sex chromosomes are pseudoautosomal. Nature. 1985 Oct 24;317(6039):687–692. doi: 10.1038/317687a0. [DOI] [PubMed] [Google Scholar]
  5. Davies K. E., Mandel J. L., Weissenbach J., Fellous M. Report of the committee on the genetic constitution of the X and Y chromosomes. Cytogenet Cell Genet. 1987;46(1-4):277–315. doi: 10.1159/000132481. [DOI] [PubMed] [Google Scholar]
  6. Disteche C. M., Casanova M., Saal H., Friedman C., Sybert V., Graham J., Thuline H., Page D. C., Fellous M. Small deletions of the short arm of the Y chromosome in 46,XY females. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7841–7844. doi: 10.1073/pnas.83.20.7841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donis-Keller H., Green P., Helms C., Cartinhour S., Weiffenbach B., Stephens K., Keith T. P., Bowden D. W., Smith D. R., Lander E. S. A genetic linkage map of the human genome. Cell. 1987 Oct 23;51(2):319–337. doi: 10.1016/0092-8674(87)90158-9. [DOI] [PubMed] [Google Scholar]
  8. FERGUSON-SMITH M. A. KARYOTYPE-PHENOTYPE CORRELATIONS IN GONADAL DYSGENESIS AND THEIR BEARING ON THE PATHOGENESIS OF MALFORMATIONS. J Med Genet. 1965 Jun;2(2):142–155. doi: 10.1136/jmg.2.2.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  10. Ferguson-Smith M. A. X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome. Lancet. 1966 Aug 27;2(7461):475–476. doi: 10.1016/s0140-6736(66)92778-4. [DOI] [PubMed] [Google Scholar]
  11. Geldwerth D., Bishop C., Guellaën G., Koenig M., Vergnaud G., Mandel J. L., Weissenbach J. Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome. EMBO J. 1985 Jul;4(7):1739–1743. doi: 10.1002/j.1460-2075.1985.tb03844.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goodfellow P. J., Darling S. M., Thomas N. S., Goodfellow P. N. A pseudoautosomal gene in man. Science. 1986 Nov 7;234(4777):740–743. doi: 10.1126/science.2877492. [DOI] [PubMed] [Google Scholar]
  13. Hook E. B., Warburton D. The distribution of chromosomal genotypes associated with Turner's syndrome: livebirth prevalence rates and evidence for diminished fetal mortality and severity in genotypes associated with structural X abnormalities or mosaicism. Hum Genet. 1983;64(1):24–27. doi: 10.1007/BF00289473. [DOI] [PubMed] [Google Scholar]
  14. Koenig M., Camerino G., Heilig R., Mandel J. L. A DNA fragment from the human X chromosome short arm which detects a partially homologous sequence on the Y chromosomes long arm. Nucleic Acids Res. 1984 May 25;12(10):4097–4109. doi: 10.1093/nar/12.10.4097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Magenis R. E., Tochen M. L., Holahan K. P., Carey T., Allen L., Brown M. G. Turner syndrome resulting from partial deletion of Y chromosome short arm: localization of male determinants. J Pediatr. 1984 Dec;105(6):916–919. doi: 10.1016/s0022-3476(84)80077-3. [DOI] [PubMed] [Google Scholar]
  16. Mattei M. G., Philip N., Passage E., Moisan J. P., Mandel J. L., Mattei J. F. DNA probe localization at 18p113 band by in situ hybridization and identification of a small supernumerary chromosome. Hum Genet. 1985;69(3):268–271. doi: 10.1007/BF00293038. [DOI] [PubMed] [Google Scholar]
  17. Moses M. J., Counce S. J., Paulson D. F. Synaptonemal complex complement of man in spreads of spermatocytes, with details of the sex chromosome pair. Science. 1975 Jan 31;187(4174):363–365. [PubMed] [Google Scholar]
  18. Müller U., Lalande M., Donlon T., Latt S. A. Moderately repeated DNA sequences specific for the short arm of the human Y chromosome are present in XX males and reduced in copy number in an XY female. Nucleic Acids Res. 1986 Feb 11;14(3):1325–1340. doi: 10.1093/nar/14.3.1325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nazareth H. R., Moreira-Filho C. A., Cunha A. J., Vieira-Filho J. P., Lengyel A. M., Lima M. C. H-Y antigen in 46,XY pure testicular dysgenesis. Am J Med Genet. 1979;3(2):149–154. doi: 10.1002/ajmg.1320030206. [DOI] [PubMed] [Google Scholar]
  20. Page D. C., Bieker K., Brown L. G., Hinton S., Leppert M., Lalouel J. M., Lathrop M., Nystrom-Lahti M., de la Chapelle A., White R. Linkage, physical mapping, and DNA sequence analysis of pseudoautosomal loci on the human X and Y chromosomes. Genomics. 1987 Nov;1(3):243–256. doi: 10.1016/0888-7543(87)90051-6. [DOI] [PubMed] [Google Scholar]
  21. Page D. C., Brown L. G., de la Chapelle A. Exchange of terminal portions of X- and Y-chromosomal short arms in human XX males. 1987 Jul 30-Aug 5Nature. 328(6129):437–440. doi: 10.1038/328437a0. [DOI] [PubMed] [Google Scholar]
  22. Page D. C., Harper M. E., Love J., Botstein D. Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution. Nature. 1984 Sep 13;311(5982):119–123. doi: 10.1038/311119a0. [DOI] [PubMed] [Google Scholar]
  23. Page D. C., Mosher R., Simpson E. M., Fisher E. M., Mardon G., Pollack J., McGillivray B., de la Chapelle A., Brown L. G. The sex-determining region of the human Y chromosome encodes a finger protein. Cell. 1987 Dec 24;51(6):1091–1104. doi: 10.1016/0092-8674(87)90595-2. [DOI] [PubMed] [Google Scholar]
  24. Page D. C. Sex reversal: deletion mapping the male-determining function of the human Y chromosome. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):229–235. doi: 10.1101/sqb.1986.051.01.028. [DOI] [PubMed] [Google Scholar]
  25. Pearson P. L., Bobrow M. Definitive evidence for the short arm of the Y chromosome associating with the X chromosome during miosis in the human male. Nature. 1970 Jun 6;226(5249):959–961. doi: 10.1038/226959a0. [DOI] [PubMed] [Google Scholar]
  26. Petit C., Levilliers J., Weissenbach J. Physical mapping of the human pseudo-autosomal region; comparison with genetic linkage map. EMBO J. 1988 Aug;7(8):2369–2376. doi: 10.1002/j.1460-2075.1988.tb03081.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Petit C., de la Chapelle A., Levilliers J., Castillo S., Noël B., Weissenbach J. An abnormal terminal X-Y interchange accounts for most but not all cases of human XX maleness. Cell. 1987 Jun 5;49(5):595–602. doi: 10.1016/0092-8674(87)90535-6. [DOI] [PubMed] [Google Scholar]
  28. Pritchard C. A., Goodfellow P. J., Goodfellow P. N. Mapping the limits of the human pseudoautosomal region and a candidate sequence for the male-determining gene. Nature. 1987 Jul 16;328(6127):273–275. doi: 10.1038/328273a0. [DOI] [PubMed] [Google Scholar]
  29. Rosenfeld R. G., Luzzatti L., Hintz R. L., Miller O. J., Koo G. C., Wachtel S. S. Sexual and somatic determinants of the human Y chromosome: studies in a 46,XYp- phenotypic female. Am J Hum Genet. 1979 Jul;31(4):458–468. [PMC free article] [PubMed] [Google Scholar]
  30. Rouyer F., Simmler M. C., Johnsson C., Vergnaud G., Cooke H. J., Weissenbach J. A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes. Nature. 1986 Jan 23;319(6051):291–295. doi: 10.1038/319291a0. [DOI] [PubMed] [Google Scholar]
  31. Rouyer F., Simmler M. C., Page D. C., Weissenbach J. A sex chromosome rearrangement in a human XX male caused by Alu-Alu recombination. Cell. 1987 Nov 6;51(3):417–425. doi: 10.1016/0092-8674(87)90637-4. [DOI] [PubMed] [Google Scholar]
  32. Rouyer F., Simmler M. C., Vergnaud G., Johnsson C., Levilliers J., Petit C., Weissenbach J. The pseudoautosomal region of the human sex chromosomes. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):221–228. doi: 10.1101/sqb.1986.051.01.027. [DOI] [PubMed] [Google Scholar]
  33. Schellhas H. F. Malignant potential of the dysgenetic gonad. Part 1. Obstet Gynecol. 1974 Aug;44(2):298–309. [PubMed] [Google Scholar]
  34. Simmler M. C., Rouyer F., Vergnaud G., Nyström-Lahti M., Ngo K. Y., de la Chapelle A., Weissenbach J. Pseudoautosomal DNA sequences in the pairing region of the human sex chromosomes. Nature. 1985 Oct 24;317(6039):692–697. doi: 10.1038/317692a0. [DOI] [PubMed] [Google Scholar]
  35. Simpson J. L., Blagowidow N., Martin A. O. XY gonadal dysgenesis: genetic heterogeneity based upon clinical observations, H-Y antigen status and segregation analysis. Hum Genet. 1981;58(1):91–97. doi: 10.1007/BF00284155. [DOI] [PubMed] [Google Scholar]
  36. Simpson J. L., Christakos A. C., Horwith M., Silverman F. S. Gonadal dysgenesis in individuals with apparently normal chromosomal complements: tabulation of cases and compilation of genetic data. Birth Defects Orig Artic Ser. 1971 May;7(6):215–228. [PubMed] [Google Scholar]
  37. Vergnaud G., Page D. C., Simmler M. C., Brown L., Rouyer F., Noel B., Botstein D., de la Chapelle A., Weissenbach J. A deletion map of the human Y chromosome based on DNA hybridization. Am J Hum Genet. 1986 Feb;38(2):109–124. [PMC free article] [PubMed] [Google Scholar]
  38. Wang T. S., Pearson B. E., Suomalainen H. A., Mohandas T., Shapiro L. J., Schröder J., Korn D. Assignment of the gene for human DNA polymerase alpha to the X chromosome. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5270–5274. doi: 10.1073/pnas.82.16.5270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wieacker P., Voiculescu J., Müller C. R., Ropers H. H. An XX male with a single STS gene dose. Cytogenet Cell Genet. 1983;35(1):72–74. doi: 10.1159/000131841. [DOI] [PubMed] [Google Scholar]
  40. Yen P. H., Allen E., Marsh B., Mohandas T., Wang N., Taggart R. T., Shapiro L. J. Cloning and expression of steroid sulfatase cDNA and the frequent occurrence of deletions in STS deficiency: implications for X-Y interchange. Cell. 1987 May 22;49(4):443–454. doi: 10.1016/0092-8674(87)90447-8. [DOI] [PubMed] [Google Scholar]
  41. de la Chapelle A. The etiology of maleness in XX men. Hum Genet. 1981;58(1):105–116. doi: 10.1007/BF00284157. [DOI] [PubMed] [Google Scholar]

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