Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells

Judith Pratt Rossiter, Michele Young, Michelle L. Kimberland, Pierre Hutter, Rhett P. Ketterling, Jane Gitschier, Jürgen Horst, Michael A. Morris, Daniel J Schaid, Philippe De Moerloose, Steve S. Sommer, Haig H. Kazazian, Stylianos E. Antonarakis

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

The factor VIII gene, which is defective in hemophilia A, is located in the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells.

Original languageEnglish (US)
Pages (from-to)1035-1039
Number of pages5
JournalHuman Molecular Genetics
Volume3
Issue number7
StatePublished - Jul 1994

Fingerprint

Factor VIII
Hemophilia A
Germ Cells
Inversion
Genes
Cells
Gene
Cell
Mothers
Homologous Recombination
X Chromosome
Chromosomes
Polymorphism
Introns
DNA
Recombination
Pairing
Chromosome
Haemophilia
Factors

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)

Cite this

Rossiter, J. P., Young, M., Kimberland, M. L., Hutter, P., Ketterling, R. P., Gitschier, J., ... Antonarakis, S. E. (1994). Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Human Molecular Genetics, 3(7), 1035-1039.

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. / Rossiter, Judith Pratt; Young, Michele; Kimberland, Michelle L.; Hutter, Pierre; Ketterling, Rhett P.; Gitschier, Jane; Horst, Jürgen; Morris, Michael A.; Schaid, Daniel J; De Moerloose, Philippe; Sommer, Steve S.; Kazazian, Haig H.; Antonarakis, Stylianos E.

In: Human Molecular Genetics, Vol. 3, No. 7, 07.1994, p. 1035-1039.

Research output: Contribution to journalArticle

Rossiter, JP, Young, M, Kimberland, ML, Hutter, P, Ketterling, RP, Gitschier, J, Horst, J, Morris, MA, Schaid, DJ, De Moerloose, P, Sommer, SS, Kazazian, HH & Antonarakis, SE 1994, 'Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells', Human Molecular Genetics, vol. 3, no. 7, pp. 1035-1039.
Rossiter JP, Young M, Kimberland ML, Hutter P, Ketterling RP, Gitschier J et al. Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. Human Molecular Genetics. 1994 Jul;3(7):1035-1039.
Rossiter, Judith Pratt ; Young, Michele ; Kimberland, Michelle L. ; Hutter, Pierre ; Ketterling, Rhett P. ; Gitschier, Jane ; Horst, Jürgen ; Morris, Michael A. ; Schaid, Daniel J ; De Moerloose, Philippe ; Sommer, Steve S. ; Kazazian, Haig H. ; Antonarakis, Stylianos E. / Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells. In: Human Molecular Genetics. 1994 ; Vol. 3, No. 7. pp. 1035-1039.
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