The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103

M. Neerman-Arbez, S. E. Antonarakis, J. L. Blouin, S. Zeinali, Mojtaba Akhtari, Y. Afshar, E. G.D. Tuddenham

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Abstract

Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factor V and coagulation factor VIII are diminished. In order to map and subsequently clone the gene responsible for this phenotype, DNAs from 19 families (16 from Iran, 2 from Pakistan, and 1 from Algeria) with a total of 32 affected individuals were collected for a genomewide linkage search using genotypes of highly informative DNA polymorphisms. All pedigrees except two contained at least one consanguineous marriage. A maximum LOD score (Z(max)) of 14.82 for θ = .02 was generated with marker D18S1129 in 18q21; LOD scores >9 were obtained for several other markers-D18S849, D18S1103, D18S64, and D18S862. Multipoint analysis resulted in Z(max) = 18.91 for the interval between D18S1129 and D18S64. Informative recombinants placed the locus for F5F8D between D18S849 and D18S1103, in an interval of ≃1 cM. These results are similar to the recently reported linkage of this disease to chromosome 18q in Jewish families (Nichols et al. 1997) and provide evidence that the same gene is responsible for all FSF8D among human populations. The difference in clinical severity of the phenotype in unrelated families, as well as the failure to detect a specific haplotype of DNA polymorphisms in the consanguineous Iranian families, suggests the existence of different molecular defects in the FSF8D gene. There exists an apparently gap-free contig with CEPH YACs linking the two markers on either side of the critical region. Positional cloning efforts are now in progress to clone the FSF8D gene.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalAmerican Journal of Human Genetics
Volume61
Issue number1
DOIs
StatePublished - Jan 1 1997

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Factor V
Hemophilia A
Phentolamine
Genes
DNA
Clone Cells
Algeria
Phenotype
Pakistan
Factor VIII
Pedigree
Iran
Marriage
Haplotypes
Organism Cloning
Chromosomes
Genotype
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Neerman-Arbez, M., Antonarakis, S. E., Blouin, J. L., Zeinali, S., Akhtari, M., Afshar, Y., & Tuddenham, E. G. D. (1997). The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103. American Journal of Human Genetics, 61(1), 143-150. https://doi.org/10.1086/513897

The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103. / Neerman-Arbez, M.; Antonarakis, S. E.; Blouin, J. L.; Zeinali, S.; Akhtari, Mojtaba; Afshar, Y.; Tuddenham, E. G.D.

In: American Journal of Human Genetics, Vol. 61, No. 1, 01.01.1997, p. 143-150.

Research output: Contribution to journalArticle

Neerman-Arbez, M, Antonarakis, SE, Blouin, JL, Zeinali, S, Akhtari, M, Afshar, Y & Tuddenham, EGD 1997, 'The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103', American Journal of Human Genetics, vol. 61, no. 1, pp. 143-150. https://doi.org/10.1086/513897
Neerman-Arbez, M. ; Antonarakis, S. E. ; Blouin, J. L. ; Zeinali, S. ; Akhtari, Mojtaba ; Afshar, Y. ; Tuddenham, E. G.D. / The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103. In: American Journal of Human Genetics. 1997 ; Vol. 61, No. 1. pp. 143-150.
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