Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

Sergio D.J. Pena, Kátia T. De Souza, Mariza De Andrade, Ranajit Chakraborty

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the small alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, we observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of 'cooperative' changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

Original languageEnglish
Pages (from-to)723-727
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number2
DOIs
StatePublished - 18 Jan 1994

Keywords

  • cooperative mutations
  • gene conversion
  • linkage disequilibrium
  • replication slippage
  • tandemly repeat polymorphisms

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