title: Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene.
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.
authors.affiliation: Núcelo de Genética Médica de Minas Gerais (GENE/MG), Belo Horizonte Brazil.
authors.forename: S D
authors.initials: SD
authors.lastname: Pena
authors.forename: K T
authors.initials: KT
authors.lastname: de Souza
authors.forename: M
authors.initials: M
authors.lastname: de Andrade
authors.forename: R
authors.initials: R
authors.lastname: Chakraborty
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D001938:Brazil; D002648:Child; D017931:DNA Primers / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D044465:White People / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004276:DNA, Satellite; D014841:von Willebrand Factor