Pena S D, de Souza K T, de Andrade M, Chakraborty R
Núcelo de Genética Médica de Minas Gerais (GENE/MG), Belo Horizonte Brazil.
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):723-7. doi: 10.1073/pnas.91.2.723.
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.
在血管性血友病因子（vWF）基因的第40内含子处，存在两个GATA重复多态性位点，它们在物理上相隔212 bp。在第一个位点（vWF1位点），在巴西高加索人群中观察到7个分离的重复等位基因，在第二个位点（vWF2位点）有8个等位基因，通过对该DNA区域的PCR扩增检测到。对个体的单倍型分析显示，在检测的338条染色体样本中有36种不同的单倍型。每个位点各代之间以及不同性别的等位基因频率没有显著差异，基因型频率符合哈迪-温伯格预期。位点之间的连锁不平衡非常显著，等位基因大小呈正相关；也就是说，位点上的大等位基因倾向于一起出现，小等位基因也是如此。每个位点的变异性似乎是以逐步的方式出现的，这表明复制滑动是产生新等位基因的一种可能机制。然而，与整个区域变异逐步产生的预测相反，我们观察到单倍型数量增加，这表明位点之间存在某种形式的“协同”变化，这可能是由于基因转换，或者是这些重复多态性位点产生新变异的共同控制机制。高度的多态性（vWF1和vWF2位点的基因多样性值分别为72%和78%，单倍型水平为93%）使得这些标记物可用于亲子鉴定、遗传咨询和个体识别目的。
