van Dijk K W, Sasso E H, Milner E C
Virginia Mason Research Center, Seattle, WA 98101.
J Immunol. 1991 May 15;146(10):3646-51.
In this study, we analyze the human VH4 gene family and find it to exhibit a level of polymorphism similar to that of the much larger VH3 family. A cloned VH4 probe detected an average of 10 hybridizing BgIII restriction fragments in genomic DNA derived from 75 unrelated individuals and a total of 15 distinct bands. Of these 15 restriction fragments, 12 were polymorphic, as demonstrated by band absence in some individuals. Oligonucleotide probes specific to CDR1 and CDR2 sequences of known VH4 genes detected limited numbers of bands and revealed sequence polymorphisms that correlated with several of the RFLP detected by the cloned probe. The prevalence of the individual polymorphic restriction fragments was highly variable, ranging from 1% to 97%, with a mean prevalence of 51%. These values resemble those previously observed among VH3 elements. Analysis of linkage disequilibrium suggests that most VH4 gene segments are in genetic equilibrium. These results indicate that the VH4 loci, like those of VH3, are dominated by relatively few, perhaps two to four, alleles/locus and further suggest that the haplotype organization of the human VH locus is very complex.
在本研究中，我们分析了人类VH4基因家族，发现其多态性水平与大得多的VH3家族相似。一个克隆的VH4探针在来自75个无关个体的基因组DNA中平均检测到10个杂交的BgIII限制性片段以及总共15条不同的条带。在这15个限制性片段中，12个是多态性的，这在一些个体中表现为条带缺失。针对已知VH4基因的CDR1和CDR2序列的寡核苷酸探针检测到的条带数量有限，并揭示了与克隆探针检测到的一些限制性片段长度多态性相关的序列多态性。各个多态性限制性片段的流行率高度可变，范围从1%到97%，平均流行率为51%。这些值与先前在VH3元件中观察到的值相似。连锁不平衡分析表明，大多数VH4基因片段处于遗传平衡状态。这些结果表明，VH4基因座与VH3基因座一样，每个基因座由相对较少的，可能两到四个等位基因主导，并且进一步表明人类VH基因座的单倍型组织非常复杂。
