OBJECTIVES The 3' regulatory region of the immunoglobulin heavy chain gene (IGH) includes the HS1.2 enhancer displaying length polymorphism with four known variants. The goal of the research was to provide an overview of this variability and of its evolutionary significance across human populations. MATERIALS AND METHODS We compiled published and original data on HS1.2 polymorphism in 3,100 subjects from 26 human populations. Moreover, we imputed the haplotypic arrangement of the HS1.2 region in the 1000 Genomes Project (1KGP). In this dataset, imputation could also be obtained for the G1m-G3m allotype by virtue of the precise correspondence between serological types and amino acid (and DNA) substitutions in IGHG1 and IGHG3. RESULTS HS1.2 variant frequencies displayed similar patterns of continental partitioning as those reported in the literature for the physically neighboring IGHG1-IGHG3 system. The 1KGP data revealed that linkage disequilibrium (LD) can explain the spread of joint HS1.2-IGHG1-IGHG3 associations across continents and within continental populations, with stronger LD out of Africa and the features of an evolutionarily stable genomic block with differential expression in lymphoblastoid cell lines. DISCUSSION Strong population structuring involves at least the entire 70 kb genomic region here considered, due to the tight LD which maintained HS1.2, IGHG1, and IGHG3 in nonrandom arrangements. This might be key to better understand the evolutionary path of the entire genomic region driven by immune response capabilities, during the formation of continental gene pools.

中文翻译：

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人类大陆人群中Ig重链和Gm单倍型3'调控区的一致变异。

目的免疫球蛋白重链基因（IGH）的3'调控区包括HS1.2增强子，具有四个已知变异的长度多态性。该研究的目的是概述这种变异性及其在整个人群中的进化意义。材料和方法我们收集了来自26个人群的3,100名受试者的HS1.2多态性的已出版和原始数据。此外，我们推测了1000个基因组计划（1KGP）中HS1.2区域的单倍型排列。在该数据集中，由于血清型类型与IGHG1和IGHG3中的氨基酸（和DNA）取代之间的精确对应关系，也可以为G1m-G3m同种异型获得估算值。结果HS1。2个变体频率显示出与大陆相邻IGHG1-IGHG3系统的文献报道相似的大陆划分模式。1KGP数据显示，连锁不平衡（LD）可以解释HS1.2-IGHG1-IGHG3联合协会在各大洲和各大洲人群中的传播，其中LD在非洲以外更强，并且在进化上稳定并具有差异表达。淋巴母细胞系。讨论由于此处的紧密LD使HS1.2，IGHG1和IGHG3保持非随机排列，因此强大的种群结构至少涉及此处考虑的整个70 kb基因组区域。这可能是在大陆基因库形成过程中更好地了解由免疫反应能力驱动的整个基因组区域的进化途径的关键。