Department of Genetics and Developmental Biology, Southeast University School of Medicine and The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University, Nanjing, China.
PLoS One. 2012;7(1):e30268. doi: 10.1371/journal.pone.0030268. Epub 2012 Jan 18.
CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It recognizes several pathogens of important public health concern. In particular, a highly polymorphic variable number tandem repeat (VNTR) at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases. To gain insight into the origin and evolution of this VNTR in CLEC4M, we studied 21 Africans, 20 Middle Easterns, 35 Europeans, 38 Asians, 13 Oceania, and 18 Americans (a total of 290 chromosomes) from the (Human Genome Diversity Panel) HGDP-CEPH panel; these samples covered most of alleles of this VNTR locus present in human populations. We identified a limited number of haplotypes among the basic repeat subunits that is 69 base pairs in length. Only 8 haplotypes were found. Their sequence identities were determined in the 290 chromosomes. VNTR alleles of different repeat length (from 4 to 9 repeats) were analyzed for composition and orientation of these subunits. Our results showed that the subunit configuration of the same repeat number of VNTR locus from different populations were, in fact, virtually identical. It implies that most of the VNTR alleles existed before dispersion of modern humans outside Africa. Further analyses indicate that the present diversity profile of this locus in worldwide populations is generated from the effect of migration of different tribes and neutral evolution. Our findings do not support the hypothesis that the origin of the VNTR alleles were arisen by independent (separate) mutation events and caused by differential allele advantage and natural selection as suggested by previous report based on SNP data.
CLEC4M 是一种 C 型凝集素基因，作为细胞黏附受体和病原体识别受体。它识别几种重要的公共卫生关注的病原体。特别是，CLEC4M 颈部区域的高度多态性可变数串联重复 (VNTR) 与某些传染病的遗传易感性有关。为了深入了解 CLEC4M 中这种 VNTR 的起源和进化，我们研究了来自 (人类基因组多样性面板) HGDP-CEPH 面板的 21 名非洲人、20 名中东人、35 名欧洲人、38 名亚洲人、13 名大洋洲人和 18 名美国人（共 290 条染色体）；这些样本涵盖了人类群体中存在的这种 VNTR 基因座的大多数等位基因。我们在基本重复亚基中发现了数量有限的单倍型，其长度为 69 个碱基对。只发现了 8 种单倍型。它们的序列同一性在 290 条染色体中确定。分析了不同重复长度（4 至 9 个重复）的 VNTR 等位基因，以确定这些亚基的组成和方向。我们的结果表明，来自不同人群的 VNTR 基因座相同重复数的亚基配置实际上几乎相同。这意味着大多数 VNTR 等位基因在现代人离开非洲之前就已经存在了。进一步的分析表明，目前该基因座在全球人口中的多样性模式是由不同部落迁移和中性进化的影响产生的。我们的研究结果不支持这样的假设，即 VNTR 等位基因的起源是由独立（单独）的突变事件引起的，并由先前基于 SNP 数据的报告中提出的差异等位基因优势和自然选择引起的。
