Colobran R, Comas D, Faner R, Pedrosa E, Anglada R, Pujol-Borrell R, Bertranpetit J, Juan M
Laboratori d'Immunobiologia per a la Recerca i Aplicacions Diagnòstiques, Banc de Sang i Teixits, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain.
Genes Immun. 2008 Jun;9(4):279-88. doi: 10.1038/gene.2008.15. Epub 2008 Mar 27.
The recent description of a large amount of copy number variation (CNV) in the human genome has extended the concept of genome diversity. In this study we integrate the analysis of CNV and single nucleotide polymorphisms (SNPs) in the human CCL4L chemokine gene. CCL4L is a nonallelic copy of CCL4/MIP-1beta chemokine and displays a CNV that also includes the CCL3L gene, a nonallelic copy of CCL3/MIP-1alpha. This CNV and two functionally relevant CCL4L SNPs (rs4796195 and rs3744595) have been recently associated to HIV pathology in three independent studies. We have quantified the CCL4L copy number and genotyped both SNPs in samples from HGDP-CEPH Diversity Panel. A strong correlation between CCL4L CNV and one of the SNPs analyzed is found, whereas no significant linkage disequilibrium is found between the two SNPs despite their close distance (647 bp), suggesting a recent appearance of the second SNP when the diversity in the first one and CNV had already been generated. The present study points out that in genes with CNV, it may be a key issue to combine the assessment of gene copy number with the genotyping of relevant SNPs to understand the phenotypic impact of genome variation in the immune response.
近期对人类基因组中大量拷贝数变异（CNV）的描述扩展了基因组多样性的概念。在本研究中，我们整合了人类CCL4L趋化因子基因中CNV和单核苷酸多态性（SNP）的分析。CCL4L是CCL4/MIP-1β趋化因子的一个非等位基因拷贝，并且显示出一种CNV，该CNV还包括CCL3L基因，即CCL3/MIP-1α的一个非等位基因拷贝。最近在三项独立研究中，这种CNV以及两个功能相关的CCL4L SNP（rs4796195和rs3744595）已与HIV病理学相关联。我们对来自HGDP-CEPH多样性面板样本中的CCL4L拷贝数进行了定量，并对两个SNP进行了基因分型。我们发现CCL4L CNV与所分析的其中一个SNP之间存在很强的相关性，然而尽管两个SNP距离很近（647 bp），但未发现它们之间存在显著的连锁不平衡，这表明第二个SNP是在第一个SNP的多样性以及CNV已经产生之后才出现的。本研究指出，在具有CNV的基因中，将基因拷贝数评估与相关SNP的基因分型相结合，对于理解免疫反应中基因组变异的表型影响可能是一个关键问题。
