Population structure in copy number variation and SNPs in the CCL4L chemokine gene

Genes Immun. 2008 Jun;9(4):279-88. doi: 10.1038/gene.2008.15. Epub 2008 Mar 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa South of the Sahara
  • Alleles
  • Americas
  • Asian People / genetics
  • Chemokine CCL4 / genetics*
  • Gene Dosage*
  • Gene Frequency
  • Genetic Heterogeneity
  • Genetic Variation*
  • Genetics, Population*
  • Genome, Human
  • Heterozygote
  • Humans
  • Oceania
  • Polymorphism, Single Nucleotide*

Substances

  • Chemokine CCL4