Estrutura populacional e diversidade de variações em número de cópias (CNVs) de genes do sistema imune em populações nativas da América do Sul

Abstract

Copy number variablle regions (CNVRs) are formally defined as a segment of DNA ranging from one kilobase to several megabases in size and with variable copy number in comparison to the usual copy number of two of a reference genome. These regions represent a significant part of human genetic variation and reveal degrees of diversity and overall patterns of genetic structure comparable to single nucleotide polymorphism (SNP) diversity. Their presence in genomic regions harboring dosage-sensitive genes may have functional impacts that account for associations between rare and common copy numbervariation (CNV) and a variety of comp ex genetic diseases. In the present study we aimed to estimate the diversity of genes that show CNV inNative American populations whose sampling is aways underrepresented in genetic studies and limited to populations from the HGDP CEPH commercial panel. We analyzed the frequency distribution of the muticopy immune system beta-defensin region, CCL3L1/CCL4L1, FCGR3A, FCGR3B and FCGR2C genes, and the allelic variants FCGR3B-HNA1a/1b, FCGR2C-Q57X and DEFB103-CladeI/II in a large sample set of autochthonous Peruvian Native Americans Ashaninka, Monte Carmelo and Shimaa populations using the Paralogue Ratio Test (PRT) technique. The results were compared to published data to investigate the existence of differentiall diplotype distributions in NativeAmericans from South Americans and brought up to date information concerning their CNV diversity. Amerindians tend to display an increased frequency of deletion events in the FCGR3B gene and of the FCGR3B HNA1a alotype, and duplication of CCL3L1/CCL4L1 copy number. Especially, the Shimaa population shows a higher frequency of the sevencopies diplotype at the beta-defensin region. These results posit possible impacts to expression profiles of the involved immunegenes in the presented population in the context of evolutionary global genomic diversity, with implications for future epidemiological studies on susceptibility to autoimmune and infectious diseases.