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Open Access Short Report

Variations in CCL3L gene cluster sequence and non-specific gene copy numbers

Sadeep Shrestha1*, Mawuli Nyaku1 and Jeffrey C Edberg2

Author Affiliations

1 Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, 1665 University Blvd, RPHB Room 217L, Birmingham, Alabama 35294-0022, USA

2 Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 1530 3rd Avenue South, Shelby 207, Birmingham, Alabama 35294-2182, USA

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BMC Research Notes 2010, 3:74  doi:10.1186/1756-0500-3-74

Published: 16 March 2010

Abstract

Background

Copy number variations (CNVs) of the gene CC chemokine ligand 3-like1 (CCL3L1) have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene.

Findings

Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence.

Conclusions

This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.