Discovery of copy number variants by multiplex amplifiable probe hybridization (MAPH) in candidate pigmentation genes

Abstract

Background: Copy Number Variants (CNVs) contribute to a large fraction of genetic diversity and some of them have been reported to offer an evolutionary advantage.

Aim: To identify CNVs in pigmentary loci that could contribute to human skin pigmentation diversity.

Subjects and methods: This study assessed the existence of CNVs in every exon of candidate genes: TYR, TYRP1, DCT, MC1R and SLC24A5, using the Multiplex Amplifiable Probe Hybridization technique (MAPH). This study analysed a total of 99 DNA samples of unrelated individuals from different populations. Validation and further analysis in a larger Spanish sample were performed by RT-qPCR.

Results: Five CNVs were identified by MAPH: DCT exons 4 and 8, TYR exon 1 and SLC24A5 exons 1 and 4. Real-time quantitative PCR (RT-qPCR) confirmed the CNV in exon 1 of SLC24A5. This study further analysed the 5′ promoter region of SLC24A5 and found another CNV in this region. However, no association was found between the CNV and the degree of pigmentation.

Conclusion: Although the functional role of these structural variants in pigmentation should be the subject of future work, the results emphasize the need to consider all classes of variation (both SNPs and CNVs) when exploring the genetics of skin pigmentation.

• Evolution
• human diversity
• mutation
• natural selection

Acknowledgements

We thank Prof. John Armour for his invaluable help in the design and performance of the experiments.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This work was supported by the former Spanish Ministerio de Ciencia e Innovación, project CGL2008-04066/BOS to S.A.; by the Dpt. Educacion, Universidades e Investigación of the Basque Government, project IT542-10 to C.R.; the University of the Basque Country program UFI11/09; and a predoctoral fellowship from the Dpt. Educación, Universidades e Investigación of the Basque Government to S.L. (BFI09.248).

Supplementary material available online

Supplementary Material Table SI