Functional genetics of common phenotypes:
the case of human pigmentation
8 March 2012
The single nucleotide polymorphism (SNP) rs12913832, located within an intron of the gene HERC2, is the most strongly human pigmentation associated genetic marker. At the same time this SNP is the most predictive genetic marker for human eye colour, and also is highly informative for human hair colour prediction, which all has been established previously for forensic applications by researchers of the Forensic Genomics Consortium Netherlands (FGCN).
Now Mijke Visser and Manfred Kayser from the Department of Forensic Molecular Biology of Erasmus MC and FGCN, together with Robert-Jan Palstra from the Erasmus MC Department of Cell Biology, have investigated the biological function of HERC2 rs12913832.
In this study, recently published in Genome Research’s March issue and highlighted in the March issue of Nature Reviews Genetics, they showed that a small (and highly conserved) region around this SNP functions as an enhancer that regulates gene expression of the neighbouring pigmentation gene OCA2. This enhancer element interacts with the promoter region of OCA2 by forming a long-range chromatin loop. In addition, the three authors demonstrated that allelic variation of this common non-coding SNP disrupts the regulatory potential of the enhancer element, and affects the interaction between the enhancer and the OCA2 promoter. This results in altered OCA2 expression which in turn affects human pigmentation.
This study highlights the functional role of non-coding DNA variants in common human phenotypes and is expected to be relevant for better understanding of common disease traits.
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