Endocrine Abstracts

It is ten years since we identified the human melanocortin 1 receptor (MC1R) as the locus that underpins red hair, freckling and sun sensitivity. The MC1R is not the only gene that is important in human pigmentation, but it does seem to play a significant role. A striking aspect of the MC1R is the degree of genetic diversity. I review how a combination of laboratory and genetic epidemiological studies has shown how a single locus, that in some instances behaves close to a Mendelian trait can, due to a range of mutations with variable functional effects, produce a graded response. Whereas it is possible to report striking associations between MC1R variants and physiological traits – with odds ratios of greater than 30 for red hair – when we relate sequence diversity to disease states, the odds ratios we see are much lower and, in this particular context, are probably of no clinical use. It remains a useful thought experiment to imagine what we would have discovered if we had just used anonymous SNPs.