A little color in our lives

For the general public, all too many reports on genetic phenomena are either very abstract or extremely scary: either it is some phenomenon never before discussed in the popular press or some sort of new risk factor for a dreaded disease. It is nice to see progress on traits which are non-threatening and which can be scored by most individuals. Such visible traits are often used in introductory instruction. While the rare and exotic may be striking, it is far more exciting to discover that science is tackling a trait you see in someone near-and-dear, a trait you see sported on a daily basis. Thanks to the glory of random Medline search noise, I discovered just such a paper (open access!), greatly apropos my dear Amanda.

What the paper found is that explaining the modulation of hair color by two known genes of relevance, Mc1r and agouti, is insufficient. The color pattern known as brindle doesn't fit these results, and they identify a new genetic region (K) responsible for brindling.

Color phenotypes are fun to look at because they are so easy, and because they can often simply illustrate some of the more complex genetic phenomena. A classic example are tortoiseshell and calico cats, which are nearly always female and are due to X-inactivation (I think XXY male cats are viable, and therefore could exhibit these colors). In this case, the various color loci and alleles exhibit epistasis, the hiding (Gr: "stand upon") of the phenotype from one locus due to the genotype at another locus. For example, an Mc1r allele known to encode a truncated (and therefore non-functional) protein prevents any combination of K and agouti alleles from producing a black coat.

Now this is just a mapping paper, and so the gene in question has not been pinpointed. The paper points to there being ~250 genes in the interval in question, with nothing rolling over on first glance. However, they suggest that looking at non-SNP markers, such as simple nucleotide repeats, and additional pedigrees should enable a candidate to be identified.

What will also be interesting, and perhaps not make this discovery quite so benign, is whether variants at this locus affect energy metabolism. Due to some deep evolutionary links (that, alas, I've forgotten the details), coat color mutations often result in weight regulation disorders or severe developmental defects. Both of the other genes mentioned in the paper, Mc1r and Agouti, are important areas for obesity and diabetes research, particularly since Mc1r is in a class of proteins (GPCRs) which has historically been targetable by oral medications. Beige mutant shows both weight and developmental issues, and steel (a grey phenotype) has a host of developmental problems. The brindle phenotype is not known in humans, so it will be interesting to see if (a) the gene is functional in humans (b) has variation across human populations and (c) whether that variation is linked to subtle variations in phenotype