Viewing the male-specific chromosome Y in a new light

Several complex disorders (including auto-immune, inflammatory and cardiovascular diseases) display a strong sex bias that cannot be explained solely on the basis of differences in sex hormone production.1 While it then becomes logical to consider the potential contributions of sex chromosomes, the latter have long constituted sort of a ‘blind spot’ in genetic association studies. For reasons that include lack of coverage, difficulties in genotype calling and the fact that chromosome X is not fully inactivated in females, the vast majority of genome-wide association studies (GWAS) have either not analyzed chromosome X properly or (most frequently) ignored it altogether. New computational methods are beginning to emerge to overcome these shortcomings.2, 3 The situation is even more complicated for the male-specific portion of chromosome Y (MSY). Because MSY is transmitted in its entirety from father to son, polymorphisms on this chromosome are not useful in linkage-disequilibrium-based studies. One additional hurdle might in fact have been a ‘cultural one’: because of MSY losing most of its genes in the course of evolution, it has often been considered a ‘degenerative’ chromosome and a ‘genetic wasteland’ that plays no role beyond testis determination and sperm production,1 and therefore not worthy of attention.