Sunday, May 31, 2009

KITLG associated with testicular germ cell tumors   posted by p-ter @ 5/31/2009 08:20:00 PM

Two papers in Nature Genetics report today that variation in KITLG is associated with development of testicular germ cell tumors. Regular readers of this site will recognize that gene name: KITLG is also one of the important loci contributing to differences in skin pigmentation between human populations. The authors are aware of this:
As KITLG has a role in determining level of pigmentation, we postulated that inherited variation at this locus could provide a genetic explanation for the observed differences in TGCT incidence in whites and blacks. KITLG has undergone strong positive selection in the European and East Asian populations, with an extended haplotype of 400 kb. Data from HapMap phase 3 show significant differences (P = 4.3 times 10e-20) in the frequency of the risk alleles of KITLG (rs3782179 and rs4474514) when comparing the CEU (major allele frequency = 0.80) and ASW (African ancestry in Southwest United States: major allele frequency = 0.25) populations. This finding suggests that inherited variation in KITLG may explain, in part, the observed differences in TGCT incidence between whites and blacks.
This makes for quite a nice story--selection for lighter pigmentation in Europeans appears to have led to the increase in frequency of a linked variant that causes increased risk of TGCT. As we understand more about the genetics of human traits, I suspect that examples like this--where traits are correlated due to selection on one impacting the other simply due to physical proximity--will become rather common.