Finger and toe ratios in humans and mice: implications for the aetiology of diseases influenced by HOX genes.

The differentiation of gonads, fingers, and toes is influenced by HOXA and HOXD genes. Therefore variation in the development of the gonads, and their fetal products such as testosterone, may be reflected in the morphology of the fingers and toes. One trait, the relative length of the second and fourth digits (2D:4D), shows sex differences (lower values in males) which are determined early, and 2D:4D has been found to correlate with fetal growth, sperm counts, family size, autism, myocardial infarction, and breast cancer. HOX genes are highly conserved in mammals and they influence the differentiation of all the fingers and toes. We suggest that (a) 2D:4D and other ratios of finger and toe length show sex differences throughout the mammals including humans and mice, (b) finger and toe ratios correlate with sex determination, the fetal production of sex steroids, and fetal programming of disease, and (c) HOX gene influences on sex determination, the morphogenesis of the urinogenital system, fertility, haematopoiesis, and breast cancer suggests that finger and toe ratios in humans and mice may correlate with many sex dependent diseases.