In genetics, X marks the spot. The X chromosome, one of the two sex-determining chromosomes in humans, has become increasingly popular for scientists studying chromosome inactivation, the mosaic expression of genes in females and the genetics of sex differences. Researchers at the University of Helsinki, joining this wave of X chromosome investigations, have founding a correlation between the X chromosome and human height. This correlation may explain the height difference in females and males.
Chromosomes are organized structures of DNA that contain genes, regulatory elements and DNA-bound proteins. The human genome is comprised of 23 pairs of chromosomes: 22 pairs of autosomes and one pair of sex chromosomes. As suggested by the name, the sex chromosomes determine sex identity. In human males, the sex chromosome pair is made up of one X chromosome and one Y chromosome. In human females, this pair is of two X chromosomes. This sex difference in X dosage seems to be relevant to the height disparity between males and females.
Samuli Ripatti, a professor at the University of Helsinki and the head researcher of this study, suggests that there is a direct correlation between the two copies of X chromosomes and women and their tendency to be shorter than men. In addition to working at the University of Helsinki, Ripatti leads a research group at the Institute for Molecular Medicine Finland (FIMM). Ripatti’s research at FIMM focuses on genetic modifiers and the development of statistical methods for genetic risk elimination.
The double dosage of X chromosomes in females necessitates of silencing during development. This means one of the two copies of the X chromosome is marked so that it is not expressed. Ripatti and his team identified a height associated variant near a gene on the X chromosome that is able to escape this silencing process. This localization means that this particular height variant, which has been associated with a shorter stature, has an increased chance of expression in the X chromosome. Because females have two X chromosomes and thus are likely to have double the expression of this height variant, they are inclined to be shorter than males
This study analyzed genetic variation in the X chromosomes of 25,000 Northern Europeans. Coming to conclusions from such genetic screens is difficult, noted Taru Tukiainen, a postdoctoral research fellow at the Massachusetts General Hospital in Boston. Results must consider sex differences in X chromosome dosage compensation and the process of X chromosome silencing in addition to normal genetic variation. Nevertheless, this Ripatti’s team rose to the challenge and has since revealed a new biological insight into sex differences.
