Colm Nestor

X chromosome dosage compensation through the lens of human genetics! Females have two X chromosomes, but males have one. To compensate for this, one X is randomly inactivated in female cells. Some genes escape from this inactivation. Because both males and females are functionally hemizygous for chromosome X, X-linked genes are thought to upregulate their expression to match autosomes (Ohno's hypothesis, 1967) With availability of large scale human genetic data, we can test the effect of these dosage compensations through genetic analysis! Using UK Biobank genetic data, here the authors tested 48 quantitative traits separately in males and females and found: - Chr X heritability (X-h2) is ~2x higher in males than females (supports random X inactivation in females that dilutes the average) - In height, X-h2 in females > males suggesting more frequent escape from X inactivation for height-associated genes - per allele effect is larger for X genes than autosomal genes (supporting Ohno's hypothesis) Fascinating work! Fu et al. AJHG cell.com/ajhg/fulltext/S0002…