Evolutionary perspective suggests candidate genes for variation in Turner Syndrome phenotype

2015-06-25T16:24:56Z (GMT) by Melissa Wilson Sayres Kara Schaffer

Tremendous phenotypic variation exists across people with Turner syndrome (45,X). This variation likely stems from differential dosage of genes on the X chromosome. In this study we take an evolutionary approach to rank candidate genes that may affect phenotype across people with Turner Syndrome. X-inactivation is the process whereby all X chromosomes in excess of one are silenced. However, about 15% of the genes on the silenced X chromosome escape this inactivation and are candidates for affecting phenotype in people with Turner syndrome. We analyze patterns of DNA methylation from 46,XX and 45,X individuals, to inform about X-inactivation status, comparing this with studies about X-inactivation status from cell-lines, to classify genes on the human X chromosome into those that may be more dosage sensitive. We then analyze patterns of gene expression conservation across five tissues and ten species by class of X-linked gene, to learn which may be more evolutionarily conserved, and thus more likely to affect phenotype when dosage is altered from typical levels.