Concerning the eXclusion in human genomics: the choice of sex chromosome representation in the human genome drastically affects the number of identified variants

摘要:   Over the past 30 years, a community of scientists has pieced together every base pair of the human reference genome from telomere to telomere. Interestingly, most human genomics studies omit more than 5% of the genome from their analyses. Under “normal” circumstances, omitting any chromosome(s) from an analysis of the human genome would be a cause for concern, with the exception being sex chromosomes. Sex chromosomes in eutherians share an evolutionary origin as an ancestral pair of autosomes. In humans, they share 3 regions of high-sequence identity (∼98–100%), which, along with the unique transmission patterns of the sex chromosomes, introduce technical artifacts in genomic analyses. However, the human X chromosome bears numerous important genes, including more “immune response” genes than any other chromosome, which makes its exclusion irresponsible when sex …