Researchers Tally, Rank Mendelian Disease Genes With Pipeline Approach

In npj Genomic Medicine, researchers at the Chinese University of Hong Kong and elsewhere present a pipeline for "estimating and ranking" carrier frequencies related to recessively inherited or X-linked Mendelian conditions. Using whole-genome or exome sequences for diverse individuals in the Genome Aggregation Database, along with specific variant filtering and annotation steps, the team focused in on autosomal recessive disease variants in more than 2,500 genes and on almost 200 X-linked disease genes, establishing ancestry-specific variant carrier rates and gene ranks that were subsequently validated using whole-genome sequence data for tens of thousands more individuals from the Singapore 10K Genome Project, the China Metabolic Analytics Project, and the Westlake BioBank for Chinese pilot project. The approach "is readily adaptable to new genome-wide sequencing data and to prospective novel recessive genes," the authors write, noting that "carrier frequencies in a given population would be one of the most critically considered aspects for [newborn screening] and [expanded carrier screening]."