Estimation of the carrier frequencies and proportions of potential patients by detecting causative gene variants associated with autosomal recessive bone dysplasia using a whole-genome reference panel of Japanese individuals

Abstract

Bone dysplasia: Estimating carrier frequency with bioinformatics A bioinformatics approach helps estimate carrier frequency of a rare inherited bone disease which causes abnormalities in skeletal shape and structure. Autosomal recessive bone dysplasias affect bone and cartilage development and result from inheriting two mutated genes, one from each parent. Junichi Sugawara, Tohoku University, Sendai, Japan, and colleagues used mutation databases and a bioinformatics tool for variant interpretation to detect 198 pathogenic variants in 54 genes associated with autosomal recessive bone dysplasia in a whole-genome reference panel of 3,552 general Japanese individuals (3.5KJPNv2). They then estimated the frequency of people in the sample carrying bone dysplasia mutations and the expected proportion in whom the disorder could manifest, which compared well with reported incidence rates in the general population. These findings could prove useful for calculating the risk of bone dysplasia in the future children of carrier parents.