Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders.

ABSTRACT:

Background

Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs.

Methods

Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 co

SUBMITTER: Lal D 

PROVIDER: S-EPMC7079346 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature