Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes.

ABSTRACT:

Background

Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the distal intestine. Previous studies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not fitting the current knowledge have thus often been ignored. We identify and validate novel HSCR genes using whole exome sequencing (WES), burden tests, in silico prediction, unbiased in vivo analyses of the mutated genes in zebrafish, and expression analyses in zebrafish, mouse, and human.

Results

We performed de novo mutation (DNM) screening on 24 HSCR trios. We identify 28 DNMs in 21 different genes. Eight of the DNMs we identified o

SUBMITTER: Gui H 

PROVIDER: S-EPMC5343413 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature