Exploring the susceptible or pathogenic genes of biliary atresia by monozygotic twins’ pedigrees

Abstract

Objective Currently the pathogenesis of biliary atresia (BA) has remained unclear.This study was to explore the susceptible or pathogenic genes of BA by monozygotic twins’ pedigrees at whole exome level. Methods Five monozygotic twins’ BA pedigrees were collected.There were 4 pedigrees in discordance for BA and 1 pedigree in accordance for BA.After a definite diagnosis of type Ⅲ BA by intraoperative cholangiography, they underwent Kasai operation.Their clinical data were collected and 4 ml peripheral venous blood samples obtained from all family members of 5 monozygotic twins’ BA pedigrees.DNA was isolated from whole peripheral venous blood.Whole exome sequencing was employed and data quality was controlled strictly.The results of 5 pedigrees were analyzed for detecting genetic mutations. Results Twins in F5 pedigree were in accordance for BA.Two compound heterozygous mutations (SSPO, TTN) were shared by two patients in a recessive mode.And 2/6 patients had the mutation of gene ABCA13 in the mode of incomplete penetrance.Located in a conserved sequence, the mutation played a detrimental role in the structure and function of protein.IFNA10 was correlated with the incidence of BA by family-based association test. Conclusions The strategy of exploring the susceptible or pathogenic genes in BA through monozygotic twins’ BA pedigrees at exome level using multiple models is a feasible approach for elucidating the etiology of BA.The mutations of SSPO, ABCA13 and IFNA10 may be associated with BA type Ⅲ. Key words: Biliary atresia; Susceptible genes; Pathogenic genes; Whole exome sequence