Genetic investigation into an increased susceptibility to biliary atresia in an extended New Zealand Māori family

• DOI: 10.1186/s12920-018-0440-0
• Publication Date: 2018-12-18T13:07:47Z
• Authors: Sophia R. Cameron...; Justin Wilde; Andrew Gray; Rick Tankard; Melanie Bahlo; David Markie; Helen M. Evans; Stephen P. Robertson
• Keywords: Exome; Candidate gene

Biliary atresia (BA), a fibrosing disorder of the developing biliary tract leading to liver failure in infancy, has an elevated incidence indigenous New Zealand (NZ) Māori. We investigated high rate BA group children (n = 12) belonging single Māori iwi (or 'tribe', related through remote ancestor). Population and geographical data was used estimate sub-groups, pedigree linking most affected constructed from oral documented history. Array genotyping examine hypotheses about inheritance possible genetic risk factor, history population, Exome Sequencing search for candidate genes. Most these 7) link self-reported carry 50-fold increase over unrelated (χ2 296P < 0.001, 95% CI 23–111). Genetic analysis using FEstim SNP array genotypes revealed no evidence consanguinity between parents (FEstim: F (2,21) 0.469, P > 0.63). Genome-wide quantitation intervals contiguous, homozygous-by-state markers reached similar conclusion (F (2,399) 1.99, 0.138). Principal component investigation with STRUCTURE found increased allele frequency either recessive variant, or additive, low-risk variants due reproductive isolation. To identify causal factors, datasets were scrutinised shared rare coding across 8 individuals. No rare, non-synonymous, phylogenetically conserved common 6 more children. The substantially development this subgroup could be mediated by but exhibits properties indicative recent Resolution any loci may rely on extensive genomic sequencing studies other mechnaisms such as copy number variation.