Gene network analysis of candidate loci for human anorectal malformations.
Anorectal malformations (ARMs) are birth defects that require surgery and carry significant chronic morbidity. Our earlier genome-wide copy number variation (CNV) study had provided a wealth of candidate loci. To find out whether these candidate loci are related to important developmental pathways, we have performed an extensive literature search coupled with the currently available bioinformatics tools. This has allowed us to assign both genic and non-genic CNVs to interrelated pathways known to govern the development of the anorectal region. We have linked 11 candidate genes to the WNT signalling pathway and 17 genes to the cytoskeletal network. Interestingly, candidate genes with similar functions are disrupted by the same type of CNV. The gene network we discovered provides evidence that rare mutations in different interrelated genes may lead to similar phenotypes, accounting for genetic heterogeneity in ARMs. Classification of patients according to the affected pathway and lesion type should eventually improve the diagnosis and the identification of common genes/molecules as therapeutic targets.
Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Emily H M
EH
Wong
Chun-Laam
CL
Ng
Vincent Chi-Hang
VC
Lui
Man-ting
MT
So
Stacey S
SS
Cherny
Pak-Chung
PC
Sham
Paul Kwong-Hang
PK
Tam
Maria-Mercè
MM
Garcia-Barceló
D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D053263:Gene Regulatory Networks; D056426:Genetic Loci / Q000235:genetics*; D023281:Genomics; D006801:Humans; D015398:Signal Transduction / Q000235:genetics