Exome sequencing in a family segregating for celiac disease

A M Szperl, I Ricaño-Ponce, J K Li, P Deelen, A Kanterakis, V Plagnol, Freerk van Dijk, H J Westra, G Trynka, C. J. Mulder, M Swertz, Cisca Wijmenga, H C H Zheng

OnderzoeksoutputAcademicpeer review

12 Citaten (Scopus)


Celiac disease is a multifactorial disorder caused by an unknown number of genetic factors interacting with an environmental factor. Hence, most patients are singletons and large families segregating with celiac disease are rare. We report on a three-generation family with six patients in which the inheritance pattern is consistent with an autosomal dominant model. To date, 27 loci explain up to 40% of the heritable disease risk. We hypothesized that part of the missing heritability is because of low frequency or rare variants. Such causal variants could be more prominent in multigeneration families where private mutations might co-segregate with the disease. They can be identified by linkage analysis combined with whole exome sequencing. We found three linkage regions on 4q32.3-4q33, 8q24.13-8q24.21 and 10q23.1-10q23.32 that segregate with celiac disease in this family. We performed exome sequencing on two affected individuals to investigate the positional candidate regions and the remaining exome for causal nonsense variants. We identified 12 nonsense mutations with a low frequency (minor allele frequency

Originele taal-2English
Pagina's (van-tot)138-147
Aantal pagina's10
TijdschriftClinical Genetics
Nummer van het tijdschrift2
StatusPublished - aug-2011

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