Analysis for molecular-pathogenesis of Hirschsprung disease. As a model of multifactorial disease

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[Background] Rapid proceeding of human genome project, we got many knowledge for genetic defects of simple mendelian diseases. But simple mendelian diseases were rare diseases ; frequency was 1.25% of born infants. Now our interest goes toward common disease. Multifactorial disease occurs under influence of genetic basis and environmental status. Now we do not have a tool to understand these complicated phenomena. Simple scheme was necessary to understand multifactorial disease. Now we choose the Hirschsprung disease as model of multigenetic disease without environmental factors[Subjects and method] Hirschsprung disease is a common digestive disease in young children. Evidence was 1/5000 and predominance in male. The disease has relatively high incidence and is genetic disease without environmental factors. Hirschsprung disease is a good candidate for simple multigenetic disease. To date, extensive mutational analysis of candidate genes of Hirsch sprung disease, only 50% of patients were identified disease causative mutation. We think this disease has occurred gene and gene interactions among candidate genes (EDN3,EDNRB, SOX10 and GDNF). We applied two-combined approach, RET gene mutational analysis and haplotype based case control study.[Results] We found RET mutation in 5 cases (total 34 sporadic cases) and 1 familial case. Haplotype based case control study showed no relationship between specific haploype and disease.