Impact of mutations and polymorphisms in transporter families on population health

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Transporters play crucial roles in transporting biological substances. We have focused our attention to the effects of mutations of transporters on population health.1. Lysinuric protein intolerance (LPI) was a disease caused by a mutation of basic amino acid transporter SLC7A7. LPI is controllable by early intervention at infancy. It is endemic in Iwate while its prevalence is very small in other areas in Japan. Its early intervention, therefore, is one of the public health issues specific to Iwate. We conduced genetic epidemiological study and had shown a founder mutation of R41OX mutation in SLC7A7. Excess prevalence of LPI was attributed to a high gene frequency of this founder mutation.2. We embarked a mass screening program using molecular diagnosis for LPI. The mass screening program turned out to be cost effective and reliable as a diagnosis tool.3. We also conducted genetic epidemiology in a local cluster of Osler-Rendu-Weber disease, polycystic Kidney and a local goiter unknown pathogenesis.4. We tried to evaluate functionally the mutated proteins in an attempt to develop a general methodology to predict ftinctional alterations. In this project, we evaluated mutations of proinsulin Akita as-an example.The prevalences of genetic diseases are very widely perturbed by the population history and social systems. It is necessary to promote research activities for genetic epidemiology and functional proteomics.