Prevalence of hereditary recessive diseases is high in Middle Eastern Arab societies, mainly due to the high rate of consanguineous marriages. This project will systematically identify and collect families with neurogenetic diseases on a consanguineous background in Arab villages of Israel and the Palestinian Authority. Detailed phenotypic description and a structured diagnostic work-up will provide a reliable clinical diagnosis.

Since recessive diseases in consanguineous families are usually caused by homozygous mutations, homozygosity mapping will serve as the major tool to define chromosomal loci for the diseases. Subsequently, candidate genes will be analyzed in chromosomal regions of shared homozygosity. This approach will (1) identify new families with rare genetic diseases and provide them with a molecular diagnosis and genetic counseling and (2) help to map new loci and identify novel disease genes. To the latter end, genes in candidate regions will be assessed by next generation sequencing. Mutational effects in newly identified genes will be characterized on a biochemical and proteomic level. Regional epidemiology will identify the most prevalent hereditary diseases as important targets for future coordinated prevention and support programs.