Our Bedouin community of ~170,000 is characterized by ~60% consanguineous marriages and 8-9 children per couple, leading to a high incidence of autosomal recessive diseases. A comprehensive organization of community education, molecular research and clinical implementation has been set up. We have generated effective novel software that facilitates finding disease-associated loci using Affymetrix SNP arrays, and a unique bioinformatics tool (S2G = Syndrome to Gene) to identify the disease genes within the defined loci. Using these tools, we recently identified 14 novel disease genes, 5 of them for severe neurological diseases: infantile neuroaxonal dystrophy (INAD) is a storage disease caused by mutations in phopholipase PLA2G6; a severe recessive phenotype of mental retardation and cerebral palsy is due to a mutation in UQCRQ of mitochondrial complex 3; Birk Barel genomic imprinting mental retardation syndrome is due to mutation in potassium channel KCNK9; Lethal congenital arthrogryposis can be caused by mutations in either ERBB3 or PIP5K1C, which directs ERBB3 internalization. These findings, with dozens of novel mutations we found in known disease genes, are being implemented as free carrier testing, prenatal diagnoses and pre-implantation genetic diagnoses, leading to a dramatic two-fold reduction in infant mortality in our Bedouin community over the past 4 years.

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