Autozygosity mapping and identification of recessive disease in genes in consanguineous families. (360G-Wellcome-078751_Z_05_Z)

Autosomal recessively inherited diseases are an important cause of morbidity and mortality, particularly in communities where consanguineous relationships are common. Worldwide at least 1 billion people live in communities were consanguinity rates are > 20%. Nevertheless, the identification of recessive disease genes allows reliable diagnostic and carrier testing to be offered to at risk families and, critically, often provides novel insights into the function of gene products and their role in fundamental biological processes. Autozygosity mapping is an effective and efficient strategy for mapping recessive genes in consanguineous kindreds. The combination of autozygosity mapping, identification of conserved haplotypes and mutation analysis of candidate genes has proved to be a most successful approach for characterisation of recessive disease genes and novel insights into pathophysiology and normal cellular processes. We are requesting funding to identify novel disease genes in consanguineous families with neurodevelopmental and ocular autosomal recessive disorders. Thus we will (i) prospectively ascertain and bank DNA on consanguineous families with recessivedisorders, (ii) undertake autozygosity mapping studies in selected families with unmapped disorders, (iii) identify disease genes by a candidate-positional cloning strategy. This study will provide a basis for developing novel diagnostic markers for recessive disorder (expediting the prospect of prenatal and carrier testing) and functional studies of key human developmental pathways.