Özet:
Autozygosity mapping is a frequently used powerful method for discovering loci for autosomal recessive diseases resulting from consanguineous marriages. Gene localization is an initial step for the identification of genes responsible for such disorders. Identification of a disease gene would enable us to better understand its functions, investigate the underlying cellular mechanisms, and provide critical insights into the pathogenesis of the disease. It can also improve the drug development and enable diagnostic and prenatal genetic testing. Computer programs developed to analyze data obtained by such studies are very helpful in finding the most likely gene locus, supplying ease and speed to studies. In the framework of this study, autozygosity mapping was performed to identify the gene loci for two rare autosomal recessive disorders: early onset progressive encephalopathy with myoclonus and dystonia (PEMD) and infantile neuroaxonal dystrophy (INAD). Computer based parametric tests including two and multi-point lod score analyses were also performed to assess the significance of the linkage data generated by autozygosity mapping and further candidate locus evaluation. The gene responsible for PEMD was localized to a maximum 3.26 Mb-interval on telomere of chromosome 16p. Among the 173 genes residing in the identified locus, 25 could be assigned as candidate genes. For INAD, on the other hand, no significant genetic linkage to any locus could be detected.
