Rapid advances in genotyping and sequencing technology have dramatically accelerated
the discovery of genes underlying human disease. Elucidating the function of such genes
and understanding their role in pathogenesis, however, remain challenging. Here, we
introduce a genomic strategy to characterize such genes functionally, and we apply it to
LRPPRC, a poorly studied gene that is mutated in Leigh syndrome, French-Canadian type
(LSFC). We utilize RNA interference to engineer an allelic series of cellular models in which …