Mendelian Disease Genes Prioritized Using Tissue-Specific Expression Clues

Investigators at Tokyo Medical and Dental University, Daiichi Sankyo, and other centers present a tissue-specific transcriptomic- and proteomic-based approach for prioritizing Mendelian disease gene candidates in the Journal of Human Genetics. After demonstrating the veracity of the tissue-specific score (TS) approach using simulated sequence data and transcriptome and proteome profiles for almost 400 genes implicated in Mendelian conditions affecting the brain, blood, metabolic, mitochondrial, skeletal muscle, or heart tissues, the team used a similar approach to prioritize potential congenital neurodevelopment disorder genes found with exome sequences from more than a dozen individuals. "We showed that the TS score, especially Protein TS score in certain tissues, is useful in prioritizing disease-causing genes in [whole-exome sequence] analysis," the authors write, adding that "[w]e believe our study will provide important baseline information for the development of effective indicators to discover novel disease-causing genes."