| Literature DB >> 25259927 |
Shinya Yamamoto1, Manish Jaiswal2, Wu-Lin Charng3, Tomasz Gambin4, Ender Karaca5, Ghayda Mirzaa6, Wojciech Wiszniewski7, Hector Sandoval5, Nele A Haelterman8, Bo Xiong8, Ke Zhang9, Vafa Bayat8, Gabriela David8, Tongchao Li8, Kuchuan Chen8, Upasana Gala8, Tamar Harel7, Davut Pehlivan5, Samantha Penney7, Lisenka E L M Vissers10, Joep de Ligt10, Shalini N Jhangiani11, Yajing Xie12, Stephen H Tsang13, Yesim Parman14, Merve Sivaci15, Esra Battaloglu15, Donna Muzny16, Ying-Wooi Wan17, Zhandong Liu18, Alexander T Lin-Moore5, Robin D Clark19, Cynthia J Curry20, Nichole Link5, Karen L Schulze2, Eric Boerwinkle21, William B Dobyns22, Rando Allikmets13, Richard A Gibbs16, Rui Chen23, James R Lupski24, Michael F Wangler25, Hugo J Bellen26.
Abstract
Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human data sets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health.Entities:
Mesh：
Year: 2014 PMID： 25259927 PMCID： PMC4298142 DOI： 10.1016/j.cell.2014.09.002
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850