A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases.

TitleA drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases.
Publication TypeJournal Article
Year of Publication2014
AuthorsYamamoto, S, Jaiswal, M, Charng, W-L, Gambin, T, Karaca, E, Mirzaa, G, Wiszniewski, W, Sandoval, H, Haelterman, NA, Xiong, B, Zhang, K, Bayat, V, David, G, Li, T, Chen, K, Gala, U, Harel, T, Pehlivan, D, Penney, S, Vissers, LELM, de Ligt, J, Jhangiani, SN, Xie, Y, Tsang, SH, Parman, Y, Sivaci, M, Battaloglu, E, Muzny, DM, Wan, Y-W, Liu, Z, Lin-Moore, AT, Clark, RD, Curry, CJ, Link, N, Schulze, KL, Boerwinkle, E, Dobyns, WB, Allikmets, R, Gibbs, RA, Chen, R, Lupski, JR, Wangler, MF, Bellen, HJ
JournalCell
Volume159
Issue1
Pagination200-14
Date Published2014 Sep 25
ISSN1097-4172
KeywordsAnimals, Disease, Disease Models, Animal, Drosophila melanogaster, Genetic Testing, Humans, Inheritance Patterns, RNA Interference, X Chromosome
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.

DOI10.1016/j.cell.2014.09.002
Alternate JournalCell
PubMed ID25259927
PubMed Central IDPMC4298142
Grant ListHHMI_BELLEN_H / / Howard Hughes Medical Institute / United States
R01 EY018213 / EY / NEI NIH HHS / United States
K08 NS076547 / NS / NINDS NIH HHS / United States
K08NS076547 / NS / NINDS NIH HHS / United States
K12 GM084897 / GM / NIGMS NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States
5R01GM067858 / GM / NIGMS NIH HHS / United States
RC4 GM096355 / GM / NIGMS NIH HHS / United States
U54 HD083092 / HD / NICHD NIH HHS / United States
R24 EY019861 / EY / NEI NIH HHS / United States
P30 EY019007 / EY / NEI NIH HHS / United States
P30 HD024064 / HD / NICHD NIH HHS / United States
EY019007 / EY / NEI NIH HHS / United States
K23 NS078056 / NS / NINDS NIH HHS / United States
5K12GM084897 / GM / NIGMS NIH HHS / United States
T32 NS043124 / NS / NINDS NIH HHS / United States
EY021163 / EY / NEI NIH HHS / United States
R01 EY021163 / EY / NEI NIH HHS / United States
1RC4GM096355-01 / GM / NIGMS NIH HHS / United States
T32 NS043124-11 / NS / NINDS NIH HHS / United States
R01 GM067858 / GM / NIGMS NIH HHS / United States
EY019861 / EY / NEI NIH HHS / United States
R01 NS058529 / NS / NINDS NIH HHS / United States
R01NBS058529 / / PHS HHS / United States
K23NS078056 / NS / NINDS NIH HHS / United States
5P30HD024064 / HD / NICHD NIH HHS / United States