A Drosophila Genetic Resource of Mutants to Study Mechanisms Underlying Human Genetic Diseases


YAMAMOTO S., JAISWAL M., CHARNG W., GAMBIN T., KARACA E. , Mirzaa G., ...Daha Fazla

CELL, cilt.159, ss.200-214, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 159 Konu: 1
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.cell.2014.09.002
  • Dergi Adı: CELL
  • Sayfa Sayıları: ss.200-214

Özet

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.