Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila

BMC Genomics

Research Article

Elijah R. Pilcher¹  Christopher S. Nelson¹  Kenneth A. Wilson²  Rachel B. Brem³  Pankaj Kapahi⁴  Jennifer N. Beck⁵ 

[1] Buck Institute for Research on Aging, 8001 Redwood Blvd., 94947, Novato, CA, USA;Buck Institute for Research on Aging, 8001 Redwood Blvd., 94947, Novato, CA, USA;Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA;Buck Institute for Research on Aging, 8001 Redwood Blvd., 94947, Novato, CA, USA;Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA;Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA, USA;Buck Institute for Research on Aging, 8001 Redwood Blvd., 94947, Novato, CA, USA;Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA;Department of Urology, University of California, San Francisco, CA, USA;Buck Institute for Research on Aging, 8001 Redwood Blvd., 94947, Novato, CA, USA;Department of Urology, University of California, San Francisco, CA, USA;

关键词: GWAS;    Drosophila;    Nutrition;    Obesity;    Dietary restriction;   

DOI  :  10.1186/s12864-016-3137-9

 received in 2016-04-07, accepted in 2016-09-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundObesity-related diseases are major contributors to morbidity and mortality in the developed world. Molecular diagnostics and targets of therapies to combat nutritional imbalance are urgently needed in the clinic. Invertebrate animals have been a cornerstone of basic research efforts to dissect the genetics of metabolism and nutrient response. We set out to use fruit flies reared on restricted and nutrient-rich diets to identify genes associated with starvation resistance, body mass and composition, in a survey of genetic variation across the Drosophila Genetic Reference Panel (DGRP).ResultsWe measured starvation resistance, body weight and composition in DGRP lines on each of two diets and used several association mapping strategies to harness this panel of phenotypes for molecular insights. We tested DNA sequence variants for a relationship with single metabolic traits and with multiple traits at once, using a scheme for cross-phenotype association mapping; we focused our association tests on homologs of human disease genes and common polymorphisms; and we tested for gene-by-diet interactions. The results revealed gene and gene-by-diet associations between 17 variants and body mass, whole-body triglyceride and glucose content, or starvation resistance. Focused molecular experiments validated the role in body mass of an uncharacterized gene, CG43921 (which we rename heavyweight), and previously unknown functions for the diacylglycerol kinase rdgA, the huntingtin homolog htt, and the ceramide synthase schlank in nutrient-dependent body mass, starvation resistance, and lifespan.ConclusionsOur findings implicate a wealth of gene candidates in fly metabolism and nutrient response, and ascribe novel functions to htt, rdgA, hwt and schlank.

【 授权许可】

CC BY   
© The Author(s). 2016