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

Content Provider	Springer Nature : BioMed Central
Author	Nelson, Christopher S. Beck, Jennifer N. Wilson, Kenneth A. Pilcher, Elijah R. Kapahi, Pankaj Brem, Rachel B.
Abstract	Background Obesity-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). Results We 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. Conclusions Our findings implicate a wealth of gene candidates in fly metabolism and nutrient response, and ascribe novel functions to htt, rdgA, hwt and schlank.
Related Links	https://bmcgenomics.biomedcentral.com/counter/pdf/10.1186/s12864-016-3137-9.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14712164
DOI	10.1186/s12864-016-3137-9
Journal	BMC Genomics
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2016-11-04
Access Restriction	Open
Subject Keyword	Life Sciences Microarrays Proteomics Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Drosophila GWAS Nutrition Obesity Dietary restriction
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	3.5/2023
5-Year Journal Impact Factor	4.1/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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