Cargando…
Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila
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 d...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095962/ https://www.ncbi.nlm.nih.gov/pubmed/27809764 http://dx.doi.org/10.1186/s12864-016-3137-9 |
_version_ | 1782465382111510528 |
---|---|
author | Nelson, Christopher S. Beck, Jennifer N. Wilson, Kenneth A. Pilcher, Elijah R. Kapahi, Pankaj Brem, Rachel B. |
author_facet | Nelson, Christopher S. Beck, Jennifer N. Wilson, Kenneth A. Pilcher, Elijah R. Kapahi, Pankaj Brem, Rachel B. |
author_sort | Nelson, Christopher S. |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3137-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5095962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50959622016-11-07 Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila Nelson, Christopher S. Beck, Jennifer N. Wilson, Kenneth A. Pilcher, Elijah R. Kapahi, Pankaj Brem, Rachel B. BMC Genomics Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3137-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-04 /pmc/articles/PMC5095962/ /pubmed/27809764 http://dx.doi.org/10.1186/s12864-016-3137-9 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Nelson, Christopher S. Beck, Jennifer N. Wilson, Kenneth A. Pilcher, Elijah R. Kapahi, Pankaj Brem, Rachel B. Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila |
title | Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila |
title_full | Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila |
title_fullStr | Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila |
title_full_unstemmed | Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila |
title_short | Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila |
title_sort | cross-phenotype association tests uncover genes mediating nutrient response in drosophila |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095962/ https://www.ncbi.nlm.nih.gov/pubmed/27809764 http://dx.doi.org/10.1186/s12864-016-3137-9 |
work_keys_str_mv | AT nelsonchristophers crossphenotypeassociationtestsuncovergenesmediatingnutrientresponseindrosophila AT beckjennifern crossphenotypeassociationtestsuncovergenesmediatingnutrientresponseindrosophila AT wilsonkennetha crossphenotypeassociationtestsuncovergenesmediatingnutrientresponseindrosophila AT pilcherelijahr crossphenotypeassociationtestsuncovergenesmediatingnutrientresponseindrosophila AT kapahipankaj crossphenotypeassociationtestsuncovergenesmediatingnutrientresponseindrosophila AT bremrachelb crossphenotypeassociationtestsuncovergenesmediatingnutrientresponseindrosophila |