Genome-wide association analysis of radiation resistance in Drosophila melanogaster.
Ionizing radiation is genotoxic to cells. Healthy tissue toxicity in patients and radiation resistance in tumors present common clinical challenges in delivering effective radiation therapies. Radiation response is a complex, polygenic trait with unknown genetic determinants. The Drosophila Genetic...
| Hlavní autoři: | , , , , , , |
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| Médium: | Článek |
| Jazyk: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Edice: | PLoS ONE |
| On-line přístup: | http://europepmc.org/articles/PMC4133248?pdf=render |
| _version_ | 1828964345469468672 |
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| author | Mahesh Vaisnav Chao Xing Hung-Chih Ku Daniel Hwang Strahinja Stojadinovic Alexander Pertsemlidis John M Abrams |
| author_facet | Mahesh Vaisnav Chao Xing Hung-Chih Ku Daniel Hwang Strahinja Stojadinovic Alexander Pertsemlidis John M Abrams |
| author_sort | Mahesh Vaisnav |
| collection | DOAJ |
| description | Ionizing radiation is genotoxic to cells. Healthy tissue toxicity in patients and radiation resistance in tumors present common clinical challenges in delivering effective radiation therapies. Radiation response is a complex, polygenic trait with unknown genetic determinants. The Drosophila Genetic Reference Panel (DGRP) provides a model to investigate the genetics of natural variation for sensitivity to radiation.Radiation response was quantified in 154 inbred DGRP lines, among which 92 radiosensitive lines and 62 radioresistant lines were classified as controls and cases, respectively. A case-control genome-wide association screen for radioresistance was performed. There are 32 single nucleotide polymorphisms (SNPs) associated with radio resistance at a nominal p<10(-5); all had modest effect sizes and were common variants with the minor allele frequency >5%. All the genes implicated by those SNP hits were novel, many without a known role in radiation resistance and some with unknown function. Variants in known DNA damage and repair genes associated with radiation response were below the significance threshold of p<10(-5) and were not present among the significant hits. No SNP met the genome-wide significance threshold (p = 1.49 × 10(-7)), indicating a necessity for a larger sample size.Several genes not previously associated with variation in radiation resistance were identified. These genes, especially the ones with human homologs, form the basis for exploring new pathways involved in radiation resistance in novel functional studies. An improved DGRP model with a sample size of at least 265 lines and ideally up to 793 lines is recommended for future studies of complex traits. |
| first_indexed | 2024-12-14T10:47:56Z |
| format | Article |
| id | doaj.art-b74e4cc7325f4f069ec73f1ec1ef1e9c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T10:47:56Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b74e4cc7325f4f069ec73f1ec1ef1e9c2022-12-21T23:05:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10485810.1371/journal.pone.0104858Genome-wide association analysis of radiation resistance in Drosophila melanogaster.Mahesh VaisnavChao XingHung-Chih KuDaniel HwangStrahinja StojadinovicAlexander PertsemlidisJohn M AbramsIonizing radiation is genotoxic to cells. Healthy tissue toxicity in patients and radiation resistance in tumors present common clinical challenges in delivering effective radiation therapies. Radiation response is a complex, polygenic trait with unknown genetic determinants. The Drosophila Genetic Reference Panel (DGRP) provides a model to investigate the genetics of natural variation for sensitivity to radiation.Radiation response was quantified in 154 inbred DGRP lines, among which 92 radiosensitive lines and 62 radioresistant lines were classified as controls and cases, respectively. A case-control genome-wide association screen for radioresistance was performed. There are 32 single nucleotide polymorphisms (SNPs) associated with radio resistance at a nominal p<10(-5); all had modest effect sizes and were common variants with the minor allele frequency >5%. All the genes implicated by those SNP hits were novel, many without a known role in radiation resistance and some with unknown function. Variants in known DNA damage and repair genes associated with radiation response were below the significance threshold of p<10(-5) and were not present among the significant hits. No SNP met the genome-wide significance threshold (p = 1.49 × 10(-7)), indicating a necessity for a larger sample size.Several genes not previously associated with variation in radiation resistance were identified. These genes, especially the ones with human homologs, form the basis for exploring new pathways involved in radiation resistance in novel functional studies. An improved DGRP model with a sample size of at least 265 lines and ideally up to 793 lines is recommended for future studies of complex traits.http://europepmc.org/articles/PMC4133248?pdf=render |
| spellingShingle | Mahesh Vaisnav Chao Xing Hung-Chih Ku Daniel Hwang Strahinja Stojadinovic Alexander Pertsemlidis John M Abrams Genome-wide association analysis of radiation resistance in Drosophila melanogaster. PLoS ONE |
| title | Genome-wide association analysis of radiation resistance in Drosophila melanogaster. |
| title_full | Genome-wide association analysis of radiation resistance in Drosophila melanogaster. |
| title_fullStr | Genome-wide association analysis of radiation resistance in Drosophila melanogaster. |
| title_full_unstemmed | Genome-wide association analysis of radiation resistance in Drosophila melanogaster. |
| title_short | Genome-wide association analysis of radiation resistance in Drosophila melanogaster. |
| title_sort | genome wide association analysis of radiation resistance in drosophila melanogaster |
| url | http://europepmc.org/articles/PMC4133248?pdf=render |
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