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PLoS One. 2014 Aug 14;9(8):e104858. doi: 10.1371/journal.pone.0104858. eCollection 2014.

Genome-wide association analysis of radiation resistance in Drosophila melanogaster.

Author information

1
Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas, United States of America.
2
McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, Texas, United States of America.
3
Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas, United States of America.
4
Greehey Children's Cancer Research Institute, Departments of Pediatrics and Cellular & Structural Biology, UT Health Science Center at San Antonio, San Antonio, Texas, United States of America.

Abstract

BACKGROUND:

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.

METHODS AND FINDINGS:

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.

CONCLUSIONS:

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.

PMID:
25121966
PMCID:
PMC4133248
DOI:
10.1371/journal.pone.0104858
[Indexed for MEDLINE]
Free PMC Article

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