Research Paper Volume 11, Issue 23 pp 11244—11267
Identification of novel genes associated with longevity in Drosophila melanogaster - a computational approach
- 1 School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
- 2 Current address: Faculty of Science and Engineering, Anglia Ruskin University, Cambridge, Cambridgeshire CB1 1PT, UK
received: September 2, 2019 ; accepted: November 18, 2019 ; published: December 3, 2019 ;https://doi.org/10.18632/aging.102527
How to Cite
Copyright © 2019 Hall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Despite a growing number of studies on longevity in Drosophila, genetic factors influencing lifespan are still poorly understood. In this paper we propose a conceptually new approach for the identification of novel longevity-associated genes and potential target genes for SNPs in non-coding regions by utilizing the knowledge of co-location of various loci, governed by the three-dimensional architecture of the Drosophila genome. Firstly, we created networks between genes/genomic regions harboring SNPs deemed to be significant in two longevity GWAS summary statistics datasets using intra- and inter-chromosomal interaction frequencies (Hi-C data) as a measure of co-location. These networks were further extended to include regions strongly interacting with previously selected regions. Using various network measures, literature search and additional bioinformatics resources, we investigated the plausibility of genes found to have genuine association with longevity. Several of the newly identified genes were common between the two GWAS datasets and these possessed human orthologs. We also found that the proportion of non-coding SNPs in borders between topologically associated domains is significantly higher than expected by chance. Assuming co-location, we investigated potential target genes for non-coding SNPs. This approach therefore offers a stepping stone to identification of novel genes and SNP targets linked to human longevity.