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Lyman, R. A.

Publications and source records attributed to Lyman, R. A..

2 recordsLinked to original sources

The Drosophila melanogaster Genetic Reference Panel, Version 3 (DGRP3)

Drosophila melanogaster is a leading animal model for understanding basic genetic principles for biomedical research and for quantitative, population and evolutionary genetics and genomics. The D. melanogaster Genetic Reference Panel (DGRP) of [~]200 inbred strains with full genome sequences is a publicly available resource for genome wide association (GWA) studies of quantitative traits, systems genetics, and population genomic analyses. However, the small size of the DGRP limits the power to map rare variants or variants with small effect sizes. Here, we describe the DGRP Version 3 (DGRP3), consisting of full genome sequences from 1,233 inbred lines, of which 1,037 are currently extant. The DGRP3 harbors extensive genetic diversity, with 8,760,339 molecular polymorphisms including single nucleotide polymorphisms, insertions, deletions, inversions, tandem duplications and complex rearrangements. We identified 80,894 damaging variants and 4,550 genes with at least one loss-of-function haplotype. We inferred 16 mitochondrial haplotype groups, determined the microbial composition, and quantified the numbers of sensory bristles for the DGRP3 lines. We performed GWA analyses for inbreeding depression, host control of microbiome composition, and numbers of sensory bristles, identifying novel candidate variants and genes for each. The accompanying online tool (flydgrp.org) implements state-of-the-art association mapping methods and provides results for users DGRP3 data.

genomics↗

Arsenic Toxicity in the Drosophila Brain at Single Cell Resolution

Arsenic is an ubiquitous environmental toxicant with harmful physiological effects, including neurotoxicity. Modulation of arsenic-induced gene expression in the brain cannot be readily studied in human subjects. However, Drosophila allows quantification of transcriptional responses to neurotoxins at single cell resolution across the entire brain in a single analysis. We exposed Drosophila melanogaster to a chronic dose of NaAsO that does not cause rapid lethality and measured survival and negative geotaxis as a proxy of sensorimotor integration. Females survive longer than males but show earlier physiological impairment in climbing ability. Single-nuclei RNA sequencing showed widespread sex-antagonistic transcriptional responses with modulation of gene expression in females biased toward neuronal cell populations and in males toward glial cells. However, differentially expressed genes implicated similar biological pathways. Evolutionary conservation of fundamental processes of the nervous system enabled us to translate arsenic-induced changes in transcript abundances from the Drosophila model to orthologous human neurogenetic networks.

genetics↗