Biology subjects

Hanson, K. M.

Publications and source records attributed to Hanson, K. M..

4 recordsLinked to original sources

bioRxiv2026

A genomewide association study for bristle number variation in Drosophila melanogaster

Decades of research has uncovered a wealth of mechanistic information about the development of sensory bristles in Drosophila melanogaster. By studying large-effect, often loss-of-function mutations, many genes have been associated with bristle development, morphology, patterning, and number. Equally, the number of bristles present in certain areas of the fly cuticle is a classic quantitative trait, the genetic basis of which has been studied using a range of tools, from artificial selection to QTL (Quantitative Trait Locus) mapping. Such studies have often implicated well-understood bristle development genes as contributing to natural variation in bristle number. Here we contribute to the study of bristle number genetic variation in flies by executing a GWAS (genomewide association study). We generated whole genome sequences for 897 phenotyped male D. melanogaster individuals derived from a wild-derived, but lab-adapted outbred population, revealing - following quality control and filtering - over 780,000 variants with frequencies greater than 5%. Using these data we estimated the SNP (Single Nucleotide Polymorphism) heritability for ABN (abdominal bristle number) and SBN (sternopleural bristle number) as 0.28 and 0.35, respectively. These values indicate that our set of genotyped variants collectively explain a substantial fraction of the variance in phenotype in the mapping panel. Subsequently, genome scans revealed 1085 (ABN) and 211 (SBN) genomewide significant sites, and - due to extensive LD (Linkage Disequilibrium) in our panel - nearly all these sites are clustered into three locations; We find a GWAS hit for ABN in the middle of chromosome 3L, and hits for SBN at the tip of the X chromosome (where several prior mapping studies have resolved QTL for bristle number), and on 2L. Surveying existing studies that identified genes that control bristle number/development, we highlight several candidates that may segregate for causative, functional variants.

genetics↗

bioRxiv2025

The Illusion of Polygenicity in Poolseq studies: Insufficient Power Can Mask Simple Genetic Architectures

Pool-seq (pooled sequencing) combines DNA from multiple individuals prior to sequencing, enabling population-level allele frequency estimation without individual genotyping. When employed in Genome Wide Association Studies (GWAS) pool-seq faces a fundamental power limitation in that errors on allele frequency estimates are proportional to sequence coverage. Although this power limitation is widely appreciated, pool-seq GWAS lacking unambiguous hits are often interpreted as showing a highly polygenic genetic architecture. We illustrate the limitation of inferring architecture from Manhattan plots using empirical data from a Drosophila zinc resistance mapping study. Despite achieving an average of >700x sequencing coverage in case and control pools, a directly ascertained SNP-based GWAS failed to reveal clear evidence for major-effect loci. A unique feature of the dataset is that an advanced intercross multiparent population, with known founders, was employed as the base population for the GWAS. We leverage this unique population structure to carry out a second GWAS using imputed haplotype frequency estimates, which in contrast revealed localized regions of major effect. A third reanalysis of the same data using imputed SNP genotypes derived from the founder haplotype frequency estimates uncovered a similar major gene architecture. The key difference between approaches lies in statistical power: directly ascertained SNP counts have errors proportional to sequencing coverage whereas known founder imputation-based approaches can be considerably more accurate. This work highlights that insufficiently powered GWAS studies can mask simple genetic architectures and create the illusion of polygenicity through statistical noise alone.

genetics↗

bioRxiv2025

High-throughput genetic mapping discovers novel zinc toxicity response loci in Drosophila melanogaster

Heavy metals are a widespread environmental contaminant, and even low levels of some metals can disrupt cellular processes and result in DNA damage. However, the consequences of metal exposure are variable among individuals, with susceptibility to metal toxicity representing a complex trait influenced by genetic and non-genetic factors. To uncover toxicity response genes, and better understand responses to metal toxicity, we sought to dissect resistance to zinc, a metal required for normal cellular function, which can be toxic at high doses. To facilitate efficient, powerful discovery of Quantitative Trait Loci (QTL) we employed extreme, or X-QTL mapping, leveraging a multiparental, recombinant Drosophila melanogaster population. Our approach involved bulk selection of zinc-resistant individuals, sequencing several replicate pools of selected and control animals, and identified QTL as genomic positions showing consistent allele frequency shifts between treatments. We successfully identified seven regions segregating for resistance/susceptibility alleles, and implicated several strong candidate genes. Phenotypic characterization of populations derived from selected or control animals revealed that our selection procedure resulted in greater egg-to-adult emergence, and a reduced developmental delay on zinc media. We subsequently measured emergence and development time for a series of midgut-specific RNAi gene knockdowns and matched genetic controls raised in both zinc-supplemented and normal media. This identified ten genes with significant genotype-by-treatment effects, including pHCl-2, which encodes a zinc sensor protein. Our work highlights recognized and novel contributors to zinc toxicity resistance in flies, and provides a pathway to a broader understanding of the biological impact of metal toxicity. ARTICLE SUMMARYStarting with an outbred Drosophila melanogaster population we repeatedly selected for groups of individuals showing high resistance to toxic levels of zinc during development. Pooled sequencing of these groups, along with matched groups of control individuals, enabled the identification of seven genomic regions - or QTL - contributing to zinc toxicity resistance. Midgut-specific RNAi of genes implicated by these QTL yielded ten genes impacting developmental traits in zinc-supplemented media, including MTF-1 (a metal response transcription factor) and pHCl-2 (a zinc sensor protein).

genetics↗

bioRxiv2024

Dynamic Changes in Gene Expression Through Aging in Drosophila melanogaster Heads

Work in many systems has shown large-scale changes in gene expression during aging. However, many studies employ just two, arbitrarily-chosen timepoints at which to measure expression, and can only observe an increase or a decrease in expression between "young" and "old" animals, failing to capture any dynamic, non-linear changes that occur throughout the aging process. We used RNA sequencing to measure expression in male head tissue at 15 timepoints through the lifespan of an inbred Drosophila melanogaster strain. We detected >6,000 significant, age-related genes, nearly all of which have been seen in previous fly aging expression studies, and which include several known to harbor lifespan-altering mutations. We grouped our gene set into 28 clusters via their temporal expression change, observing a diversity of trajectories; some clusters show a linear change over time, while others show more complex, non-linear patterns. Notably, re-analysis of our dataset comparing the earliest and latest timepoints - mimicking a two-timepoint design - revealed fewer differentially-expressed genes (around 4,500). Additionally, those genes exhibiting complex expression trajectories in our multi-timepoint analysis were most impacted in this re-analysis; Their identification, and the inferred change in gene expression with age, was often dependent on the timepoints chosen. Informed by our trajectory-based clusters, we executed a series of gene enrichment analyses, identifying enriched functions/pathways in all clusters, including the commonly seen increase in stress- and immune-related gene expression with age. Finally, we developed a pair of accessible shiny apps to enable exploration of our differential expression and gene enrichment results.

genomics↗