Browsing by Subject "Comparative genomics"

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    Comparative genomics of the sheep blow fly Lucilia cuprina
    (Office of the Vice Chancellor for Research, 2016-04-08) Picard, Christine J.; Andere, Anne A.
    Insects employ different adaptive strategies in response to selective pressures, such as competition for limited resources. Carrion insects provide the ideal case to study these fundamental processes of adaptive evolution due to the intense selective pressures placed on developing larvae with limited food resources, their widespread and abundant distributions, and the presence of geographically distinct populations with specialized adaptations. One adaptation is facultative ectoparasitism, where the insect strikes a healthy animal and feeds on the living flesh, providing a developmental advantage over competitor fly species, but causing significant harm to the host. Lucilia species, which hybridize in the wild and form geographically distinct subpopulations in other regions, are diverging, meaning that we can observe and quantify early biological adaptive processes that govern speciation as they are occurring over hundreds, instead of millions, of years. The draft genome of a North American male Lucilia cuprina fly (carrion breeder) was assembled using a combination of short and long read sequences. This genome is compared to an existing Australian draft genome (ectoparasite) by elucidating genomic structure in key adaptive processes (i.e. immune system evasion) via high-throughput re-sequencing of parasitic specimens, gene prediction and annotation. The carcass colonized by or animal parasitized by both species, with some geographic overlap, provides a semi-controlled environment within the larger context of the ecosystem to sample a large number of individuals with similar life history strategies, allowing for direct comparative studies to elucidate the correlation between structure and function in the genomes of carrion flies – allowing us to understand biological adaptation and speciation.
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    Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder
    (Springer Nature, 2022-08-03) Hesam-Shariati, Sonia; Overs, Bronwyn J.; Roberts, Gloria; Toma, Claudio; Watkeys, Oliver J.; Green, Melissa J.; Pierce, Kerrie D.; Edenberg, Howard J.; Wilcox, Holly C.; Stapp, Emma K.; McInnis, Melvin G.; Hulvershorn, Leslie A.; Nurnberger, John I.; Schofield, Peter R.; Mitchell, Philip B.; Fullerton, Janice M.; Medical and Molecular Genetics, School of Medicine
    Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS; n = 41) compared against the bottom two quintiles (Low-BD-PRS; n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. One differentially methylated probe (DMP) (cg00933603; p = 3.54 × 10-7) in VARS2, a mitochondrial aminoacyl-tRNA synthetase, remained significantly hypomethylated after multiple-testing correction. Overall, BD-PRS appeared to broadly impact epigenetic processes, with 1,183 genes mapped to nominal DMPs (p < 0.05); these displayed convergence with genes previously associated with BD, schizophrenia, chronotype, and risk taking. We tested poly-methylomic epigenetic profiles derived from nominal DMPs in two independent samples (n = 54 and n = 82, respectively), and conducted an exploratory evaluation of the effects of family environment, indexing cohesion and flexibility. This study highlights an important interplay between heritable risk and epigenetic factors, which warrant further exploration.