Biology subjects

Long, J. D.

Publications and source records attributed to Long, J. D..

3 recordsLinked to original sources

bioRxiv2019

Genetic overlap between psychiatric disorders and neuropsychiatric symptoms in HD

Huntingtons disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized exam of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown. We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders, and of intelligence, and testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n=5160) of HD patients. Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence. In general, polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD.

genetics↗

bioRxiv2019

Conspecifics, not plant reproductive tissues, reduce omnivore prey consumption

Plant reproductive tissues (PRTs) can decrease (via reduced consumption) or increase (via numerical response) an omnivores consumption of animal prey. Although PRTs can increase predation pressure through numerical responses of omnivores, PRTs may also suppress predation by increasing omnivore interactions with conspecifics. Despite this potential, studies of the impacts of PRTs on predation by omnivores often overlook the effect of these tissues on intraspecific interactions between omnivores. We designed three studies to examine how PRTs and conspecific density impact prey consumption by ladybeetle omnivores. First, we assessed how PRTs impact scale insect consumption by isolated ladybeetles. Second, we measured how PRTs influence ladybeetle prey suppression when numerical responses were possible. Third, because initial experiments suggested the consumption rates of individual ladybeetles depended upon conspecific density, we compared per capita consumption rates of ladybeetles across ladybeetle density. PRTs did not influence prey consumption by isolated ladybeetles. When numerical responses were possible, PRTs did not influence total predation on prey despite increasing ladybeetle density, suggesting that PRTs decreased per capita prey consumption by ladybeetles. The discrepancy between our lab and field studies is likely a consequence of differences in ladybeetle density - the presence of only two other conspecifics decreased per capita prey consumption by 76%. Our findings suggest that PRTs may not alter the population level effects of omnivores on prey when omnivore numerical responses are offset by reductions in per capita predation rate.

ecology↗

bioRxiv2019

Huntington's disease onset is determined by length of uninterrupted CAG, not encoded polyglutamine, and is modified by DNA maintenance mechanisms

The effects of variable, glutamine-encoding, CAA interruptions indicate that a property of the uninterrupted HTT CAG repeat sequence, distinct from huntingtins polyglutamine segment, dictates the rate at which HD develops. The timing of onset shows no significant association with HTT cis-eQTLs but is influenced, sometimes in a sex-specific manner, by polymorphic variation at multiple DNA maintenance genes, suggesting that the special onset-determining property of the uninterrupted CAG repeat is a propensity for length instability that leads to its somatic expansion. Additional naturally-occurring genetic modifier loci, defined by GWAS, may influence HD pathogenesis through other mechanisms. These findings have profound implications for the pathogenesis of HD and other repeat diseases and question a fundamental premise of the "polyglutamine disorders".

genetics↗