Biology subjects

Holl, K.

Publications and source records attributed to Holl, K..

3 recordsLinked to original sources

bioRxiv2018

Genome wide association study of body weight, body mass index, adiposity, and fasting glucose in 3,173 outbred rats

Objective Obesity is influenced by genetic and environmental factors. Despite success of human genome wide association studies (GWAS), the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify genetic loci underlying obesity and related morphometric and metabolic traits.Methods We measured obesity-relevant traits including body weight, body length, body mass index, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat GWAS to date. Genetic loci were identified using a linear mixed model that accounted for the complex family relationships of the HS and covariate to account for differences among the three phenotyping centers.Results We identified 32 independent loci, several of which contained only a single gene (e.g. Epha5, Nrg1 and Klhl14) or obvious candidate genes (Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and extensive pleiotropy at individual loci.Conclusions These studies demonstrate utility of HS rats for investigating the genetics of obesity related traits across institutions and identify several candidate genes for future functional testing.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genetics↗

bioRxiv2018

Dissociating addiction-related endophenotypes: Incentive salience attribution, sensation-seeking and novelty-seeking are independent traits in male and female heterogeneous stock rats

There are a number of traits that are thought to increase susceptibility to addiction, and some of these are modeled in preclinical studies. For example, \"sensation-seeking\" is predictive of the initial propensity to take drugs; whereas \"novelty-seeking\" predicts compulsive drug-seeking behavior. In addition, the propensity to attribute incentive salience to reward cues can predict the propensity to approach drug cues, and reinstatement or relapse, even after relatively brief periods of drug exposure. The question addressed here is the extent to which these three vulnerability factors are related; that is, predictive of one another. Some relationships have been reported in small samples, but here a large sample of 1,598 outbred male and female heterogeneous stock rats were screened for Pavlovian conditioned approach behavior (to obtain an index of incentive salience attribution; sign-tracking), and subsequently tested for sensation-seeking and novelty-seeking. Despite the large N there were no significant correlations between these traits, in either males or females. There were, however, novel relationships between multiple measures of incentive salience attribution and, based on these findings, we generated a new metric that captures \"incentive value\". Furthermore, there were sex differences on measures of incentive salience attribution and sensation-seeking behavior that were not previously apparent.

animal behavior and cognition↗

bioRxiv2018

Extended regions of suspected mis-assembly in the rat reference genome

We performed whole-genome sequencing for eight inbred rat strains commonly used in genetic mapping studies, and they are the founders of the NIH heterogeneous stock (HS) outbred colony. We provide their sequences and variant calls to the rat genomics community. When analyzing the variant calls we identified regions with unusually high heterozygosity. We show that these regions are consistent across the eight inbred strains, including the BN strain, which was the basis of the rat reference genome. These regions show significantly higher read depth than other regions in the genome. The evidence suggests that these regions may contain segmental duplications that are incorrectly overlaid in the reference genome. We provide masks for these suspected regions of mis-assembly as a resource for the community to flag potentially false interpretations of mapping results or functional data.

genomics↗