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Biology subjects

Klingström, T.

Publications and source records attributed to Klingström, T..

2 recordsLinked to original sources

Population history of Swedish cattle breeds: estimates and model checking

In this work, we use linkage disequilibrium-based methods to estimate recent population history from genotype data in Swedish cattle breeds, as well as international Holstein and Jersey cattle data for comparison. Our results suggest that these breeds have been effectively large up until recently, when they declined around the onset of systematic breeding. The inferred trajectories were qualitatively similar, with a large historical population and one decline. We used population genetic simulation to check the inferences. When comparing simulations from the inferred population histories to real data, the proportion low-frequency variants in real data was different than was implied by the inferred population histories, and there was somewhat higher genomic inbreeding in real data than implied by the inferred histories. The inferred population histories imply that much of the variation we see today is transient, and it will be lost as the populations settle into a new equilibrium, even if efforts to maintain effective population size at current levels are successful.

genetics↗

Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo, image-based, large-scale genetic screen in zebrafish

A meta-analysis of genome-wide association studies (GWAS) identified eight loci that are associated with heart rate variability (HRV), but candidate genes in these loci remain uncharacterized. We developed an image- and CRISPR/Cas9-based pipeline to systematically characterize candidate genes for HRV in live zebrafish embryos. Nine zebrafish orthologues of six human candidate genes were targeted simultaneously in eggs from fish that transgenically express GFP on smooth muscle cells (Tg[acta2:GFP]), to visualize the beating heart. An automated analysis of repeated 30s recordings of beating atria in 381 live, intact zebrafish embryos at 2 and 5 days post-fertilization highlighted genes that influence HRV (hcn4 and si:dkey-65j6.2 [KIAA1755]); heart rate (rgs6 and hcn4); and the risk of sinoatrial pauses and arrests (hcn4). Exposure to 10 or 25{micro}M ivabradine - an open channel blocker of HCNs - for 24h resulted in a dose-dependent higher HRV and lower heart rate at 5 days post-fertilization. Hence, our screen confirmed the role of established genes for heart rate and rhythm (RGS6 and HCN4); showed that ivabradine reduces heart rate and increases HRV in zebrafish embryos, as it does in humans; and highlighted a novel gene that plays a role in HRV (KIAA1755).

genomics↗