Project description:BackgroundUnraveling the relationship between genetic variation and phenotypic traits remains a fundamental challenge in biology. Mapping variants underlying complex traits while controlling for confounding environmental factors is often problematic. To address this, we establish a vertebrate genetic resource specifically to allow for robust genotype-to-phenotype investigations. The teleost medaka (Oryzias latipes) is an established genetic model system with a long history of genetic research and a high tolerance to inbreeding from the wild.ResultsHere we present the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel: the first near-isogenic panel of 80 inbred lines in a vertebrate model derived from a wild founder population. Inbred lines provide fixed genomes that are a prerequisite for the replication of studies, studies which vary both the genetics and environment in a controlled manner, and functional testing. The MIKK panel will therefore enable phenotype-to-genotype association studies of complex genetic traits while allowing for careful control of interacting factors, with numerous applications in genetic research, human health, drug development, and fundamental biology.ConclusionsHere we present a detailed characterization of the genetic variation across the MIKK panel, which provides a rich and unique genetic resource to the community by enabling large-scale experiments for mapping complex traits.
Project description:We conducted a high-throughput sequencing study to measure whole brain miRNA expression levels in alcohol naïve animals in the LXS panel of recombinant inbred (RI) mouse strains. We then combined the sequencing data with genotype data, microarray gene expression data, and data on alcohol-related behavioral phenotypes such as 'Drinking in the dark', 'Sleep time', and 'Low dose activation' from the same RI panel.
Project description:This study aimed to perform gene expression quantitative trait locus mapping (eQTL) in the livers of a panel of 36 laboratory inbred strains. Mice were dosed with a saline solution by oral gavage and sacrificed at 24 hours. Livers were removed at sacrifice, RNA was extracted and gene expression was assayed using the Agilent G4121A array. Keywords: eQTL, mouse, liver
Project description:BackgroundThe teleost medaka (Oryzias latipes) is a well-established vertebrate model system, with a long history of genetic research, and multiple high-quality reference genomes available for several inbred strains. Medaka has a high tolerance to inbreeding from the wild, thus allowing one to establish inbred lines from wild founder individuals.ResultsWe exploit this feature to create an inbred panel resource: the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel. This panel of 80 near-isogenic inbred lines contains a large amount of genetic variation inherited from the original wild population. We use Oxford Nanopore Technologies (ONT) long read data to further investigate the genomic and epigenomic landscapes of a subset of the MIKK panel. Nanopore sequencing allows us to identify a large variety of high-quality structural variants, and we present results and methods using a pan-genome graph representation of 12 individual medaka lines. This graph-based reference MIKK panel genome reveals novel differences between the MIKK panel lines and standard linear reference genomes. We find additional MIKK panel-specific genomic content that would be missing from linear reference alignment approaches. We are also able to identify and quantify the presence of repeat elements in each of the lines. Finally, we investigate line-specific CpG methylation and performed differential DNA methylation analysis across these 12 lines.ConclusionsWe present a detailed analysis of the MIKK panel genomes using long and short read sequence technologies, creating a MIKK panel-specific pan genome reference dataset allowing for investigation of novel variation types that would be elusive using standard approaches.
Project description:We conducted a timeseries experiment on a recombinant inbred line (RIL) panel of Caenorhabditis elegans derived from a NL5901 x SCH4856 cross. These RILs carry a human alpha-synuclein gene in an N2 and a CB4856 genetic background respectively. We grew synchronized populations of the nematodes (70 RILs, N2, CB4856, NL5901, and SCH4856) under normal conditions (20 degrees Celcius, feeding on Escherichia coli OP50) for 120 hours. The goal of the experiment was to identify loci affecting gene expression in the presence of human alpha-synuclein
Project description:High-density lipoproteins (HDL) are nanoparticles with >80 associated proteins, phospholipids, cholesterol and cholesteryl esters. We have identified and quantified the ultracentrifugation isolated HDL proteome across 93 strains of mice, a diverse inbred strains of mice, Hybrid Mouse Diversity Panel (HMDP).
Project description:Hepatosteatosis underlies several diseases including type 2 diabetes, cardiovascular disease and liver disease. Unfortunately, our understanding of the contributing pathways that initiate and advance hepatosteatosis to subsequent complications is still poorly understood. Here, we take advantage of recent developments in “omics” technologies to perform high resolution proteomics (>5000 proteins) and quantitative lipidomics (>300 lipids) on livers from 107 genetically diverse inbred mouse strains from the hybrid mouse diversity panel. Integration of these data allowed us to define novel regulators of lipid metabolism in the liver.
Project description:Transcriptomes performed on left ventricular heart samples from mice of the hybrid mouse diversity panel, a set of over a hundred inbred strains of mice. In this project, the strains were challenged with Isoproterenol, a beta-adrenergic agonist to induce cardiac hypertrophy and failure. Results are useful for the analysis of heart-related traits in mice