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Biology subjects

Ward, R. R.

Publications and source records attributed to Ward, R. R..

2 recordsLinked to original sources

Hi-C sequencing data from cortex laboratory rats

The three-dimensional conformation and packaging of chromosomes modulates the spatial organization of the nucleus, orchestrating DNA replication and repair, maintaining genome stability and integrity, and regulating gene expression. Hi-C methods provide high-resolution data on chromatin-to-chromatin interactions both within and among chromosomes at a genome-wide scale. Hi-C resolves topologically-associated domains (TADs) and chromatin loops that are linked to cell-specific transcriptional control. We present a comprehensive Hi-C dataset generated from the frontal cortex of laboratory rats, encompassing a diverse group of inbred strains (SHR/OlaIpcv, BN-Lx/Cub, BXH6/Cub, HXB2/Ipcv, HXB10/Ipcv, HXB23/Ipcv, HXB31/Ipcv, LE/Stm, F344/Stm) and an F1 hybrid (SHR/Olalpcv x BN/NHsdMcwi). This dataset serves as a valuable resource for studying the mechanisms by which three-dimensional chromatin architecture governs gene expression in the brain. Strain-specific variations in genome organization can illuminate the influence of chromatin structure on gene expression, neuronal functionality, and the predisposition to neurological and behavioral disorders.

genomics↗

Pangenome reconstruction in rats enhances genotype-phenotype mapping and novel variant discovery

The HXB/BXH family of recombinant inbred rat strains is a unique genetic resource that has been extensively phenotyped over 25 years, resulting in a vast dataset of quantitative molecular and physiological phenotypes. We built a pangenome graph from 10x Genomics Linked-Read data for 31 recombinant inbred rats to study genetic variation and association mapping. The pangenome includes 0.2Gb of sequence that is not present the reference mRatBN7.2, confirming the capture of substantial additional variation. We validated variants in challenging regions, including complex structural variants resolving into multiple haplotypes. Phenome-wide association analysis of validated SNPs uncovered variants associated with glucose/insulin levels and hippocampal gene expression. We propose an interaction between Pirl1l1, chromogranin expression, TNF- levels, and insulin regulation. This study demonstrates the utility of linked-read pangenomes for comprehensive variant detection and mapping phenotypic diversity in a widely used rat genetic reference panel.

genomics↗