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

Autor: Villani F; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA., Guarracino A; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA., Ward RR; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center., Green T; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center., Emms M; Institute of Genetics and Biophysics, National Research Council, Naples, 80111, Italy., Pravenec M; Institute of Physiology, Czech Academy of Sciences, 14200 Prague, Czech Republic., Prins P; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA., Garrison E; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA., Williams RW; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA., Chen H; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center., Colonna V; Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.; Institute of Genetics and Biophysics, National Research Council, Naples, 80111, Italy.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 15. Date of Electronic Publication: 2024 Apr 15.
DOI: 10.1101/2024.01.10.575041
Abstrakt: 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-α 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.
Databáze: MEDLINE
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