High-quality mouse reference genomes reveal the structural complexity of the murine protein-coding landscape

TL;DR

Researchers created high-quality mouse genomes to better understand complex immune-related regions and improve genetic studies.

Contribution

The study provides new high-quality mouse genomes that resolve complex genomic regions and improve RNA-seq analysis.

Findings

Resolved complex genomic regions like MHC, defensin cluster, and T cell receptor.

Identified over 400 genes with VNTR polymorphisms in coding regions.

Improved RNA-seq read mapping and gene expression analysis using strain-specific genomes.

Abstract

We present a collection of 17 high-quality long-read inbred mouse strain genomes with complete annotation (contig N50s of 0.8–33.9 Mbp). This collection includes 12 widely used classical laboratory strains and 5 wild-derived strains. We have resolved previously incomplete genomic regions, including the major histocompatibility complex (MHC), defensin cluster, T cell receptor, and Ly49 complexes. Hundreds of non-reference genes from previous publications not found in GRCm39, such as Defa1, Raet1a, and Klra20 (Ly49T), were localized in the new reference genomes. We conducted a genome-wide scan of variable number tandem repeats (VNTRs) within the coding regions, identifying over 400 genes with VNTR polymorphisms with up to 600 repeat copies and repeat units reaching 990 nucleotides. Our strain-specific annotations enhance RNA sequencing (RNA-seq) analyses, as demonstrated in PWK/PhJ, where we observed a 5.1% improvement in read mapping and expression-level differences in 2.1% of coding genes compared to using GRCm39.

•Collection of high-quality mouse reference genomes•Insights into the structural complexity of key regions of the mouse genome•Impact of using a strain-specific genome for RNA-seq analysis

Collection of high-quality mouse reference genomes

Insights into the structural complexity of key regions of the mouse genome

Impact of using a strain-specific genome for RNA-seq analysis

Helmy et al. provide a collection of high-quality mouse reference genomes. They were able to resolve some of the most complex regions among mouse genomes that are involved in immune defense. These findings have an impact on a variety of mouse genetics experiments as well as the usage of mice as an animal model for medical research.

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