Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology

Ashbrook, David G.; Lu, Lu

doi:10.5772/intechopen.96173

Cited by 2 publications

(1 citation statement)

References 193 publications

(229 reference statements)

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“…In this way, phenotypes collected across decades, continents and environments can be coherently coanalyzed, providing new insight from legacy data 95 . Furthermore, by crossing two BXD strains any of 22,350 isogenic F1 hybrids can be generateda massive diallel cross (DAX) 11,98 . Thus, there are well over 22,000 reproducible "clones" of F1 hybrids that can be generated from the current BXD families, each of which carries one chromosome from each of its BXD parents, and is therefore fully 'in silico' sequenced in advance.…”

Section: Discussionmentioning

confidence: 99%

Private and sub-family specific mutations of founder haplotypes in the BXD family reveal phenotypic consequences relevant to health and disease

Ashbrook

Sasani

Maksimov

et al. 2022

Preprint

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The BXD recombinant inbred (RI) mouse strains are the largest and most deeply phenotyped inbred panel of vertebrate organisms. RIs allow phenotyping of isogenic individuals across virtually any environment or treatment. We performed whole genome sequencing and generated a compendium of SNPs, indels, short tandem repeats, and structural variants in these strains and used them to analyze phenomic data accumulated over the past 50 years.We show that BXDs segregate >6 million variants with high minor allele which are dervied from the C57BL/6J and DBA/2J founders and use this dense variant set to define ‘infinite’ marker maps and a novel family-level pangenome. We additionally characterize rates and spectra de novo variants which have accumulated over 20-200 generations of inbreeding, and have largely been ignored previously. Overall, the uniquely rich phenome when linked with WGS enables a new type of integrative modeling of genotype-to-phenotype relations.

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Section: Discussionmentioning

confidence: 99%

Private and sub-family specific mutations of founder haplotypes in the BXD family reveal phenotypic consequences relevant to health and disease

Ashbrook

Sasani

Maksimov

et al. 2022

Preprint

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The potential of integrating human and mouse discovery platforms to advance our understanding of cardiometabolic diseases

Jurrjens

Seldin

Giles

et al. 2023

eLife

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Cardiometabolic diseases encompass a range of interrelated conditions that arise from underlying metabolic perturbations precipitated by genetic, environmental, and lifestyle factors. While obesity, dyslipidaemia, smoking, and insulin resistance are major risk factors for cardiometabolic diseases, individuals still present in the absence of such traditional risk factors, making it difficult to determine those at greatest risk of disease. Thus, it is crucial to elucidate the genetic, environmental, and molecular underpinnings to better understand, diagnose, and treat cardiometabolic diseases. Much of this information can be garnered using systems genetics, which takes population-based approaches to investigate how genetic variance contributes to complex traits. Despite the important advances made by human genome-wide association studies (GWAS) in this space, corroboration of these findings has been hampered by limitations including the inability to control environmental influence, limited access to pertinent metabolic tissues, and often, poor classification of diseases or phenotypes. A complementary approach to human GWAS is the utilisation of model systems such as genetically diverse mouse panels to study natural genetic and phenotypic variation in a controlled environment. Here, we review mouse genetic reference panels and the opportunities they provide for the study of cardiometabolic diseases and related traits. We discuss how the post-GWAS era has prompted a shift in focus from discovery of novel genetic variants to understanding gene function. Finally, we highlight key advantages and challenges of integrating complementary genetic and multi-omics data from human and mouse populations to advance biological discovery.

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Recombinant Inbred Mice as Models for Experimental Precision Medicine and Biology

Cited by 2 publications

References 193 publications

Private and sub-family specific mutations of founder haplotypes in the BXD family reveal phenotypic consequences relevant to health and disease

Private and sub-family specific mutations of founder haplotypes in the BXD family reveal phenotypic consequences relevant to health and disease

The potential of integrating human and mouse discovery platforms to advance our understanding of cardiometabolic diseases

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