Modeling diseases in multiple mouse strains for precision medicine studies.

Area of Science:

• Genetics
• Pharmacogenomics
• Animal Models

Background:

• Phenotypic variability in patients with genetic disorders poses a challenge for research.
• Genome-wide association studies (GWAS) require large patient cohorts, which are often unavailable for rare diseases.
• Utilizing inbred mouse strains offers a controlled system to study genetic influences on disease.

Purpose of the Study:

• To explore the utility of mouse models for studying the genetic basis of phenotypic variability.
• To enhance the statistical power and reduce the cost of genome-wide association studies (GWAS) for rare disorders.
• To investigate the applicability of this approach in pharmacogenomics.

Main Methods:

• Generating disease models in mice through genetic or chemical interventions across diverse genetic backgrounds.
• Assessing clinical phenotypes in these mouse models.
• Leveraging known single nucleotide polymorphism (SNP) catalogs of inbred strains for bioinformatics analysis.

Main Results:

• Mouse models provide a viable platform to investigate genetic contributions to phenotypic diversity.
• The use of inbred strains with available SNP data streamlines GWAS by eliminating the need for individual mouse genotyping.
• This methodology is applicable to both rare disease research and pharmacogenomics.

Conclusions:

• Mouse models are valuable tools for dissecting the genetic underpinnings of phenotypic variability in human diseases.
• Employing inbred strains significantly facilitates and economizes genome-wide association studies (GWAS), especially for rare conditions.
• The described approach holds promise for advancing pharmacogenomic research.