# Systems Genetic Analysis of Multi-parent Crosses

> **NIH NIH R01** · JACKSON LABORATORY · 2021 · $492,343

## Abstract

PROJECT SUMMARY/ABSTRACT
Forward genetic studies using animal models represent an important tool for the discovery of physiological and
biochemical mechanisms that cause human disease. Genetic studies in model organisms complement direct
human studies, with advantages that include the ability to apply experimental perturbations and to control both
environmental conditions and genetic makeup of study populations. Access to disease-relevant tissues
provides opportunities for large-scale molecular profiling and deep physiological phenotyping. Traditional
forward genetic experiments in animal models employed crosses between two inbred strains. New genetic
populations, derived from more than two founder strains, are being developed for rodents and other model
organisms to serve as community resources for systems genetics studies. These multi-parent populations
provide improved mapping precision, and their greater genetic variability enables their use for a broader set of
disease phenotypes than any one bi-parental population.
Multi-parent populations present new analytical challenges, including haplotype reconstruction, the treatment
of multiple founder alleles, the need to account for population structure, the use of the distribution of SNP
alleles across founder strains to home in on causal SNPs. High dimensional phenotypes present additional
challenges and opportunities, with each new technology requiring special care, but with mediation analysis and
causal network modeling providing valuable insights into possible disease mechanisms. Software tools that
implement the best analysis methods and make them readily accessible, along with interactive data analysis
and visualization tools that enable exploration of these high-dimensional data, empower researchers to explore
systems genetics data on multi-parent populations.
With these general goals, our specific aims are to (1) Develop statistical methods for the genetic analysis of
multi-parent cross designs, including methods for haplotype reconstruction with low-pass genotyping-by-
sequencing data, identification of subsets of causal SNPs underlying a QTL, multiple-QTL modeling, and the
dissection of contributions to heritability; (2) Develop statistical methods for genetic analysis of high-
dimensional phenotypes, including mediation analysis and causal network modeling; and (3) Develop next-
generation software for system genetic analysis with high-dimensional data, including multi-parent populations
and interactive data visualization tools. These aims will support and facilitate the growing use of genetically
diverse multi-parent populations in biomedical research.

## Key facts

- **NIH application ID:** 10242781
- **Project number:** 5R01GM070683-15
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Karl W Broman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $492,343
- **Award type:** 5
- **Project period:** 2004-04-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242781

## Citation

> US National Institutes of Health, RePORTER application 10242781, Systems Genetic Analysis of Multi-parent Crosses (5R01GM070683-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10242781. Licensed CC0.

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