# Genetic contribution to degenerative tendon and ligament rupture in Equus ferus caballus

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $170,867

## Abstract

Project Summary/Abstract
 There is a fundamental gap in understanding the genetic contribution to site-specific spontaneous
tendon/ligament rupture. The Achilles tendon, rotator cuff, and anterior cruciate ligament are often diseased.
Such conditions represent acute damage of a chronically degenerated tendon/ligament. Continued existence
of this knowledge gap represents an important problem because, until it is filled, understanding how the large
number of genetic variants that contribute to risk of spontaneous tendon/ligament rupture will remain largely
incomprehensible. The long-term goal is to discover spontaneous tendon/ligament rupture causal genetic
variants. Our overall objective is to discover candidate genetic variants by comprehensive genomic dissection
of equine degenerative suspensory ligament desmitis (DSLD), an excellent large animal model of spontaneous
tendon/ligament rupture. The genomic architecture of horses acts to increase Power for SNP association by
within-breed genome-wide association study (GWAS) as linkage disequilibrium is increased relative to the
human genome. The central hypothesis is that DSLD has an important genetic component that is Mendelian.
This hypothesis has been formulated on the basis of preliminary data produced in the applicant’s laboratory.
The rationale for the proposed research is that knowledge of the genomic architecture underpinning DSLD and
discovery of candidate genetic variants in the equine model will enable new and innovative approaches to
prevention and treatment of human spontaneous tendon/ligament rupture and also provide a new treatment
model. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Use
RNA sequencing (RNA-Seq) to identify differentially expressed genes in ruptured DSLD tissue and 2) Discover
DSLD rupture candidate genetic variants by GWAS and subsequent region-based analysis of whole genome
sequence (WGS) data. Under the first aim, differentially expressed genes will be identified by analyzing the
transcriptome in diseased tissue to assess disturbances to biological networks. Under the second aim,
genomic single nucleotide polymorphisms (SNPs) will be used for discovery GWAS. We will test our working
hypothesis that DSLD is a Mendelian disease that is explained by a genetic variant that is shared across
DSLD-affected breeds. A shared variant is more likely to be strongly linked to human disease. The work is
innovative as it departs from the usual GWAS approach by studying an equine model. New research horizons
are expected to be attainable as a result. The proposed research is significant, because it is expected to
discover a novel spontaneous tendon/ligament rupture candidate genetic variant and the associated biological
pathways. This work will help clarify common pathways that are disturbed in the pathogenesis of spontaneous
tendon/ligament rupture. Large effect variants identified in the equine model will provide new targets ...

## Key facts

- **NIH application ID:** 9899206
- **Project number:** 5R21AR073301-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** PETER MUIR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $170,867
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899206

## Citation

> US National Institutes of Health, RePORTER application 9899206, Genetic contribution to degenerative tendon and ligament rupture in Equus ferus caballus (5R21AR073301-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899206. Licensed CC0.

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