# Genetic architecture of thermotolerance traits in beef cattle: a novel integration of SNP and breed-of-origin effects

**Authors:** Gabriel A. Zayas, Camila Santos Rojas, Eduardo E. Rodriguez, Aakilah S. Hernandez, Ashley M. Beard, Fahad Rafiq, Kaitlyn M. Sarlo Davila, Raluca G. Mateescu

PMC · DOI: 10.3389/fgene.2025.1576966 · Frontiers in Genetics · 2025-04-30

## TL;DR

This study explores how genetic factors from different cattle breeds influence heat tolerance traits, aiming to improve beef cattle resilience to rising temperatures.

## Contribution

The study introduces a novel integration of SNP and breed-of-origin effects to uncover the genetic architecture of thermotolerance traits in beef cattle.

## Key findings

- Significant QTLs for hair length traits were identified on BTA20 and BTA19, with breed-of-origin effects playing a key role.
- Integrated SNP + BOA models revealed novel QTLs and provided greater resolution than single-effect models.
- Functional enrichment analysis linked hair length and thermoregulation traits to MAPK and estrogen signaling pathways.

## Abstract

Rising temperatures increasingly expose beef cattle to heat stress, reducing productivity and welfare, especially in tropical climates. Crossbreeding Bos t. taurus and Bos t. indicus has emerged as a critical strategy to balance the production efficiency of taurine breeds with the superior thermotolerance of indicine breeds. Understanding the genetic architecture of thermotolerance traits is essential for improving heat resilience in beef cattle populations.

Phenotypes for short hair length (SHL, undercoat) and long hair length (LHL, topcoat), sweat gland area (SGA), and thermal stress slope (TSS), a measure of body temperature fluctuations under heat stress, were collected from 3,962 crossbred Angus-Brahman heifers. Heifers were genotyped, and breed-of-origin (BOA) for each marker was determined using LAMP-LD. Genome-wide association studies were conducted using SNP-only, BOA-only, and integrated SNP + BOA models to identify quantitative trait loci (QTLs) associated with thermotolerance traits. Genes in QTL regions were used for functional enrichment analysis using Gene Ontology (GO) and KEGG pathways.

Significant QTLs for SHL and LHL were identified on BTA20, overlapping the PRLR gene. A QTL on BTA19 for SHL and LHL was driven solely by BOA effects, with Brahman BOA associated with shorter hair lengths. For SGA, six suggestive QTLs were detected, predominantly linked to Angus-derived alleles associated with reduced sweat gland area. For TSS, a significant QTL on BTA1 exhibited a strong BOA effect, with Angus BOA associated with higher TSS values, indicative of reduced thermoregulatory efficiency. Integrated SNP + BOA models provided greater resolution and revealed novel QTLs compared to single-effect models. Functional enrichment using GO and KEGG identified MAPK and estrogen signaling pathways in both LHL and TSS, indicating potential overlap in the biological processes influencing hair length and thermoregulation.

This study demonstrates the value of integrating BOA with SNP-based models to uncover the genetic architecture of thermotolerance traits in beef cattle. By better capturing breed-specific contributions, these findings enhance our understanding of thermoregulation and provide actionable insights for improving heat resilience in cattle.

## Linked entities

- **Genes:** PRLR (prolactin receptor) [NCBI Gene 5618]

## Full-text entities

- **Genes:** DCBLD2 (discoidin, CUB and LCCL domain containing 2) [NCBI Gene 524608] {aka CLCP1-like}, MAP3K3 (mitogen-activated protein kinase kinase kinase 3) [NCBI Gene 4215] {aka CCM5, MAPKKK3, MEKK3}, CCDC47 (coiled-coil domain containing 47) [NCBI Gene 57003] {aka GK001, MSTP041, THNS}, WIF1 (WNT inhibitory factor 1) [NCBI Gene 533672], PRLR (prolactin receptor) [NCBI Gene 281422] {aka SPRLR}, HSF1 (heat shock transcription factor 1) [NCBI Gene 506235] {aka HSF}, Prkca (protein kinase C, alpha) [NCBI Gene 18750] {aka Pkca}, ECM1 (extracellular matrix protein 1) [NCBI Gene 524222], MSRB3 (methionine sulfoxide reductase B3) [NCBI Gene 617849], LEMD3 (LEM domain containing 3) [NCBI Gene 530659], Lemd3 (LEM domain containing 3) [NCBI Gene 380664] {aka Man1}, Grip1 (glutamate receptor interacting protein 1) [NCBI Gene 74053] {aka 4931400F03Rik, GRIP, eb}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, Msrb3 (methionine sulfoxide reductase B3) [NCBI Gene 320183] {aka D430026P16Rik, I-8-23, MsrB2}, Abca5 (ATP-binding cassette, sub-family A member 5) [NCBI Gene 217265] {aka ABC13, B930033A02Rik, mKIAA1888}, HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 282254] {aka HSP70, HSP70-1, HSP70-2, HSPA1, HSPA1B, HSPA2}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, NFKBIZ (NFKB inhibitor zeta) [NCBI Gene 282713] {aka MAIL}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, ALCAM (activated leukocyte cell adhesion molecule) [NCBI Gene 281614], FILIP1L (filamin A interacting protein 1 like) [NCBI Gene 504954], GRIP1 [NCBI Gene 525592], Wipi1 (WD repeat domain, phosphoinositide interacting 1) [NCBI Gene 52639] {aka 4930533H01Rik, D11Ertd498e}, Wif1 (Wnt inhibitory factor 1) [NCBI Gene 24117] {aka WIF-1}
- **Diseases:** alopecia (MESH:D000505), epidermal blistering (MESH:D001768), BOA (MESH:D007280), Fraser syndrome (MESH:D058497), Buschke-Ollendorff syndrome (MESH:C537415), inflammatory (MESH:D007249), junction defects (MESH:D020511), LHL (MESH:D000094024), nevi (MESH:D009506), skin syndactyly (MESH:D013576), SHL (MESH:D006201), hypertrichosis (MESH:D006983), osteopoikilosis (MESH:D010023), SGA (MESH:D013543), dermo (MESH:C536612)
- **Chemicals:** ethanol (MESH:D000431), BOA (-), chlorhexidine (MESH:D002710), lidocaine (MESH:D008012), paraffin (MESH:D010232), formalin (MESH:D005557), calcium (MESH:D002118)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913]
- **Mutations:** rs3423104800, rs210687570, rs42969983, rs41922675

## Full text

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## Figures

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## References

89 references — full list in the complete paper: https://tomesphere.com/paper/PMC12075150/full.md

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Source: https://tomesphere.com/paper/PMC12075150