Animal Molecular Breeding, 2025, Vol.15, No.1, 1-8 http://animalscipublisher.com/index.php/amb 1 Research Insight Open Access The Genetic Basis of High-Altitude Adaptation in Goats Insights from CRISPR-Based Functional Genomics Jingya Li, Mengyue Chen Animal Science Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: mengyue.chen@cuixi.org Animal Molecular Breeding, 2025, Vol.15, No.1 doi: 10.5376/amb.2025.15.0001 Received: 10 Dec., 2024 Accepted: 15 Jan., 2025 Published: 26 Jan., 2025 Copyright © 2025 Li and Chen, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li J.Y., and Chen M.Y., 2025, The genetic basis of high-altitude adaptation in goats insights from CRISPR-based functional genomics, Animal Molecular Breeding, 15(1): 1-8 (doi: 10.5376/amb.2025.15.0001) Abstract Goats are precious livestock in mountainous regions, subjected to environmental stresses such as hypoxia, cold stress, and excessive ultraviolet radiation. Elucidation of the genetic mechanism of their adaptation to high altitude is needed if molecular breeding and production performance are to be improved under extreme conditions. This study summarizes the physiological characteristics of high-altitude goats including adaptive respiratory, circulatory, immune, and reproductive system adaptation; advances in the identification of candidate adaptive genes by genome-wide association and selective sweep studies; and epigenetics and non-coding RNA functions in adaptive regulation. This study particularly targets using CRISPR/Cas9 technology to facilitate functional verification of key genes and multi-omics integration for the reconstruction of adaptive regulatory networks, and to probe the key molecular mechanisms essential for high-altitude survival such as the HIF signaling pathway and redox balance. The feasibility and limitations of using CRISPR technology in goat genetic innovation are examined for leads in future studies on adaptive breeding under suboptimal environments. Keywords Plateau adaptation; Goats; CRISPR/Cas9; Functional genomics; Hypoxia response 1 Introduction High-altitude plateaus, such as the Qinghai-Tibetan Plateau, possess severe environments with hypoxia, cold, intense ultraviolet radiation, and limited supply of forage. Resident animals, particularly goats, experience heavy physiological and genetic stresses from these environments. To survive these environments, goats developed particular adaptations like enhanced oxygen transport mechanisms, efficient metabolic pathways, and robust immunity. It is significant to appreciate these adaptations to improve livestock productivity and resilience in high-altitude regions (Li et al., 2023). Goats play a crucial role in livelihoods at the community level in high-altitude regions. They constitute a principal source of meat, milk, fiber, and cash income, especially where other forms of agriculture cannot be practiced (He et al., 2018). Economically, goats play a vital role in that they contribute meaningfully to family incomes as well as food security. Goats also assist in vegetation and land use management in a manner that results in sustainable agriculture. Their ability to survive on marginal soils makes them indispensable in the socioeconomic structure of plateau societies (Jin et al., 2020; Li et al., 2022). Investigating the genetic basis of high-altitude adaptation in goats is essential for breeding program development to enhance resilience and productivity. Advances in genome editing technologies, particularly CRISPR/Cas9, have revolutionized functional genomics research to date. CRISPR enables precise manipulation of target genes, making it possible to validate candidate genes associated with adaptation traits. Applying CRISPR technology to research goats may be fruitful in accelerating the breeding of animals with enhanced qualities for high-altitude ecosystems and hence increasing sustainable livestock production in such challenging ecosystems. 2 Adaptive Traits and Physiological Characteristics of Plateau Goats 2.1 Plateau-adapted changes in the respiratory and hematological systems Plateau goats such as the Tibetan cashmere goat have evolved specific respiratory and hematological adaptations to sustain themselves in hypoxic high-altitude environments. Genetic differentiation exists for key oxygen-sensing
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