Genome-Wide Detection of Copy Number Variants in Chinese Indigenous Horse Breeds and Verification of CNV-Overlapped Genes Related to Heat Adaptation of the Jinjiang Horse.
Abstract: In the present study, genome-wide CNVs were detected in a total of 301 samples from 10 Chinese indigenous horse breeds using the Illumina Equine SNP70 Bead Array, and the candidate genes related to adaptability to high temperature and humidity in Jinjiang horses were identified and validated. We determined a total of 577 CNVs ranging in size from 1.06 Kb to 2023.07 Kb on the 31 pairs of autosomes. By aggregating the overlapping CNVs for each breed, a total of 495 CNVRs were detected in the 10 Chinese horse breeds. As many as 211 breed-specific CNVRs were determined, of which 64 were found in the Jinjiang horse population. By removing repetitive CNV regions between breeds, a total of 239 CNVRs were identified in the Chinese indigenous horse breeds including 102 losses, 133 gains and 4 of both events (losses and gains in the same region), in which 131 CNVRs were novel and only detected in the present study compared with previous studies. The total detected CNVR length was 41.74 Mb, accounting for 1.83% of the total length of equine autosomal chromosomes. The coverage of CNVRs on each chromosome varied from 0.47% to 15.68%, with the highest coverage on ECA 12, but the highest number of CNVRs was detected on ECA1 and ECA24. A total of 229 genes overlapping with CNVRs were detected in the Jinjiang horse population, which is an indigenous horse breed unique to the southeastern coast of China exhibiting adaptability to high temperature and humidity. The functional annotation of these genes showed significant relation to cellular heat acclimation and immunity. The expression levels of the candidate genes were validated by heat shock treatment of various durations on fibroblasts of horses. The results show that the expression levels of were significantly increased among the different heat shock durations. The expression level of and declined from the beginning of heat shock to 2 h after heat shock and then showed a gradual increase until it reached the highest value at 6 h and 10 h of heat shock, respectively. Breed-specific CNVRs of Chinese indigenous horse breeds were revealed in the present study, and the results facilitate mapping CNVs on the whole genome and also provide valuable insights into the molecular mechanisms of adaptation to high temperature and humidity in the Jinjiang horse.
Publication Date: 2022-03-28 PubMed ID: 35456409PubMed Central: PMC9033042DOI: 10.3390/genes13040603Google Scholar: Lookup
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Summary
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The study focuses on identifying and verifying genome-wide copy number variants (CNVs) associated with heat adaptation traits in Chinese indigenous horse breeds, particularly the Jinjiang breed which is known for its adaptability to high temperature and humidity conditions.
Methodology and Approach
- The researchers selected a total of 301 samples from 10 different Chinese indigenous horse breeds for the study.
- They applied the Illumina Equine SNP70 Bead Array technology, a genotype scanning method designed specifically for horse genome investigations to detect CNVs.
- A total of 577 CNVs, varying in size, were identified in the 31 pairs of autosomes of the breeds studied.
- The overlapping CNVs for each breed were aggregated, leading to the detection of 495 CNVRs (Copy Number Variant Regions) among all the breeds studied.
- The breed-specific CNVRs were separated out, among which 64 were specific to the Jinjiang horse breed.
Detection of Copy Number Variant Regions (CNVRs)
- Reports show 211 breed-specific CNVRs, with Jinjiang horse breed having 64 of them.
- Repetitive CNV regions between breeds were removed, leading to the identification of 239 CNVRs in the Chinese indigenous horse breeds.
- These CNVRs included unique losses, gains and bimodal events (both loss and gain in the same region).
- There were 131 novel CNVRs only detected in this study entrails previously unidentified.
- The total detected CNVR length accounted for 1.83% of the total length of equine autosomal chromosomes, with variances in coverage across different chromosomes.
Validation and Implication of Findings
- They identified and analyzed a total of 229 genes overlapping with CNVRs in the Jinjiang horse breed.
- These genes showed a significant correlation with cellular heat acclimation and immunity, which reinforce the breed’s adaptability to high temperature and humidity.
- The expression levels of these candidate genes were validated by heat shock treatment of various durations on horse fibroblasts (a type of cell).
- The results indicated fluctuating expression levels of certain genes during different durations of the heat shock treatment, providing insights into cellular response to heat stress.
Conclusion
- This study unveils the breed-specific CNVRs of Chinese indigenous horse breeds.
- The research not only provides a comprehensive genome map for these breeds but also sheds light on the molecular mechanisms related to adaptation to high temperature and humidity in the Jinjiang horse.
Cite This Article
APA
Wang M, Liu Y, Bi X, Ma H, Zeng G, Guo J, Guo M, Ling Y, Zhao C.
(2022).
Genome-Wide Detection of Copy Number Variants in Chinese Indigenous Horse Breeds and Verification of CNV-Overlapped Genes Related to Heat Adaptation of the Jinjiang Horse.
Genes (Basel), 13(4), 603.
https://doi.org/10.3390/genes13040603 Publication
Researcher Affiliations
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
- Equine Center, China Agricultural University, Beijing 100193, China.
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, Beijing 100193, China.
- National Engineering Laboratory for Animal Breeding, Beijing 100193, China.
- Beijing Key Laboratory for Genetic Improvement of Livestock and Poultry, Beijing 100193, China.
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
- Equine Center, China Agricultural University, Beijing 100193, China.
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, Beijing 100193, China.
- National Engineering Laboratory for Animal Breeding, Beijing 100193, China.
- Beijing Key Laboratory for Genetic Improvement of Livestock and Poultry, Beijing 100193, China.
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
- Equine Center, China Agricultural University, Beijing 100193, China.
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, Beijing 100193, China.
- National Engineering Laboratory for Animal Breeding, Beijing 100193, China.
- Beijing Key Laboratory for Genetic Improvement of Livestock and Poultry, Beijing 100193, China.
- Shaanxi Key Laboratory for Animal Conservation, Shaanxi Institute of Zoology, Xi'an 710032, China.
- Jinjiang Animal Husbandry and Veterinary Station, Quanzhou 362200, China.
- Jinjiang Animal Husbandry and Veterinary Station, Quanzhou 362200, China.
- Jinjiang Animal Husbandry and Veterinary Station, Quanzhou 362200, China.
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
- College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
- Equine Center, China Agricultural University, Beijing 100193, China.
- Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, Beijing 100193, China.
- National Engineering Laboratory for Animal Breeding, Beijing 100193, China.
- Beijing Key Laboratory for Genetic Improvement of Livestock and Poultry, Beijing 100193, China.
MeSH Terms
- Adaptation, Physiological / genetics
- Animals
- China
- DNA Copy Number Variations / genetics
- Genome
- Horses / genetics
- Thermotolerance / genetics
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 51 references
- Feuk L, Carson AR, Scherer SW. Structural variation in the human genome.. Nat Rev Genet 2006 Feb;7(2):85-97.
- Clop A, Vidal O, Amills M. Copy number variation in the genomes of domestic animals.. Anim Genet 2012 Oct;43(5):503-17.
- Xu L, Hou Y, Bickhart DM, Zhou Y, Hay el HA, Song J, Sonstegard TS, Van Tassell CP, Liu GE. Population-genetic properties of differentiated copy number variations in cattle.. Sci Rep 2016 Mar 23;6:23161.
- Paudel Y, Madsen O, Megens HJ, Frantz LA, Bosse M, Crooijmans RP, Groenen MA. Copy number variation in the speciation of pigs: a possible prominent role for olfactory receptors.. BMC Genomics 2015 Apr 22;16(1):330.
- Upadhyay M, da Silva VH, Megens HJ, Visker MHPW, Ajmone-Marsan P, Bâlteanu VA, Dunner S, Garcia JF, Ginja C, Kantanen J, Groenen MAM, Crooijmans RPMA. Distribution and Functionality of Copy Number Variation across European Cattle Populations.. Front Genet 2017;8:108.
- Dupuis MC, Zhang Z, Durkin K, Charlier C, Lekeux P, Georges M. Detection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy.. Anim Genet 2013 Apr;44(2):206-8.
- Wang W, Wang S, Hou C, Xing Y, Cao J, Wu K, Liu C, Zhang D, Zhang L, Zhang Y, Zhou H. Genome-wide detection of copy number variations among diverse horse breeds by array CGH.. PLoS One 2014;9(1):e86860.
- Metzger J, Philipp U, Lopes MS, da Camara Machado A, Felicetti M, Silvestrelli M, Distl O. Analysis of copy number variants by three detection algorithms and their association with body size in horses.. BMC Genomics 2013 Jul 18;14:487.
- Rosengren Pielberg G, Golovko A, Sundström E, Curik I, Lennartsson J, Seltenhammer MH, Druml T, Binns M, Fitzsimmons C, Lindgren G, Sandberg K, Baumung R, Vetterlein M, Strömberg S, Grabherr M, Wade C, Lindblad-Toh K, Pontén F, Heldin CH, Sölkner J, Andersson L. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.. Nat Genet 2008 Aug;40(8):1004-9.
- Lucke JN, Hall GN. Further studies on the metabolic effects of long distance riding: Golden Horseshoe Ride 1979.. Equine Vet J 1980 Oct;12(4):189-92.
- Fielding CL, Magdesian KG, Rhodes DM, Meier CA, Higgins JC. Clinical and biochemical abnormalities in endurance horses eliminated from competition for medical complications and requiring emergency medical treatment: 30 cases (2005-2006).. J Vet Emerg Crit Care (San Antonio) 2009 Oct;19(5):473-8.
- Brownlow MA, Dart AJ, Jeffcott LB. Exertional heat illness: a review of the syndrome affecting racing Thoroughbreds in hot and humid climates.. Aust Vet J 2016 Jul;94(7):240-7.
- Takahashi Y, Takahashi T. Risk factors for exertional heat illness in Thoroughbred racehorses in flat races in Japan (2005-2016).. Equine Vet J 2020 May;52(3):364-368.
- Raymond C, Matthews T, Horton RM. The emergence of heat and humidity too severe for human tolerance.. Sci Adv 2020 May;6(19):eaaw1838.
- Verdegaal EJMM, Howarth GS, McWhorter TJ, Boshuizen B, Franklin SH, Vidal Moreno de Vega C, Jonas SE, Folwell LE, Delesalle CJG. Continuous Monitoring of the Thermoregulatory Response in Endurance Horses and Trotter Horses During Field Exercise: Baselining for Future Hot Weather Studies.. Front Physiol 2021;12:708737.
- Ma H, Wang S, Zeng G, Guo J, Guo M, Dong X, Hua G, Liu Y, Wang M, Ling Y, Ding X, Zhao C, Wu C. The Origin of a Coastal Indigenous Horse Breed in China Revealed by Genome-Wide SNP Data.. Genes (Basel) 2019 Mar 21;10(3).
- Wang K, Li M, Hadley D, Liu R, Glessner J, Grant SF, Hakonarson H, Bucan M. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data.. Genome Res 2007 Nov;17(11):1665-74.
- Solé M, Ablondi M, Binzer-Panchal A, Velie BD, Hollfelder N, Buys N, Ducro BJ, François L, Janssens S, Schurink A, Viklund Å, Eriksson S, Isaksson A, Kultima H, Mikko S, Lindgren G. Inter- and intra-breed genome-wide copy number diversity in a large cohort of European equine breeds.. BMC Genomics 2019 Oct 22;20(1):759.
- Corbi-Botto CM, Morales-Durand H, Zappa ME, Sadaba SA, Peral-García P, Giovambattista G, Díaz S. Genomic structural diversity in Criollo Argentino horses: Analysis of copy number variations.. Gene 2019 May 5;695:26-31.
- Schurink A, da Silva VH, Velie BD, Dibbits BW, Crooijmans RPMA, Franҫois L, Janssens S, Stinckens A, Blott S, Buys N, Lindgren G, Ducro BJ. Copy number variations in Friesian horses and genetic risk factors for insect bite hypersensitivity.. BMC Genet 2018 Jul 30;19(1):49.
- Kader A, Liu X, Dong K, Song S, Pan J, Yang M, Chen X, He X, Jiang L, Ma Y. Identification of copy number variations in three Chinese horse breeds using 70K single nucleotide polymorphism BeadChip array.. Anim Genet 2016 Oct;47(5):560-9.
- Ghosh S, Das PJ, McQueen CM, Gerber V, Swiderski CE, Lavoie JP, Chowdhary BP, Raudsepp T. Analysis of genomic copy number variation in equine recurrent airway obstruction (heaves).. Anim Genet 2016 Jun;47(3):334-44.
- Ghosh S, Qu Z, Das PJ, Fang E, Juras R, Cothran EG, McDonell S, Kenney DG, Lear TL, Adelson DL, Chowdhary BP, Raudsepp T. Copy number variation in the horse genome.. PLoS Genet 2014 Oct;10(10):e1004712.
- Doan R, Cohen N, Harrington J, Veazey K, Juras R, Cothran G, McCue ME, Skow L, Dindot SV. Identification of copy number variants in horses.. Genome Res 2012 May;22(5):899-907.
- Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features.. Bioinformatics 2010 Mar 15;26(6):841-2.
- Howe KL, Achuthan P, Allen J, Allen J, Alvarez-Jarreta J, Amode MR, Armean IM, Azov AG, Bennett R, Bhai J, Billis K, Boddu S, Charkhchi M, Cummins C, Da Rin Fioretto L, Davidson C, Dodiya K, El Houdaigui B, Fatima R, Gall A, Garcia Giron C, Grego T, Guijarro-Clarke C, Haggerty L, Hemrom A, Hourlier T, Izuogu OG, Juettemann T, Kaikala V, Kay M, Lavidas I, Le T, Lemos D, Gonzalez Martinez J, Marugán JC, Maurel T, McMahon AC, Mohanan S, Moore B, Muffato M, Oheh DN, Paraschas D, Parker A, Parton A, Prosovetskaia I, Sakthivel MP, Salam AIA, Schmitt BM, Schuilenburg H, Sheppard D, Steed E, Szpak M, Szuba M, Taylor K, Thormann A, Threadgold G, Walts B, Winterbottom A, Chakiachvili M, Chaubal A, De Silva N, Flint B, Frankish A, Hunt SE, IIsley GR, Langridge N, Loveland JE, Martin FJ, Mudge JM, Morales J, Perry E, Ruffier M, Tate J, Thybert D, Trevanion SJ, Cunningham F, Yates AD, Zerbino DR, Flicek P. Ensembl 2021.. Nucleic Acids Res 2021 Jan 8;49(D1):D884-D891.
- Xie C, Mao X, Huang J, Ding Y, Wu J, Dong S, Kong L, Gao G, Li CY, Wei L. KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases.. Nucleic Acids Res 2011 Jul;39(Web Server issue):W316-22.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
- Yong YH, Wang P, Jia RM, Gooneratne R, Robert Wang HC, Liao M, Ju XH. SOCS3 control the activity of NF-κB induced by HSP70 via degradation of MyD88-adapter-like protein (Mal) in IPEC-J2 cells.. Int J Hyperthermia 2019;36(1):151-159.
- Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) Immunotherapy.. Cold Spring Harb Perspect Biol 2018 Aug 1;10(8).
- Fontanesi L, Martelli PL, Beretti F, Riggio V, Dall'Olio S, Colombo M, Casadio R, Russo V, Portolano B. An initial comparative map of copy number variations in the goat (Capra hircus) genome.. BMC Genomics 2010 Nov 17;11:639.
- Cicconardi F, Chillemi G, Tramontano A, Marchitelli C, Valentini A, Ajmone-Marsan P, Nardone A. Massive screening of copy number population-scale variation in Bos taurus genome.. BMC Genomics 2013 Feb 26;14:124.
- Lupski JR, Stankiewicz P. Genomic disorders: molecular mechanisms for rearrangements and conveyed phenotypes.. PLoS Genet 2005 Dec;1(6):e49.
- Giuffra E, Törnsten A, Marklund S, Bongcam-Rudloff E, Chardon P, Kijas JM, Anderson SI, Archibald AL, Andersson L. A large duplication associated with dominant white color in pigs originated by homologous recombination between LINE elements flanking KIT.. Mamm Genome 2002 Oct;13(10):569-77.
- Norris BJ, Whan VA. A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep.. Genome Res 2008 Aug;18(8):1282-93.
- Tang J, Shen X, Yang Y, Yang H, Qi A, Yang S, Qu K, Lan X, Huang B, Chen H. Two Different Copy Number Variations of the CLCN2 Gene in Chinese Cattle and Their Association with Growth Traits.. Animals (Basel) 2021 Dec 26;12(1).
- Bovo S, Ribani A, Muñoz M, Alves E, Araujo JP, Bozzi R, Charneca R, Di Palma F, Etherington G, Fernandez AI, García F, García-Casco J, Karolyi D, Gallo M, Gvozdanović K, Martins JM, Mercat MJ, Núñez Y, Quintanilla R, Radović Č, Razmaite V, Riquet J, Savić R, Schiavo G, Škrlep M, Usai G, Utzeri VJ, Zimmer C, Ovilo C, Fontanesi L. Genome-wide detection of copy number variants in European autochthonous and commercial pig breeds by whole-genome sequencing of DNA pools identified breed-characterising copy number states.. Anim Genet 2020 Aug;51(4):541-556.
- Brocchieri L, Conway de Macario E, Macario AJ. hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions.. BMC Evol Biol 2008 Jan 23;8:19.
- Baldwin AS Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights.. Annu Rev Immunol 1996;14:649-83.
- Barnes PJ, Karin M. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.. N Engl J Med 1997 Apr 10;336(15):1066-71.
- Ghosh S, May MJ, Kopp EB. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.. Annu Rev Immunol 1998;16:225-60.
- Paszek A, Kardyńska M, Bagnall J, Śmieja J, Spiller DG, Widłak P, Kimmel M, Widlak W, Paszek P. Heat shock response regulates stimulus-specificity and sensitivity of the pro-inflammatory NF-κB signalling.. Cell Commun Signal 2020 May 24;18(1):77.
- Schell MT, Spitzer AL, Johnson JA, Lee D, Harris HW. Heat shock inhibits NF-kB activation in a dose- and time-dependent manner.. J Surg Res 2005 Nov;129(1):90-3.
- Liu Y, Yu W. Heat shock-mediated regulation of IκB-α at the post-transcriptional level by HuR.. Mol Med Rep 2014 Feb;9(2):553-9.
- Li J, Liu Y, Duan P, Yu R, Gu Z, Li L, Liu Z, Su L. NF‑κB regulates HSF1 and c‑Jun activation in heat stress‑induced intestinal epithelial cell apoptosis.. Mol Med Rep 2018 Feb;17(2):3388-3396.
- Zininga T, Ramatsui L, Shonhai A. Heat Shock Proteins as Immunomodulants.. Molecules 2018 Nov 1;23(11).
- Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, Yao Y. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers.. Pharmacol Ther 2014 Feb;141(2):125-39.
- Crépieux P, Kwon H, Leclerc N, Spencer W, Richard S, Lin R, Hiscott J. I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain.. Mol Cell Biol 1997 Dec;17(12):7375-85.
- Krebs DL, Hilton DJ. SOCS proteins: negative regulators of cytokine signaling.. Stem Cells 2001;19(5):378-87.
- Sun D, Chen D, Du B, Pan J. Heat shock response inhibits NF-kappaB activation and cytokine production in murine Kupffer cells.. J Surg Res 2005 Nov;129(1):114-21.
- Wong HR, Ryan M, Wispé JR. Stress response decreases NF-kappaB nuclear translocation and increases I-kappaBalpha expression in A549 cells.. J Clin Invest 1997 May 15;99(10):2423-8.
Citations
This article has been cited 2 times.- Kim YM, Ha SJ, Seong HS, Choi JY, Baek HJ, Yang BC, Choi JW, Kim NY. Identification of Copy Number Variations in Four Horse Breed Populations in South Korea.. Animals (Basel) 2022 Dec 12;12(24).
- Laseca N, Molina A, Valera M, Antonini A, Demyda-Peyrás S. Copy Number Variation (CNV): A New Genomic Insight in Horses.. Animals (Basel) 2022 Jun 2;12(11).
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