PERSPECTIVAS DO USO DE MARCADORES MOLECULARES NO MELHORAMENTO GENÉTICO DE EQUINOS DE CORRIDA DA RAÇA QUARTO DE MILHA
Palavras-chave:
cavalos, desempenho, gene candidato, QTL, SNPsResumo
A utilização de marcadores moleculares trouxe grande progresso ao melhoramento genético de espécies comerciais destinados a produção, como bovinos, suínos e aves, principalmente com o aumento da acurácia de predição de valores genéticos e precocidade na seleção de animais superiores. Isto ocorreu por meio do uso de alguns poucos marcadores ligados a Locos de Características Quantitativas – QTL (Seleção Assistida por Marcadores) ou pela estimação de efeitos de milhares deles simultaneamente (Estudos de Ampla Associação do Genoma – GWAS ou Seleção Genômica – GS). Por outro lado, em outras espécies domésticas, incluindo os equinos, o emprego desta biotecnologia ainda é pouco explorado. Os primeiros estudos a identificar variantes genéticas ligadas a melhores desempenhos em corridas foram realizados recentemente na raça Puro-Sangue Inglês (PSI), resultando na implantação de testes genéticos que auxiliam criadores na seleção de animais com maior potencial genético. Esta revisão tem por objetivo descrever a atual situação dos marcadores moleculares aplicados à cavalos de corrida e as perspectivas do seu uso no melhoramento genético de equinos de corrida Quarto de Milha, raça de grande importância no mundo e também no Brasil.
Referências
Bowling AT, Ruvinsky A. Genetics of Horse. Oxon, UK: CAB International; 2000.
Food and Agriculture Organization. The Global Livestock Production and Health Atlas
(GLiPHA) [Internet]. Rome: FAO; 2011 [cited 2011 Nov 20]. Available from:
Lima RAS, Shirota R, Barros GSC. Estudo do Complexo do Agronegócio Cavalo no
Brasil. Piracicaba: CEPEA - Centro de Estudos Avançados em Economia Aplicada -
ESALQ/USP; 2006.
Food and Agriculture Organization. The horse, the wheel and language [Internet]. Rome:
FAO; 2006 [cited 2008 Oct 4]. Available from: http://www.fao.org/.
Anthony DW. The horse, the wheel and language. Princeton: Princeton University Press;
p.199-220.
Arnason T. Bright future for research in horse breeding! J Anim Breed Genet.
;130:167-9.
Almeida FQ, Silva VP. Progresso científico em equideocultura na 1ª década do século
XXI. Rev Bras Zootec. 2010;39:119-29.
Koenen EPC, Van Veldhuizen AE, Brascampa EW. Genetic parameters of linear scored
conformation traits and their relation to dressage and show-jumping performance in the
Dutch Warmblood Riding Horse population. Liv Prod Sci. 1995;43:85-94.
Wallin L, Strandberg E, Philipsson J. Genetic correlations between field test results of
Swedish Warmblood Riding Horses as 4-year-olds and life time performance results in
dressage and show jumping. Liv Prod Sci. 2003;82:61-71.
Bokor A, Blouin C, Langlois B, Stefler J. Genetic parameters of racing merit of
Thoroughbred horses in steeplechase races. Ital J Anim Sci. 2005;4:43-5.
Dias RG, Pereira AC, Negrão CE, Krieger JE. Polimorfismos genéticos determinantes da
performance física em atletas de elite. Rev Bras Med Esp. 2007;13:211-6.
Schröder W, Klostermann A, Stock KF, Distl O. A genome-wide association study for
quantitative trait loci of show-jumping in Hanoverian Warmblood horses. Anim Genet.
;43:392-400.
Freeman DW. Physical conditioning of horses. Stillwater, Okla: Oklahoma State
University, Division of Agricultural Sciences and Natural Resources; 2013. 14. Hill EM, Gu J, Eivers SS, Fonseca RG, McGiveny BA, Govindarajan P, et al. A sequence
polymorphism in MSTN predicts sprinting ability and racing stamina in Thoroughbred
Horses. PLoS One. 2010;5:1-6.
Breazile JE. Fisiologia do Músculo Esquelético. In: Swenson MJ, Reece WO. Fisiologia
dos animais domésticos. 11a ed. Rio de Janeiro: Guanabara; 1996. p.777-93.
Hoppeler H, Howald H, Conley K, Lindstedt SL, Claassen H, Vock P, et al. Endurance
training in humans: aerobic capacity and structure of skeletal muscle. J Appl Physiol.
;59:320-7.
Ferraz GC, Teixeira Neto AR, Lacerda Neto JC, Pereira MC, Queiroz Neto A. Respostas
ao exercício de intensidade crescente em equinos: alterações na glicose, insulina e lactato.
Cienc Anim Bras. 2009;10:1334-40.
Nelson DL, COX MM. Lehninger Principles of Biochemistry. New York, NY: WH
Freeman and Company; 2005.
Fitts RH. Cellular mechanisms of muscle fatigue. Physiol Rev. 1994;74:49-94.
Hogan MC, Gladden LB, Kurdak SS, Poole DC. Increased [lactate] in working dog
muscle reduces tension development independent of pH. Med Sci Sports Exerc.
;27:371-7.
Ferreira ME, Grattapalia D. Introdução ao uso de marcadores moleculares em análise
genética. Brasília: Embrapa-Cenargen; 1998.
O'Brien SJ, Graves JA. Report of the committee on comparative gene mapping.
Cytogenet Cell Genet. 1990;55:406-33.
Moody DE, Pomp D, Newman S, MacNeil MD. Characterization of DNA
polymorphisms in three populations of Hereford cattle and their associations with growth
and maternal EPD in line 1 Herefords. J Anim Sci. 1996;74:1784-93.
Haley CS. Livestock QTLs - bringing home the bacon? Trends Genet. 1995;11:488-92.
Womack JE. The goals and status of the bovine gene map. J Dairy Sci. 1993;76:1199-
Regitano LCA. Importância da genética molecular para o melhoramento de ruminantes.
In: Anais do V Simpósio da Sociedade Brasileira de Melhoramento Animal; 2004;
Pirassununga/SP. Pirassununga/SP; 2004.
Kwok PY, Gu Z. Single nucleotide polymorphism libraries: why and how are we
building them? Mol Med Today. 1999;5:538-43.
Guimarães PEM, Costa MCR. SNPs: Sutis diferenças de um código. Biotecnologia Cienc
Desenvolvimento. 2002;26:24-7.
Nakaya HI, Amaral PP, Louro R, Lopes A, Fachel AA, Moreira YB, et al. Genome
mapping and expression analyses of human intronic noncoding RNAs reveal tissuespecific patterns and enrichment in genes related to regulation of transcription. Genome
Biol. 2007;8:R43.
Caetano AR. Marcadores SNP: conceitos básicos, aplicações no manejo e no
melhoramento animal e perspectivas para o futuro. Rev Bras Zootec. 2009;38:64-71.
Chowdhary BP. Equine genomics. Iowa, EUA: John Wiley & Sons, Inc; 2013.
Doan R, Cohen ND, Sawyer J, Ghaffari N, Johnson CD, Dindot SV. Whole-genome
sequencing and genetic variant analysis of a Quarter Horse mare. BMC Genomics.
;13:78.
Brunberg E, Andersson L, Cothran G, Sandberg K, Mikko S, Lindgren G. A missense
mutation in PMEL17 is associated with the Silver coat color in the horse. BMC Genet.
;7:46.
Rosengren PG, Golovko A, Sundstrom E. Positional identification of the grey coat color
mutation in horse. In: 7th Dorothy Russell Havemeyer International Equine Genome
Mapping Workshop; 2007; Tahoe City, CA, EUA. Tahoe City, CA, EUA; 2007.
Reissmann M, Bierwolf J, Brockmann GA. Two SNPs in the SILV gene are associated
with silver coat colour in ponies. Anim Genet. 2007;38:1-6.
Hansen M1, Knorr C, Hall AJ, Broad TE, Brenig B. Sequence analysis of the equine
SLC26A2 gene locus on chromosome 14q15-q21. Cytogenet Genome Res. 2007;118:55-
Tryon RC, White SD, Bannasch DL. Homozygosity mapping approach identifies a
missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the
American Quarter Horse. Genomics. 2007;90:93-102.
Young AE, Bower LP, Affolter VK, De Cock HE, Ferraro GL, Bannasch DL. Evaluation
of FOXC2 as a candidate gene for chronic progressive lymphedema in draft horses. Vet J.
;174:397-9.
Solberg OD, Jackson KA, Millon LV, Stott JL, Vandenplas ML, Moore JN, et al.
Genomic characterization of equine interleukin-4 receptor alpha-chain (IL4R). Vet
Immunol Immunopathol. 2004;97:187-94.
Brown JJ, Ollier WE, Thomson W, Matthews JB, Carter SD, Binns M, et al. TNF-alpha
SNP haplotype frequencies in equidae. Tissue Antigens. 2006;67:377-82.
Rios JJ, Perelygin AA, Long MT, Lear TL, Zharkikh AA, Brinton MA, et al.
Characterization of the equine 2-5 oligoadenylate synthetase 1 (OAS1) and ribonuclease
L (RNASEL) innate immunity genes. BMC Genomics. 2007;8:313.
Hamann H, Jude R, Sieme H, Mertens U, Töpfer-Petersen E, Distl O, et al. A
polymorphism within the equine CRISP3 gene is associated with stallion fertility in
Hanoverian warmblood horses. Anim Genet. 2007;38:259-64.
Giesecke K, Hamann H, Stock KF, Woehlke A, Sieme H, Distl O. Evaluation of
SPATA1-associated markers for stallion fertility. Anim Genet. 2009;40:359-65.
Momozawa Y, Takeuchi Y, Tozaki T, Kikusui T, Hasegawa T, Raudsepp T, et al.
Sequence, detection of polymorphisms and radiation hybrid mapping of the equine
catechol-O-methyltransferase gene. Anim Genet. 2005;36:190.
Momozawa Y, Takeuchi Y, Tozaki T, Kikusui T, Hasegawa T, Raudsepp T, et al.
Polymorphism identification, RH mapping, and association analysis with the anxiety trait
of the equine serotonin transporter (SLC6A4) gene. J Vet Med Sci. 2006;68:619-21.
Hanzawa K, Lear TL, Piumi F, Bailey E. Mapping of equine potassium chloride cotransporter (SLC12A4) and amino acid transporter (SLC7A10) and preliminary studies
on associations between SNPs from SLC12A4, SLC7A10 and SLC7A9 and osmotic
fragility of erythrocytes. Anim Genet. 2002;33:455-9.
Reeben M, Koho NM, Raekallio M, Hyyppä S, Pösö AR. MCT1 and CD147 gene
polymorphisms in standardbred horses. Equine Vet J Suppl. 2006;36:322-5.
McGivney BA, McGettigan PA, Browne JA, Evans AC, Fonseca RG, Loftus BJ, et al.
Characterization of the equine skeletal muscle transcriptome identifies novel functional
responses to exercise training. BMC Genomics. 2010;11:398.
Hill EW, Gu J, McGivney BA, MacHugh DE. Targets of selection in the Thoroughbred
genome contain exercise-relevant gene SNPs associated with elite racecourse
performance. Anim Genet. 2010;41 Suppl 2:56-63.
Gu J, Machugh DE, McGiveny BA, Park SDE, Katz LM, Hill EM. Association of
sequence variants in CKM (creatine kinase, muscle) and COX4I2 (cytochrome c oxidase,
subunit 4, isoform 2) genes with racing performance in Thoroughbred horses. Equine Vet
J. 2010;42:569-75.
Cook D, Gallagher P, Bailey E. Illumina Equine SNP50 Bead Chip Investigation of
Adolescent idiopathic lordosis among American Saddlebred Horses. J Equine Vet Sci.
;29:315-6.
Cook D, Gallagher P, Bailey E. Genetics of swayback in American Saddlebred horses.
Anim Genet. 2010;41:64-71.
Lykkjen S, Dolvik NI, McCue ME, Rendahl AK, Mickelson JR, Roed KH. Genomewide
association analysis of osteochondrosis of the tibiotarsal joint in Norwegian Standardbred
trotters. Anim Genet. 2010;41:111-20.
Teyssèdre S, Dupuis MC, Guérin G, Schibler L, Denoix JM, Elsen JM, et al. Genomewide association studies for osteochondrosis in French Trotters. J Anim Sci. 2012;90:45-53.
Dupuis MC, Zhang Z, Druet T, Denoix JM, Charlier C, Lekeux P, et al. Results of a
haplotype-based GWAS for recurrent laryngeal neuropathy in the horse. Mamm Genome.
;22:613-20.
Eberth J, Swerczak T, Bailey E. Investigation of Dwarfism Among Miniature Horses
using the Illumina Horse SNP50 Bead Chip. J Equine Vet Sci. 2009;29:315.
Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, Streeter C. Whole-genome SNP
association in the horse: Identification of a deletion in Myosin a responsible for Lavender
Foal Syndrome. PLoS Genet. 2010;6:e1000909.
Hill EW, McGivney BA, Gu J, Whiston R, Machugh DEA. Genome-wide SNPassociation study confirms a sequence variant (g66493737C>T) in the equine myostatin
(MSTN) gene as the most powerful predictor of optimum racing distance for
Thoroughbred racehorses. BMC Genomics. 2010;11:1-10.
Binns MM, Boehler DA, Lambert DH. Identification of the myostatin locus (MSTN) as
having a major effect on optimum racing distance in the Thoroughbred horse in the USA.
Anim Genet. 2010;41:154-8.
Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS, Axelsson J, et al.
Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse
Breeds. PLoS Genet. 2013;9:1-17.
Associação Brasileira dos criadores de cavalos Quarto de Milha. Quarto de milha: origem
[Internet]. São Paulo; 2015 [cited 2015 Jan 15]. Available from:
http://www.abqm.com.br/a-raca/origem-qm.
Ellersieck MR, Lock WE, Vogt DW, Aipperspach R. Genetic evaluation of cutting scores
in horses. J Equine Vet Sci. 1985;5:287-9.
Hintz RL. Genetics performance in the horse. J Equine Vet Sci. 1980;51:582-94.
Wagoner DM. Equine genetics and selection procedures. Dallas: Equine Research
Publications; 1978.
America’s Horse Daily. All About the Racing American Quarter Horse [Internet].
Amarillo, TX: American Quarter Horse Association; 2013 [cited 2013 Nov 12].
Available from: http://americashorsedailycom/all-about-the-racing-american-quarterhorse/.
Villela LCV, Mota MDS, Oliveira HN. Genetic parameters of racing performance traits
of Quarter horses in Brazil. J Anim Breed Genet. 2002;4:229-34.
Mota MDS, Abrahão AR. Environmental factors affecting time in Quarter Horse races.
Arch Zootec. 2004;53:95-8.
Corrêa MJM, Mota MDS. Genetic evaluation of performance traits in Brazilian Quarter
Horse. J Appl Genet. 2007;48:145-51.
Evans JW. Horses: a guide to selection, care and enjoyment Freeman and Company. 2a
ed. New York: WH Freeman; 1989.
Bray MS, Hagberg JM, Perusse L, Rankinen T, Roth SM, Wolfarth B, et al. The human
gene map for performance and health-related fitness phenotypes: The 2006-2007 update.
Med Sci Sports Exerc. 2009;41:35-73.
Tozaki T, Miyake T, Kakoi H, Gawahara H, Sugita S, Hasegawa T, et al. A genome-wide
association study for racing performances in Thoroughbreds clarifies a candidate region
near the MSTN gene. Anim Genet. 2010;41:28-35.
Gu J, Orr N, Park SD, Katz LM, Sulimova G, Machugh DE, et al. A genome scan for
positive selection in Thoroughbred horses. PLoS One. 2009;4:1-17.
Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, et al.
Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice.
Nature. 2012;488:642-6.
Gallagher SM, Castorino JJ, Wang D, Philp NJ. Monocarboxylate transporter 4 regulates
maturation and trafficking of CD147 to the plasma membrane in the metastatic breast
cancer cell line MDA-MB-231. Cancer Res. 2007;67:4182-9.
Grobet L, Martin LJR, Poncelet D, Pirottin D, Brouwers B, Riquet J, et al. A deletion in
the myostatin gene causes double-muscling in cattle. Nat Genet. 1997;17:71-4.
Kambadur R, Sharma M, Smith TPL, Bass JJ. Mutations in myostatin (GDF-8) in double
muscled Belgian Blue and Piedmontese cattle. Genome Res. 1997;7:910-6.
Clop A, Marcq F, Takeda H, Pirottin D, Tordoir X, Bibé B, et al. A mutation creating a
potential illegitimate microRNA target site in the myostatin gene affects muscularity in
sheep. Nat Genet. 2006;38:813-8.
Nishi M, Yasue A, Nishimatu S, Nohno T, Yamaoka T, Itakura M, et al. A missense
mutant myostatin causes hyperplasia without hypertrophy in the mouse muscle. Biochem
Biophys Res Commun. 2002;293:247-51.
Schuelke M, Wagner KR, Stolz LE, Hübner C, Riebel T, Kömen W, et al. Myostatin
mutation associated with gross muscle hypertrophy in a child. N Engl J Med.
;350:2682-8.
Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, et al. A
mutation in the myostatin gene increases muscle mass and enhances racing performance
in heterozygote dogs. PLoS Genet. 2007;3:e79.
Petersen JL, Valberg SJ, Mickelson JR, McCue ME. Haplotype diversity in the equine
myostatin gene with focus on variants associated with race distance propensity and
muscle fiber type proportions. Anim Genet. 2014;45:827-35.
Hong CS, Park BY, Saint-Jeannet JP. The function of Dmrt genes in vertebrate
development: It is not just about sex. Dev Biol. 2007;310:1-9. 83. Promerova M, Andersson LS, Juras R, Penedo MCT, Reissmann M, Tozaki T, et al.
Worldwide frequency distribution of the ‘Gait keeper’ mutation in the DMRT3 gene.
Anim Genet. 2014;45:274-82.
Van Deursen J, Heerschap A, Oerlemans F, Ruitenbeek W, Jap P, Laak H, et al. Skeletal
muscles of mice deficient in muscle creatine kinase lack burst activity. Cell.
;74:621-31.
Echegaray M, Rivera MA. Role of creatine kinase isoenzymes on muscular and
cardiorespiratory endurance: genetic and molecular evidence. Sports Med. 2001;31:919-
Welle S, Bhatt K, Thornton CA. Inventory of high-abundance mRNAs in skeletal muscle
of normal men. Genome Res. 1999;9:p506-13.
Eivers SS, Mcgivney BA, Fonseca RG, Machugh DE, Menson K, Park SD, et al.
Alterations in oxidative gene expression in equine skeletal muscle following exercise and
training. Physiol Genomics. 2010;40:83-93.
Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA. Analysis of global mRNA
expression in human skeletal muscle during recovery from endurance exercise. FASEB J.
;19:1498-500.
Wende AR, Huss JM, Schaeffer PJ, Giguere V, Kelly DP. PGC-1alpha coactivates PDK4
gene expression via the orphan nuclear receptor ERR alpha: a mechanism for
transcriptional control of muscle glucose metabolism. Mol Cell Biol. 2005;25:684-94.
Arany Z. PGC-1 coactivators and skeletal muscle adaptations in health and disease. Curr
Opin Genet Dev. 2008;5:426-34.
Chinsomboon J, Ruas J, Gupta RK, Thom R, Shoag J, Rowe GC, et al. The
transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal
muscle. Proc Natl Acad Sci USA. 2009;106:21401-6.
Scarpulla RC. Nuclear control of respiratory chain expression by nuclear respiratory
factors and PGC-1-related coactivator. Ann NY Acad Sci. 2008;1147:321-34.
Pilegaard H, Neufer PD. Transcriptional regulation of pyruvate dehydrogenase kinase 4
in skeletal muscle during and after exercise. Proc Nutr Soc. 2004;63:221-6.
Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL. HIF-1 regulates
cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell.
;129:111-22.
Koho NM, Hyyppä S, Pösö AR. Monocarboxylate transporters (MCT) as lactate carriers
in equine muscle and red blood cells. Equine Vet J Suppl. 2006;36:354-8.
Merezhinskaya N, Fishbein WN. Monocarboxylate transporters: Past, present, and future.
Histol Histopathol. 2009;24:243-64.
Wilson MC, Meredith D, Fox JE, Manoharan C, Davies AJ, Halestrap AP. Basigin
(CD147) is the target for organomercurial inhibition of monocarboxylate transporter
isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70). J
Biol Chem. 2005;280:27213-21.
Mykkänen AK, Koho NM, Reeben M, McGowan CM, Pösö AR. MCT1, MCT4 and
CD147 gene polymorphisms in healthy horses and horses with myopathy. Res Vet Sci.
;913:473-7.
Koho NM, Mykkänen AK, Reeben M, Raekallio MR, Ilves M, Pösö AR. Sequence
variations and two levels of MCT1 and CD147 expression in red blood cells and gluteus
muscle of horses. Gene. 2012;491:65-70.
Pereira GL, Regitano LCA, Meira CT, Matteis R, Nadalini EC, Regatieri IC, et al.
Variants of MSTN and DMRT3 genes in Quarter Horses. In: Anais do 60º Congresso
Brasileiro de Genética; 2014; Guarujá/SP. Guarujá/SP; 2014.
Regatieri IC, Pereira GL, Curi RA, Ferraz GC, Queiroz-Neto A. SNPs of equine genes
encoding MCT1 and CD147 proteins in Arabians and Quarter Horses. In: Anais do 60º
Congresso Brasileiro de Genética; 2014; Guarujá/SP. Guarujá/SP; 2014.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Este obra está licenciado com uma Licença Creative Commons Atribuição-NãoComercial 4.0 Internacional.