RESUMO
Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait.
Assuntos
Proteína Morfogenética Óssea 3/genética , Craniossinostoses/genética , Cães/genética , Variação Genética , Locos de Características Quantitativas , Crânio/metabolismo , Animais , Evolução Biológica , Cruzamento , Mapeamento Cromossômico , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Mutação de Sentido Incorreto , Animais de Estimação , Fenótipo , Crânio/anatomia & histologia , Peixe-Zebra/genéticaRESUMO
Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.
Assuntos
Regulação da Temperatura Corporal , Cães/genética , Cães/fisiologia , Temperatura Alta , Cadeias Pesadas de Miosina/genética , Resistência Física/genética , Alaska , Animais , Cruzamento , Mapeamento Cromossômico , Genoma , Estudo de Associação Genômica Ampla , Genótipo , Desequilíbrio de Ligação , Proteínas do Tecido Nervoso/genética , Condicionamento Físico Animal , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Regiões Promotoras Genéticas , Seleção GenéticaRESUMO
The Alaskan sled dog offers a unique mechanism for studying the genetics of elite athletic performance. They are a group of mixed breed dogs, comprised of multiple common breeds, and a unique breed entity seen only as a part of the sled dog mix. Alaskan sled dogs are divided into 2 primary groups as determined by their racing skills. Distance dogs are capable of running over 1000 miles in 10 days, whereas sprint dogs run much shorter distances, approximately 30 miles, but in faster times, that is, 18-25 mph. Finding the genes that distinguish these 2 types of performers is likely to illuminate genetic contributors to human athletic performance. In this study, we tested for association between polymorphisms in 2 candidate genes; angiotensin-converting enzyme (ACE) and myostatin (MSTN) and enhanced speed and endurance performance in 174 Alaskan sled dogs. We observed 81 novel genetic variants within the ACE gene and 4 within the MSTN gene, including a polymorphism within the ACE gene that significantly (P value 2.38 × 10(-5)) distinguished the sprint versus distance populations.
Assuntos
Cães/genética , Peptidil Dipeptidase A/genética , Resistência Física/genética , Polimorfismo de Nucleotídeo Único/genética , Corrida/fisiologia , Alaska , Animais , Sequência de Bases , Desequilíbrio de Ligação , Dados de Sequência Molecular , Miostatina/genética , Resistência Física/fisiologia , Análise de Sequência de DNARESUMO
Coat color and type are essential characteristics of domestic dog breeds. Although the genetic basis of coat color has been well characterized, relatively little is known about the genes influencing coat growth pattern, length, and curl. We performed genome-wide association studies of more than 1000 dogs from 80 domestic breeds to identify genes associated with canine fur phenotypes. Taking advantage of both inter- and intrabreed variability, we identified distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R-spondin-2, fibroblast growth factor-5, and keratin-71, respectively), that together account for most coat phenotypes in purebred dogs in the United States. Thus, an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes.