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Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

ABSTRACT: The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.

SUBMITTER: Vaysse A

PROVIDER: S-EPMC3192833 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

Vaysse Amaury A Ratnakumar Abhirami A Derrien Thomas T Axelsson Erik E Rosengren Pielberg Gerli G Sigurdsson Snaevar S Fall Tove T Seppälä Eija H EH Hansen Mark S T MS Lawley Cindy T CT Karlsson Elinor K EK Bannasch Danika D Vilà Carles C Lohi Hannes H Galibert Francis F Fredholm Merete M Häggström Jens J Hedhammar Ake A André Catherine C Lindblad-Toh Kerstin K Hitte Christophe C Webster Matthew T MT

PLoS genetics 20111013 10

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genet ...[more]

PMID: 22022279

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Project description:The significant morphological differences and abundant germplasm resources of Chinese indigenous dog breeds can be attributed to the diverse geographical environment, including plateaus, mountains, and a long history of raising dogs. The combination of both natural and artificial selection during the past several thousand years has led to hundreds of dog breeds with distinct morphological traits and environmental adaptations. China is one of the earliest countries to domesticate dogs and there are more than 50 ancient indigenous dog breeds. In this study, the run of homozygosity (ROH) and proportion of the autosomal genome covered by ROHs (FROH) were calculated for 10 dog breeds that are the most representative Chinese indigenous dogs based on 170K SNP microarray. The results of FROH showed that the Chuandong hound dogs (HCSSC) have the highest level of inbreeding among the tested breeds. The inbreeding in HCSSC occurred more recently than the Liangshan dogs (SCLSQ) dogs because of more numbers of long ROHs in HCSSC dogs, and the former also have higher inbreeding degree. In addition, there are significant differences in the inbreeding degree among different subpopulations of the same breed, such as the Thin dogs from Shaanxi and Shandong province. To explore genome-wide selection signatures among different breeds, including coat color, ear shape, and altitude adaptability, we performed genome selection analyses of FST and cross population extended haplotype homozygosity (XP-EHH). For the coat color, the FST analysis between Xiasi dogs (XSGZ) and HCSSC dogs was performed and identified multiple genes involved in coat color, hair follicle, and bone development, including MC1R, KITLG, SOX5, RSPO2, and TBX15. For the plateau adaptability, we performed FST and XP-EHH analyses between dogs from Tibet (Tibetan Mastiffs and Nyingchi dogs) and plain regions (Guangxi Biwei dogs GXBWQ and Guandong Sharpei dogs). The results showed the EPAS1 gene in dogs from Tibet undergo strong selection. Multiple genes identified for selection signals based on different usage of dogs. Furthermore, the results of ear shape analyses showed that MSRB3 was likely to be the main gene causing the drop ear of domestic dogs. Our study provides new insights into further understanding of Chinese indigenous dogs.

Project description:BackgroundA run of homozygosity (ROH) is a consecutive tract of homozygous genotypes in an individual that indicates it has inherited the same ancestral haplotype from both parents. Genomic inbreeding can be quantified based on ROH. Genomic regions enriched with ROH may be indicative of selection sweeps and are known as ROH islands. We carried out ROH analyses in five Chinese indigenous sheep breeds; Altay sheep (n = 50 individuals), Large-tailed Han sheep (n = 50), Hulun Buir sheep (n = 150), Short-tailed grassland sheep (n = 150), and Tibetan sheep (n = 50), using genotypes from an Ovine Infinium HD SNP BeadChip.ResultsA total of 18,288 ROH were identified. The average number of ROH per individual across the five sheep breeds ranged from 39 (Hulun Buir sheep) to 78 (Large-tailed Han sheep) and the average length of ROH ranged from 0.929 Mb (Hulun Buir sheep) to 2.544 Mb (Large-tailed Han sheep). The effective population size (Ne) of Altay sheep, Large-tailed Han sheep, Hulun Buir sheep, Short-tailed grassland sheep and Tibetan sheep were estimated to be 81, 78, 253, 238 and 70 five generations ago. The highest ROH-based inbreeding estimate (FROH) was 0.0808 in Large-tailed Han sheep, whereas the lowest FROH was 0.0148 in Hulun Buir sheep. Furthermore, the highest proportion of long ROH fragments (> 5 Mb) was observed in the Large-tailed Han sheep breed which indicated recent inbreeding. In total, 49 ROH islands (the top 0.1% of the SNPs most commonly observed in ROH) were identified in the five sheep breeds. Three ROH islands were common to all the five sheep breeds, and were located on OAR2: 12.2-12.3 Mb, OAR12: 78.4-79.1 Mb and OAR13: 53.0-53.6 Mb. Three breed-specific ROH islands were observed in Altay sheep (OAR15: 3.4-3.8 Mb), Large-tailed Han sheep (ORA17: 53.5-53.8 Mb) and Tibetan sheep (ORA5:19.8-20.2 Mb). Collectively, the ROH islands harbored 78 unique genes, including 19 genes that have been documented as having associations with tail types, adaptation, growth, body size, reproduction or immune response.ConclusionDifferent ROH patterns were observed in five Chinese indigenous sheep breeds, which reflected their different population histories. Large-tailed Han sheep had the highest genomic inbreeding coefficients and the highest proportion of long ROH fragments indicating recent inbreeding. Candidate genes in ROH islands could be used to illustrate the genetic characteristics of these five sheep breeds. Our findings contribute to the understanding of genetic diversity and population demography, and help design and implement breeding and conservation strategies for Chinese sheep.

Project description:BACKGROUND:Dogs [Canis lupus familiaris] were the first animal species to be domesticated and continue to occupy an important place in human societies. Recent studies have begun to reveal when and where dog domestication occurred. While much progress has been made in identifying the genetic basis of phenotypic differences between dog breeds we still know relatively little about the genetic changes underlying the phenotypes that differentiate all dogs from their wild progenitors, wolves [Canis lupus]. In particular, dogs generally show reduced aggression and fear towards humans compared to wolves. Therefore, selection for tameness was likely a necessary prerequisite for dog domestication. With the increasing availability of whole-genome sequence data it is possible to try and directly identify the genetic variants contributing to the phenotypic differences between dogs and wolves. RESULTS:We analyse the largest available database of genome-wide polymorphism data in a global sample of dogs 69 and wolves 7. We perform a scan to identify regions of the genome that are highly differentiated between dogs and wolves. We identify putatively functional genomic variants that are segregating or at high frequency [>?=?0.75 Fst] for alternative alleles between dogs and wolves. A biological pathways analysis of the genes containing these variants suggests that there has been selection on the 'adrenaline and noradrenaline biosynthesis pathway', well known for its involvement in the fight-or-flight response. We identify 11 genes with putatively functional variants fixed for alternative alleles between dogs and wolves. The segregating variants in these genes are strong candidates for having been targets of selection during early dog domestication. CONCLUSIONS:We present the first genome-wide analysis of the different categories of putatively functional variants that are fixed or segregating at high frequency between a global sampling of dogs and wolves. We find evidence that selection has been strongest around non-synonymous variants. Strong selection in the initial stages of dog domestication appears to have occurred on multiple genes involved in the fight-or-flight response, particularly in the catecholamine synthesis pathway. Different alleles in some of these genes have been associated with behavioral differences between modern dog breeds, suggesting an important role for this pathway at multiple stages in the domestication process.

Dataset Information

Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

Publications

Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

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