PLoS Genet. 2011 Oct;7(10):e1002316. doi: 10.1371/journal.pgen.1002316. Epub 2011 Oct 13.
Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.
Vaysse A,
Ratnakumar A,
Derrien T,
Axelsson E,
Rosengren Pielberg G,
Sigurdsson S,
Fall T,
Seppälä EH,
Hansen MS,
Lawley CT,
Karlsson EK;
LUPA Consortium,
Bannasch D,
Vilà C,
Lohi H,
Galibert F,
Fredholm M,
Häggström J,
Hedhammar A,
André C,
Lindblad-Toh K,
Hitte C,
Webster MT.
Battaille G, Clercx C, Druet T, Farnir F, Faust N, Georges M, Lequarre AS, Merveille AC, Momozawa Y, Pamplona MR, Peeters D, Ahlgren K, Andersson L, Arendt M, Barrio ÁM, Carlborg Ö, Johansson C, Kämpe O, Lindblad-Toh K, Meadows J, Pielberg G, Ratnakumar A, Tengvall K, Webster M, Andersson G, Björnerfeldt S, Gustafsson S, Häggström J, Hansson J, Hedhammar Å, Höglund K, Kierczak M, Ljungvall I, Melin M, Sundberg K, Kennedy L, Massey J, Ollier W, Rothwell S, Ahonen S, Hytönen M, Kyöstilä K, Lohi H, Nevalainen E, Fredholm M, Madsen MB, Mogensen MS, Courtay-Cahen C, Mellersh C, Starkey M, Dahlgren S, Lingaas F, Storengen LM, Wiik C, Boerkamp K, Fieten H, Leegwater P, Rutteman G, Van Steenbeek F, Leeb T, Owczarek-Lipska M, Aguirre-Hernandez J, Sargan D, Andre C, Hitte C, Thomas A, Chetboul V, Gouni V, Tiret L, Catchpole B, Hendricks A, Bonastre AS, Quilez J, Callanan S, Nolan C, Dukes-McEwan J, Copeland-Stephenson H, Favrot C, Wess G, Wolf J, Millar K, Boland A, Lathrop M, Zelenika D, Quinnell RJ, Philipp U.
Source
Institut de Génétique et Développement de Rennes, CNRS-UMR6061, Université de Rennes 1, Rennes, France.
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.
- PMID:
- 22022279
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC3192833
Free PMC ArticleFigure 1Neighbor-joining tree constructed from raw genetic distances representing relationships between samples.
More than 170,000 SNPs were genotyped in 46 diverse dog breeds plus wolves using the CanineHD array. The boxer branches are longer, which likely represents the influence of ascertainment bias, as the SNPs were discovered from sequence alignments involving the boxer reference sequence.
PLoS Genet. 2011 October;7(10):e1002316.
Figure 2Identification of variants with large differences in allele frequencies between breeds that are associated with phenotypic variation.
The top panel shows the variation in pairwise fixation index (see text for definition) at SNPs across the genome on the CanineHD array. The bottom panel shows GWAS for three traits (curly tail, drop ear, and sociality) with signals that correspond to SNPs with high population differentiation. P-values from breed permutations are also shown.
PLoS Genet. 2011 October;7(10):e1002316.
Figure 3Map of regions with extreme differentiation between dog breeds as identified by single-SNP FST.
All regions with at least one SNP with FST >0.55 and minor allele frequency >15% are shown. Numbers correspond to the regions in Table 2, which contain at least two nearby SNPs that pass these thresholds.
PLoS Genet. 2011 October;7(10):e1002316.
Figure 4Variation in allele frequencies of the SNPs with the strongest association to drop ear (chr10:11,072,007) and body size (chr10:11,169,956).
A) The frequency of these two SNPs in each breed is plotted against the classification of each breed according to body size and drop ear phenotype. The first SNP shows continuous variation in frequency between breeds, and correlates with drop ear class (1 = pricked ear, 5 = dropped ear). At the second SNP, one allele has very high frequency in some small breeds, but very low frequency in all other breeds. A set of small breeds with high minor allele frequency at this SNP are marked. B) The allele frequencies at these SNPs are consistent with the presence of three haplotypes, associated with different combinations of these traits.
PLoS Genet. 2011 October;7(10):e1002316.
Figure 5Patterns of polymorphism in a 3 Mb region where variation is associated with drop ear, body size, and boldness phenotypes.
The top panel describes variation compared to the reference sequence in pools of 3 drop ear (Lagotto, Lag; Leonberger, Leo; Bernese Mountain Dog; BMD) and 3 pricked ear breeds (Schipperke, Sch; Finnish Spitz, FSp; Chinese Crested, CCr). Blue lines represent homozygous (fixed) differences from the reference sequence and red lines represent SNPs that are polymorphic in the breed pool. The positions of GWAS associations for drop ear (E) body size (S) and boldness (B) are shown. The positions of genes are also displayed (vertical bars correspond to exons). The second panel displays the levels of relative heterozygosity in all drop ear breeds compared with all prick ear breeds in 100 kb windows. The third panel shows the number of SNPs that are fixed for different alleles in drop and prick ear breeds. Green segments represent SNPs fixed for the reference allele in drop ear breeds, and black segments represent SNPs fixed for the reference allele in pricked ear breeds.
PLoS Genet. 2011 October;7(10):e1002316.
Publication Types
MeSH Terms