A selective sweep of >8 Mb on chromosome 26 in the Boxer genome

Abstract

Background: Modern dog breeds display traits that are either breed-specific or shared by a few breeds as a result of genetic bottlenecks during the breed creation process and artificial selection for breed standards. Selective sweeps in the genome result from strong selection and can be detected as a reduction or elimination of polymorphism in a given region of the genome.

Results: Extended regions of homozygosity, indicative of selective sweeps, were identified in a genome-wide scan dataset of 25 Boxers from the United Kingdom genotyped at ~20,000 single-nucleotide polymorphisms (SNPs). These regions were further examined in a second dataset of Boxers collected from a different geographical location and genotyped using higher density SNP arrays (~170,000 SNPs). A selective sweep previously associated with canine brachycephaly was detected on chromosome 1. A novel selective sweep of over 8 Mb was observed on chromosome 26 in Boxer and for a shorter region in English and French bulldogs. It was absent in 171 samples from eight other dog breeds and 7 Iberian wolf samples. A region of extended increased heterozygosity on chromosome 9 overlapped with a previously reported copy number variant (CNV) which was polymorphic in multiple dog breeds.

Conclusion: A selective sweep of more than 8 Mb on chromosome 26 was identified in the Boxer genome. This sweep is likely caused by strong artificial selection for a trait of interest and could have inadvertently led to undesired health implications for this breed. Furthermore, we provide supporting evidence for two previously described regions: a selective sweep on chromosome 1 associated with canine brachycephaly and a CNV on chromosome 9 polymorphic in multiple dog breeds.

Figure 1

Genome-wide plot of the averaged observed heterozygosity with the 50-SNP sliding window for set A (a) and set B (b). The x-axis corresponds to SNPs sort by chromosomes (differently coloured) and position and the y-axis represents the 10-logarithm of the averaged observed heterozygosity calculated with sliding windows of 50 SNPs, for which 0.1 and 1.0% quantiles of the empirical distribution are displayed.

Figure 2

Pattern of alternate heterozygous/homozygous genotypes in a 1.5-Mb region corresponding to a described CNV on CFA 9. In the x-axis, the start and end positions of both the chromosome region shown and the CNV are indicated.

Figure 3

ROHs on CFA 1 and CFA 26 in non-brachycephalic and brachycephalic breeds other than Boxer. In the top panels, MAF values for the pool of non-brachycephalic breeds (grey squares) and German shepherd dog (grey crosses) are shown. For CFA 1, the region associated with brachycephaly by Bannasch et al. (CFA 1:59,536,208-59,832,965 bp) [7] is indicated (red lines). For CFA 26, the red lines show the extent of the ROH in Boxer for comparison with the other breeds.

Figure 4

Genetic content of the ROH on CFA 26. (a) Annotated elements in the dog genome (CanFam2.0) as well as regions of synteny with H. sapiens and M. musculus are shown. CFA 26:3,008,718-11,914,284 bp maps to two syntenic regions in H. sapiens: Hs 12:121,547,433-133,784,108 bp (S1) and Hs 12:110,448,771-121,498,418 (S2). The end position for S2 is defined relative to the end of the ROH in dog though indeed synteny extends longer. Note that the order of the syntenic regions relative to the dog sequence indicates rearrangements events in the species; also, the different orientation of the sequences, indicated with arrows preceding the chromosome number in the compared species, designates an inversion in the orientation between H. sapiens and C. familiaris for S1. Regions of extended homozygosity for Boxer, English bulldog and French bulldog and the region of ~700 Kb shared in all three are indicated. (b) Averaged observed heterozygosity along CFA 26 in Boxer. Minimum values are shown for three window sizes: 10- and 50-SNPs, CFA 26:8.86 Mb (x); 20-SNPs, CFA 26:10.44 Mb (+).