Variant detection and runs of homozygosity in next generation sequencing data elucidate the genetic background of Lundehund syndrome

Runs of homozygosity for Lundehund specific regions in 500-SNP windows. The chromosomal position of ROH regions, number of SNPs in these regions (n), size in base pairs (size_bp), canine genes (gene) and human orthologues (human gene) are shown. (XLSX 88 kb

Identification of Quantitative Trait Loci (QTL) for Canine Hip Dysplasia and Canine Elbow Dysplasia in Bernese Mountain Dogs

<div><p>A genome-wide association study for canine hip dysplasia (CHD) and canine elbow dysplasia (CED) using the Illumina canine high density bead chip had been performed for 174 Bernese mountain dogs. General and mixed linear model analysis identified two different regions with single nucleotide polymorphisms (SNPs) on dog chromosome (CFA) 14 significantly associated with CHD and a further significantly CHD-associated region on CFA37. For CED, four SNPs on CFA11 and 27 were significantly associated. The identified SNPs of four associated regions included nearby candidate genes. These possible positional candidates were the genes <em>PON2</em> on CFA14 and <em>FN1</em> on CFA37 for CHD and the genes <em>LMNB1</em> on CFA11 and <em>WNT10B</em> on CFA27 for CED.</p> </div

Effective Population Size, Extended Linkage Disequilibrium and Signatures of Selection in the Rare Dog Breed Lundehund

<div><p>The Lundehund is an old dog breed with remarkable anatomical features including polydactyly in all four limbs and extraordinary flexibility of the spine. We genotyped 28 Lundehund using the canine Illumina high density beadchip to estimate the effective population size (N_e) and inbreeding coefficients as well as to identify potential regions of positive selection. The decay of linkage disequilibrium was slow with r² = 0.95 in 50 kb distance. The last 7-200 generations ago, Ne was at 10-13. An increase of N_e was noted in the very recent generations with a peak value of 19 for N_e at generation 4. The FROH estimated for 50-, 65- and 358-SNP windows were 0.87, 087 and 0.81, respectively. The most likely estimates for F_ROH after removing identical-by-state segments due to linkage disequilibria were at 0.80-0.81. The extreme loss of heterozygosity has been accumulated through continued inbreeding over 200 generations within a probably closed population with a small effective population size. The mean inbreeding coefficient based on pedigree data for the last 11 generations (F_Ped = 0.10) was strongly biased downwards due to the unknown coancestry of the founders in this pedigree data. The long-range haplotype test identified regions with genes involved in processes of immunity, olfaction, woundhealing and neuronal development as potential targets of selection. The genes <i>QSOX2</i>, <i>BMPR1B</i> and <i>PRRX2</i> as well as <i>MYOM1</i> are candidates for selection on the Lundehund characteristics small body size, increased number of digits per paw and extraordinary mobility, respectively.</p></div

Genomic region with a significant association for canine elbow dysplasia on dog chromosome (CFA) 27 at 4.0–8.5 Mb.

<p>The −log₁₀P-values of all 241 SNPs in this region and the genes annotated according to the dog genome assembly build 2.1 are shown.</p

Number of runs of homozygosity (ROH) per length category for the different minimum SNP length thresholds used for ROH detection.

<p>Number of runs of homozygosity (ROH) per length category for the different minimum SNP length thresholds used for ROH detection.</p

Number of Bernese mountain dogs genotyped on the Illumina high density beadchip.

<p>Number of dogs stratified by sex, canine hip dysplasia (CHD) and canine elbow dysplasia (CED) scores are given. Controls include dogs free from CHD and CED. Cases for CHD or CED are dogs classified with CHD-scores B or C or dogs classified with CED scores I, II or III. All dogs affected by CED, but three dogs were free from CHD.</p

Manhattan plot of −log₁₀P-values of the genome-wide association study for the canine elbow dysplasia score in Bernese mountain dogs using a general model analysis.

<p>On the X-axis, the SNPs are given by dog chromosome number. The −log₁₀P-values for each SNP genotype effect are plotted against the SNP position on each chromosome. Chromosomes are differentiated by colors. The color keys are given below the plot. The blue line indicates the threshold of the −log₁₀P-values for genome-wide significance after correcting for multiple testing.</p

Q-Q-plot of expected −log₁₀P-values versus observed−log₁₀P-values from the general model analysis for canine hip dysplasia score in Bernese mountain dogs.

<p>Shown are all 96,412 SNPs included in the genome-wide association analysis with the grey line corresponding to the null hypothesis of no association.</p

Ancestral population size of the Lundehund in the last 1000 generations.

<p>The effective population size (N_e) was estimated from the mean r² for the 38 canine autosomes.</p

Genomic region with a significant association for canine hip dysplasia on dog chromosome (CFA) 14 at 59.5–60.0 Mb.

<p>The −log₁₀P-values of all 41 SNPs in this region and the genes annotated according to the dog genome assembly build 2.1 are shown.</p