| 1. |
- Vaysse, Amaury, et al.
(författare)
-
Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping
- 2011
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:10, s. e1002316-
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Axelsson, Erik, et al.
(författare)
-
The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels
- 2021
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:9
-
Tidskriftsartikel (refereegranskat)abstract
- Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.
|
|
| 3. |
- Lord, Peter, et al.
(författare)
-
Rate of change of heart size before congestive heart failure in dogs with mitral regurgitation
- 2010
-
Ingår i: Journal of Small Animal Practice. - : Wiley. - 0022-4510 .- 1748-5827. ; 51, s. 210-218
-
Tidskriftsartikel (refereegranskat)abstract
- Methods: Records and radiographs from 24 cavalier King Charles spaniels with mitral regurgitation were used. Vertebral heart scale (24 dogs), and left atrial dimension and left ventricular end diastolic and end systolic diameters (18 dogs) and their rate of increase were measured at intervals over years to the onset of congestive heart failure. They were plotted against time to onset of congestive heart failure.Results: Dimensions and rates of change of all parameters were highest at onset of congestive heart failure, the difference between observed and chance outcome being highly significant using a two-tailed chi-square test (P < 0 center dot 001).Clinical significance: The left heart chambers increase in size rapidly only in the last year before the onset of congestive heart failure. Increasing left ventricular end systolic dimension is suggestive of myocardial failure before the onset of congestive heart failure. Rate of increase of heart dimensions may be a useful indicator of impending congestive heart failure.
|
|
| 4. |
|
|
| 5. |
- Ljungvall, Ingrid, et al.
(författare)
-
Cardiac Troponin I Is Associated with Severity of Myxomatous Mitral Valve Disease, Age, and C-Reactive Protein in Dogs
- 2010
-
Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 24:1, s. 153-159
-
Tidskriftsartikel (refereegranskat)abstract
- Background Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described. Objective To investigate whether plasma concentrations of cTnI and CRP are associated with severity of MMVD, and investigate potential associations of dog characteristics on cTnI and CRP concentrations. Animals Eighty-one client-owned dogs with MMVD of varying severity. Methods Dogs were prospectively recruited for the study. Dogs were classified according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA. Results Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0.008-0.029] ng/mL, P = .0011) and severe (0.043 [0.031-0.087] ng/mL, P < .0001) MMVD, compared with healthy dogs (0.001 [0.001-0.004] ng/mL). Dogs with severe MMVD also had higher cTnI concentrations than dogs with mild (0.003 [0.001-0.024] ng/mL, P < .0001) and moderate (P = .0019) MMVD. There were significant associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration. Conclusions and Clinical Importance Analysis of cTnI concentration has potential to increase knowledge of overall cardiac remodeling in dogs with MMVD. However, effect of age on cTnI needs consideration when assessing cTnI.
|
|
| 6. |
- Ljungvall, Ingrid, et al.
(författare)
-
Use of signal analysis of heart sounds and murmurs to assess severity of mitral valve regurgitation attributable to myxomatous mitral valve disease in dogs
- 2009
-
Ingår i: AMERICAN JOURNAL OF VETERINARY RESEARCH. - : American Veterinary Medical Association (AVMA). - 0002-9645. ; 70:5, s. 604-613
-
Tidskriftsartikel (refereegranskat)abstract
- Objective-To investigate use of signal analysis of heart sounds and murmurs in assessing severity of mitral valve regurgitation (mitral regurgitation [MR]) in dogs with myxomatous mitral valve disease (MMVD). Animals-77 client-owned dogs. Procedures-Cardiac sounds were recorded from dogs evaluated by use of auscultatory and echocardiographic classification systems. Signal analysis techniques were developed to extract 7 sound variables (first frequency peak, murmur energy ratio, murmur duration > 200 Hz, sample entropy and first minimum of the auto mutual information function of the murmurs, and energy ratios of the first heart sound [S1] and second heart sound [S2]). Results-Significant associations were detected between severity of MR and all sound variables, except the energy ratio of S1. An increase in severity of MR resulted in greater contribution of higher frequencies, increased signal irregularity, and decreased energy ratio of S2. The optimal combination of variables for distinguishing dogs with high-intensity murmurs from other dogs was energy ratio of S2 and murmur duration > 200 Hz (sensitivity, 79%; specificity, 71%) by use of the auscultatory classification. By use of the echocardiographic classification, corresponding variables were auto mutual information, first frequency peak, and energy ratio of S2 (sensitivity, 88%; specificity, 82%). Conclusions and Clinical Relevance-Most of the investigated sound variables were significantly associated with severity of MR, which indicated a powerful diagnostic potential for monitoring MMVD. Signal analysis techniques could be valuable for clinicians when performing risk assessment or determining whether special care and more extensive examinations are required.
|
|
| 7. |
- Rivera, Patricio, et al.
(författare)
-
Mammary tumor development in dogs is associated with BRCA1 and BRCA2
- 2009
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 69:22, s. 8770-8774
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a major contributor to overall morbidity and mortality in women. Several genes predisposing to breast cancer have been identified, but the majority of risk factors remain unknown. Even less is known about the inherited risk factors underlying canine mammary tumors (CMT). Clear breed predispositions exist, with 36% of English springer spaniels (ESS) in Sweden being affected. Here, we evaluate 10 human breast cancer genes (BRCA1, BRCA2, CHEK2, ERBB2, FGFR2, LSP1, MAP3K1, RCAS1, TOX3, and TP53) for association with CMTs. Sixty-three single-nucleotide polymorphisms (SNPs; four to nine SNPs per gene) were genotyped by iPLEX in female ESS dogs, 212 CMT cases and 143 controls. Two genes, BRCA1 and BRCA2, were significantly associated with CMT (Bonferroni corrected P = 0.005 and P = 0.0001, respectively). Borderline association was seen for FGFR2. Benign and malignant cases were also analyzed separately. Those findings supported the association to BRCA1 and BRCA2 but with a stronger association to BRCA1 in malignant cases. Both BRCA1 and BRCA2 showed odds ratios of approximately 4. In conclusion, this study indicates that BRCA1 and BRCA2 contribute to the risk of CMT in ESS, suggesting that dogs may serve as a good model for human breast cancer.
|
|
| 8. |
|
|
| 9. |
- Carlsson, Carolina, et al.
(författare)
-
Size and Shape of Right Heart Chambers in Mitral Valve Regurgitation in Small-Breed Dogs
- 2009
-
Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 23, s. 1007-1013
-
Tidskriftsartikel (refereegranskat)abstract
- RH chambers are not significantly dilated in dogs with mild to moderate MR without CHF. In CHF, RH chambers enlarge and also may be compressed by the LH chambers. Pulmonary hypertension probably is present in some dogs with CHF. Increased sternal contact is not a useful sign of right-sided heart dilatation in MR.
|
|
| 10. |
- Hansson, Kerstin, et al.
(författare)
-
Pulmonary Blood Volume in Mitral Regurgitation in Cavalier King Charles Spaniels
- 2010
-
Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 24, s. 1393-1399
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary edema and venous congestion are well-recognized signs of congestive heart failure (CHF) in advanced canine chronic mitral regurgitation (MR). However, little is known about pulmonary blood volume (PBV), blood pulmonary transit time (PTT), and the regulation of these.Objectives: To measure and evaluate the relationships of PBV, forward stroke volume (FSV), and heart rate normalized blood pulmonary transit time (nPTT) in healthy dogs and dogs with MR.Animals: Thirty-three Cavalier King Charles Spaniels; 11 healthy, 4 in modified New York Heart Association (NYHA) class I, 11 in class II, and 7 in CHF.Methods: Heart rate normalized PTTs were measured by radionuclide angiocardiography. Left ventricular end diastolic and systolic diameter, left atrial/aortic root ratio, and FSV were measured by echocardiography. PBV and pulmonary blood volume index (PBVI) were calculated by established formulas.Results: PBVI was 308 +/- 56 (mean +/- SD) mL/m(2) for healthy dogs, 287 +/- 51mL/m(2) in NYHA class I, 360 +/- 66 mL/m(2) in Class II, and 623 +/- 232 mL/m(2) in CHF (P - .0008). Heart rate normalized PTT, not FSV, was a predictor of PBV (r - 0.92 and 0.02, respectively).Conclusions and Clinical Importance: Increased PBV, not decreased FSV, is the main cause of increased nPTT in MR. Increased nPTT can be used as an indicator of abnormal cardiopulmonary function in dogs with MR.
|
|
