Popular Sire Research Articles

Evidence of Positive Selection for a Glycogen Synthase (GYS1) Mutation in Domestic Horse Populations

A dominantly inherited gain-of-function mutation in the glycogen synthase (GYS1) gene, resulting in excess skeletal muscle glycogen, has been identified in more than 30 horse breeds. This mutation is associated with the disease Equine Polysaccharide Storage Myopathy Type 1, yet persists at high frequency in some breeds. Under historical conditions of daily work and limited feed, excess muscle glycogen may have been advantageous, driving the increase in frequency of this allele. Fine-scale DNA sequencing in 80 horses and genotype assays in 279 horses revealed a paucity of haplotypes carrying the mutant allele when compared with the wild-type allele. Additionally, we found increased linkage disequilibrium, measured by relative extended haplotype homozygosity, in haplotypes carrying the mutation compared with haplotypes carrying the wild-type allele. Coalescent simulations of Belgian horse populations demonstrated that the high frequency and extended haplotype associated with the GYS1 mutation were unlikely to have arisen under neutrality or due to population demography. In contrast, in Quarter Horses, elevated relative extended haplotype homozygosity was associated with multiple haplotypes and may be the result of recent population expansion or a popular sire effect. These data suggest that the GYS1 mutation underwent historical selection in the Belgian, but not in the Quarter Horse.

Centronuclear Myopathy in Labrador Retrievers: A Recent Founder Mutation in the PTPLA Gene Has Rapidly Disseminated Worldwide

Centronuclear myopathies (CNM) are inherited congenital disorders characterized by an excessive number of internalized nuclei. In humans, CNM results from ∼70 mutations in three major genes from the myotubularin, dynamin and amphiphysin families. Analysis of animal models with altered expression of these genes revealed common defects in all forms of CNM, paving the way for unified pathogenic and therapeutic mechanisms. Despite these efforts, some CNM cases remain genetically unresolved. We previously identified an autosomal recessive form of CNM in French Labrador retrievers from an experimental pedigree, and showed that a loss-of-function mutation in the protein tyrosine phosphatase-like A (PTPLA) gene segregated with CNM. Around the world, client-owned Labrador retrievers with a similar clinical presentation and histopathological changes in muscle biopsies have been described. We hypothesized that these Labradors share the same PTPLAcnm mutation. Genotyping of an international panel of 7,426 Labradors led to the identification of PTPLAcnm carriers in 13 countries. Haplotype analysis demonstrated that the PTPLAcnm allele resulted from a single and recent mutational event that may have rapidly disseminated through the extensive use of popular sires. PTPLA-deficient Labradors will help define the integrated role of PTPLA in the existing CNM gene network. They will be valuable complementary large animal models to test innovative therapies in CNM.

Sizing up dogs

Sizing up dogs

Identification and characterization of hierarchical structures in dog breeding schemes, a novel method applied to the Norfolk Terrier1

Popular sires, a limited population size, and the founder event are widely considered the main reasons for the low genetic diversity observed in many dog breeds. However, these factors have had only a small role in the historic decrease in diversity observed in the Norfolk Terrier breed. We show that the decrease in this breed has been mainly due to large, popular kennels. Dogs from these kennels have, on average, larger genetic contributions to subsequent generations than others. A test for the presence of a popular kennel effect is proposed and applied (P < 0.001). These kennels were found to be the same as nuclei of selection existing in other livestock species. This result revealed a hierarchical structure of dog breeding schemes, with an asymmetric gene flow predominantly from the nuclei toward the main population. Possible reasons for this structure and implications for future population management are discussed. The main reason is probably that the breed type was established by large, popular kennels and that small kennel breeders used their stud dogs to benefit from the achievements of the popular kennels. Many kennels, however, were unable to make their own substantial genetic contributions to the breed.

A genealogical survey of Australian registered dog breeds

Breeding practices were analysed for 32 registered dog breeds representing very small registries (120 Central Asian shepherd dogs) through to very large registries (252,521 German shepherd dogs) in Australia. The vast majority (91%) of registered kennels in Australia that were sampled did not regularly employ either close breeding or popular sire usage in their kennels and the weighted mean inbreeding coefficient of Australian pedigree dogs was <5%. Australian breed mean inbreeding coefficients ranged from 0% (Central Asian shepherd dog) to 10.1% (Bichon Frise). Breed effective population sizes ranged from 26 (Ibizan hound) to 1090 (Golden retriever), comparable with other species of domesticated animals. The relatively low levels of inbreeding suggest that pedigree dog disorders are unlikely to arise frequently from the use of popular sires or close breeding in Australian registered dog breeds. It is possible that deleterious allele fixation might be driven by founder effects, genetic drift or adverse selection practices, which were not assessed in this analysis. European popular sire definitions should be revisited for rare breeds.

Genetic diversity, inbreeding and breeding practices in dogs: Results from pedigree analyses

Pedigree analysis constitutes a classical approach for the study of the evolution of genetic diversity, genetic structure, history and breeding practices within a given breed. As a consequence of selection pressure, management in closed populations and historical bottlenecks, many dog breeds have experienced considerable inbreeding and show (on the basis of a pedigree approach) comparable diversity loss compared to other domestic species. This evolution is linked to breeding practices such as the overuse of popular sires or mating between related animals. The popular sire phenomenon is the most problematic breeding practice, since it has also led to the dissemination of a large number of inherited defects. The practice should be limited by taking measures such as restricting the number of litters (or offspring) per breeding animal.

Mating practices and the dissemination of genetic disorders in domestic animals, based on the example of dog breeding

On the basis of simulations and genealogical data of ten dog breeds, three popular mating practices (popular sire effect, line breeding, close breeding) were investigated along with their effects on the dissemination of genetic disorders. Our results showed that the use of sires in these ten breeds is clearly unbalanced. Depending on the breed, the effective number of sires represented between 33% and 70% of the total number of sires. Mating between close relatives was also found to be quite common, and the percentage of dogs inbred after two generations ranged from 1% to about 8%. A more or less long-term genetic differentiation, linked to line breeding practices, was also emphasized in most breeds. F(IT) index based on gene dropping proved to be efficient in differentiating the effects of the different mating practices, and it ranged from -1.3% to 3.2% when real founders were used to begin a gene dropping process. Simulation results confirmed that the popular sire practice leads to a dissemination of genetic disorders. Under a realistic scenario, regarding the imbalance in the use of sires, the dissemination risk was indeed 4.4 times higher than under random mating conditions. In contrast, line breeding and close breeding practices tend to decrease the risk of the dissemination of genetic disorders.

Simulation study on the effects of excluding offspring information for genetic evaluation versus using genomic markers for selection in dog breeding

Different modes of selection in dogs were studied with a special focus on the availability of disease information. Canine hip dysplasia (CHD) in the German shepherd dog was used as an example. The study was performed using a simulation model, comparing cases when selection was based on phenotype, true or predicted breeding value, or genomic breeding value. The parameters in the simulation model were drawn from the real population data. The data on all parents and 40% of their progeny were assumed to be available for the genetic evaluation carried out by Gibbs sampling. With respect to the use of disease records on progeny, three scenarios were considered: random exclusion of disease data (no restrictions, N), general exclusion of disease data (G) and exclusion of disease data for popular sires (P). One round of selection was considered, and the response was expressed as change of mean CHD score, proportion of dogs scored as normal, proportion of dogs scored as clearly affected and true mean breeding value in progeny of popular sires in comparison with all sires. When no restrictions on data were applied, selection on breeding value was three times more efficient than when some systematic exclusion was practised. Higher selection response than in the exclusion cases was achieved by selecting on the basis of genomic breeding value and CHD score. Genomic selection would therefore be the method of choice in the future.

Global priorities for animal breeding and conservation work

Global priorities for animal breeding and conservation work

Frequencies of bovine PrP gene polymorphisms in Holstein and Japanese Black bulls in Japan

ABSTRACTWe screened for Japanese Black and Holstein bull sire samples to detect single nucleotide polymorphisms (SNPs) involving animo‐acid substitutions in the bovine prion gene in the entire coding region of the PRNP gene. Although three silent SNPs were found, we could not detect any SNP with animo‐acid substitution. We also examined the polymorphism of the octapeptide repeat number in these samples. There was no homozygous bull with repeat number 5. The frequency of heterozygous (6/5) bulls was 8% in the Japanese Black bull and 4% in the Holstein bull, respectively. The bull samples used in this study contain popular elite sires, so it appears that the polymorphisms of prion protein (PrP) are rather difficult to find in these two breeds in Japan, except for polymorphism of the octapeptide repeat number.

Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison's disease in Portuguese Water Dogs

Addison's disease, an immune-mediated disorder caused by destruction of the adrenal glands, is a rare disorder of Western European populations. Studies indicate that the disorder is polygenic in nature, involving specific alleles of the CTLA-4, DRB1*04 and DQ, Cyp27B1, VDR and MIC-A and -B loci. A similar immune form of Addison's disease occurs in several breeds of domestic dog, with frequencies ranging from 1.5 to 9.0%. The high frequency of the disease in domestic dog breeds likely reflects the small number of founders associated with many breeds, subsequent inbreeding, and the frequent use of popular sires. The Portuguese Water Dog (PWD) is a significantly affected breed. An analysis of 11,384 PWDs surveyed between 1985 and 1996 suggests a breed-specific disease incidence of 1.5%. As with humans, the disease is typically of late onset. This study involves a genetic comparison of Addison's disease in the PWD to the analogous disease in humans. The study is facilitated by the existence of complete pedigrees and a relatively high degree of inbreeding among PWDs. The breed originated from 31 founders, with 10 animals responsible for 90% of the current gene pool. We describe, specifically, the identification of two disease-associated loci, on Canis familiaris (CFA) chromosomes CFA12 and 37, which are syntenic with the human DRB1 histocompatibility locus alleles HLA-DRB1*04 and DRB1*0301, and to a locus for immunosuppression syntenic with CTLA-4. Strong similarities exist therefore in the complex genetic background of Addison's disease in humans and in the PWD. With the completion of the canine and human genome sequence, the purebred dog is set to become an important comparative model for Addison's as well as other human immune disorders.

National survey of owner-directed aggression in English Springer Spaniels

To determine prevalence of owner-directed aggression and identify associated environmental and genetic factors in English Springer Spaniels. Prevalence survey. 1,053 adult English Springer Spaniels. A mail survey was sent to 2,400 randomly selected owners of adult American Kennel Club-registered English Springer Spaniels. Dogs with a history of aggression to family members and familiar humans were compared with dogs without such a history. 1,053 questionnaires (56.1% of the 1,877 delivered) were completed. A history of owner-directed growling or more intense aggression was reported in 510 (48.4%) dogs. Two hundred seventy-seven (26.3%) dogs had bitten a human in the past; 65.2% of bites were directed at familiar (owner or nonowner) adults and children. Variables associated with owner-directed aggression included sex of dog (male), neuter status (neutered, regardless of sex), show or bench lines, age > 4 years, aggression to unfamiliar adults and children, acquisition from a hobby breeder, less responsiveness to obedience cues, and a specific kennel and 1 popular sire from that kennel in a 4-generation pedigree. Owner-directed aggression in adult English Springer Spaniels was associated with a number of environmental, sex-related, and inherited factors. To reduce the risk of aggression, prospective owners might seek a female, hunting-type English Springer Spaniel from an experienced breeder. However, because risk factors are broad and varied, there are limitations to the extent to which behavior can be predicted and further study is needed of the inheritance of aggression in this breed.

Canine Genomics and Genetics: Running with the Pack

ABSTRACTThe domestication of the dog from its wolf ancestors is perhaps the most complex genetic experiment in history, and certainly the most extensive. Beginning with the wolf, man has created dog breeds that are hunters or herders, big or small, lean or squat, and independent or loyal. Most breeds were established in the 1800s by dog fanciers, using a small number of founders that featured traits of particular interest. Popular sire effects, population bottlenecks, and strict breeding programs designed to expand populations with desirable traits led to the development of what are now closed breeding populations, with limited phenotypic and genetic heterogeneity, but which are ideal for genetic dissection of complex traits. In this review, we first discuss the advances in mapping and sequencing that accelerated the field in recent years. We then highlight findings of interest related to disease gene mapping and population structure. Finally, we summarize novel results on the genetics of morphologic variation.

Association of markers in the bovine CAPN1 gene with meat tenderness in large crossbred populations that sample influential industry sires1,2

Two previously identified single-nucleotide polymorphism markers located within the micromolar calcium-activated neutral protease gene (CAPN1) were evaluated for their association with variation in meat tenderness using one commercial sample of Simmental x Angus crossbred calves and one multibreed, crossbred research herd. The commercial sample included 362 animals sired by 23 registered Simmental bulls bred to unregistered Angus cows and represented current industry animals in which to test the predictive merit of the markers. The second sample was a research herd including 564 steers from the Germplasm Evaluation Cycle VII population at the U.S. Meat Animal Research Center, produced with semen from popular sires of the seven Bos taurus beef breeds with the most registrations in the United States (Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental) on Angus, Hereford, and MARC III cows. These animals form a relatively outbred population that constituted a stringent test of the predictive merit of the genetic markers, although small groups were half-sibs. Warner-Bratzler shear force measurements were used to determine tenderness phenotypes for all animals. The populations were genotyped for two markers that predict variation at amino acid positions 316 and 530 of the mu-calpain polypeptide, produced by the CAPN1 gene. Minor allele frequencies for markers 316 and 530 in the commercial sample were 0.17 and 0.37, respectively, and in the Cycle VII animals, were 0.20 and 0.28, respectively. Both markers showed association with shear force in the commercial sample (P = 0.04) and the Cycle VII population (P = 0.02), supporting the hypothesis that they represent potential markers to aid selection for improved meat tenderness in commercial populations of beef cattle in the United States.

The domestic dog genome

The domestic dog genome

Warner-Bratzler shear force values and ranges of steaks from cattle of known sires (2003)

Carcass data and Warner-Bratzler shear force (WBSF) data on strip loin steaks were collected from nearly 8,500 cattle in contemporary groups of progeny from the more popular sires in 14 different beef cattle breeds in the Carcass Merit Traits project funded by Beef Checkoff dollars, the breed associations, and MMI Genomics. In addition, trained sensory panel evaluations were conducted on over 2,500 strip loin steaks from contemporary groups of progeny from five sires included in the DNA marker validation component of the project. The correlation between WBSF and tenderness scored by the trained sensory panel was -0.82, indicating that as WBSF increased, tenderness scored by the sensory panel decreased. Our results showed that a WBSF value of ≥11.0 lb generally results in a sensory score of slightly tough or tougher. In this study, 22.8% of the cattle had WBSF values ≥11.0 lb and 26.3% had sensory scores of slightly tough or tougher. The phenotypic range of WBSF means for sires within breeds ranged from 1.9 to 6.6 lb. The phenotypic range of WBSF means across breeds was 8.9 lb, whereas the range among sires across breeds was a dramatic 14.4 lb. The phenotypic range for flavor intensity scores among sires within and across breeds was much smaller than for tenderness, with juiciness scores being intermediate. The 40 widely used sires that produced progeny with steaks that were unacceptable in tenderness in this study might be expected to be sires of several thousand bulls used in commercial herds. This demonstrates that seedstock producers should aggressively utilize sires that have genetics for tender meat.

Prediction of Transmitting Abilities for Holstein Type Traits

Heritabilities and genetic and phenotypic correlations among 14 linear type traits were estimated from Holstein Association data by multiple trait REML. Data used for parameter estimation were records of 779,391 daughters of 871 sires included in the January 1988 sire evaluation. Each daughter was represented by her appraisal closest to 30 mo of age. Highest heritability was .37 for stature, and lowest was .10 for foot angle. Gains in reliability from using correlated traits in multiple trait prediction were large for some traits (up to 60% for foot angle for cows). Final score variance parameters were estimated from 953,596 records, which were 43% of records included in the national sire evaluation. Sire models that adjusted or did not adjust for merit of mates were compared. Heritability of final score was .27 with adjustment for merit of mates by subtraction of predicted transmitting ability of dam from daughter's record compared with .29 if mate was ignored. Evaluations for type for several popular older sires were reduced moderately by adjustment for merit of mates, but estimated genetic trend increased slightly. An improved genetic grouping procedure that considers group effects as inherited was adapted for use in sire models. Parameter estimates and models presented were implemented by the Holstein Association for computing July 1988 genetic evaluations for linear traits and final score.

EFFECT OF THE POPULAR SIRE

Journal Article EFFECT OF THE POPULAR SIRE: A Statistical Study of Three Varieties of Terriers—Over Forty Per Cent. of the Puppies Sired by Approximately Twenty Per Cent. of the Stud Dogs—Popularity and Prepotency—A Cause of Variation Get access WILLIAMS HAYNES WILLIAMS HAYNES Author of “Practical Dog Breeding,” etc. Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 6, Issue 11, November 1915, Pages 494–496, https://doi.org/10.1093/oxfordjournals.jhered.a109022 Published: 01 November 1915