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Showing papers by "George M. Happ published in 2006"


Journal ArticleDOI
TL;DR: A further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown are reported.
Abstract: Dogs exhibit a range of immune-mediated conditions including a lymphocytic thyroiditis which has many similarities to Hashimoto's thyroiditis in man. We have recently reported an association in Doberman Pinschers between canine hypothyroidism and a rare DLA class II haplotype that contains the DLA-DQA1*00101 allele. We now report a further series of 173 hypothyroid dogs in a range of breeds where a significant association with DLA-DQA1*00101 is shown.

77 citations


Journal ArticleDOI
TL;DR: Three dog-leucocyte antigen (DLA) genes, DLA-DRB1, DQA1 and DQB1, were characterized by sequence-based typing and assigned to haplotypes for each dog and one rare haplotype was found at an increased frequency in the affected dogs compared to the unaffected dogs.
Abstract: Canine hypothyroid disease is similar to Hashimoto's disease in humans, which has been shown to be associated with human major histocompatibility complex (MHC) genes. We have collected 27 Doberman Pinschers affected with primary hypothyroid disease and compared their MHC class II haplotypes with 129 unaffected Doberman Pinschers. Three dog-leucocyte antigen (DLA) genes, DLA-DRB1, DQA1 and DQB1, were characterized by sequence-based typing and assigned to haplotypes for each dog. One rare haplotype was found at an increased frequency in the affected dogs compared to the unaffected dogs (Odds ratio = 2.43, P < 0.02). This haplotype has only been found in Doberman Pinschers and Labradors to date.

61 citations


Journal ArticleDOI
TL;DR: It is suggested that the linkage disequilibrium between the causative mutation and these genes has been disrupted by recombination in this population, and the gene responsible for the QTL effects on porcine chromosome 15 probably resides some distance away from INHA and STAR.
Abstract: INHA) and 0.19 (U53020:c.499G>T of STAR) respectively. The INHA and STAR genotypes were not associated with ovulation rate (P ¼ 0.84 and P ¼ 0.95 respectively) or age at puberty (P ¼ 0.32 and P ¼ 0.75 respectively) in this data set. Due to a lack of association of these single nucleotide polymorphism (SNPs) with ovulation rate, we suggest that the linkage disequilibrium between the causative mutation and these genes has been disrupted by recombination in this population, and the gene responsible for the QTL effects on porcine chromosome 15 probably resides some distance away from INHA and STAR. Acknowledgements: The authors thank Bree Quigley, Sue Hauver, Kris Simmerman and Linda Flathman for expert technical assistance and Sherry Kluver for manuscript preparation. Mention of trade names or commercial products is solely for the purpose of providing information and does not imply recommendation, endorsement or exclusion of other suitable

19 citations


Journal ArticleDOI
TL;DR: Routine screening of Alaskan husky dogs, as part of the state outreach science programme, identified a new DLA-DQA1 allele, DQA 1*01801, in one animal, and data suggest that husky alleles share as much similarity to wolf alleles as to dog alleles.
Abstract: The canine Major Histocompatibility Complex (MHC) plays a central role in immune response. Variation in the class II genes, DLA-DRB1, DQA1 and DQB1, has been documented in many studies (1, 2). More recently, extensive interbreed but minimal intrabreed variation has been noted (3, 4). The MHC is likely to influence immune mediated diseases, and recent research has shown DLA allele associations with canine rheumatoid arthritis (5) and hypothyroidism (6). Screening new breeds of dogs often reveals new DLA alleles (2). Routine screening of Alaskan husky dogs, as part of the state outreach science programme, identified a new DLA-DQA1 allele, DQA1*01801, in one animal. We obtained DNA samples from the father and three littermates. The mother was unavailable for testing. When the family was typed for three DLA class II loci, the new DQA1 allele was found to be on a haplotype with new DRB1 and DQB1 alleles (DRB1*07001 and DQB1*05001), inherited by two of four pups from the father. Interestingly the father also carried a second new DRB1 allele (DRB1*07801), which was inherited by the other two pups. In total the father had four new alleles. Figure 1 shows the haplotypes and their inheritance within the family. DRB1*07001 is most similar to DRB1*06401 (an allele previously only found in wolves), with eight amino acid differences. DRB1*07801 is most similar to DRB1*02001 (a commonly found allele in dogs) with six amino acid differences. DQA1*01801 is most similar to DQA1*01101 and DQA1*01301 (both alleles previously only found in wolves), with one and two amino acid differences, respectively. DQB1*05001 is most similar to DQB1*01501 (an allele with a wide breed distribution in dogs) with four amino acid differences. While most dog sled owners actively avoid crossbreeding with wolves, since they have too many characteristics that are undesirable in sled dogs, these data suggest that husky alleles share as much similarity to wolf alleles as to dog alleles. Accession numbers: DLA-DRB1*07001 (AM075474), DLA-DRB1*07801 (AM075482), DLA-DQA1*01801 (AM182471), DLA-DQB1*05001 (AM182474). Allele names have been officially assigned by the DLA nomenclature committee. Sequence alignments are available from http://www.ebi.ac.uk/ ipd/mhc/dLa/index.html.

2 citations