Identification of further DLA‐DRB1 and DQA1 alleles in the dog

Kennedy, L. J.; Hall, Laurence S.; Carter, Stuart; Barnes, A.; Bell, Sarah Beth; Bennett, David; Ollier, Bill; Thomson, Wendy

doi:10.1046/j.1365-2370.2000.00189.x

Cited by 19 publications

(14 citation statements)

References 10 publications

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“…In both of our study populations, the DRB exon displayed greater allelic variability than the DQA exon, and this pattern has been reported for multiple other species (Gyllensten et al. , 1994; Kennedy et al. , 2000; Seddon & Ellegren, 2002; Weber et al.…”

Section: Discussionsupporting

confidence: 85%

Effects of contrasting demographic histories on selection at major histocompatibility complex loci in two sympatric species of tuco-tucos (Rodentia: Ctenomyidae)

Cutrera

Lacey

Mora

et al. 2010

Biological Journal of the Linnean Society

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To explore the impact of history on selection and genetic structure at functional loci, we compared patterns of major histocompatibility complex (MHC) variability in two sympatric species of ctenomyid rodents with different demographic backgrounds. Although Ctenomys talarum has experienced a stable demographic history, Ctenomys australis has undergone a recent demographic expansion. Accordingly, we predicted that MHC allele frequency distributions should be more skewed, differences between coding and noncoding regions should be less pronounced, and evidence of current selection on MHC loci should be reduced in C. australis relative to C. talarum. To test these predictions, we compared variation at the MHC class II DRB and DQA genes with that at multiple neutral markers, including DQA intron 2, the mitochondrial control region, and 8-12 microsatellite loci. These analyses supported the first two of our predictions but indicated that estimates of selection (based on w-values) were greater for C. australis. Further exploration of these data, however, revealed differences in the time frames over which selection appears to have acted on each species, with evidence of contemporary selection on MHC loci being limited to C. talarum. Collectively, these findings indicate that demographic history can substantially influence genetic structure at functional loci and that the effects of history on selection may be temporally complex and dynamic.

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Section: Discussionsupporting

confidence: 85%

Effects of contrasting demographic histories on selection at major histocompatibility complex loci in two sympatric species of tuco-tucos (Rodentia: Ctenomyidae)

Cutrera

Lacey

Mora

et al. 2010

Biological Journal of the Linnean Society

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“…The number of DLA class II alleles and haplotypes among dogs in general and purebreds in particular is very limited. 2,19,24 At least 143 DRB1, 26 DQA1, and 66 DQB1 alleles have been formally designated to date in all dogs, with a limited number still to be identified and/or named (L. J. Kennedy, personal communication, 2010).…”

Section: Discussionmentioning

confidence: 99%

Dog Leukocyte Antigen Class II–Associated Genetic Risk Testing for Immune Disorders of Dogs: Simplified Approaches Using Pug Dog Necrotizing Meningoencephalitis as a Model

et al. 2011

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Abstract. A significantly increased risk for a number of autoimmune and infectious diseases in purebred and mixed-breed dogs has been associated with certain alleles or allele combinations of the dog leukocyte antigen (DLA) class II complex containing the DRB1, DQA1, and DQB1 genes. The exact level of risk depends on the specific disease, the alleles in question, and whether alleles exist in a homozygous or heterozygous state. The gold standard for identifying high-risk alleles and their zygosity has involved direct sequencing of the exon 2 regions of each of the 3 genes. However, sequencing and identification of specific alleles at each of the 3 loci are relatively expensive and sequencing techniques are not ideal for additional parentage or identity determination. However, it is often possible to get the same information from sequencing only 1 gene given the small number of possible alleles at each locus in purebred dogs, extensive homozygosity, and tendency for disease-causing alleles at each of the 3 loci to be strongly linked to each other into haplotypes. Therefore, genetic testing in purebred dogs with immune diseases can be often simplified by sequencing alleles at 1 rather than 3 loci. Further simplification of genetic tests for canine immune diseases can be achieved by the use of alternative genetic markers in the DLA class II region that are also strongly linked with the disease genotype. These markers consist of either simple tandem repeats or single nucleotide polymorphisms that are also in strong linkage with specific DLA class II genotypes and/or haplotypes. The current study uses necrotizing meningoencephalitis of Pug dogs as a paradigm to assess simple alternative genetic tests for disease risk. It was possible to attain identical necrotizing meningoencephalitis risk assessments to 3-locus DLA class II sequencing by sequencing only the DQB1 gene, using 3 DLA class IIlinked simple tandem repeat markers, or with a small single nucleotide polymorphism array designed to identify breed-specific DQB1 alleles.

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“…The DRB1 primers were from Wagner (5). The DQA1 forward primer was from Wagner (6), and the reverse from Kennedy (7). The DQB1 forward primer was designed by Wagner (personal communication) and the reverse by Kennedy (previously unpublished).…”

Section: Methodsmentioning

confidence: 99%

“…For SBT, all PCR reactions were performed with 100 ng DNA in a 25‐µL reaction containing 1 × KCl based PCR buffer and final concentrations of 0.1–0.25 µM for each primer, 200 µM each dNTP, 1.5–2.0 mM MgCl 2 and 2 units of Taq polymerase (Bioline, London, UK; Qiagen, Crawley, UK; ABgene, Epsom, UK) (5, 7, 8).…”

Section: Methodsmentioning

confidence: 99%

Evidence for extensive DLA polymorphism in different dog populations

et al. 2002

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Many of the genes within the Canine Major Histocompatibility Complex are highly polymorphic. Most of the alleles defined to date for DLA-DRB1, DQA1 and DQB1 come from the analysis of European or North American pure bred dogs. Little is known about DLA gene polymorphisms in other dog populations. We have studied Alaskan Husky dogs and Brazilian mongrel dogs and compared them with a panel of 568 European dogs and 40 Alaskan gray wolves. DNA sequence based typing was used to characterize a series of 12 Alaskan Huskies and 115 Brazilian mongrels for their DLA-DRB1, DQA1 and DQB1 alleles. Within these dogs, 22 previously undescribed DLA class II alleles were identified: 10 DRB1, 5 DQA1 and 7 DQB1 alleles. All these alleles were found in more than one animal, and, in some cases, as a homozygote. Several alleles initially observed in Alaskan gray wolves were found in these dogs. Each new allele was found in specific haplotypic combinations. Many new DLA class II haplotypes were identified. Several of the new alleles and haplotypes were also identified in the European dogs used for comparison. One new haplotype, containing a previously unknown DLA-DRB1 allele together with DQA1 and DQB1 alleles only seen before in gray wolves, was found in 20 Brazilian dogs, including three homozygous animals. It appears likely that the extent of polymorphism of the DLA genes will increase substantially as dogs from a wider geographic distribution are studied. This has major implications for the study of disease susceptibility and immune responsiveness in dogs.

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Identification of further DLA‐DRB1 and DQA1 alleles in the dog

Abstract: Three novel DLA-DRB1 alleles and one novel DQA1 allele have been identified in a panel of 367 dogs. These were suggested by unusual reaction patterns found in sequence specific oligonucleotide probing (SSOP) data. Four new alleles were confirmed using DNA cloning and sequencing.

Cited by 19 publications

References 10 publications

Effects of contrasting demographic histories on selection at major histocompatibility complex loci in two sympatric species of tuco-tucos (Rodentia: Ctenomyidae)

Effects of contrasting demographic histories on selection at major histocompatibility complex loci in two sympatric species of tuco-tucos (Rodentia: Ctenomyidae)

Dog Leukocyte Antigen Class II–Associated Genetic Risk Testing for Immune Disorders of Dogs: Simplified Approaches Using Pug Dog Necrotizing Meningoencephalitis as a Model

Evidence for extensive DLA polymorphism in different dog populations

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