Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs
Exocrine pancreatic insufficiency (EPI) is a disease wherein pancreatic acinar cells fail to synthesize and secrete sufficient amounts of digestive enzymes for normal digestion of food. EPI affects many dog breeds, with a dramatically higher prevalence in the German shepherd dog (GSD) population. In...
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| Veröffentlicht in: | Immunogenetics (New York) 2013-07, Vol.65 (7), p.501-509 |
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| creator | Tsai, Kate L. Starr-Moss, Alison N. Venkataraman, Gopalakrishnan M. Robinson, Christopher Kennedy, Lorna J. Steiner, Jörg M. Clark, Leigh Anne |
| description | Exocrine pancreatic insufficiency (EPI) is a disease wherein pancreatic acinar cells fail to synthesize and secrete sufficient amounts of digestive enzymes for normal digestion of food. EPI affects many dog breeds, with a dramatically higher prevalence in the German shepherd dog (GSD) population. In this breed and perhaps others, EPI most often results from degeneration of the acinar cells of the pancreas, a hereditary disorder termed pancreatic acinar atrophy (PAA). Evidence of lymphocytic infiltration indicates that PAA is an autoimmune disease, but the genetic etiology remains unclear. Data from global gene expression and single nucleotide polymorphism profiles in the GSD suggest the involvement of the major histocompatibility complex [MHC; dog leukocyte antigen (DLA)]. To determine if alleles of the MHC influence development of EPI, genotyping of polymorphic class I (DLA-88) and II loci (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was carried out for 70 affected and 63 control GSDs, and four-locus haplotypes were determined. One haplotype containing a novel allele of DLA-88 is very highly associated with EPI (OR > 17;
P
= 0.000125), while two haplotypes were found to confer protection from EPI (
P
= 0.00087 and 0.0115). Described herein is the genotyping of MHC class I and II loci in a GSD cohort, establishment of four-locus haplotypes, and association of alleles/haplotypes with EPI. |
| doi_str_mv | 10.1007/s00251-013-0704-y |
| format | Article |
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P
= 0.000125), while two haplotypes were found to confer protection from EPI (
P
= 0.00087 and 0.0115). Described herein is the genotyping of MHC class I and II loci in a GSD cohort, establishment of four-locus haplotypes, and association of alleles/haplotypes with EPI.</description><identifier>ISSN: 0093-7711</identifier><identifier>EISSN: 1432-1211</identifier><identifier>DOI: 10.1007/s00251-013-0704-y</identifier><identifier>PMID: 23604463</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Acinar Cells - immunology ; Acinar Cells - pathology ; Allergology ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Antigens ; Atrophy ; Autoimmune Diseases - genetics ; Autoimmune Diseases - immunology ; Autoimmune Diseases - pathology ; Autoimmune Diseases - veterinary ; Base Sequence ; Biomedical and Life Sciences ; Biomedicine ; Biopsy ; Breeding ; Cell Biology ; Disease ; Dog Diseases - genetics ; Dog Diseases - immunology ; Dog Diseases - pathology ; Dogs - genetics ; Dogs - immunology ; Enzymes ; Exocrine Pancreatic Insufficiency - genetics ; Exocrine Pancreatic Insufficiency - immunology ; Exocrine Pancreatic Insufficiency - pathology ; Exocrine Pancreatic Insufficiency - veterinary ; Female ; Gene Function ; Genes ; Genotype ; Haplotypes ; Haplotypes - genetics ; Histocompatibility Antigens Class I - genetics ; Histocompatibility Antigens Class I - immunology ; Human Genetics ; Immunology ; Leukocytes ; Lymphocytes ; Male ; Medical research ; Molecular Sequence Data ; Original Paper ; Pancreas ; Pathogenesis ; Peptides ; Point Mutation ; Polymorphism ; Polymorphism, Single Nucleotide ; Sequence Alignment ; Sequence Homology ; Species Specificity ; Veterinary medicine</subject><ispartof>Immunogenetics (New York), 2013-07, Vol.65 (7), p.501-509</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><rights>Springer-Verlag Berlin Heidelberg 2013 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-7e1286fc73e07b3bff8ab8f95840136fd2392679f6cbb1be1e487bee9c416bd73</citedby><cites>FETCH-LOGICAL-c569t-7e1286fc73e07b3bff8ab8f95840136fd2392679f6cbb1be1e487bee9c416bd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00251-013-0704-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00251-013-0704-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23604463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsai, Kate L.</creatorcontrib><creatorcontrib>Starr-Moss, Alison N.</creatorcontrib><creatorcontrib>Venkataraman, Gopalakrishnan M.</creatorcontrib><creatorcontrib>Robinson, Christopher</creatorcontrib><creatorcontrib>Kennedy, Lorna J.</creatorcontrib><creatorcontrib>Steiner, Jörg M.</creatorcontrib><creatorcontrib>Clark, Leigh Anne</creatorcontrib><title>Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs</title><title>Immunogenetics (New York)</title><addtitle>Immunogenetics</addtitle><addtitle>Immunogenetics</addtitle><description>Exocrine pancreatic insufficiency (EPI) is a disease wherein pancreatic acinar cells fail to synthesize and secrete sufficient amounts of digestive enzymes for normal digestion of food. EPI affects many dog breeds, with a dramatically higher prevalence in the German shepherd dog (GSD) population. In this breed and perhaps others, EPI most often results from degeneration of the acinar cells of the pancreas, a hereditary disorder termed pancreatic acinar atrophy (PAA). Evidence of lymphocytic infiltration indicates that PAA is an autoimmune disease, but the genetic etiology remains unclear. Data from global gene expression and single nucleotide polymorphism profiles in the GSD suggest the involvement of the major histocompatibility complex [MHC; dog leukocyte antigen (DLA)]. To determine if alleles of the MHC influence development of EPI, genotyping of polymorphic class I (DLA-88) and II loci (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was carried out for 70 affected and 63 control GSDs, and four-locus haplotypes were determined. One haplotype containing a novel allele of DLA-88 is very highly associated with EPI (OR > 17;
P
= 0.000125), while two haplotypes were found to confer protection from EPI (
P
= 0.00087 and 0.0115). Described herein is the genotyping of MHC class I and II loci in a GSD cohort, establishment of four-locus haplotypes, and association of alleles/haplotypes with EPI.</description><subject>Acinar Cells - immunology</subject><subject>Acinar Cells - pathology</subject><subject>Allergology</subject><subject>Amino Acid Sequence</subject><subject>Amino Acid Substitution</subject><subject>Animals</subject><subject>Antigens</subject><subject>Atrophy</subject><subject>Autoimmune Diseases - genetics</subject><subject>Autoimmune Diseases - immunology</subject><subject>Autoimmune Diseases - pathology</subject><subject>Autoimmune Diseases - veterinary</subject><subject>Base Sequence</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biopsy</subject><subject>Breeding</subject><subject>Cell Biology</subject><subject>Disease</subject><subject>Dog Diseases - genetics</subject><subject>Dog Diseases - immunology</subject><subject>Dog Diseases - pathology</subject><subject>Dogs - genetics</subject><subject>Dogs - immunology</subject><subject>Enzymes</subject><subject>Exocrine Pancreatic Insufficiency - genetics</subject><subject>Exocrine Pancreatic Insufficiency - immunology</subject><subject>Exocrine Pancreatic Insufficiency - pathology</subject><subject>Exocrine Pancreatic Insufficiency - veterinary</subject><subject>Female</subject><subject>Gene Function</subject><subject>Genes</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>Histocompatibility Antigens Class I - immunology</subject><subject>Human Genetics</subject><subject>Immunology</subject><subject>Leukocytes</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical research</subject><subject>Molecular Sequence Data</subject><subject>Original Paper</subject><subject>Pancreas</subject><subject>Pathogenesis</subject><subject>Peptides</subject><subject>Point Mutation</subject><subject>Polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Sequence Alignment</subject><subject>Sequence Homology</subject><subject>Species Specificity</subject><subject>Veterinary 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Genetics</topic><topic>Immunology</topic><topic>Leukocytes</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical research</topic><topic>Molecular Sequence Data</topic><topic>Original Paper</topic><topic>Pancreas</topic><topic>Pathogenesis</topic><topic>Peptides</topic><topic>Point Mutation</topic><topic>Polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Sequence Alignment</topic><topic>Sequence Homology</topic><topic>Species Specificity</topic><topic>Veterinary medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsai, Kate L.</creatorcontrib><creatorcontrib>Starr-Moss, Alison N.</creatorcontrib><creatorcontrib>Venkataraman, Gopalakrishnan M.</creatorcontrib><creatorcontrib>Robinson, Christopher</creatorcontrib><creatorcontrib>Kennedy, Lorna J.</creatorcontrib><creatorcontrib>Steiner, Jörg M.</creatorcontrib><creatorcontrib>Clark, Leigh 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsai, Kate L.</au><au>Starr-Moss, Alison N.</au><au>Venkataraman, Gopalakrishnan M.</au><au>Robinson, Christopher</au><au>Kennedy, Lorna J.</au><au>Steiner, Jörg M.</au><au>Clark, Leigh Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs</atitle><jtitle>Immunogenetics (New York)</jtitle><stitle>Immunogenetics</stitle><addtitle>Immunogenetics</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>65</volume><issue>7</issue><spage>501</spage><epage>509</epage><pages>501-509</pages><issn>0093-7711</issn><eissn>1432-1211</eissn><abstract>Exocrine pancreatic insufficiency (EPI) is a disease wherein pancreatic acinar cells fail to synthesize and secrete sufficient amounts of digestive enzymes for normal digestion of food. EPI affects many dog breeds, with a dramatically higher prevalence in the German shepherd dog (GSD) population. In this breed and perhaps others, EPI most often results from degeneration of the acinar cells of the pancreas, a hereditary disorder termed pancreatic acinar atrophy (PAA). Evidence of lymphocytic infiltration indicates that PAA is an autoimmune disease, but the genetic etiology remains unclear. Data from global gene expression and single nucleotide polymorphism profiles in the GSD suggest the involvement of the major histocompatibility complex [MHC; dog leukocyte antigen (DLA)]. To determine if alleles of the MHC influence development of EPI, genotyping of polymorphic class I (DLA-88) and II loci (DLA-DRB1, DLA-DQA1, and DLA-DQB1) was carried out for 70 affected and 63 control GSDs, and four-locus haplotypes were determined. One haplotype containing a novel allele of DLA-88 is very highly associated with EPI (OR > 17;
P
= 0.000125), while two haplotypes were found to confer protection from EPI (
P
= 0.00087 and 0.0115). Described herein is the genotyping of MHC class I and II loci in a GSD cohort, establishment of four-locus haplotypes, and association of alleles/haplotypes with EPI.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>23604463</pmid><doi>10.1007/s00251-013-0704-y</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acinar Cells - immunology Acinar Cells - pathology Allergology Amino Acid Sequence Amino Acid Substitution Animals Antigens Atrophy Autoimmune Diseases - genetics Autoimmune Diseases - immunology Autoimmune Diseases - pathology Autoimmune Diseases - veterinary Base Sequence Biomedical and Life Sciences Biomedicine Biopsy Breeding Cell Biology Disease Dog Diseases - genetics Dog Diseases - immunology Dog Diseases - pathology Dogs - genetics Dogs - immunology Enzymes Exocrine Pancreatic Insufficiency - genetics Exocrine Pancreatic Insufficiency - immunology Exocrine Pancreatic Insufficiency - pathology Exocrine Pancreatic Insufficiency - veterinary Female Gene Function Genes Genotype Haplotypes Haplotypes - genetics Histocompatibility Antigens Class I - genetics Histocompatibility Antigens Class I - immunology Human Genetics Immunology Leukocytes Lymphocytes Male Medical research Molecular Sequence Data Original Paper Pancreas Pathogenesis Peptides Point Mutation Polymorphism Polymorphism, Single Nucleotide Sequence Alignment Sequence Homology Species Specificity Veterinary medicine |
| title | Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs |
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