Lorna Kennedy - Academia.edu (original) (raw)

Papers by Lorna Kennedy

Research paper thumbnail of Additional file 4: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S4. Frequency of DLA three-locus haplotypes in European (79 controls, 43 AD and 29 SLO) and... more Table S4. Frequency of DLA three-locus haplotypes in European (79 controls, 43 AD and 29 SLO) and North American (80 controls, 45 AD and 19 SLO) bearded collies. Bolded values indicate statistical differences in haplotype frequency according to geographical region as determined by the z-ratio test for independent proportions. Haplotype codes are as used in Table 5; additional codes added as needed. (DOCX 16 kb)

Research paper thumbnail of Additional file 2: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S2. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 61) vs controls... more Table S2. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 61) vs controls (n = 122) in bearded collies. Bolded values were statistically significant at α = 0.05 (DOCX 19 kb)

Research paper thumbnail of Additional file 14: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S14. Primer sequences used for DLA class II haplotyping (DOCX 13 kb)

Research paper thumbnail of Additional file 8: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S8. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 11) vs controls... more Table S8. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 11) vs controls (n = 13) in Leonbergers. Bolded values were statistically significant at α = 0.05 (DOCX 16 kb)

Research paper thumbnail of Additional file 5: Figures S5 and S6. of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

Biplots of the first two PCs in supertype clusters of DLA-DRB1 (Figure S5) and DLA-DQB1 loci (Fig... more Biplots of the first two PCs in supertype clusters of DLA-DRB1 (Figure S5) and DLA-DQB1 loci (Figure S6). The biplots were done using the ggbiplot function in R. Ellipses show Normal contour lines with 68% probability for each cluster. (ZIP 20Â kb)

Research paper thumbnail of Additional file 6: Table S3. of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

Result table for segregation of heterozygous and homozygous offspring in different mating cross t... more Result table for segregation of heterozygous and homozygous offspring in different mating cross types for the MHC loci, the three-locus haplotype and the MHC supertype levels, heterozygous mothers combined and the numbers of offspring that inherited maternal shared or paternal non-shared allele from their father. (XLSX 12Â kb)

Research paper thumbnail of Additional file 1: Table S1. of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

MHC genotype data and sample information for the dog families. (XLSX 53Â kb)

Research paper thumbnail of Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype

Research paper thumbnail of MHC class II polymorphism is associated with a canine SLE-related disease complex

Research paper thumbnail of Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

Canine Medicine and Genetics

Background Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number... more Background Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number of pathological mechanisms are thought to contribute to the aetiopathogenesis of relative or absolute insulin deficiency, including immune-mediated destruction of pancreatic beta cells. DM risk varies considerably between different dog breeds, suggesting that genetic factors are involved and contribute susceptibility or protection. Associations of particular dog leucocyte antigen (DLA) class II haplotypes with DM have been identified, but investigations to date have only considered all breeds pooled together. The aim of this study was to analyse an expanded data set so as to identify breed-specific diabetes-associated DLA haplotypes. Methods The 12 most highly represented breeds in the UK Canine Diabetes Register were selected for study. DLA-typing data from 646 diabetic dogs and 912 breed-matched non-diabetic controls were analysed to enable breed-specific analysis of the DLA. Dogs wer...

Research paper thumbnail of Comparative MHC nomenclature: report from the ISAG/IUIS-VIC committee 2018

Immunogenetics, Jan 24, 2018

Significant progress has been made over the last decade in defining major histocompatibility comp... more Significant progress has been made over the last decade in defining major histocompatibility complex (MHC) diversity at the nucleotide, allele, haplotype, diplotype, and population levels in many non-human species. Much of this progress has been driven by the increased availability and reduced costs associated with nucleotide sequencing technologies. This report provides an update on the activities of the comparative MHC nomenclature committee which is a standing committee of both the International Society for Animal Genetics (ISAG) and the International Union of Immunological Societies (IUIS) where it operates under the umbrella of the Veterinary Immunology Committee (VIC). A previous report from this committee in 2006 defined the role of the committee in providing guidance in the development of a standardized nomenclature for genes and alleles at MHC loci in non-human species. It described the establishment of the Immuno Polymorphism Database, IPD-MHC, which continues to provide p...

Research paper thumbnail of Single nucleotide polymorphisms in major histocompatibility class II haplotypes are associated with potential resistance to inflammatory bowel disease in German shepherd dogs

Veterinary immunology and immunopathology, 2016

German shepherd dogs (GSD) in the UK are at increased risk of developing the Inflammatory Bowel D... more German shepherd dogs (GSD) in the UK are at increased risk of developing the Inflammatory Bowel Disaese (IBD). IBD is believed to be a multifactorial immune mediated disease affecting genetically predisposed dogs. The aim of the current study was to investigate whether susceptibility to IBD in GSD is associated with the major histocompatibility complex (MHC) class II locus (Dog Leukocyte Antigen, DLA). Sequence-based genotyping of the three polymorphic DLA genes DLA-DRB1, -DQA1 and -DQB1 was performed in 56 GSDs affected by IBD and in 50 breed-matched controls without any history of gastrointestinal signs. The haplotype DLA-DRB1*015:02-DQA1*006:01-DQB1*023:01 was found to be present only in the control population and was associated with a reduced risk of IBD (P<0.001). In contrast, the haplotype DLA-DRB1*015:01-DQA1*006:01-DQB1*003:01 was associated with IBD (Odds ratio [OR]=1.93, confidence interval [CI]=1.02-3.67, P=0.05). This study has identified an association between DLA-ty...

Research paper thumbnail of MYD88 and functionally related genes are associated with multiple infections in a model population of Kenyan village dogs

Molecular biology reports, 2016

The purpose of this study was to seek associations between immunity-related molecular markers and... more The purpose of this study was to seek associations between immunity-related molecular markers and endemic infections in a model population of African village dogs from Northern Kenya with no veterinary care and no selective breeding. A population of village dogs from Northern Kenya composed of three sub-populations from three different areas (84, 50 and 55 dogs) was studied. Canine distemper virus (CDV), Hepatozoon canis, Microfilariae (Acantocheilonema dracunculoides, Acantocheilonema reconditum) and Neospora caninum were the pathogens studied. The presence of antibodies (CDV, Neospora), light microscopy (Hepatozoon) and diagnostic PCR (Microfilariae) were the methods used for diagnosing infection. Genes involved in innate immune mechanisms, NOS3, IL6, TLR1, TLR2, TLR4, TLR7, TLR9, LY96, MYD88, and three major histocompatibility genes class II genes were selected as candidates. Single nucleotide polymorphism (SNP) markers were detected by Sanger sequencing, next generation sequenci...

Research paper thumbnail of TIGIT gene variants and thyroid disease susceptibility in dogs and humans

Endocrine Abstracts, 2016

Research paper thumbnail of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

Canine Genetics and Epidemiology, 2016

Research paper thumbnail of DNA archive for companion animals

The Veterinary Record, Jul 1, 2007

Research paper thumbnail of DLA-DRBI, DQAI, and DQBI alleles and haplotypes in North American gray wolves

The Journal of Heredity, 2007

Research paper thumbnail of Cytotoxic Monoclonal Antibodies

In Dupont B Immunobiology of Hla Histocompatibility Testing 1987 Springer Verlag New York, 1989

Research paper thumbnail of Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog

Veterinary Immunology and Immunopathology, Aug 2, 1999

Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on ind... more Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on individual allele frequencies exists, either for specific breeds or cross breeds, and the full extent of the polymorphism at each of these loci is still not known. We have used sequence-specific oligonucleotide probing (SSOP) to characterise a series of 367 dogs for their DRB1 and DQA1 alleles. These included individual animals from over 60 different breeds, with numbers per breed ranging from 1 to 39. DLA types were generated from 218 dogs for DRB1 and from 330 dogs for DQA1, while 181 dogs were characterised for both these loci. The frequency of individual DRB1 and DQA1 alleles showed considerable interbreed variation, e.g. 83% of West Highland White Terriers were DRB1*01 as opposed to 9% of Collies. No breed had &gt;9 of the 22 DRB1 types defined in this study; several breeds had only two DRB1 types. DLA-DQA1 showed less variation in allele numbers per breed, but also showed considerable interbreed frequency variation. Haplotype analysis revealed over 44 different DRB1/DQA1 combinations. Of these, 25 were in a number of animals, and also in an animal that was homozygous for one or both of these loci. Some DRB1 alleles could be found in combination with several different DQA1 alleles, while others were only present in one haplotypic combination. DLA allele frequency data in normal dogs will be critical for disease association studies. It may also be possible to use haplotype data to establish the genetic relationships between different dog breeds.

Research paper thumbnail of Frequency and distribution of alleles of canine MHC‐II DLA‐DQB1, DLA‐DQA1 and DLA‐DRB1 in 25 representative American Kennel Club breeds

Tissue Antigens, Sep 1, 2005

The frequency and distribution of dog leucocyte antigens (DLA) class II -DQA1, -DQB1 and -DRB1 al... more The frequency and distribution of dog leucocyte antigens (DLA) class II -DQA1, -DQB1 and -DRB1 alleles were determined for 25 American Kennel Club (AKC) registered dog breeds, representing 360 dogs from each of the seven major performance categories. Six to twenty-eight (average n=11) dogs were studied per group, with the exception of the Akita dog (n=94). All dogs were unrelated with no common grandparents based on AKC pedigree records (F-value &amp;amp;lt;0.125). DLA class II allelic diversity was broad across breeds; 31/61 published DLA-DRB1 alleles, 11/18 published DLA-DQA1 alleles and 31/47 published DLA-DQB1 alleles were found among the 25 breeds. However, allelic diversity was severely limited within a breed. Seventeen of the DLA-DRB1 alleles were each found in only a single breed, and only seven alleles were shared by seven or more breeds. DLA-DRB1*00101 and DLA-DRB1*01501 were shared by 16 and 19 breeds, respectively. DLA-DQA1*00101 and DLA-DQA1*00601 alleles were shared by many breeds. The Rough Collie (DLA-DQA1*00901), English Setter (DLA-DQA1*00101) and Scottish Terrier (DLA-DQA1*00101) were monoallelic for DLA-DQA1. Eleven DLA-DQB1 alleles were each found only in a single breed and only seven alleles were shared by six or more breeds. DLA-DQB1*00201 and DLA-DQB1*02301 were shared by 17 and 18 breeds, respectively. Forty per cent of dogs typed were homozygous at DLA-DRB1, 52% at DLA-DQA1 and 44% at DLA-DQB1. Nine new DLA class II alleles were identified; three for DRB1 and six for DQB1. Comparison of our study of North American purebred dogs to previous European DLA surveys showed a similar use of common alleles consistent with known founder effects. However, more alleles were detected in European breeds, compared to their North American descendents, indicating that additional DLA class II diversity was lost when European breeds were established in North America.

Research paper thumbnail of Additional file 4: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S4. Frequency of DLA three-locus haplotypes in European (79 controls, 43 AD and 29 SLO) and... more Table S4. Frequency of DLA three-locus haplotypes in European (79 controls, 43 AD and 29 SLO) and North American (80 controls, 45 AD and 19 SLO) bearded collies. Bolded values indicate statistical differences in haplotype frequency according to geographical region as determined by the z-ratio test for independent proportions. Haplotype codes are as used in Table 5; additional codes added as needed. (DOCX 16 kb)

Research paper thumbnail of Additional file 2: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S2. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 61) vs controls... more Table S2. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 61) vs controls (n = 122) in bearded collies. Bolded values were statistically significant at α = 0.05 (DOCX 19 kb)

Research paper thumbnail of Additional file 14: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S14. Primer sequences used for DLA class II haplotyping (DOCX 13 kb)

Research paper thumbnail of Additional file 8: of DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds

Table S8. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 11) vs controls... more Table S8. Allele frequency and odds ratio (OR) for Addison's disease (AD; n = 11) vs controls (n = 13) in Leonbergers. Bolded values were statistically significant at α = 0.05 (DOCX 16 kb)

Research paper thumbnail of Additional file 5: Figures S5 and S6. of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

Biplots of the first two PCs in supertype clusters of DLA-DRB1 (Figure S5) and DLA-DQB1 loci (Fig... more Biplots of the first two PCs in supertype clusters of DLA-DRB1 (Figure S5) and DLA-DQB1 loci (Figure S6). The biplots were done using the ggbiplot function in R. Ellipses show Normal contour lines with 68% probability for each cluster. (ZIP 20Â kb)

Research paper thumbnail of Additional file 6: Table S3. of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

Result table for segregation of heterozygous and homozygous offspring in different mating cross t... more Result table for segregation of heterozygous and homozygous offspring in different mating cross types for the MHC loci, the three-locus haplotype and the MHC supertype levels, heterozygous mothers combined and the numbers of offspring that inherited maternal shared or paternal non-shared allele from their father. (XLSX 12Â kb)

Research paper thumbnail of Additional file 1: Table S1. of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

MHC genotype data and sample information for the dog families. (XLSX 53Â kb)

Research paper thumbnail of Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype

Research paper thumbnail of MHC class II polymorphism is associated with a canine SLE-related disease complex

Research paper thumbnail of Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds

Canine Medicine and Genetics

Background Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number... more Background Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number of pathological mechanisms are thought to contribute to the aetiopathogenesis of relative or absolute insulin deficiency, including immune-mediated destruction of pancreatic beta cells. DM risk varies considerably between different dog breeds, suggesting that genetic factors are involved and contribute susceptibility or protection. Associations of particular dog leucocyte antigen (DLA) class II haplotypes with DM have been identified, but investigations to date have only considered all breeds pooled together. The aim of this study was to analyse an expanded data set so as to identify breed-specific diabetes-associated DLA haplotypes. Methods The 12 most highly represented breeds in the UK Canine Diabetes Register were selected for study. DLA-typing data from 646 diabetic dogs and 912 breed-matched non-diabetic controls were analysed to enable breed-specific analysis of the DLA. Dogs wer...

Research paper thumbnail of Comparative MHC nomenclature: report from the ISAG/IUIS-VIC committee 2018

Immunogenetics, Jan 24, 2018

Significant progress has been made over the last decade in defining major histocompatibility comp... more Significant progress has been made over the last decade in defining major histocompatibility complex (MHC) diversity at the nucleotide, allele, haplotype, diplotype, and population levels in many non-human species. Much of this progress has been driven by the increased availability and reduced costs associated with nucleotide sequencing technologies. This report provides an update on the activities of the comparative MHC nomenclature committee which is a standing committee of both the International Society for Animal Genetics (ISAG) and the International Union of Immunological Societies (IUIS) where it operates under the umbrella of the Veterinary Immunology Committee (VIC). A previous report from this committee in 2006 defined the role of the committee in providing guidance in the development of a standardized nomenclature for genes and alleles at MHC loci in non-human species. It described the establishment of the Immuno Polymorphism Database, IPD-MHC, which continues to provide p...

Research paper thumbnail of Single nucleotide polymorphisms in major histocompatibility class II haplotypes are associated with potential resistance to inflammatory bowel disease in German shepherd dogs

Veterinary immunology and immunopathology, 2016

German shepherd dogs (GSD) in the UK are at increased risk of developing the Inflammatory Bowel D... more German shepherd dogs (GSD) in the UK are at increased risk of developing the Inflammatory Bowel Disaese (IBD). IBD is believed to be a multifactorial immune mediated disease affecting genetically predisposed dogs. The aim of the current study was to investigate whether susceptibility to IBD in GSD is associated with the major histocompatibility complex (MHC) class II locus (Dog Leukocyte Antigen, DLA). Sequence-based genotyping of the three polymorphic DLA genes DLA-DRB1, -DQA1 and -DQB1 was performed in 56 GSDs affected by IBD and in 50 breed-matched controls without any history of gastrointestinal signs. The haplotype DLA-DRB1*015:02-DQA1*006:01-DQB1*023:01 was found to be present only in the control population and was associated with a reduced risk of IBD (P<0.001). In contrast, the haplotype DLA-DRB1*015:01-DQA1*006:01-DQB1*003:01 was associated with IBD (Odds ratio [OR]=1.93, confidence interval [CI]=1.02-3.67, P=0.05). This study has identified an association between DLA-ty...

Research paper thumbnail of MYD88 and functionally related genes are associated with multiple infections in a model population of Kenyan village dogs

Molecular biology reports, 2016

The purpose of this study was to seek associations between immunity-related molecular markers and... more The purpose of this study was to seek associations between immunity-related molecular markers and endemic infections in a model population of African village dogs from Northern Kenya with no veterinary care and no selective breeding. A population of village dogs from Northern Kenya composed of three sub-populations from three different areas (84, 50 and 55 dogs) was studied. Canine distemper virus (CDV), Hepatozoon canis, Microfilariae (Acantocheilonema dracunculoides, Acantocheilonema reconditum) and Neospora caninum were the pathogens studied. The presence of antibodies (CDV, Neospora), light microscopy (Hepatozoon) and diagnostic PCR (Microfilariae) were the methods used for diagnosing infection. Genes involved in innate immune mechanisms, NOS3, IL6, TLR1, TLR2, TLR4, TLR7, TLR9, LY96, MYD88, and three major histocompatibility genes class II genes were selected as candidates. Single nucleotide polymorphism (SNP) markers were detected by Sanger sequencing, next generation sequenci...

Research paper thumbnail of TIGIT gene variants and thyroid disease susceptibility in dogs and humans

Endocrine Abstracts, 2016

Research paper thumbnail of No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

Canine Genetics and Epidemiology, 2016

Research paper thumbnail of DNA archive for companion animals

The Veterinary Record, Jul 1, 2007

Research paper thumbnail of DLA-DRBI, DQAI, and DQBI alleles and haplotypes in North American gray wolves

The Journal of Heredity, 2007

Research paper thumbnail of Cytotoxic Monoclonal Antibodies

In Dupont B Immunobiology of Hla Histocompatibility Testing 1987 Springer Verlag New York, 1989

Research paper thumbnail of Interbreed variation of DLA-DRB1, DQA1 alleles and haplotypes in the dog

Veterinary Immunology and Immunopathology, Aug 2, 1999

Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on ind... more Although 36 DLA-DRB1 and 10 DLA-DQA1 allele sequences have been published to date, no data on individual allele frequencies exists, either for specific breeds or cross breeds, and the full extent of the polymorphism at each of these loci is still not known. We have used sequence-specific oligonucleotide probing (SSOP) to characterise a series of 367 dogs for their DRB1 and DQA1 alleles. These included individual animals from over 60 different breeds, with numbers per breed ranging from 1 to 39. DLA types were generated from 218 dogs for DRB1 and from 330 dogs for DQA1, while 181 dogs were characterised for both these loci. The frequency of individual DRB1 and DQA1 alleles showed considerable interbreed variation, e.g. 83% of West Highland White Terriers were DRB1*01 as opposed to 9% of Collies. No breed had &gt;9 of the 22 DRB1 types defined in this study; several breeds had only two DRB1 types. DLA-DQA1 showed less variation in allele numbers per breed, but also showed considerable interbreed frequency variation. Haplotype analysis revealed over 44 different DRB1/DQA1 combinations. Of these, 25 were in a number of animals, and also in an animal that was homozygous for one or both of these loci. Some DRB1 alleles could be found in combination with several different DQA1 alleles, while others were only present in one haplotypic combination. DLA allele frequency data in normal dogs will be critical for disease association studies. It may also be possible to use haplotype data to establish the genetic relationships between different dog breeds.

Research paper thumbnail of Frequency and distribution of alleles of canine MHC‐II DLA‐DQB1, DLA‐DQA1 and DLA‐DRB1 in 25 representative American Kennel Club breeds

Tissue Antigens, Sep 1, 2005

The frequency and distribution of dog leucocyte antigens (DLA) class II -DQA1, -DQB1 and -DRB1 al... more The frequency and distribution of dog leucocyte antigens (DLA) class II -DQA1, -DQB1 and -DRB1 alleles were determined for 25 American Kennel Club (AKC) registered dog breeds, representing 360 dogs from each of the seven major performance categories. Six to twenty-eight (average n=11) dogs were studied per group, with the exception of the Akita dog (n=94). All dogs were unrelated with no common grandparents based on AKC pedigree records (F-value &amp;amp;lt;0.125). DLA class II allelic diversity was broad across breeds; 31/61 published DLA-DRB1 alleles, 11/18 published DLA-DQA1 alleles and 31/47 published DLA-DQB1 alleles were found among the 25 breeds. However, allelic diversity was severely limited within a breed. Seventeen of the DLA-DRB1 alleles were each found in only a single breed, and only seven alleles were shared by seven or more breeds. DLA-DRB1*00101 and DLA-DRB1*01501 were shared by 16 and 19 breeds, respectively. DLA-DQA1*00101 and DLA-DQA1*00601 alleles were shared by many breeds. The Rough Collie (DLA-DQA1*00901), English Setter (DLA-DQA1*00101) and Scottish Terrier (DLA-DQA1*00101) were monoallelic for DLA-DQA1. Eleven DLA-DQB1 alleles were each found only in a single breed and only seven alleles were shared by six or more breeds. DLA-DQB1*00201 and DLA-DQB1*02301 were shared by 17 and 18 breeds, respectively. Forty per cent of dogs typed were homozygous at DLA-DRB1, 52% at DLA-DQA1 and 44% at DLA-DQB1. Nine new DLA class II alleles were identified; three for DRB1 and six for DQB1. Comparison of our study of North American purebred dogs to previous European DLA surveys showed a similar use of common alleles consistent with known founder effects. However, more alleles were detected in European breeds, compared to their North American descendents, indicating that additional DLA class II diversity was lost when European breeds were established in North America.