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Introduction
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Publications
Publications (248)
MHC genes are highly polymorphic as antigen presenting molecules for adaptive immune response in vertebrates. In this study, we evaluated the diversity of dog leukocyte antigen (DLA) class II genes among two Korean breeds, the Sapsaree and the Jindo, and three Chinese native breeds, Tibetan Mastiff, Pug, and Pekingese, and determined their genetic...
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, suggesti...
Background:
Canine hypoadrenocorticism is an immune-mediated endocrinopathy that shares both clinical and pathophysiological similarities with Addison's disease in humans. Several dog breeds are overrepresented in the disease population, suggesting that a genetic component is involved, although this is likely to be polygenic. Previous research has...
The classical class I and class II molecules of the major histocompatibility complex (MHC) play crucial roles in immune responses to infectious pathogens and vaccines as well as being important for autoimmunity, allergy, cancer and reproduction. These classical MHC genes are the most polymorphic known, with roughly 10,000 alleles in humans. In chic...
Background
Primary hypoadrenocorticism (Addison’s disease, AD) and symmetrical lupoid onychodystrophy (SLO) are two clinical conditions with an autoimmune etiology that occur in multiple dog breeds. In man, autoimmunity is associated with polymorphisms in immune-related genes that result in a reduced threshold for, or defective regulation of, T cel...
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 technologie...
The village and street dogs represent a unique model of canine populations. In the absence of selective breeding and veterinary care, they are subject mostly to natural selection. Their analyses contribute to understanding general mechanisms governing the genetic diversity, evolution and adaptation. In this study, we analyzed the genetic diversity...
Estimation of the population substructure across MHC loci in the Kenyan village dogs (K = 3) using Structure software.
(TIF)
The allelic frequencies of 27 microsatellite loci for Kenyan (n = 150) and European dogs (n = 68).
(DOCX)
Number of alleles per locus. number of effective alleles per locus and fixation index for microsatellite markers in Kenyan village dog subpopulations and European dogs.
MK–Mt. Kulal. MN–Mt. Ngyiro. LK–Lake Turkana. E–European dogs. SEM standard error of the mean.
(DOCX)
Principal coordinates analysis (PCoA) (first and second coordinate) of survivor (n = 21) and Mt. Kulal (n = 39) dogs based on microsatellite markers.
(TIF)
Observed and expected heterozygosities and observed number of alleles for 27 loci of microsatellite for Kenyan dogs, European dogs and Survivor dogs.
SEM standard error of the mean.
(DOCX)
Observed and expected heterozygosities for 27 microsatellie loci for Kenyan dogs subpopulations.
MK- Mt. Kulal. MN- Mt. Ngyiro. LK- Lake Turkana.
(DOCX)
The allelic frequencies of MHC loci for Kenyan dogs subpopulations (n = 41 Mt. Kulal dogs, 47 Mt. Ngyiro dogs, 47 Lake Turkana dogs).
(DOCX)
Observed and expected heterozygosities, observed number of alleles and number of loci out of HWE for 10 microsatellite loci (FHC2010, FHC2054, FHC2079, PEZ1, PEZ3, PEZ5, PEZ6, PEZ8, PEZ12, PEZ20) for Kenyan dogs, European dogs (group of 24 pure breeds and 6 mongrels) and four groups of pure breeds- Basset, Bernese Mountain Dog, European Terrier and...
Tajima´s test of selective neutrality.
(DOCX)
Principal coordinates analysis (PCoA) (first and second coordinate) of survivor (n = 21) and Mt. Kulal dogs (n = 39) based on SNP markers.
(TIF)
Observed, expected heterozygosities and number of genotypes for 16 SNP loci for Kenyan dogs. European dogs and Survivor dogs.
* Not the same alleles. ** only AA and Aa genotypes.
(DOCX)
Observed. expected heterozygosities. number of genotypes and MAF for 16 SNP loci for Kenyan dogs subpopulations.
MK- Mt. Kulal. MN- Mt. Ngyiro. LK- Lake Turkana* Not the same alleles. ** only AA and Aa genotypes.
(DOCX)
The correlation of Reynolds genetic distances for three types of markers.
NS Non-significant, **P<0.01.
(DOCX)
Graphical representation of the estimated membership of the Kenyan and European dogs in each of the inferred clusters (K = 3) based on microsatellite markers.
(TIF)
Graphical representation of the estimated membership of the Kenyan and European dogs in each of the inferred clusters (K = 3) based on SNP markers.
(TIF)
The allelic frequencies of 16SNP markers for Kenyan dogs subpopulations, entire Kenyan dogs population and European dogs.
(DOCX)
The allelic frequencies of 27 microsatellite loci for Kenyan dogs subpopulations (n = 50 Mt. Kulal dogs, 50 Mt. Ngyiro dogs, 50 Lake Turkana dogs).
(DOCX)
Observed. expected heterozygosities and number of alleles for MHC loci for Kenyan village dogs subpopulations.
(DOCX)
Fixation indices over all Kenyan village dogs (n = 150) for microsatellite markers.
(DOCX)
Molecular diversity of microsatellites: Number of alleles.
observed (Ho) and expected (He) heterozygosities and loci out of HWE.
(DOCX)
Major histocompatibility complex (MHC) genes in mammals include highly polymorphic class I and class II genes that are critical for donor-recipient matching for transplantation. Dogs have served as an effective, directly translatable model for stem/progenitor cell transplantation. Previous analyses of MHC class I genes in dogs point to a single hig...
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, 5...
Background
Despite decades of studying, the mechanisms maintaining high diversity in the genes of the Major Histocompatibility Complex (MHC) are still puzzling scientists. In addition to pathogen recognition and other functions, MHC molecules may act prenatally in mate choice and in maternal-foetal interactions. These interactions are potential sel...
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 com...
Background: The autoimmune thyroid diseases, primary autoimmune hypothyroidism (AH) and Graves hyperthyroidism (GD), represent the most prevalent endocrine disorders. Although clinically distinct, they share several genetic susceptibility loci, many of which remain unidentified.
TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domains), e...
Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes,...
Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback...
Administration of insulin for treatment of diabetes mellitus in dogs can stimulate an immune response, with a proportion of animals developing anti-insulin antibodies (AIA). For an IgG antibody response to occur, this would require B cell presentation of insulin peptides by major histocompatibility complex (MHC) class II molecules, encoded by dog l...
A retrospective study of the clinicopathological features of presumed and confirmed cases of idiopathic inflammatory polymyopathy in the Hungarian Vizsla dog and guidelines for breeding.
369 medical records were reviewed (1992-2013) and 77 Hungarian Vizslas were identified with a case history consistent with idiopathic inflammatory polymyopathy. In...
Beagles are commonly used in vaccine trials as part of the regulatory approval process. Genetic restriction within this breed and the impact this might have on vaccine responses is rarely considered. This study was designed to characterise diversity of dog leucocyte antigen (DLA) class II genes in a breeding colony of laboratory Beagles, whose offs...
CANINE hypoadrenocorticism results from structural damage/functional defects of the adrenal cortex. In human beings, 21 hydroxylase autoantibodies are an early marker for a clinically similar condition (Addison's disease) in 80–90 per cent of patients (Betterle and others 1999, Falorni and others 1995, 1997, Laureti and others 1998), but these anti...
Background:
Canine diabetes is a common endocrine disorder with an estimated breed-related prevalence ranging from 0.005% to 1.5% in pet dogs. Increased prevalence in some breeds suggests that diabetes in dogs is influenced by genetic factors and similarities between canine and human diabetes phenotypes suggest that the same genes might be associa...
Non-suppurative meningoencephalitis is a breed-restricted canine neuroinflammatory disorder affecting young greyhounds in Ireland. A genetic risk factor is suspected because of the development of disease in multiple siblings and an inability to identify a causative infectious agent. The aim of this study was to examine potential associations betwee...
Canine anal furunculosis (AF) is characterised by ulceration and fistulation of perianal tissue and is a disease that particularly affects German shepherd dogs (GSDs). There are some similarities between AF and perianal Crohn's disease (CD) in man. An immune-mediated aetiopathogenesis for AF has been suggested due to tissue pathology, a major histo...
Maintaining effective immune response is an essential factor in the survival of small populations. One of the most important immune gene regions is the highly polymorphic Major Histocompatibility Complex (MHC). We investigated how a population bottleneck and recovery have influenced the diversity and selection in three MHC class II loci, DLA-DRB1,...
Canine hypoadrenocorticism is believed to be an immune-related condition. It is rare in the overall dog population but shows a breed-related predisposition with Standard poodles and Portuguese water dogs having a greater prevalence of the condition. It shares many similarities with human primary adrenal insufficiency and is believed to be a natural...
Canine diabetes mellitus (DM) shares many similarities with human type 1 diabetes (T1D). It is a complex genetic disorder, which shows marked differences in breed susceptibility, with Samoyed dogs being highly susceptible, whereas the Boxer breed is relatively resistant. A number of immune response genes, which have been associated with human T1D,...
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 res...
Haplotype counts for the two breeds with only suggestive or no significant associations
Haplotype counts for the six breeds with significant associations
A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associati...
Canine hypoadrenocorticism is an endocrine disorder characterised by inadequate secretion of steroid hormones from the adrenal glands. Pathology results from immune-mediated destruction of the adrenal cortex, which is similar to that seen in the human Addison's disease. Both the canine and human diseases have similar clinical presentation, with the...
Background
Dogslife is the first large-scale internet-based longitudinal study of canine health. The study has been designed to examine how environmental and genetic factors influence the health and development of a birth cohort of UK-based pedigree Labrador Retrievers.
Results
In the first 12 months of the study 1,407 Kennel Club (KC) registered...
Small isolated populations often show lower genetic variability. Demographic bottlenecks lead to loss of genetic variation too. Arctic foxes (Vulpes lagopus) have been isolated since the Pleistocene on Mednyi and Bering Islands (Commander Islands). In 1970–1980, the Mednyi population passed through a severe bottleneck due to a mange outbreak. Previ...
Diabetes mellitus is a common endocrinopathy in companion animals, characterised by hyperglycaemia, glycosuria and weight loss, resulting from an absolute or relative deficiency in the pancreatic hormone insulin. There are breed differences in susceptibility to diabetes mellitus in dogs, with the Samoyed breed being overrepresented, while Boxers ar...
Chronic hepatitis (CH) is common in dogs in the United Kingdom. An increased prevalence of the disease is seen in the English Springer spaniel (ESS), and this breed suffer from a severe form with young to middle aged female dogs being predisposed. The disease shares histological features with those of human viral hepatitis, although the specific ae...
Background:
The current disease model for leishmaniasis suggests that only a proportion of infected individuals develop clinical disease, while others are asymptomatically infected due to immune control of infection. The factors that determine whether individuals progress to clinical disease following Leishmania infection are unclear, although pre...
Distribution of EMP1 across SNP sets of candidate regions. Sets comprise SNPs in the following regions: 6 (CFA 4:61.2–63.2 Mb), 7 (CFA 4: 70.5–74.5 Mb), 8 (CFA 4: 74.8–76.9 Mb), 19 (CFA 9: 40.0–46.5 Mb) and 22 (CFA 10: 29.6–31.5 Mb).
(TIFF)
Genome-wide plot of the absolute mean SNP effects estimated with BayesB for Model 1 (A), Model 2 (B) and Model 3 (C). The peak on CFA 4: 61–77 Mb (red segment) consistent across Models 1–3 coincided with both the strongest association in GWAS analysis and the region in which SNP sets covering candidate genes were significant (EMP1<0.01).
(TIFF)
Genetic stratification. (A) relative genetic variance explained by the 219 MDS dimensions extracted; (B) MDS plot for the first two MDS dimensions (C1 and C2) with healthy infected and affected samples coloured differently. The percentage of relative genetic variance explained by each dimension is indicated as well as the genomic inflation factor (...