scholarly journals Haplotyping MHC class IIa by high throughput screening in an isolated sheep population

2020 ◽  
Author(s):  
K.L. Dicks ◽  
J.M. Pemberton ◽  
K.T. Ballingall ◽  
S.E. Johnston

AbstractInvestigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within the DQA1 gene enabled detection of a recombinant SNP haplotype. The panel of 13 SNPs was genotyped in 5951 sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of a recombinant SNP haplotype.

Author(s):  
Kara L Dicks ◽  
Josephine M Pemberton ◽  
Keith T Ballingall ◽  
Susan E Johnston

Abstract Investigating the current evolutionary processes acting on a highly polymorphic gene region, such as the major histocompatibility complex (MHC), requires extensive population data for both genotypes and phenotypes. The MHC consists of several tightly linked loci with both allelic and gene content variation, making it challenging to genotype. Eight class IIa haplotypes have previously been identified in the Soay sheep (Ovis aries) of St. Kilda using Sanger sequencing and cloning, but no single locus is representative of all haplotypes. Here, we exploit the closed nature of the island population of Soay sheep and its limited haplotypic variation to identify a panel of SNPs that enable imputation of MHC haplotypes. We compared MHC class IIa haplotypes determined by Sanger sequence-based genotyping of 135 individuals to their SNP profiles generated using the Ovine Infinium HD BeadChip. A panel of 11 SNPs could reliably determine MHC diplotypes, and two additional SNPs within the DQA1 gene enabled detection of a recombinant haplotype affecting only the SNPs downstream of the expressed genes. The panel of 13 SNPs was genotyped in 5951 Soay sheep, of which 5349 passed quality control. Using the Soay sheep pedigree, we were able to trace the origin and inheritance of the recombinant SNP haplotype. This SNP-based method has enabled the rapid generation of locus-specific MHC genotypes for large numbers of Soay sheep. This volume of high-quality genotypes in a well-characterized population of free-living sheep will be valuable for investigating the mechanisms maintaining diversity at the MHC.


Parasitology ◽  
1992 ◽  
Vol 105 (3) ◽  
pp. 481-492 ◽  
Author(s):  
F. M. D. Gulland ◽  
M. Fox

SUMMARYThe epidemiology of nematode infections of Soay sheep on the island of St Kilda over a period of 2 years (August 1988–August 1990) spanning a host population crash is described. Infective larvae (L3) levels on pasture were high (2422±365 L3/kg D.M. grass in midsummer 1988) when host population density was high, decreasing after the sheep population declined by 70% in early 1989 (601 ±14 L3/kg D.M. in midsummer 1989). The availability of infective larvae to sheep increased during the winter of 1988–1989, probably as a result of concentration of existing larvae on grass as vegetation was destroyed by bad weather and overgrazing. Increased availability of pre-parasitic stages was accompanied by a marked increased in faecal egg counts from sheep of all ages and both sexes. Prevalence and intensity of infection (faecal egg counts) were higher in males than females throughout the 2-year study (χ2 = 208.3, P < 0.005 and F1.2000 = 304, P < 0.001 respectively), except during the lambing periods, and decreased with age in both sexes. Changes in prevalence and intensity of strongyle infections were associated with changes in host population density. Prevalence and intensity of Dictyocaulus filaria larvae in faeces increased during the host population crash. Infection intensity decreased with age (F1.203 = 44.02, P < 0.001) and was higher in males than females (F1.203 = 13.45, P < 0.001).


Genetika ◽  
2013 ◽  
Vol 45 (2) ◽  
pp. 611-619
Author(s):  
Oindrila Raha ◽  
B Sarkar ◽  
P. Veerraju ◽  
G. Sudhakar ◽  
P. Raychaudhuri ◽  
...  

Background. The major histocompatibility complex class I chain-related gene A (MICA) (OMIM-600169) is a polymorphic gene in the HLA region expressed mainly by epithelial cells. The MICA protein encoded by the allele influences the activation of NK cells, which modify ?-cells destruction and has been found to be involved in susceptibility of T1DM. Objective. The aim of this study was to find the association of MICA alleles with T1DM among eastern Indian population. Subjects and methods.Study was conducted in 134 eastern Indian patients and with 137 healthy controls for the possible role of MICA gene in T1DM pathogenesis. Results. The MICA*A5 microsatellite allele, showed significantly higher frequencies in patients than controls (p=0.003, OR= 1.746, CI= 1.206-2.528). MICA A*6 was found to be protective in our study (p=<0.01, OR=0.406, CI= 0.268-0.616).


Behaviour ◽  
2004 ◽  
Vol 141 (8) ◽  
pp. 999-1020 ◽  
Author(s):  
◽  
◽  

AbstractHerbivorous ungulates live in a spatially heterogeneous environment making foraging decisions at a range of hierarchical scales, from bite size to landscape. We investigated the factors that control intake rate in Soay sheep (Ovis aries) when discrete items of food were sparsely distributed at the feeding station scale. Within the feeding station we varied the difficulty of accessing food, distance between items of food, difficulty of finding the food and complexity of the feeding station and recorded how intake rate responded in relation to body size, mouth size and the sex of the animal. Our findings demonstrated how increasing difficulty of accessing food, and increasing complexity of the feeding station negatively affected intake rate. The expected mechanistic response that smaller animals or animals with smaller mouth size were better at handling discrete small items of food, was overridden by individual and sexual differences in behaviour. We also considered that intake rate within a feeding station could be maximised by optimising the spatial pattern of offtake, and the results clearly indicated that both sexes tended to show clustered patterns of offtake. Animals of the same sex responded in a similar way to the difficulty in handling food items; males persevered more than females and consequently were less handicaped by having larger mouths. We discussed these results in relation to behavioural and body mass differences between the sexes and animals.


2018 ◽  
Vol 115 (7) ◽  
pp. 1552-1557 ◽  
Author(s):  
Karl P. Phillips ◽  
Joanne Cable ◽  
Ryan S. Mohammed ◽  
Magdalena Herdegen-Radwan ◽  
Jarosław Raubic ◽  
...  

The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host–pathogen “Red Queen” coevolution, it has not been demonstrated in the context of natural MHC diversity. Here, we experimentally tested whether novel MHC variants (both alleles and functional “supertypes”) increased resistance of guppies (Poecilia reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure-controlled infection trials with wild-sourced parasites, and Gyrodactylus-naïve host fish that were F2 descendants of crossed wild populations. Hosts carrying MHC variants (alleles or supertypes) that were new to a given parasite population experienced a 35–37% reduction in infection intensity, but the number of MHC variants carried by an individual, analogous to heterozygosity in single-locus systems, was not a significant predictor. Our results provide direct evidence of novel MHC variant advantage, confirming a fundamental mechanism underpinning the exceptional polymorphism of this gene family and highlighting the role of immunogenetic novelty in host–pathogen coevolution.


PLoS Genetics ◽  
2019 ◽  
Vol 15 (11) ◽  
pp. e1008461 ◽  
Author(s):  
Alexandra M. Sparks ◽  
Kathryn Watt ◽  
Rona Sinclair ◽  
Jill G. Pilkington ◽  
Josephine M. Pemberton ◽  
...  

1996 ◽  
Vol 74 (10) ◽  
pp. 1812-1818 ◽  
Author(s):  
Denis Réale ◽  
Patrick Boussès ◽  
Jean-Louis Chapuis

In contrast to most populations of sexually dimorphic ungulates, a 3-year study revealed a tertiary sex ratio (the number of males per female at sexual maturity) strongly biased towards males in the Île Longue feral sheep (Ovis aries) population (Kerguelen subantarctic archipelago). This population presents a main winter lambing season and a secondary summer lambing period. The sex ratios of lambs and lamb carcasses were even. The skewed sex ratio of adults was therefore attributed to shorter longevity of females. We showed that (i) male monthly mortality followed a bimodal distribution with peaks corresponding to the two rutting periods. Male mortality was, however, highest during the winter even though less rutting occurred in this season than in the summer, suggesting that harsher winter conditions enhance the cost of mating competition; (ii) female mortality was related to the rutting activity of males but not to lambing. Female mortality peaked in the summer despite plentiful food resources. This period corresponds to the main rutting peak, suggesting a high survival cost of mating for females. Female mortality due to male harassment was confirmed by direct observations and examination of females injured during rutting periods. This situation may be due to a strongly male-biased operational sex ratio in the population, associated with an inability of males to establish a stable dominance hierarchy within a large flock.


1980 ◽  
Vol 22 (4) ◽  
pp. 497-506 ◽  
Author(s):  
Nancy E. Simpson

The genetics of diabetes mellitus in man has been reviewed. The evidence for genetic heterogeneity on clinical, biochemical and HLA (histocompatibility leukocyte antigens) data is presented. An attempt is made to interpret the meaning of the associations of the disease and certain HLA antigens and the complement factor, properdin in populations and in families. The population data can be best explained by the linkage disequilibrium hypothesis requiring tight linkage between the DS (diabetes susceptibility) locus and those in the MHC (major histocompatibility complex). Linkage between the DS locus and MHC from family data is estimated to be about 14%, which is not likely tight enough to be compatible with the population data; and a one locus or one allele hypothesis and genetic heterogeneity is postulated as the best explanation of the incompatibility between population and family data. It is still impossible to precisely define the exact genetic hypothesis for diabetes in man.


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