scholarly journals The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)

2019 ◽  
Author(s):  
A. M. Sparks ◽  
K. Watt ◽  
R. Sinclair ◽  
J. G. Pilkington ◽  
J. M. Pemberton ◽  
...  
Keyword(s):  
Immune Responses ◽  
Genetic Architecture ◽  
Wild Population ◽  
Natural Populations ◽  
Natural Conditions ◽  
Soay Sheep ◽  
Histocompatibility Complex ◽  
Immune Traits ◽  
Antibody Levels ◽  
Host Parasite

AbstractHost-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural populations. Variation in immune responses to infection is likely to shape the outcome of these interactions, with important consequences for the fitness of both host and parasite. However, little is known about how genetic variation contributes to variation in immune responses under natural conditions. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematodeTeladorsagia circumcinctain the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable, ranging from 0.21 to 0.39 in lambs and from 0.23 to 0.57 in adults. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively; this region was adjacent to two candidate loci, the Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex on chromosome 18. Adult IgE levels and lamb IgG levels were associated with the major histocompatibility complex (MHC) on chromosome 20. This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.Author summaryHost-parasite interactions are powerful drivers of evolutionary and ecological dynamics in natural populations. Variation in immune responses to infection shapes the outcome of these interactions, with important consequences for the ability of the host and parasite to survive and reproduce. However, little is known about how much genes contribute to variation in immune responses under natural conditions. Our study investigates the genetic architecture of variation in three antibody types, IgA, IgE and IgG in a wild population of Soay sheep on the St Kilda archipelago in North-West Scotland. Using data collected over 26 years, we show that antibody levels have a heritable basis in lambs and adults and are stable over lifetime of individuals. We also identify several genomic regions with large effects on immune responses. Our study offers the first insights into the genetic control of immunity in a wild population, which is essential to understand how immune profiles vary in challenging natural conditions and how natural selection maintains genetic variation in complex immune traits.

scholarly journals The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)

PLoS Genetics ◽  
2019 ◽  
Vol 15 (11) ◽  
pp. e1008461 ◽  
Author(s):  
Alexandra M. Sparks ◽  
Kathryn Watt ◽  
Rona Sinclair ◽  
Jill G. Pilkington ◽  
Josephine M. Pemberton ◽  
...  
Keyword(s):  
Immune Responses ◽  
Genetic Architecture ◽  
Wild Population ◽  
Ovis Aries ◽  
Soay Sheep

scholarly journals Host-pathogen coevolution increases genetic variation in susceptibility to infection

2018 ◽  
Author(s):  
Elizabeth ML Duxbury ◽  
Jonathan P Day ◽  
Davide Maria Vespasiani ◽  
Yannik Thüringer ◽  
Ignacio Tolosana ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Genetic Variants ◽  
Genetic Architecture ◽  
Natural Populations ◽  
Major Effect ◽  
Cross Infection ◽  
Host Susceptibility ◽  
Susceptibility To Infection ◽  
Host Parasite Interactions ◽  
Host Parasite

AbstractIt is common to find considerable genetic variation in susceptibility to infection in natural populations. We have investigated whether natural selection increases this variation by testing whether host populations show more genetic variation in susceptibility to pathogens that they naturally encounter than novel pathogens. In a large cross-infection experiment involving four species of Drosophila and four host-specific viruses, we always found greater genetic variation in susceptibility to viruses that had coevolved with their host. We went on to examine the genetic architecture of resistance in one host species, finding that there are more major-effect genetic variants in coevolved host-parasite interactions. We conclude that selection by pathogens increases genetic variation in host susceptibility, and much of this effect is caused by the occurrence of major-effect resistance polymorphisms within populations.

scholarly journals The Impact of Environmental Heterogeneity on Genetic Architecture in a Wild Population of Soay Sheep

Genetics ◽  
2009 ◽  
Vol 181 (4) ◽  
pp. 1639-1648 ◽  
Author(s):  
Matthew R. Robinson ◽  
Alastair J. Wilson ◽  
Jill G. Pilkington ◽  
Tim H. Clutton-Brock ◽  
Josephine M. Pemberton ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Environmental Heterogeneity ◽  
Wild Population ◽  
Soay Sheep ◽  
The Impact

scholarly journals A genomic region containing RNF212 and CPLX1 is associated with sexually-dimorphic recombination rate variation in Soay sheep (Ovis aries)

2015 ◽  
Author(s):  
Susan E. Johnston ◽  
Camillo Bérénos ◽  
Jon Slate ◽  
Josephine M. Pemberton
Keyword(s):  
Recombination Rate ◽  
Genetic Architecture ◽  
Wild Population ◽  
Genomic Region ◽  
Ovis Aries ◽  
Rate Variation ◽  
Recombination Rates ◽  
Heritable Variation ◽  
Soay Sheep ◽  
Recombination Rate Variation

ABSTRACTMeiotic recombination breaks down linkage disequilibrium and forms new haplotypes, meaning thatit is an important driver of diversity in eukaryotic genomes. Understanding the causes of variation in recombination rate is important in interpreting and predicting evolutionary phenomena and forunderstanding the potential of a population to respond to selection. However, despite attention inmodel systems, there remains little data on how recombination rate varies at the individual level in natural populations. Here, we used extensive pedigree and high-density SNP information in a wild population of Soay sheep (Ovis aries) to investigate the genetic architecture of individual autosomal recombination rate. Individual rates were high relative to other mammal systems, and were higher in males than in females (autosomal map lengths of 3748 cM and 2860 cM, respectively). The heritability of autosomal recombination rate was low but significant in both sexes(h2 = 0.16 & 0.12 in females and males, respectively). In females, 46.7% of the heritable variation was explained by a sub-telomeric region on chromosome 6; a genome-wide association study showed the strongest associations at the locus RNF212, with further associations observed at a nearby ~374kb region of complete linkage disequilibrium containing three additional candidate loci, CPLX1, GAK and PCGF3. A second region on chromosome 7 containing REC8 and RNF212B explained 26.2% of the heritable variation in recombination rate in both sexes. Comparative analyses with 40 other sheep breeds showed that haplotypes associated with recombination rates are both old and globally distributed. Both regions have been implicated in rate variation in mice, cattle and humans, suggesting a common genetic architecture of recombination rate variation in mammals.AUTHOR SUMMARYRecombination offers an escape from genetic linkage by forming new combinations of alleles, increasing the potential for populations to respond to selection. Understanding the causes and consequences of individual recombination rates are important in studies of evolution and genetic improvement, yet little is known on how rates vary in natural systems. Using data from a wild population of Soay sheep, we show that individual recombination rate is heritable and differs between the sexes, with the majority of genetic variation in females explained by a genomic region containing thegenes RNF212 and CPLX1.

scholarly journals MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese

2021 ◽  
Vol 11 (6) ◽  
pp. 564
Author(s):  
Chin-Man Wang ◽  
Keng-Poo Tan ◽  
Yeong-Jian Jan Wu ◽  
Jing-Chi Lin ◽  
Jian-Wen Zheng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Healthy Controls ◽  
Hla B27 ◽  
Host Immune Responses ◽  
Histocompatibility Complex ◽  
High Level ◽  
Coding Snp

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

scholarly journals Heritability of DNA methylation in threespine stickleback (Gasterosteus aculeatus)

Genetics ◽  
2021 ◽  
Vol 217 (1) ◽  
Author(s):  
Juntao Hu ◽  
Sara J S Wuitchik ◽  
Tegan N Barry ◽  
Heather A Jamniczky ◽  
Sean M Rogers ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Architecture ◽  
Gasterosteus Aculeatus ◽  
Additive Genetic Variance ◽  
Natural Populations ◽  
Threespine Stickleback ◽  
Phenotypic Change ◽  
Cpg Sites ◽  
Cis And Trans ◽  
Methylation Variation

Abstract Epigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24–35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.

scholarly journals Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses

2006 ◽  
Vol 19 (4) ◽  
pp. 728-762 ◽  
Author(s):  
Sue VandeWoude ◽  
Cristian Apetrei
Keyword(s):  
Immune Responses ◽  
Natural Populations ◽  
Host Immune Responses ◽  
Experimental Systems ◽  
Naturally Occurring ◽  
Immunodeficiency Virus ◽  
New Directions ◽  
Species Specific ◽  
Lentiviral Infections ◽  
Hiv Aids

SUMMARY Over 40 nonhuman primate (NHP) species harbor species-specific simian immunodeficiency viruses (SIVs). Similarly, more than 20 species of nondomestic felids and African hyenids demonstrate seroreactivity against feline immunodeficiency virus (FIV) antigens. While it has been challenging to study the biological implications of nonfatal infections in natural populations, epidemiologic and clinical studies performed thus far have only rarely detected increased morbidity or impaired fecundity/survival of naturally infected SIV- or FIV-seropositive versus -seronegative animals. Cross-species transmissions of these agents are rare in nature but have been used to develop experimental systems to evaluate mechanisms of pathogenicity and to develop animal models of HIV/AIDS. Given that felids and primates are substantially evolutionarily removed yet demonstrate the same pattern of apparently nonpathogenic lentiviral infections, comparison of the biological behaviors of these viruses can yield important implications for host-lentiviral adaptation which are relevant to human HIV/AIDS infection. This review therefore evaluates similarities in epidemiology, lentiviral genotyping, pathogenicity, host immune responses, and cross-species transmission of FIVs and factors associated with the establishment of lentiviral infections in new species. This comparison of consistent patterns in lentivirus biology will expose new directions for scientific inquiry for understanding the basis for virulence versus avirulence.

scholarly journals Hierarchy of Susceptibility of Dendritic Cell Subsets to Infection by Leishmania major: Inverse Relationship to Interleukin-12 Production

2002 ◽  
Vol 70 (7) ◽  
pp. 3874-3880 ◽  
Author(s):  
Sandrine Henri ◽  
Joan Curtis ◽  
Hubertus Hochrein ◽  
David Vremec ◽  
Ken Shortman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mhc Class Ii ◽  
Leishmania Major ◽  
Parasitophorous Vacuole ◽  
Class Ii ◽  
Host Cells ◽  
Interleukin 12 ◽  
Histocompatibility Complex ◽  
T Cell Immune Responses ◽  
Antigen Presenting

ABSTRACT Dendritic cells (DCs) are professional antigen-presenting cells which initiate and regulate T-cell immune responses. Here we show that murine splenic DCs can be ranked on the basis of their ability to phagocytose and harbor the obligately intracellular parasite Leishmania major. CD4+ CD8− DCs are the most permissive host cells for L. major amastigotes, followed by CD4− CD8− DCs; CD4− CD8+ cells are the least permissive. However, the least susceptible CD4− CD8+ DC subset was the best interleukin-12 producer in response to infection. Infection did not induce in any DC subset production of the proinflammatory cytokine gamma interferon and nitric oxide associated with the induction of Th1 responses. The number of parasites phagocytosed by DCs was low, no more than 3 organisms per cell, compared to more than 10 organisms per macrophage. In infected DCs, the parasites are located in a parasitophorous vacuole containing both major histocompatibility complex (MHC) class II and lysosome-associated membrane protein 1 molecules, similar to their location in the infected macrophage. The parasite-driven redistribution of MHC class II to this compartment indicates that infected DCs should be able to present parasite antigen.

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