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135 results for “Heterozygosity”
Data from: Exploring the mechanisms underlying a heterozygosity-fitness correlation for canine size in the Antarctic fur seal Arctocephalus gazella
Although heterozygosity-fitness correlations (HFCs) are widely reported in the literature, most studies use too few markers to allow the proximate mechanisms to be convincingly resolved. Two competing hypotheses have been proposed: the general effects hypothesis, in which marker heterozygosity correlates with genome-wide heterozygosity and hence the inbreeding coefficient f, and the local effects hypothesis, in which one or more of the markers by chance exhibit associative overdominance. To explore the relative contributions of general and local effects in a free-ranging marine mammal population, we revisited a strong HFC found using nine microsatellite loci for canine tooth size in 84 male Antarctic fur seals Arctocephalus gazella (Hoffman et al. 2010). Increasing the number of markers to 76, we find that heterozygosity is uncorrelated across markers, indicating that inbred individuals are rare or absent. Similarly, while the HFC based on overall heterozygosity is lost, stochastic simulations indicate that when an HFC is due to inbreeding depression, increasing marker number effectively invariably strengthens the HFC. Together these observations argue strongly that the original HFC was not due to inbreeding depression. In contrast, a subset of markers show individually significant effects, and these are non-randomly distributed across the marker panel, being preferentially associated with markers cloned from other species. Using BLAST searches, we were able to locate 94% of loci to unique locations in the dog genome, but the local genes are functionally diverse, and the majority cannot be linked directly to growth. Our results suggest that inbreeding depression contributes little if at all to the relationship between heterozygosity and tooth size, but that instead the primary mechanism involves associative overdominance. These findings contribute to a growing body of evidence suggesting that general effects are likely to be uncommon in natural populations
Data from: Heterozygosity predicts clutch and egg size but not plasticity in a house sparrow population with no evidence of inbreeding
We investigated the link between heterozygosity and the reaction norm attributes of reproductive performance in female house sparrows (Passer domesticus). We collected data on clutch size, egg size, hatching success, and nestling survival in 2 816 nesting attempts made by 791 marked individuals over a 16 year period. Pedigree analysis revealed no evidence of inbreeding. Neither parent-offspring regression nor an animal model revealed significant heritability in clutch or egg size. We selected 42 females that laid at least seven clutches at our study site and used a survey of 21 autosomal microsatellite loci to estimate heterozygosity for each female. We controlled for phenotypic plasticity and found that both clutch and egg size showed significant positive correlations with heterozygosity. We found no evidence that heterozygosity influenced the slope of individual reaction norms. Further analysis suggested that clutch size was affected by heterozygosity across the genome, but egg size had more complex relationships, with evidence favoring the influence of multiple loci. Given the apparent lack of inbreeding and large population size, our results suggest associative overdominance as the likely mechanism for the impact of heterozygosity, but also created a puzzle about the process producing associations between neutral markers and the genes affecting clutch size or egg size. One possible explanation is a long term residual effect of the historical bottleneck that occurred when house sparrows were introduced into North America. The existence of HFCs in a population with considerable phenotypic plasticity and little inbreeding implies that the effects of heterozygosity may be more significant than previously thought.
Data from: Heterozygosity at neutral and immune loci is not associated with neonatal mortality due to microbial infection in Antarctic fur seals
Numerous studies have reported correlations between the heterozygosity of genetic markers and fitness. These heterozygosity fitness correlations (HFCs) play a central role in evolutionary and conservation biology, yet their mechanistic basis remains open to debate. For example, fitness associations have been widely reported at both neutral and functional loci, yet few studies have directly compared the two, making it difficult to gauge the relative contributions of genome-wide inbreeding and functional genetic variation to fitness. Here, we compared the effects of neutral and immune gene heterozygosity on death from bacterial infection in Antarctic fur seal (Arctocephalus gazella) pups. We specifically developed a panel of 13 microsatellites from expressed immune genes and genotyped these together with 48 neutral loci in 234 individuals, comprising 39 pups that were classified at necropsy as having most likely died of bacterial infection together with a five times larger matched sample of healthy surviving pups. Identity disequilibrium quantified from the neutral markers was positive and significant, indicative of variance in inbreeding within the study population. However, multilocus heterozygosity did not differ significantly between healthy and infected pups at either class of marker, and little evidence was found for fitness associations at individual loci. These results support a previous study of Antarctic fur seals that found no effects of heterozygosity at nine neutral microsatellites on neonatal survival, and thereby help to refine our understanding of how HFCs vary across the life cycle. Given that non-significant HFCs are underreported in the literature, we also hope that our study will contribute towards a more balanced understanding of the wider importance of this phenomenon.
Data from: Evidence for an association between post-fledging dispersal and microsatellite multilocus heterozygosity in a large population of greater flamingos
Dispersal can be divided into three stages: departure, transience and settlement. Despite the fact that theoretical studies have emphasized the importance of heterozygosity on dispersal strategies, empirical evidence of its effect on different stages of dispersal is lacking. Here, using multi-event capture-mark-recapture models, we show a negative association between microsatellite multilocus heterozygosity (MLH; 10 loci; n = 1023) and post-fledging dispersal propensity for greater flamingos, Phoenicopterus roseus, born in southern France. We propose that the negative effects of inbreeding depression affects competitive ability and therefore more homozygous individuals are more likely to disperse because they are less able to compete within the highly saturated natal site. Finally, a model with the effect of MLH on propensity of post-fledgling dispersers to disperse to the long-distance sites of Africa was equivalent to the null model, suggesting that MLH had low to no effect on dispersal distance. Variations in individual genetic quality thus result in context-dependent heterogeneity in dispersal strategies at each stage of dispersal. Our results have important implications on fitness since sites visited early in life are known to influence site selection later on in life and future survival.
Phylogenetically under‐dispersed gut microbiomes are not correlated with host genomic heterozygosity in a genetically diverse reptile community
<p>We are providing semi-processed datasets relevant to the paper "Phylogenetically under-dispersed gut microbiomes across a range of host genetic diversity in a reptile community point to structuring by conserved host genes." Specifically, we include VCF files of RADseq data from host individuals, which are processed versions of the raw reads available at NCBI's Short Read Archive under PRJA744273. These data were processed for heterozygosity calculation using an adapted of the pipeline presented in Singhal et al. 2017, "Genetic diversity is largely unpredictable but scales with museum occurrences in a species-rich clade of Australian lizards."</p> <p>In addition, we include a database of 16S sequences from gut microbiome amplicon sequencing from the same host animals. The raw reads are available at NCBI's Short Read Archive under PRJNA746253. The sequences accessioned here are a curated, cleaned set of reference reads to which we realigned reads from each individual host.</p>
Analysis of ancestry heterozygosity suggests that hybrid incompatibilities in threespine stickleback are environment-dependent
<p>Hybrid incompatibilities occur when interactions between opposite-ancestry alleles at different loci reduce the fitness of hybrids. Most work on incompatibilities has focused on those that are 'intrinsic', meaning they affect viability and sterility in the laboratory. Theory predicts that ecological selection can also underlie hybrid incompatibilities, but tests of this hypothesis using sequence data are scarce. In this article, we compiled genetic data for F<sub>2</sub> hybrid crosses between divergent populations of threespine stickleback fish (<em>Gasterosteus aculeatus</em> L.) that were born and raised in either the field (semi-natural experimental ponds) or the laboratory (aquaria). Because selection against incompatibilities results in elevated ancestry heterozygosity, we tested the prediction that ancestry heterozygosity will be higher in pond-raised fish compared to those raised in aquaria. We found that ancestry heterozygosity was elevated by approximately 3% in crosses raised in ponds compared to those raised in aquaria. Additional analyses support a phenotypic basis for incompatibility and suggest that environment-specific single-locus heterozygote advantage is not the cause of selection on ancestry heterozygosity. Our study provides evidence that, in stickleback, a coarse—albeit indirect—signal of environment-dependent hybrid incompatibility is reliably detectable and suggests that extrinsic incompatibilities can evolve before intrinsic incompatibilities.</p>
Data from: No correlation between multi-locus heterozygosity and fitness in the common buzzard despite heterozygote advantage for plumage colour
Correlations between heterozygosity and fitness are frequently found but rarely well understood. Fitness can be affected by single loci of large effect which correlate with neutral markers via linkage disequilibrium, or as a result of variation in genome-wide heterozygosity following inbreeding. We explored these alternatives in the common buzzard, a raptor species in which three colour morphs differ in their lifetime reproductive success. Using 18 polymorphic microsatellite loci, we evaluated potential genetic differences among the morphs which may lead to subpopulation structuring and tested for correlations between three fitness-related traits and heterozygosity, both genome wide and at each locus separately. Despite their assortative mating pattern, the buzzard morphs were found to be genetically undifferentiated. Multilocus heterozygosity was only found to be correlated with a single fitness-related trait, infection with the blood parasite, Leucocytozoon buteonis, and this was via interactions with vole abundance and age. One locus also showed a significant relationship with blood parasite infection and ectoparasite infestation. The vicinity of this locus contains two genes, one of which is potentially implicated in the immune system of birds. We conclude that genome-wide heterozygosity is unlikely to be a major determinant of parasite burden and body condition in the polymorphic common buzzard.
Data from: Specific alleles at immune genes, rather than genome-wide heterozygosity, are related to immunity and survival in the critically endangered Attwater's prairie-chicken
The negative effects of inbreeding on fitness are serious concerns for populations of endangered species. Reduced fitness has been associated with lower genome-wide heterozygosity and immune gene diversity in the wild; however, it is rare that both types of genetic measures are included in the same study. Thus, it is often unclear whether the variation in fitness is due to the general effects of inbreeding, immunity-related genes or both. Here, we tested whether genome-wide heterozygosity (20 990 SNPs) and diversity at nine immune genes were better predictors of two measures of fitness (immune response and survival) in the endangered Attwater's prairie-chicken (Tympanuchus cupido attwateri). We found that postrelease survival of captive-bred birds was related to alleles of the innate (Toll-like receptors, TLRs) and adaptive (major histocompatibility complex, MHC) immune systems, but not to genome-wide heterozygosity. Likewise, we found that the immune response at the time of release was related to TLR and MHC alleles, and not to genome-wide heterozygosity. Overall, this study demonstrates that immune genes may serve as important genetic markers when monitoring fitness in inbred populations and that in some populations specific functional genes may be better predictors of fitness than genome-wide heterozygosity.
Data for: Genomic heterozygosity is associated with parasite abundance, but the effects are not mediated by host condition
<p>Whether, when, and how genetic diversity buffers individuals and populations against infectious disease risk is a critical and open question for understanding wildlife disease and zoonotic disease risk. Several, but not all, studies have found negative relationships between infection and heterozygosity in wildlife. Since they can host multiple zoonotic infections, we sampled a population of wild deer mice (<em>Peromyscus maniculatus</em>), sequenced their genomes, and examined their fecal samples for coccidia and nematode eggs. We analyzed coccidia infection status, abundance, and coinfection status in relation to per-locus and per-individual measures of heterozygosity, as well as identified SNPs associated with infection status. Since heterozygosity might affect host condition, and condition is known to affect immunity, it was included as a co-variate in the per-individual analyses and as response variable in relation to heterozygosity. Not only did coccidia-infected individuals have lower levels of genome-wide per-locus diversity across all metrics, but we found an inverse relationship between genomic diversity and severity of coccidia infection. We also found weaker evidence that coinfected individuals had lower levels of private allelic variation than all other groups. In the per-individual analyses, relationships between heterozygosity and infection were marginal but followed the same negative trends. Condition was negatively correlated with infection, but was not associated with heterozygosity, suggesting that effects of heterozygosity on infection were not mediated by host condition in this system. Association tests identified multiple loci involved in the inflammatory response, with a particular role for NF-κB signaling, supporting previous work on the genetic basis of coccidia resistance. Taken together, we find that increased genome-wide neutral diversity, the presence of specific genetic variants, and improved condition positively impact infection status. Our results underscore the importance of considering host genomic variation as a buffer against infection, especially in systems that can harbor zoonotic diseases.</p>
Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter
ClinicalTrials.gov study NCT02035046. IPD Sharing: Not stated. Countries: 1. Publications: 6.
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
ClinicalTrials.gov study NCT04981119. IPD Sharing: NO. Countries: 1. Publications: 6.
Data from: Exploring the mechanisms underlying a heterozygosity-fitness correlation for canine size in the Antarctic fur seal Arctocephalus gazella
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Data from: Heterozygosity-fitness correlations of conserved microsatellite markers in Kentish plovers Charadrius alexandrinus
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Data from: No correlation between multi-locus heterozygosity and fitness in the common buzzard despite heterozygote advantage for plumage colour
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Data from: The strength of the association between heterozygosity and probability of interannual local recruitment increases with environmental harshness in blue tits
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Data from: Strikingly high levels of heterozygosity despite 20 years of inbreeding in a clonal honey bee
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Data from: Heterozygosity-fitness correlations in a migratory bird: an analysis of inbreeding and single-locus effects
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Data from: Evidence of opposing fitness effects of parental heterozygosity and relatedness in a critically endangered marine turtle?
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Data from: Constraints on the FST–heterozygosity outlier approach
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Data from: Heterozygosity-fitness correlation at the major histocompatibility complex despite low variation in Alpine ibex (Capra ibex)
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