Linked Loci (linked + locus)

Distribution by Scientific Domains


Selected Abstracts


Assessment of SNP streak statistics using gene drop simulation with linkage disequilibrium

GENETIC EPIDEMIOLOGY, Issue 2 2010
Alun ThomasArticle first published online: 6 JUL 200
Abstract We describe methods and programs for simulating the genotypes of individuals in a pedigree at large numbers of linked loci when the alleles of the founders are under linkage disequilibrium. Both simulation and estimation of linkage disequilibrium models are shown to be feasible on a genome wide scale. The methods are applied to evaluate the statistical significance of streaks of loci at which sets of related individuals share a common allele. The effects of properly allowing for linkage disequilibrium are shown to be important as they explain many of the large observations. This is illustrated by reanalysis of a previously reported linkage of prostate cancer to chromosome 1p23. Genet. Epidemiol. 34: 119,124, 2010. © 2009 Wiley-Liss, Inc. [source]


Genetic variability of seven dog breeds based on microsatellite markers

JOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 2005
C. Schelling
Summary The present study, compared the genetic variability of seven dog breeds and a test sample from Switzerland by means of 26 microsatellite markers. Five loci were excluded from further analyses because one was monomorphic, one not in Hardy,Weinberg equilibrium in all breeds and three in linkage disequilibrium with linked loci. The proportion of shared alleles at the individual level of the remaining 21 microsatellite markers combined with the neighbour-joining method allowed for the clustering of the large majority of the individuals in accordance to their breed. The results were confirmed by analyses using a Bayesian approach for clustering and a Monte Carlo re-sampling method for individual assignment or exclusion to a given population. [source]


Fitness differences associated with Pgi SNP genotypes in the Glanville fritillary butterfly (Melitaea cinxia)

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 2 2009
L. ORSINI
Abstract Allozyme variation at the phosphoglucose isomerase (PGI) locus in the Glanville fritillary butterfly (Melitaea cinxia) is associated with variation in flight metabolic rate, dispersal rate, fecundity and local population growth rate. To map allozyme to DNA variation and to survey putative functional variation in genomic DNA, we cloned the coding sequence of Pgi and identified nonsynonymous variable sites that determine the most common allozyme alleles. We show that these single-nucleotide polymorphisms (SNPs) exhibit significant excess of heterozygotes in field-collected population samples as well as in laboratory crosses. This is in contrast to previous results for the same species in which other allozymes and SNPs were in Hardy,Weinberg equilibrium or exhibited an excess of homozygotes. Our results suggest that viability selection favours Pgi heterozygotes. Although this is consistent with direct overdominance at Pgi, we cannot exclude the possibility that heterozygote advantage is caused by the presence of one or more deleterious alleles at linked loci. [source]


Short- and long-term benefits and detriments to recombination under antagonistic coevolution

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2007
A. D. PETERS
Abstract We explored the evolution of recombination under antagonistic coevolution, concentrating on the equilibrium frequencies of modifier alleles causing recombination in initially nonrecombining populations. We found that the equilibrium level of recombination in the host depended not only on parasite virulence, but also on the strength of the modifier allele, and on whether or not the modifier was physically linked to the parasite interaction loci. Nonetheless, the maximum level of recombination for linked loci at equilibrium was about 0.3 (60% of free recombination) for interactions with highly virulent parasites; the level decreased for unlinked modifiers, and for lower levels of parasite virulence. We conclude that recombination spreads because it provides a combination of an immediate (next-generation) fitness benefit and a delayed (two or more generations) increase in the rate of response to directional selection. The relative impact of these two mechanisms depends on the virulence of parasites early in the spread of the modifier, but a trade-off between the two dictates the equilibrium modifier frequency for all nonzero virulences that we examined. In addition, population mean fitness was higher in populations at intermediate equilibria than populations fixed for free recombination or no recombination. The difference, however, was not enough on its own to overcome the two-fold cost of producing males. [source]


Detecting introgressive hybridization between free-ranging domestic dogs and wild wolves (Canis lupus) by admixture linkage disequilibrium analysis

MOLECULAR ECOLOGY, Issue 10 2006
A. VERARDI
Abstract Occasional crossbreeding between free-ranging domestic dogs and wild wolves (Canis lupus) has been detected in some European countries by mitochondrial DNA sequencing and genotyping unlinked microsatellite loci. Maternal and unlinked genomic markers, however, might underestimate the extent of introgressive hybridization, and their impacts on the preservation of wild wolf gene pools. In this study, we genotyped 220 presumed Italian wolves, 85 dogs and 7 known hybrids at 16 microsatellites belonging to four different linkage groups (plus four unlinked microsatellites). Population clustering and individual assignments were performed using a Bayesian procedure implemented in structure 2.1, which models the gametic disequilibrium arising between linked loci during admixtures, aiming to trace hybridization events further back in time and infer the population of origin of chromosomal blocks. Results indicate that (i) linkage disequilibrium was higher in wolves than in dogs; (ii) 11 out of 220 wolves (5.0%) were likely admixed, a proportion that is significantly higher than one admixed genotype in 107 wolves found previously in a study using unlinked markers; (iii) posterior maximum-likelihood estimates of the recombination parameter r revealed that introgression in Italian wolves is not recent, but could have continued for the last 70 (± 20) generations, corresponding to approximately 140,210 years. Bayesian clustering showed that, despite some admixture, wolf and dog gene pools remain sharply distinct (the average proportions of membership to wolf and dog clusters were Qw = 0.95 and Qd = 0.98, respectively), suggesting that hybridization was not frequent, and that introgression in nature is counteracted by behavioural or selective constraints. [source]


Bayesian analyses of admixture in wild and domestic cats (Felis silvestris) using linked microsatellite loci

MOLECULAR ECOLOGY, Issue 1 2006
R. LECIS
Abstract Methods recently developed to infer population structure and admixture mostly use individual genotypes described by unlinked neutral markers. However, Hardy,Weinberg and linkage disequilibria among independent markers decline rapidly with admixture time, and the admixture signals could be lost in a few generations. In this study, we aimed to describe genetic admixture in 182 European wild and domestic cats (Felis silvestris), which hybridize sporadically in Italy and extensively in Hungary. Cats were genotyped at 27 microsatellites, including 21 linked loci mapping on five distinct feline linkage groups. Genotypes were analysed with structure 2.1, a Bayesian procedure designed to model admixture linkage disequilibrium, which promises to assess efficiently older admixture events using tightly linked markers. Results showed that domestic and wild cats sampled in Italy were split into two distinct clusters with average proportions of membership Q > 0.90, congruent with prior morphological identifications. In contrast, free-living cats sampled in Hungary were assigned partly to the domestic and the wild cat clusters, with Q < 0.50. Admixture analyses of individual genotypes identified, respectively, 5/61 (8%), and 16,20/65 (25,31%) hybrids among the Italian wildcats and Hungarian free-living cats. Similar results were obtained in the past using unlinked loci, although the new linked markers identified additional admixed wildcats in Italy. Linkage analyses confirm that hybridization is limited in Italian, but widespread in Hungarian wildcats, a population that is threatened by cross-breeding with free-ranging domestic cats. The total panel of 27 loci performed better than the linked loci alone in the identification of domestic and known hybrid cats, suggesting that a large number of linked plus unlinked markers can improve the results of admixture analyses. Inferred recombination events led to identify the population of origin of chromosomal segments, suggesting that admixture mapping experiments can be designed also in wild populations. [source]


Use of linked loci as individuals or haplotypes for marker-assisted breed assignment

ANIMAL GENETICS, Issue 1 2008
A. Stella
Summary The objective of this study was to use simulation to evaluate the benefits of considering haplotypes of loci when linked single nucleotide polymorphisms are used for breed assignment. Three breeds of 10 000 females each were simulated under eight scenarios that differed according to the number of generations separating the breeds, size of breed founder populations and recombination rate between linked loci. Molecular genotypes consisted of 20 groups of three linked loci each. Breed assignment was performed in the final generation and was based on the frequency method. Haplotypes were reconstructed using the expectation,maximization algorithm. Accuracy of breed assignment was based on the frequency of correct breed assignment. Assignment accuracy increased as more genotypes (loci or haplotypes) were considered and more animals were used to estimate genotypic frequencies within breed. For most scenarios, use of haplotypes yielded equal or greater accuracies than when loci were considered independent. The advantage of haplotypes tended to increase as linkage disequilibrium between adjacent loci increased. The greatest advantage for using haplotypes was observed when recombination rate was low (0.001), breeds were separated by few generations (100), and a relatively large number of founder animals (110) was used to form new breeds. In this situation, 90% accuracy of breed assignment was achieved using nine to 14 haplotypes (i.e. 27,42 loci) depending on breed, vs. 39,57 individual loci. [source]


Limits of fine-mapping a quantitative trait

GENETIC EPIDEMIOLOGY, Issue 2 2003
Larry D. Atwood
Abstract Once a significant linkage is found, an important goal is reducing the error in the estimated location of the linked locus. A common approach to reducing location error, called fine-mapping, is the genotyping of additional markers in the linked region to increase the genetic information. The utility of fine-mapping for quantitative trait linkage analysis is largely unknown. To explore this issue, we performed a fine-mapping simulation in which the region containing a significant linkage at a 10-centiMorgan (cM) resolution was fine-mapped at 2, 1, and 0.5 cM. We simulated six quantitative trait models in which the proportion of variation due to the quantitative trait locus (QTL) ranged from 0.20,0.90. We used four sampling designs that were all combinations of 100 and 200 families of sizes 5 and 7. Variance components linkage analysis (Genehunter) was performed until 1,000 replicates were found with a maximum lodscore greater than 3.0. For each of these 1,000 replications, we repeated the linkage analysis three times: once for each of the fine-map resolutions. For the most realistic model, reduction in the average location error ranged from 3,15% for 2-cM fine-mapping and from 3,18% for 1-cM fine-mapping, depending on the number of families and family size. Fine-mapping at 0.5 cM did not differ from the 1-cM results. Thus, if the QTL accounts for a small proportion of the variation, as is the case for realistic traits, fine-mapping has little value. Genet Epidemiol 24:99,106, 2003. © 2003 Wiley-Liss, Inc. [source]


Haplotype Analysis Confirms the Association Between the HCRTR2 Gene and Cluster Headache

HEADACHE, Issue 7 2008
Innocenzo Rainero MD
Background., Several studies suggested that genetic factors play a role in cluster headache (CH) susceptibility. We found a significant association between the 1246 G>A polymorphism of the hypocretin receptor-2 (HCRTR2) gene and the disease. This association was confirmed in a large study from Germany but was not replicated in a dataset of CH patients from Northern Europe. Objective., The purpose of this study was to further evaluate the association between CH and the HCRTR2 gene using new polymorphisms, estimating the frequency of different gene haplotypes, searching for gene mutations, and evaluating the effects of the examined polymorphisms on hypocretin binding sites. Methods., We genotyped 109 CH patients and 211 healthy controls for 5 new polymorphisms of the HCRTR2 gene and we inferred different gene haplotypes. Complete HCRTR2 sequencing was undertaken for 11 independent CH patients, 5 of whom had a positive family history. The effects of the 1246 G>A polymorphism on the hypocretin binding sites were evaluated using different computer-assisted analyses. Results., Three new polymorphisms of the HCRTR2 gene resulted significantly associated with CH. The GTAAGG haplotype resulted more frequent in cases than in controls (OR: 3.68; 95% CI: 1.85-7.67). No point mutation of the HCRTR2 gene was found. Binding analyses showed that the 1246 G>A polymorphism (substitution of valine at position 308 by isoleucine) has no effect on the hypocretin binding sites but could influence the dimerization process of the receptor. Conclusion., Our data confirm previous studies suggesting that the HCRTR2 gene or a linked locus significantly modulates the risk for CH. In addition, we suggest that the V308I substitution of the HCRTR2 may interfere with the dimerization process of the receptor, thereby influencing its functional activity. [source]


Local selection and population structure in a deep-sea fish, the roundnose grenadier (Coryphaenoides rupestris)

MOLECULAR ECOLOGY, Issue 2 2010
THOMAS A. WHITE
Abstract Local populations within a species can become isolated by stochastic or adaptive processes, though it is most commonly the former that we quantify. Using presumably neutral markers we can assess the time-dependent process of genetic drift, and thereby quantify patterns of differentiation in support of the effective management of diversity. However, adaptive differences can be overlooked in these studies, and these are the very characteristics that we hope to conserve by managing neutral diversity. In this study, we used 16 hypothetically neutral microsatellite markers to investigate the genetic structure of the roundnose grenadier in the North Atlantic. We found that one locus was a clear outlier under directional selection, with FST values much greater than at the remaining loci. Differentiation between populations at this locus was related to depth, suggesting directional selection, presumably acting on a linked locus. Considering only the loci identified as neutral, there remained significant population structure over the region of the North Atlantic studied. In addition to a weak pattern of isolation by distance, we identified a putative barrier to gene flow between sample sites either side of the Charlie-Gibbs Fracture Zone, which marks the location where the sub-polar front crosses the Mid-Atlantic Ridge. This may reflect a boundary across which larvae are differentially distributed in separate current systems to some extent, promoting differentiation by drift. Structure due to both drift and apparent selection should be considered in management policy. [source]