Haplotype‐based genotyping‐by‐sequencing in oat genome research

In a de novo genotyping‐by‐sequencing (GBS) analysis of short, 64‐base tag‐level haplotypes in 4657 accessions of cultivated oat, we discovered 164741 tag‐level (TL) genetic variants containing 241224 SNPs. From this, the marker density of an oat consensus map was increased by the addition of more than 70000 loci. The mapped TL genotypes of a 635‐line diversity panel were used to infer chromosome‐level (CL) haplotype maps. These maps revealed differences in the number and size of haplotype blocks, as well as differences in haplotype diversity between chromosomes and subsets of the diversity panel. We then explored potential benefits of SNP vs. TL vs. CL GBS variants for mapping, high‐resolution genome analysis and genomic selection in oats. A combined genome‐wide association study (GWAS) of heading date from multiple locations using both TL haplotypes and individual SNP markers identified 184 significant associations. A comparative GWAS using TL haplotypes, CL haplotype blocks and their combinations demonstrated the superiority of using TL haplotype markers. Using a principal component‐based genome‐wide scan, genomic regions containing signatures of selection were identified. These regions may contain genes that are responsible for the local adaptation of oats to Northern American conditions. Genomic selection for heading date using TL haplotypes or SNP markers gave comparable and promising prediction accuracies of up to r = 0.74. Genomic selection carried out in an independent calibration and test population for heading date gave promising prediction accuracies that ranged between r = 0.42 and 0.67. In conclusion, TL haplotype GBS‐derived markers facilitate genome analysis and genomic selection in oat.     

Disequilibrium Pattern Analysis. I. Theory

We have developed a method, disequilibrium pattern analysis, for examining the disequilibrium distribution of the entire array of two locus multiallelic haplotypes in a population. It is shown that a selected haplotype will produce a distinct pattern of linkage disequilibrium values for all generations while the selection is acting. This pattern will also presumably be maintained for many generations after the selection event, until the disequilibrium pattern is eventually broken down by genetic drift and recombination. Related haplotypes, sharing an allele with a selected haplotype, assume a value of linkage disequilibrium proportional to the frequency of the unshared allele and have a single negative value of the normalized linkage disequilibrium. The analysis assumes zero linkage disequilibrium for all allelic combinations initially. The same basic results continue to apply if the selection involves a new mutant, the occurrence of which creates linkage disequilibrium for some haplotypes. The disequilibrium pattern predicted under selection is robust with respect to the influence of migration and random genetic drift. This method is applicable to population data having linked polymorphic loci including that determined from protein or DNA sequencing.     

HapScope: a software system for automated and visual analysis of functionally annotated haplotypes

We have developed a software analysis package, HapScope, which includes a comprehensive analysis pipeline and a sophisticated visualization tool for analyzing functionally annotated haplotypes. The HapScope analysis pipeline supports: (i) computational haplotype construction with an expectation-maximization or Bayesian statistical algorithm; (ii) SNP classification by protein coding change, homology to model organisms or putative regulatory regions; and (iii) minimum SNP subset selection by either a Brute Force Algorithm or a Greedy Partition Algorithm. The HapScope viewer displays genomic structure with haplotype information in an integrated environment, providing eight alternative views for assessing genetic and functional correlation. It has a user-friendly interface for: (i) haplotype block visualization; (ii) SNP subset selection; (iii) haplotype consolidation with subset SNP markers; (iv) incorporation of both experimentally determined haplotypes and computational results; and (v) data export for additional analysis. Comparison of haplotypes constructed by the statistical algorithms with those determined experimentally shows variation in haplotype prediction accuracies in genomic regions with different levels of nucleotide diversity. We have applied HapScope in analyzing haplotypes for candidate genes and genomic regions with extensive SNP and genotype data. We envision that the systematic approach of integrating functional genomic analysis with population haplotypes, supported by HapScope, will greatly facilitate current genetic disease research.     

The Effect of Linkage Disequilibrium and Family Relationships on the Reliability of Genomic Prediction

Although the concept of genomic selection relies on linkage disequilibrium (LD) between quantitative trait loci and markers, reliability of genomic predictions is strongly influenced by family relationships. In this study, we investigated the effects of LD and family relationships on reliability of genomic predictions and the potential of deterministic formulas to predict reliability using population parameters in populations with complex family structures. Five groups of selection candidates were simulated by taking different information sources from the reference population into account: (1) allele frequencies, (2) LD pattern, (3) haplotypes, (4) haploid chromosomes, and (5) individuals from the reference population, thereby having real family relationships with reference individuals. Reliabilities were predicted using genomic relationships among 529 reference individuals and their relationships with selection candidates and with a deterministic formula where the number of effective chromosome segments (M_e) was estimated based on genomic and additive relationship matrices for each scenario. At a heritability of 0.6, reliabilities based on genomic relationships were 0.002 ± 0.0001 (allele frequencies), 0.022 ± 0.001 (LD pattern), 0.018 ± 0.001 (haplotypes), 0.100 ± 0.008 (haploid chromosomes), and 0.318 ± 0.077 (family relationships). At a heritability of 0.1, relative differences among groups were similar. For all scenarios, reliabilities were similar to predictions with a deterministic formula using estimated M_e. So, reliabilities can be predicted accurately using empirically estimated M_e and level of relationship with reference individuals has a much higher effect on the reliability than linkage disequilibrium per se. Furthermore, accumulated length of shared haplotypes is more important in determining the reliability of genomic prediction than the individual shared haplotype length.     

Linkage disequilibrium in the North American Holstein population

Linkage disequilibrium was estimated using 7119 single nucleotide polymorphism markers across the genome and 200 animals from the North American Holstein cattle population. The analysis of maternally inherited haplotypes revealed strong linkage disequilibrium ( r ²   >   0.8) in genomic regions of ∼50 kb or less. While linkage disequilibrium decays as a function of genomic distance, genomic regions within genes showed greater linkage disequilibrium and greater variation in linkage disequilibrium compared with intergenic regions. Identification of haplotype blocks could characterize the most common haplotypes. Although maximum haplotype block size was over 1 Mb, mean block size was 26–113 kb by various definitions, which was larger than that observed in humans (∼10 kb). Effective population size of the dairy cattle population was estimated from linkage disequilibrium between single nucleotide polymorphism marker pairs in various haplotype ranges. Rapid reduction of effective population size of dairy cattle was inferred from linkage disequilibrium in recent generations. This result implies a loss of genetic diversity because of the high rate of inbreeding and high selection intensity in dairy cattle. The pattern observed in this study indicated linkage disequilibrium in the current dairy cattle population could be exploited to refine mapping resolution. Changes in effective population size during past generations imply a necessity of plans to maintain polymorphism in the Holstein population.     

Geographic and host‐mediated population genetic structure in a cestode parasite of the three‐spined stickleback

Comparative studies of genetic diversity and population structure can shed light on the ecological and evolutionary factors that influence host–parasite interactions. Here we examined whether geography, time and genetic variation in Alaskan three‐spined stickleback (Gasterosteus aculeatus Linneaus) hosts shape the population genetic structure of the diphyllobothridean cestode parasite Schistocephalus solidus (Müller, 1776). Host lineages and haplotypes were identified by sequencing the mitochondrial cytochrome b gene, and host population structure was assessed by Bayesian clustering analysis of allelic variation at 11 microsatellite loci. Parasite population structure was characterized according to allelic variation at eight microsatellite loci. Mantel tests and canonical redundancy analysis were conducted to evaluate the proportion of parasite genetic variation attributable to time and geography vs. host lineage, haplotype, and genotypic cluster. Host and parasite population structure were largely discordant across the study area, probably reflecting differences in gene flow, environmental influences external to the host, and genomic admixture among host lineages. We found that geography explained the greatest proportion of parasite genetic variation, but that variation also reflects time, host lineage, and host haplotype. Associations with host haplotypes suggest that one parasite genotypic cluster exhibits a narrower host range, predominantly infecting the most common host haplotypes, whereas the other parasite cluster infects all haplotypes equally, including rare haplotypes. Although experimental infection trials might prove otherwise, distributional differences in hosts preferentially infected by S. solidus could underlie the observed pattern of population structure.     

Genetic trends in a population evolving antibiotic resistance

The evolution of antibiotic resistance provides a well-documented, rapid, and recent example of a selection driven process that has occurred in many bacterial species. An exhaustive collection of Moraxella catarrhalis that spans a transition to chromosomally encoded penicillin resistance was used to analyze genetic changes accompanying the transition. The population was characterized by high haplotypic diversity with 148 distinct haplotypes among 372 isolates tested at three genomic regions. The power of a temporally stratified sample from a single population was highlighted by the finding of high genetic diversity throughout the transition to resistance, population numbers that remained high over time, and no evidence of departures from neutrality in the allele frequency spectra throughout the transition. The direct temporal analysis documented the persistence, antibiotic status, and haplotypic identity of strains undergoing apparent clonal expansions. Several haplotypes that were beta-lactamase nonproducers in early samples converted to producers in later years. Maintenance of genetic diversity and haplotype conversions from sensitive to resistant supported the hypothesis that penicillin resistance determinants spread to a diverse array of strains via horizontal exchange. Genetic differentiation between sample years, estimated by F(ST), was increasing at a rate that could cause complete haplotype turnover in less than 150 years. Widespread linkage disequilibrium among sites within one locus (copB) suggested recent mutation followed by clonal expansion. Nonrandom associations between haplotypes and resistance phenotypes provided further evidence of clonal expansion for some haplotypes. Nevertheless, the population structure was far from clonal as evidenced by a relatively low frequency of disequilibria both within sites at a second locus (M46) as well as between loci. The haplotype-antibiotic resistance association that was accompanied by gradual haplotype turnover is consistent with a hypothesis of genetic drift at marker loci with directional selection at the resistance locus.     

基于大豆胞囊线虫病抗性候选基因的SNP位点遗传变异分析

以我国363份栽培和野生大豆资源为材料, 对大豆胞囊线虫抗性候选基因(rhg1和Rhg4)的SNP位点(8个)进行遗传变异分析, 以期阐明野生和栽培大豆间遗传多样性及连锁不平衡水平差异。结果表明, 与野生大豆相比, 代表我国栽培大豆总体资源多样性的微核心种质及其补充材料的连锁不平衡水平较高(R²值为0.216)。在栽培大豆群体内, 基因内和基因间分别有100％和16.6％的SNP位点对连锁不平衡显著, 形成两个基因特异的连锁不平衡区间(Block)。在所有供试材料中共检测到单倍型46个, 野生大豆的单倍型数目(27)少于栽培大豆(31), 但单倍型多样性(0.916)稍高于栽培大豆(0.816)。单倍型大多数(67.4％)为群体所特有(31个), 其中15个为野生大豆特有单倍型。野生大豆的两个主要优势单倍型(Hap_10和Hap_11)在栽培大豆中的发生频率也明显下降, 推测野生大豆向栽培大豆进化过程中, 一方面形成了新的单倍型, 另一方面因为瓶颈效应部分单倍型的频率降低甚至消失。     

Polymorphism,haplotype composition,and selection in the <Emphasis Type="Italic">Mhc-DRB</Emphasis> of wild baboons

General patterns of organization in the major histocompatibility complex (MHC) have been successfully explained by the model of birth-and-death evolution, but understanding why certain MHC genes are maintained together into specific haplotypes remains challenging. The haplotype configurations of the functionally important class II DR region have been described in few primates and display important interspecific variability with respect to the extent of allelic variation, the number of loci and/or combinations of loci present. Understanding the evolutionary mechanisms driving such variation is conditional upon characterizing haplotypes in new species and identifying the selective pressures acting on haplotypes. This study explores the variability of haplotype configurations in the Mhc-DRB region (exon 2) for the first time in wild non-human primates, chacma baboons (Papio ursinus). Paur-DRB haplotypes were characterized through segregation studies and linkage disequilibrium. 23 Paur-DRB sequences and 15 haplotype configurations were identified in 199 animals. The Paur-DRB exon 2 is shown to be subjected to intense positive selection and frequent recombination. An approach recently developed for human vaccine studies was used to classify Paur-DRB sequences into supertypes, based on the physico-chemical properties of amino acids that are positively selected, thus most probably involved in antigen recognition. Sequences grouped into the same supertype (thus presumably sharing antigen-binding affinities) are non-randomly distributed within haplotypes, leading to an increased individual diversity of supertypes. Our results suggest that selection favoring haplotypes with complementary sets of DRB supertypes shapes functionally tuned haplotypes in this natural baboon population.     

The effect of single-nucleotide polymorphism marker selection on patterns of haplotype blocks and haplotype frequency estimates

The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation.     

Characterization of a QTL region affecting clinical mastitis and protein yield on BTA6

Quantitative trait loci affecting clinical mastitis were detected and fine mapped to a narrow region on bovine chromosome 6 in the Norwegian Red cattle population. The region includes the casein gene cluster and several candidate genes thought to influence clinical mastitis. The most significant results were found for SNPs within the Mucin 7 gene. This gene encodes an antimicrobial peptide and constitutes part of the first line of defence for the mucosal immune system. Detection of long haplotypes extending several Mb may indicate that artificial selection has influenced the haplotype structures in the region. A search for selection sweeps supports this observation and coincides with association results found both by single SNP and haplotype analyses. Our analyses identified haplotypes carrying quantitative trait loci alleles associated with high protein yield and simultaneously fewer incidences of clinical mastitis. The fact that such haplotypes are found in relative high frequencies in Norwegian Red may reflect the combined breeding goal that is characterized by selection for both milk production and disease resistance. The identification of these haplotypes raises the possibility of overcoming the unfavourable genetic correlation between these traits through haplotype-assisted selection.     

Selection of haplotype variables from a high-density marker map for genomic prediction

Background

Using haplotype blocks as predictors rather than individual single nucleotide polymorphisms (SNPs) may improve genomic predictions, since haplotypes are in stronger linkage disequilibrium with the quantitative trait loci than are individual SNPs. It has also been hypothesized that an appropriate selection of a subset of haplotype blocks can result in similar or better predictive ability than when using the whole set of haplotype blocks. This study investigated genomic prediction using a set of haplotype blocks that contained the SNPs with large effects estimated from an individual SNP prediction model. We analyzed protein yield, fertility and mastitis of Nordic Holstein cattle, and used high-density markers (about 770k SNPs). To reach an optimum number of haplotype variables for genomic prediction, predictions were performed using subsets of haplotype blocks that contained a range of 1000 to 50 000 main SNPs.

Results

The use of haplotype blocks improved the prediction reliabilities, even when selection focused on only a group of haplotype blocks. In this case, the use of haplotype blocks that contained the 20 000 to 50 000 SNPs with the highest effect was sufficient to outperform the model that used all individual SNPs as predictors (up to 1.3 % improvement in prediction reliability for mastitis, compared to individual SNP approach), and the achieved reliabilities were similar to those using all haplotype blocks available in the genome data (from 0.6 % lower to 0.8 % higher reliability).

Conclusions

Haplotype blocks used as predictors can improve the reliability of genomic prediction compared to the individual SNP model. Furthermore, the use of a subset of haplotype blocks that contains the main SNP effects from genomic data could be a feasible approach to genomic prediction in dairy cattle, given an increase in density of genotype data available. The predictive ability of the models that use a subset of haplotype blocks was similar to that obtained using either all haplotype blocks or all individual SNPs, with the benefit of having a much lower computational demand.     

GENE GENEALOGIES WITHIN THE ORGANISMAL PEDIGREES OF RANDOM-MATING POPULATIONS

Using computer simulations, we generated and analyzed genetic distances among selectively neutral haplotypes transmitted through gene genealogies with random-mating organismal pedigrees. Constraints and possible biases on haplotype distances due to correlated ancestry were evaluated by comparing observed distributions of distances to those predicted from an inbreeding theory that assumes independence among haplotype pairs. Results suggest that: 1) mean time to common ancestry of neutral haplotypes can be a reasonably good predictor of evolutionary effective population size; 2) the nonindependence of haplotype paths of descent within a given gene genealogy typically produces significant departures from the theoretical probability distributions of haplotype distances; 3) frequency distributions of distances between haplotypes drawn from “replicate” organismal pedigrees or from multiple unlinked loci within an organismal pedigree exhibit very close agreement with the theory for independent haplotypes. These results are relevant to interpretations of current molecular data on genetic distances among nonrecombining haplotypes at either nuclear or cytoplasmic loci.     

Mutation and haplotype analyses of the Werner’s syndrome gene based on its genomic structure: genetic epidemiology in the Japanese population

The correlation between mutations in the Werner’s syndrome (WRN) gene and the haplotypes of surrounding markers was studied in Japanese patients. We have elucidated the genomic structure of WRN helicase, and found five additional mutations, designated mutations 6–10. Mutations 4 and 6 were found to be the two major mutations in this population; these mutations comprised 50.8% and 17.5%, respectively, of the total in a sample of 126 apparently unrelated chromosomes. Almost all the patients homozygous for mutation 4 shared a haplotype around the WRN gene, consistent with the view that they are derived from a single ancestor. This important advantage demonstrated in the identification of the WRN gene suggests that the Japanese present a unique population for the cloning of other disease genes. The conserved haplotype was observed across 19 loci, extending a distance estimated to be more than 1.4 Mbp around the WRN gene. This haplotype is rare among random Japanese individuals. Unexpectedly, all the nine patients homozygous for mutation 6 shared a haplotype that was identical to this haplotype at 18 of these 19 markers. These results suggest that mutations 4 and 6 arose independently in almost identical rare haplotypes. The remaining mutations (1, 5, 7, 8, 9, and 10) occurred rarely, and were each associated with different haplotypes. Received: 16 December 1996 / Accepted: 16 February 1997     

Detecting and Characterizing Genomic Signatures of Positive Selection in Global Populations

Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event.     

Selection, Hitchhiking and Disequilibrium Analysis at Three Linked Loci with Application to Hla Data

The HLA system has been extensively studied from an evolutionary perspective. Although it is clear that selection has acted on the genes in the HLA complex, the nature of this selection has yet to be fully clarified. A study of constrained disequilibrium values is presented that is applicable to HLA and other less polymorphic systems with three or more linked loci, with the purpose of identifying selection events. The method uses the fact that three locus systems impose additional constraints on the range of possible disequilibrium values for any pair of loci. We have thus examined the behavior of the normalized pairwise disequilibrium measures using two locus (D'), and also three locus (D"), constraints on pairwise disequilibria in a three locus system when one of the three loci is under positive selection. The difference between these measures, delta = magnitude of D' - magnitude of D", has a distribution for the two unselected loci differing from that for the selected locus with either of the unselected loci (the hallmark is a high positive value of delta for the two unselected loci). An examination of genetic drift indicates that positive delta values are unlikely to be found in human populations in the absence of selection when recombination is greater than about 0.1%. This measure can thus provide insight into which allele of several linked loci might have been subject to selection. Application of this method to HLA haplotypes from a large French population study (Provinces Francaise) identifies selected alleles on particular haplotypes. Application of a complementary method, disequilibrium pattern analysis also confirms the action of selection on these haplotypes.     

Durability of marker-quantitative trait loci haplotypes in structured populations

Given the relative ease of identifying genetic markers linked to QTL (compared to finding the loci themselves), it is natural to ask whether linked markers can be used to address questions concerning the contemporary dynamics and recent history of the QTL. In particular, can a marker allele found associated with a QTL allele in a QTL mapping study be used to track population dynamics or the history of the QTL allele? For this strategy to succeed, the marker-QTL haplotype must persist in the face of recombination over the relevant time frame. Here we investigate the dynamics of marker-QTL haplotype frequencies under recombination, population structure, and divergent selection to assess the potential utility of linked markers for a population genetic study of QTL. For two scenarios, described as "secondary contact" and "novel allele," we use both deterministic and stochastic methods to describe the influence of gene flow between habitats, the strength of divergent selection, and the genetic distance between a marker and the QTL on the persistence of marker-QTL haplotypes. We find that for most reasonable values of selection on a locus (s < or = 0.5) and migration (m > 1%) between differentially selected populations, haplotypes of typically spaced markers (5 cM) and QTL do not persist long enough (>100 generations) to provide accurate inference of the allelic state at the QTL.     

Heterokaryon formation and parasexual recombination between vegetatively incompatible lineages in a population of the chestnut blight fungus, Cryphonectria parasitica

Heterokaryosis was recently reported in the chestnut blight fungus, Cryphonectria parasitica, in which individuals contain nuclei that are isogenic except at the mating-type locus (MAT). MAT heterokaryons were found in several natural populations, including a putatively clonal population in West Salem, Wisconsin, providing an opportunity to address the question of how heterokaryons arise. We represented relationships among RFLP fingerprint haplotypes as networks in which loop formation is considered evidence of recombination. From 1990 to 1995, this population was clonal, as indicated by a simple haplotype network without loops, and the correlation of vegetative compatibility (vc) types and mating types with haplotype lineages. By 1999, we observed loops in the haplotype network involving isolates of two vc types (WS-2 and WS-3). Isolates with haplotypes in the loops were either MAT heterokaryons, carried the opposite mating type from other isolates of the same vc type, and/or had two alleles at two or more codominant SCAR (sequence-characterized amplified region) loci. Segregation of markers and recombination were evident among single-spore isolates from one heterokaryon; these single-spore isolates had novel fingerprint haplotypes, also within the loops. In contrast, vc type WS-1, which comprises 85% of the population, was represented by a simple network with no loops, indicating a clonal lineage varying only by mutation. Almost all isolates of WS-1 had the same mating type; the exceptions were five isolates that were MAT heterokaryons. These results are consistent with the hypothesis that heterokaryons formed between vegetatively incompatible individuals, and recombination occurred by a parasexual process.     

Isolation by adaptation in Neochlamisus leaf beetles: host-related selection promotes neutral genomic divergence

This study tests how divergent natural selection promotes genomic differentiation during ecological speciation. Specifically, we use adaptive ecological divergence (here, population divergence in host plant use and preference) as a proxy for selection strength and evaluate the correlation between levels of adaptive and genetic differentiation across pairwise population comparisons. Positive correlations would reveal the pattern predicted by our hypothesis, that of 'isolation by adaptation' (IBA). Notably, IBA is predicted not only for selected loci but also for neutral loci. This may reflect the effects of divergent selection on neutral loci that are 'loosely linked' to divergently selected loci or on geneflow restriction that facilitates genetic drift at all loci, including neutral loci that are completely unlinked to those evolving under divergent selection. Here, we evaluate IBA in maple- and willow-associated populations of Neochlamisus bebbianae leaf beetles. To do so, we collected host preference data to construct adaptive divergence indices and used AFLPs (amplified fragment length polymorphisms) and mitochondrial sequences to quantify genetic differentiation. Partial Mantel tests showed significant IBA in 'pooled' analyses of putatively neutral and of putatively selected ('outlier') AFLP loci. This pattern was also recovered in 12% of 'locus-specific' analyses that separately evaluated genetic differentiation at individual neutral loci. These results provided evidence for widespread effects of selection on neutral genomic divergence. Our collective findings indicate that host-related selection may play important roles in the population genomic differentiation of both neutral and selected gene regions in herbivorous insects.     

Microsatellite diversity and crossover regions within homozygous and heterozygous SLA haplotypes of different pig breeds

Our aim was to investigate microsatellite (MS) diversity and find crossover regions at 42 polymorphic MS loci in the swine leukocyte antigen (SLA) genomic region of 72 pigs with different well-defined homozygous and heterozygous SLA haplotypes. We analyzed the genetic polymorphisms of 42 MS markers in 23 SLA homozygous-heterozygous, common pig breeds with 12 SLA serological haplotypes and 49 National Institutes of Health (NIH) and Clawn homozygous-heterozygous miniature pigs with nine SLA serological or genotyped haplotypes including four recombinant haplotypes. In comparing the same and different haplotypes, both haplospecific patterns and allelic variations were observed at the MS loci. Some of the shared haplotype blocks extended over 2 Mb suggesting the existence of strong linkage disequilibrium (LD) in the entire SLA region. Crossover regions were easily defined by the MS markers within the class I and/or III region in the NIH and Clawn recombinant haplotypes. The present haplotype comparison shows that our set of MS markers provides a fast and cost-efficient alternative, or complementary, method to the serological or sequence-based determination of the SLA alleles for the characterization of SLA haplotypes and/or the crossover regions between different haplotypes.