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Michel Veuille - One of the best experts on this subject based on the ideXlab platform.
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Geographical delimitation of a partial Selective Sweep in African Drosophila melanogaster.
Molecular Ecology, 2012Co-Authors: Lise Frezal, Stéphane Mousset, Stefano Mona, Ferdinando Meli, Michel VeuilleAbstract:Positive selection leaves characteristic footprints on DNA variation but detecting such patterns is challenging as the age, the intensity and the mode of selection as well as demography and evolutionary parameters (mutation and recombination rates) all play roles and these are difficult to disentangle. We recorded nucleotide variation in a sample of isogenic chromosomes from a western African population of Drosophila melanogaster at a locus (Fbp2) for which a partial Selective Sweep had previously been reported. We compared this locus to four other genes from the same chromosomes and from a European and an East African population. Then, we assessed Fbp2 variation in a sample of 370 chromosomes covering a comprehensive geographic sampling of 16 African localities. The signature of selection was tested while accounting for the demographic history of the populations. We found a significant signal of selection in two West African localities including Ivory Coast. Variation at Fpb2 would thus represent a case of an ongoing Selective Sweep in the range of this species. A weaker, nonsignificant, signal of selection was, however, apparent in some other populations, thus leaving open several possibilities: (i) the Selective Sweep originated in Ivory Coast and has spread to the rest of the continent; (ii) several African populations report the signature of a Selective event having occurred in an ancestral population; (iii) this genome region is subject to independent Selective events in African populations; and (iv) A neutral scenario with population subdivision and local bottleneck cannot be fully excluded to explain the molecular patterns observed in some populations.
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Signature of Selective Sweep associated with the evolution of sex-ratio drive in Drosophila simulans.
Genetics, 2004Co-Authors: Nicolas Derome, Karine Métayer, Catherine Montchamp-moreau, Michel VeuilleAbstract:In several Drosophila species, the XY Mendelian ratio is disturbed by X-linked segregation distorters (sex-ratio drive). We used a collection of recombinants between a nondistorting chromosome and a distorting X chromosome originating from the Seychelles to map a candidate sex-ratio region in Drosophila simulans using molecular biallelic markers. Our data were compatible with the presence of a sex-ratio locus in the 7F cytological region. Using sequence polymorphism at the Nrg locus, we showed that sex-ratio has induced a strong Selective Sweep in populations from Madagascar and Reunion, where distorting chromosomes are close to a 50% frequency. The complete association between the marker and the sex-ratio phenotype and the near absence of mutations and recombination in the studied fragment after the Sweep event indicate that this event is recent. Examples of Selective Sweeps are increasingly reported in a number of genomes. This case identifies the causal Selective force. It illustrates that all Selective Sweeps are not necessarily indicative of an increase in the average fitness of populations.
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Selective Sweep at the drosophila melanogaster suppressor of hairless locus and its association with the in 2l t inversion polymorphism
Genetics, 1999Co-Authors: Frantz Depaulis, Lionel Brazier, Michel VeuilleAbstract:The hitchhiking model of population genetics predicts that an allele favored by Darwinian selection can replace haplotypes from the same locus previously established at a neutral mutation-drift equilibrium. This process, known as "Selective Sweep," was studied by comparing molecular variation between the polymorphic In(2L)t inversion and the standard chromosome. Sequence variation was recorded at the Suppressor of Hairless (Su[H]) gene in an African population of Drosophila melanogaster. We found 47 nucleotide polymorphisms among 20 sequences of 1.2 kb. Neutrality tests were nonsignificant at the nucleotide level. However, these sites were strongly associated, because 290 out of 741 observed pairwise combinations between them were in significant linkage disequilibrium. We found only seven haplotypes, two occurring in the 9 In(2L)t chromosomes, and five in the 11 standard chromosomes, with no shared haplotype. Two haplotypes, one in each chromosome arrangement, made up two-thirds of the sample. This low haplotype diversity departed from neutrality in a haplotype test. This pattern supports a Selective Sweep hypothesis for the Su(H) chromosome region.
Wolfgang Stephan - One of the best experts on this subject based on the ideXlab platform.
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fine mapping and Selective Sweep analysis of qtl for cold tolerance in drosophila melanogaster
G3: Genes Genomes Genetics, 2014Co-Authors: Ricardo Wilches, Stefan Laurent, Susanne Voigt, Pablo Duchen, Wolfgang StephanAbstract:There is a growing interest in investigating the relationship between genes with signatures of natural selection and genes identified in QTL mapping studies using combined population and quantitative genetics approaches. We dissected an X-linked interval of 6.2 Mb, which contains two QTL underlying variation in chill coma recovery time (CCRT) in Drosophila melanogaster from temperate (European) and tropical (African) regions. This resulted in two relatively small regions of 131 kb and 124 kb. The latter one co-localizes with a very strong Selective Sweep in the European population. We examined the genes within and near the Sweep region individually using gene expression analysis and P-element insertion lines. Of the genes overlapping with the Sweep, none appears to be related to CCRT. However, we have identified a new candidate gene of CCRT, brinker, which is located just outside the Sweep region and is inducible by cold stress. We discuss these results in light of recent population genetics theories on quantitative traits.
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Selective Sweep in the flotillin 2 region of european drosophila melanogaster
PLOS ONE, 2013Co-Authors: Annegret Werzner, Pavlos Pavlidis, Wolfgang Stephan, Lino Ometto, Stefan LaurentAbstract:Localizing genes that are subject to recent positive selection is a major goal of evolutionary biology. In the model organism Drosophila melanogaster many attempts have been made in recent years to identify such genes by conducting so-called genome scans of selection. These analyses consisted in typing a large number of genetic markers along the genomes of a sample of individuals and then identifying those loci that harbor patterns of genetic variation, which are compatible with the ones generated by a Selective Sweep. In this study we conduct an in-depth analysis of a genomic region located on the X chromosome of D. melanogaster that was identified as a potential target of recent positive selection by a previous genome scan of selection. To this end we re-sequenced 20 kilobases around the Flotillin-2 gene (Flo-2) and conducted a detailed analysis of the allele frequencies and linkage disequilibria observed in this new dataset. The results of this analysis reveal eight genetic novelties that are specific to temperate populations of D. melanogaster and that may have arisen during the expansion of the species outside its ancestral sub-Saharan habitat since about 16,000 years ago.
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identification of x linked quantitative trait loci affecting cold tolerance in drosophila melanogaster and fine mapping by Selective Sweep analysis
Molecular Ecology, 2011Co-Authors: Pavlos Pavlidis, Annegret Werzner, Ricardo Wilches, Nicolas Svetec, Jose M Alvarezcastro, Karl W Broman, Dirk Metzler, Wolfgang StephanAbstract:Drosophila melanogaster is a cosmopolitan species that colonizes a great variety of environments. One trait that shows abundant evidence for naturally segregating genetic variance in different populations of D. melanogaster is cold tolerance. Previous work has found quantitative trait loci (QTL) exclusively on the second and the third chromosomes. To gain insight into the genetic architecture of cold tolerance on the X chromosome and to compare the results with our analyses of Selective Sweeps, a mapping population was derived from a cross between substitution lines that solely differed in the origin of their X chromosome: one originates from a European inbred line and the other one from an African inbred line. We found a total of six QTL for cold tolerance factors on the X chromosome of D. melanogaster. Although the composite interval mapping revealed slightly different QTL profiles between sexes, a coherent model suggests that most QTL overlapped between sexes, and each explained around 5-14% of the genetic variance (which may be slightly overestimated). The allelic effects were largely additive, but we also detected two significant interactions. Taken together, this provides evidence for multiple QTL that are spread along the entire X chromosome and whose effects range from low to intermediate. One detected transgressive QTL influences cold tolerance in different ways for the two sexes. While females benefit from the European allele increasing their cold tolerance, males tend to do better with the African allele. Finally, using Selective Sweep mapping, the candidate gene CG16700 for cold tolerance colocalizing with a QTL was identified.
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evidence of gene conversion associated with a Selective Sweep in drosophila melanogaster
Molecular Biology and Evolution, 2006Co-Authors: Sascha Glinka, David De Lorenzo, Wolfgang StephanAbstract:Since Drosophila melanogaster colonized Europe from tropical Africa 10 to 15 thousand years ago, it is expected that adaptation has played a major role in this species in recent times. A previously conducted multilocus scan of noncoding DNA sequences on the X chromosome in an ancestral and a derived population of D. melanogaster revealed that some loci have been affected by directional selection in the European population. We investigated if the pattern of DNA sequence polymorphism in a region surrounding one of these loci can be explained by a hitchhiking event. We found strong evidence that the studied region around the gene unc-119 was shaped by a recent Selective Sweep, including a valley of reduced heterozygosity of 83.4 kb, a skew in the frequency spectrum, and significant linkage disequilibrium on one side of the valley. This region, however, was interrupted by gene conversion events leading to a strong haplotype structure in the center of the valley of reduced variation.
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evidence for a Selective Sweep in the wapl region of drosophila melanogaster
Genetics, 2006Co-Authors: Steffen Beisswanger, Wolfgang Stephan, David De LorenzoAbstract:A scan of the X chromosome of a European Drosophila melanogaster population revealed evidence for the recent action of positive directional selection at individual loci. In this study we analyze one such region that showed no polymorphism in the genome scan (located in cytological division 2C10–2E1). We detect a 60.5-kb stretch of DNA encompassing the genes ph-d, ph-p, CG3835, bcn92, Pgd, wapl, and Cyp4d1, which almost completely lacks variation in the European sample. Loci flanking this region show a skewed frequency spectrum at segregating sites, strong haplotype structure, and high levels of linkage disequilibrium. Neutrality tests reveal that these data are unlikely under both the neutral equilibrium model and the simple bottleneck scenarios. In contrast, newly developed maximum-likelihood ratio tests suggest that strong selection has acted recently on the region under investigation, causing a Selective Sweep. Evidence that this Sweep may have originated in an ancestral population in Africa is presented.
Charles Robin - One of the best experts on this subject based on the ideXlab platform.
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structural variants and Selective Sweep foci contribute to insecticide resistance in the drosophila genetic reference panel
G3: Genes Genomes Genetics, 2018Co-Authors: Paul Battlay, Llewellyn Green, Pontus Leblanc, Joshua M Schmidt, Alexandre Fournierlevel, Nandita R Garud, Charles RobinAbstract:Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the Selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link Selective Sweeps to the particular insecticide phenotypes that could plausibly account for the drastic Selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome-wide association studies map survival on malathion to two of the largest Sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1, Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a Selective Sweep driven by insecticide use, the derived allele seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.
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structural variants and Selective Sweep foci contribute to insecticide resistance in the drosophila melanogaster genetic reference panel
bioRxiv, 2018Co-Authors: Llewellyn Green, Pontus Leblanc, Joshua M Schmidt, Alexandre Fournierlevel, Charles RobinAbstract:Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the Selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link Selective Sweep loci to the particular insecticide phenotypes that could plausibly account for the drastic Selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome wide association studies map survival to malathion to two of the largest Sweeps in the D. melanogaster genome; Ace and Cyp6g1 . Malathion survivorship also correlates with lines which have high levels of Cyp12d1 and Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a Selective Sweep driven by insecticide use, the derived state seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.
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High nucleotide diversity and limited linkage disequilibrium in Helicoverpa armigera facilitates the detection of a Selective Sweep
Heredity, 2015Co-Authors: S.v. Song, Sharon Downes, T Parker, John G. Oakeshott, Charles RobinAbstract:High nucleotide diversity and limited linkage disequilibrium in Helicoverpa armigera facilitates the detection of a Selective Sweep
Pavlos Pavlidis - One of the best experts on this subject based on the ideXlab platform.
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RAiSD detects positive selection based on multiple signatures of a Selective Sweep and SNP vectors
Communications biology, 2018Co-Authors: Nikolaos Alachiotis, Pavlos PavlidisAbstract:Selective Sweeps leave distinct signatures locally in genomes, enabling the detection of loci that have undergone recent positive selection. Multiple signatures of a Selective Sweep are known, yet each neutrality test only identifies a single signature. We present RAiSD (Raised Accuracy in Sweep Detection), an open-source software that implements a novel, to our knowledge, and parameter-free detection mechanism that relies on multiple signatures of a Selective Sweep via the enumeration of SNP vectors. RAiSD achieves higher sensitivity and accuracy than the current state of the art, while the computational complexity is greatly reduced, allowing up to 1000 times faster processing than widely used tools, and negligible memory requirements. Nikolaos Alachiotis and Pavlos Pavlidis present RAiSD, a computational method for identifying multiple signatures of Selective Sweeps using single nucleotide polymorphism vectors. They show that RAiSD has higher sensitivity and accuracy with reduced computational complexity than current methods.
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scalable linkage disequilibrium based Selective Sweep detection a performance guide
GigaScience, 2016Co-Authors: Nikolaos Alachiotis, Pavlos PavlidisAbstract:Linkage disequilibrium is defined as the non-random associations of alleles at different loci, and it occurs when genotypes at the two loci depend on each other. The model of genetic hitchhiking predicts that strong positive selection affects the patterns of linkage disequilibrium around the site of a beneficial allele, resulting in specific motifs of correlation between neutral polymorphisms that surround the fixed beneficial allele. Increased levels of linkage disequilibrium are observed on the same side of a beneficial allele, and diminish between sites on different sides of a beneficial mutation. This specific pattern of linkage disequilibrium occurs more frequently when positive selection has acted on the population rather than under various neutral models. Thus, detecting such patterns could accurately reveal targets of positive selection along a recombining chromosome or a genome. Calculating linkage disequilibria in whole genomes is computationally expensive because allele correlations need to be evaluated for millions of pairs of sites. To analyze large datasets efficiently, algorithmic implementations used in modern population genetics need to exploit multiple cores of current workstations in a scalable way. However, population genomic datasets come in various types and shapes while typically showing SNP density heterogeneity, which makes the implementation of generally scalable parallel algorithms a challenging task. Here we present a series of four parallelization strategies targeting shared-memory systems for the computationally intensive problem of detecting genomic regions that have contributed to the past adaptation of the species, also referred to as regions that have undergone a Selective Sweep, based on linkage disequilibrium patterns. We provide a thorough performance evaluation of the proposed parallel algorithms for computing linkage disequilibrium, and outline the benefits of each approach. Furthermore, we compare the accuracy of our open-source Sweep-detection software OmegaPlus, which implements all four parallelization strategies presented here, with a variety of neutrality tests. The computational demands of Selective Sweep detection algorithms depend greatly on the SNP density heterogeneity and the data representation. Choosing the right parallel algorithm for the analysis can lead to significant processing time reduction and major energy savings. However, determining which parallel algorithm will execute more efficiently on a specific processor architecture and number of available cores for a particular dataset is not straightforward.
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Selective Sweep in the flotillin 2 region of european drosophila melanogaster
PLOS ONE, 2013Co-Authors: Annegret Werzner, Pavlos Pavlidis, Wolfgang Stephan, Lino Ometto, Stefan LaurentAbstract:Localizing genes that are subject to recent positive selection is a major goal of evolutionary biology. In the model organism Drosophila melanogaster many attempts have been made in recent years to identify such genes by conducting so-called genome scans of selection. These analyses consisted in typing a large number of genetic markers along the genomes of a sample of individuals and then identifying those loci that harbor patterns of genetic variation, which are compatible with the ones generated by a Selective Sweep. In this study we conduct an in-depth analysis of a genomic region located on the X chromosome of D. melanogaster that was identified as a potential target of recent positive selection by a previous genome scan of selection. To this end we re-sequenced 20 kilobases around the Flotillin-2 gene (Flo-2) and conducted a detailed analysis of the allele frequencies and linkage disequilibria observed in this new dataset. The results of this analysis reveal eight genetic novelties that are specific to temperate populations of D. melanogaster and that may have arisen during the expansion of the species outside its ancestral sub-Saharan habitat since about 16,000 years ago.
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exploiting multi grain parallelism for efficient Selective Sweep detection
International Conference on Algorithms and Architectures for Parallel Processing, 2012Co-Authors: Nikolaos Alachiotis, Pavlos Pavlidis, Alexandros StamatakisAbstract:Selective Sweep detection localizes targets of recent and strong positive selection by analyzing single nucleotide polymorphisms (SNPs) in intra-species multiple sequence alignments. Substantial advances in wet-lab sequencing technologies currently allow for generating unprecedented amounts of molecular data. The increasing number of sequences and number of SNPs in such large multiple sequence alignments cause prohibiting long execution times for population genetics data analyses that rely on Selective Sweep theory. To alleviate this problem, we have recently implemented fine- and coarse-grain parallel versions of our open-source tool OmegaPlus for Selective Sweep detection that is based on the ω statistic. A performance issue with the coarse-grain parallelization is that individual coarse-grain tasks exhibit significant run-time differences, and hence cause load imbalance. Here, we introduce a significantly improved multi-grain parallelization scheme which outperforms both the fine-grain as well as the coarse-grain versions of OmegaPlus with respect to parallel efficiency. The multi-grain approach exploits both coarse-grain and fine-grain operations by using available threads/cores that have completed their coarse-grain tasks to accelerate the slowest task by means of fine-grain parallelism. A performance assessment on real-world and simulated datasets showed that the multi-grain version is up to 39% and 64.4% faster than the coarse-grain and the fine-grain versions, respectively, when the same number of threads is used.
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Selective Sweep of a cis regulatory sequence in a non african population of drosophila melanogaster
Molecular Biology and Evolution, 2012Co-Authors: Sarah S Saminadinpeter, Pavlos Pavlidis, Claus Kemkemer, John ParschAbstract:Although it is thought that changes in gene expression play an important role in adaptation, the identification of generegulatory sequences that have been targets of positive selection has proved difficult. Here, we identify a cis-regulatory element of the Drosophila melanogaster CG9509 gene that is associated with a Selective Sweep in a derived non-African population of the species. Expression analyses indicate that CG9509 consistently shows greater expression in non-African than in African strains of D. melanogaster. We find that a 1.8 kb region located just upstream of the CG9509 coding region is devoid of DNA sequence polymorphism in a European population sample and that this is best explained by the recent action of positive selection (within the past 4,000–10,000 years). Using a reporter gene construct and phiC31-mediated site-specific integration, we show that the European version of the CG9509 upstream region drives 2–3 times greater expression than the African version in an otherwise identical genetic background. This expression difference corresponds well to that of the native gene and indicates that sequence variation within the CG9509 upstream region can completely account for its high expression in the European population. Selection appears to have favored a quantitative increase in gene expression in the Malphigian tubule, the tissue where CG9509 is predominantly expressed.
Charles B Foster - One of the best experts on this subject based on the ideXlab platform.
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Polymorphism analysis of six selenoprotein genes: support for a Selective Sweep at the glutathione peroxidase 1 locus (3p21) in Asian populations
BMC Genetics, 2006Co-Authors: Charles B Foster, Kshama Aswath, Stephen J Chanock, Heather F Mckay, Ulrike PetersAbstract:Background There are at least 25 human selenoproteins, each characterized by the incorporation of selenium into the primary sequence as the amino acid selenocysteine. Since many selenoproteins have antioxidant properties, it is plausible that inter-individual differences in selenoprotein expression or activity could influence risk for a range of complex diseases, such as cancer, infectious diseases as well as deleterious responses to oxidative stressors like cigarette smoke. To capture the common genetic variants for 6 important selenoprotein genes ( GPX1 , GPX2 , GPX3 , GPX4 , TXNRD1 , and SEPP1 ) known to contribute to antioxidant host defenses, a re-sequence analysis was conducted across these genes with particular interest directed at the coding regions, intron-exon borders and flanking untranslated regions (UTR) for each gene in an 102 individual population representative of 4 major ethnic groups found within the United States. Results For 5 of the genes there was no strong evidence for selection according to the expectations of the neutral equilibrium model of evolution; however, at the GPX1 locus (3p21) there was evidence for positive selection. Strong confirmatory evidence for recent positive selection at the genomic region 3p21 in Asian populations is provided by data from the International HapMap project. Conclusion The SNPs and fine haplotype maps described in this report will be valuable resources for future functional studies, for population specific genetic studies designed to comprehensively explore the role of selenoprotein genetic variants in the etiology of various human diseases, and to define the forces responsible for a recent Selective Sweep in the vicinity of the GPX1 locus.
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polymorphism analysis of six selenoprotein genes support for a Selective Sweep at the glutathione peroxidase 1 locus 3p21 in asian populations
BMC Genetics, 2006Co-Authors: Charles B Foster, Kshama Aswath, Stephen J Chanock, Heather F Mckay, Ulrike PetersAbstract:There are at least 25 human selenoproteins, each characterized by the incorporation of selenium into the primary sequence as the amino acid selenocysteine. Since many selenoproteins have antioxidant properties, it is plausible that inter-individual differences in selenoprotein expression or activity could influence risk for a range of complex diseases, such as cancer, infectious diseases as well as deleterious responses to oxidative stressors like cigarette smoke. To capture the common genetic variants for 6 important selenoprotein genes (GPX1, GPX2, GPX3, GPX4, TXNRD1, and SEPP1) known to contribute to antioxidant host defenses, a re-sequence analysis was conducted across these genes with particular interest directed at the coding regions, intron-exon borders and flanking untranslated regions (UTR) for each gene in an 102 individual population representative of 4 major ethnic groups found within the United States. For 5 of the genes there was no strong evidence for selection according to the expectations of the neutral equilibrium model of evolution; however, at the GPX1 locus (3p21) there was evidence for positive selection. Strong confirmatory evidence for recent positive selection at the genomic region 3p21 in Asian populations is provided by data from the International HapMap project. The SNPs and fine haplotype maps described in this report will be valuable resources for future functional studies, for population specific genetic studies designed to comprehensively explore the role of selenoprotein genetic variants in the etiology of various human diseases, and to define the forces responsible for a recent Selective Sweep in the vicinity of the GPX1 locus.
