Allelic variation and haplotype structure of the dopamine receptor gene DRD2 in nine Indian populations

The human dopaminergic system is a significant focal point of study in the fields of neuropsychiatry and pharmacology, plus it is also a promising nuclear DNA marker in studies of human genome diversity. In this study, we assayed six polymorphic markers in the dopamine D2 receptor gene (DRD2) in 482 unrelated individuals from nine ethnic populations of India. Our results demonstrate that the six markers are highly polymorphic in all populations and the constructed haplotypes show a high level of heterozygosity. Out of the eight possible three-site haplotypes, all populations commonly shared only three haplotypes. The haplotypes exhibited fairly high frequencies across multiple populations; Kurumba population showed all eight three-site haplotypes. The ancestral haplotype (B2-D2-Al) was observed at high frequency only in the Siddi population. Haplotypes based on all six markers revealed 16 haplotypes, out of which only 6 are most common with a frequency of greater than 5% in at least one of the nine populations. But only three haplotypes were shared by all nine populations with the cumulative frequency ranging from 80.8% (Kurumba) to 96.6% (Onge). Great variation in levels of linkage disequilibrium (LD) was detected, ranging from complete LD in the Badaga to virtually no LD in the Siddi. This range of LD likely reflects different population histories, such as African ancestry in the Siddi and recent founding events in the population isolates, Badaga and Kota.     

Genetic-geographic dispersion among North Indian populations and affinities of the Jats

Variation in 13 loci across North India has been mapped using principal components and generalized distance analysis. Significant clinal variation is documented for most systems, and genetic difference bears a relation to geographic distance especially along a north-west-to-southeast inclination. Both caste and geography exert influence over the historically contentious affinities of the Jats. Author order is alphabetical     

Genetic diversity and multilocus structure in sexual Otiorhynchus alpicola populations (Goleoptera: Gurculionidae)

Otiorhynchus alpicola Boh. (Coleoptera: Curculionidae) is distributed on high mountains of central, southern and south-eastern Europe. On the Balkan peninsula, this species is patchily distributed on mountain peaks at heights over 1800 m. To examine the organization of isoenzyme variation of the ten sexual (diploid) populations, starch gel electrophoresis of enzymes was used. The average heterozygosity over 14 gene loci was 0.11. For diploid O. alpicola, F-statistics were used to assess population heterogeneity and substructuring. The data indicate that, compared with other insects, this high-altitude weevil species is genetically very differentiated (the average F _ST= 0.35). In addition, gene-flow among populations was extremely low (the estimates of N_em from Wright's F _ST and Slatkin private-allele methods were 0.47 and 0.83, respectively). Pairwise linkage disequilibrium (LD) parameters were estimated from zygotic frequencies using Burrows' method. The average rate of significant LD in analysed populations of O. alpicola was about 27%. The pattern of LD over the diploid populations indicates that stochastic factors might be a primary cause of the observed multilocus associations.     

中国美利奴羊MHC-DRB1 exon2单倍型构建及与布鲁氏菌病易感性关联分析

为研究中国美利奴羊MHC-DRB1基因exon2单倍型与布鲁氏菌易感性的关联性,本实验采用PCR直接测序法对40例布鲁氏菌血清检测阳性和阴性个体MHC-DRB1 exon2的单核苷酸多态性(SNPs)进行检测,而后运用SHEsis在线软件对筛选的SNPs构建单倍型并进行单倍型关联分析.结果显示,在270 bp的序列内共检测到41个SNPs,经Hardy-Weinberg平衡检测筛选出符合条件的SNPs有29个,连锁不平衡发现9个连锁不平衡域,而且每个block中的SNPs两两之间存在强连锁不平衡.单倍型分析显示,由于连锁不平衡存在,仅构建9种单倍型,其中只有Hap8和Hap9两种单倍型在病例-对照组中比较差异有统计学意义(P0.05).     

Haplotype structure,adaptive history and associations with exploratory behaviour of the DRD4 gene region in four great tit (Parus major) populations

The assessment of genetic architecture and selection history in genes for behavioural traits is fundamental to our understanding of how these traits evolve. The dopamine receptor D4 (DRD4) gene is a prime candidate for explaining genetic variation in novelty seeking behaviour, a commonly assayed personality trait in animals. Previously, we showed that a single nucleotide polymorphism in exon 3 of this gene is associated with exploratory behaviour in at least one of four Western European great tit (Parus major) populations. These heterogeneous association results were explained by potential variable linkage disequilibrium (LD) patterns between this marker and the causal variant or by other genetic or environmental differences among the populations. Different adaptive histories are further hypothesized to have contributed to these population differences. Here, we genotyped 98 polymorphisms of the complete DRD4 gene including the flanking regions for 595 individuals of the four populations. We show that the LD structure, specifically around the original exon 3 SNP is conserved across the four populations and does not explain the heterogeneous association results. Study‐wide significant associations with exploratory behaviour were detected in more than one haplotype block around exon 2, 3 and 4 in two of the four tested populations with different allele effect models. This indicates genetic heterogeneity in the association between multiple DRD4 polymorphisms and exploratory behaviour across populations. The association signals were in or close to regions with signatures of positive selection. We therefore hypothesize that variation in exploratory and other dopamine‐related behaviour evolves locally by occasional adaptive shifts in the frequency of underlying genetic variants.     

TNFR2基因的CA重复多态性在两个独立的白人群体中与肥胖表型的连锁和关联

我们先前通过全基因组扫描发现lp36与体重指数显提示性连锁（LOD=2．09）。肿瘤坏死因子受体2（1NFR2）定位于lp36,是肥胖的一个极好的图位和功能侯选基因。本研究采用数量传递连锁不平衡检验在两个大的独立的白人样本中进行了TNFR2基因与肥胖表型的连锁与关联检验。第一组受试者由来自79个多代家系的1836个个体组成;第二组受试者由来自157个核心家庭的636个个体组成。所检测的肥胖表型包括体重指数、脂肪量和脂肪量百分数。在多代家系中我们发现TNFR2基因变异与BMI显著连锁（P=0．0056）。结果表明,TNFR2基因是影响白人BMI变异的一个数量性状位点。     

Extensive intragenic recombination and patterns of linkage disequilibrium at the CSN3 locus in European rabbit

Kappa-casein (CSN3) plays an important role in stabilising the Ca-sensitive caseins in the micelle. The European rabbit (Oryctolagus cuniculus) CSN3 has previously been shown to possess two alleles (A and B), which differ deeply in their intronic regions (indels of 100 and 1550 nucleotides in introns 1 and 4, respectively). Furthermore, a correlation between several reproductive performance traits and the different alleles was described. However, all these data were exclusively collected in rabbit domestic breeds, preventing a deeper understanding of the extensive polymorphism observed in the CSN3 gene. Additionally, the techniques available for the typing of both indel polymorphisms were until now not suitable for large-scale studies. In this report, we describe a simple, PCR-based typing method to distinguish rabbit CSN3 alleles. We analyse both ancient wild rabbit populations from the Iberian Peninsula and France, and the more recently derived English wild rabbits and domestic stocks. A new allele (C) showing another major indel (250 bp) in intron 1 was found, but exclusively detected in Iberian wild rabbits. In addition, our survey revealed the occurrence of new haplotypes in wild populations, suggesting that intragenic recombination is important in creating genetic diversity at this locus. This easy and low cost single-step PCR-based method results in an improvement over previous described techniques, can be easily set up in a routine molecular laboratory and would probably be a valuable tool in the management of rabbit domestic breeds.     

Major histocompatibility complex variation in insular populations of the Egyptian vulture: inferences about the roles of genetic drift and selection

Insular populations have attracted the attention of evolutionary biologists because of their morphological and ecological peculiarities with respect to their mainland counterparts. Founder effects and genetic drift are known to distribute neutral genetic variability in these demes. However, elucidating whether these evolutionary forces have also shaped adaptive variation is crucial to evaluate the real impact of reduced genetic variation in small populations. Genes of the major histocompatibility complex (MHC) are classical examples of evolutionarily relevant loci because of their well-known role in pathogen confrontation and clearance. In this study, we aim to disentangle the partial roles of genetic drift and natural selection in the spatial distribution of MHC variation in insular populations. To this end, we integrate the study of neutral (22 microsatellites and one mtDNA locus) and MHC class II variation in one mainland (Iberia) and two insular populations (Fuerteventura and Menorca) of the endangered Egyptian vulture (Neophron percnopterus). Overall, the distribution of the frequencies of individual MHC alleles (n=17 alleles from two class II B loci) does not significantly depart from neutral expectations, which indicates a prominent role for genetic drift over selection. However, our results point towards an interesting co-evolution of gene duplicates that maintains different pairs of divergent alleles in strong linkage disequilibrium on islands. We hypothesize that the co-evolution of genes may counteract the loss of genetic diversity in insular demes, maximize antigen recognition capabilities when gene diversity is reduced, and promote the co-segregation of the most efficient allele combinations to cope with local pathogen communities.     

Evidence for a large-scale population structure among accessions of Arabidopsis thaliana: possible causes and consequences for the distribution of linkage disequilibrium

The existence of a large-scale population structure was investigated in Arabidopsis thaliana by studying patterns of polymorphism in a set of 71 European accessions. We used sequence polymorphism surveyed in 10 fragments of approximately 600 nucleotides and a set of nine microsatellite markers. Population structure was investigated using a model-based inference framework. Among the accessions studied, the presence of four groups was inferred using genetic data, without using prior information on the geographical origin of the accessions. Significant genetic isolation by geographical distance was detected at the group level, together with a geographical gradient in allelic richness across groups. These results are discussed with respect to the previously proposed scenario of postglacial colonization of Europe from putative glacial refugia. Finally, the contribution of the inferred structure to linkage disequilibrium among 171 pairs of essentially unlinked markers was also investigated. Linkage disequilibrium analysis revealed that significant associations detected in the whole sample were mainly due to genetic differentiation among the inferred groups. We discuss the implication of this finding for future association studies in A. thaliana.     

Genetic divergence at the synaptophysin (Syp I) locus among Norwegian coastal and north-east Arctic populations of Atlantic cod

Several nuclear RFLP loci have been discovered recently that exhibit extensive allele frequency variation among Norwegian coastal and north-east Arctic populations of Atlantic cod Gadus morhua. One of these polymorphisms was detected by hybridizing an anonymous cDNA clone (GM798) against genomic DNA digested with the restriction enzyme DraI. This cDNA clone has now been sequenced and identified as synaptophysin (Syp I), an integral synaptic vesicle membrane protein. Primers were constructed that amplify an intron of the Syp I gene that is polymorphic for the DraI site, thus making it possible to use a PCR-based assay to score the polymorphism. A total of 965 individuals sampled from the Barents Sea, coastal areas and fjords in northern Norway have been analysed for this polymorphism. The results confirm that highly significant differences exist between NE Arctic and coastal cod at the Syp I locus. A cluster analysis revealed a deep split between coastal and Arctic populations and hierarchical F-statistics indicated that about 40% of the total variation was attributable to differences between Arctic and coastal groups. The temporal stability of allele frequencies was assessed by comparing Syp I allele frequencies among samples of juveniles (0 group) captured at specific locations in fjords in consecutive years and among samples of adults and juveniles collected from the same fjord. Samples of juveniles collected in 1994 and 1995 in Malangen were genetically indistinguishable whereas juveniles sampled from Dønnesfjord and Ullsfjorden over the same 2-year period exhibited significant differences. Adults and 0-group individuals collected from the same fjord were found to be genetically indistinguishable in Malangen, but not in Balsfjorden. In addition to detecting large differences among Arctic and coastal groups, the Syp I locus suggests that genetic heterogeneity exists among resident populations of cod in different fjords and that gene flow among populations throughout northern Norway may be considerably lower than previously believed.     

Brief communication: Molecular characterization of O alleles at the ABO locus in Chilean Aymara and Huilliche Indians

A molecular characterization of alleles O1, O1variant (O1v), and the mutation G542A of the ABO blood group was performed in two Amerindian populations of Chile, the Aymara (n = 84) and the Huilliche (n = 75). In addition, a sample of 82 individuals of Santiago belonging to the mixed Chilean population was typed for comparative purposes. The polymorphisms which allow for molecular differentiation of different alleles of the O blood group were studied in genomic DNA. The mutations G188, G261-, G542A, T646A, and C771T, described for alleles O1, O1v, and G542A, were determined using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique. All individuals studied were group O homozygotes for the deletion G261-, which defines the O1 alleles. Results obtained indicate that allele O1v exhibits frequencies of 0.65, 0.81, and 0.60 in Aymara, Huilliche, and Santiago populations, respectively. The frequencies of allele O1(G542A) were 0.119, 0.113, and 0.079 in the same populations. Frequencies for alleles O1 and O1v obtained in the Chilean populations studied concur with the results obtained by other authors, respecting the greater frequency of allele O1v as well as with its heterogeneous distribution in aboriginal South American populations. In Chilean populations, Allele G542A exhibits lower frequencies than those described for indigenous populations from Brazil and may be used as an Amerind admixture marker.     

Linkage and Association Between CA Repeat Polymorphism of the TNFR2 Gene and Obesity Phenotypes in Two Independent Caucasian Populations

Previously, our group has reported a suggestive linkage evidence of 1p36 with body mass index (BMI) (LOD = 2.09). The tumor necrosis factor receptor 2 (TNFR2) at 1p36 is an excellent positional and functional candidate gene for obesity. In this study, we have investigated the linkage and association between the TNFR2 gene and obesity phenotypes in two large independent samples, using the quantitative transmission disequilibrium tests (QTDT). The first group was made up of 1 836 individuals from 79 multi-generation pedigrees. The second group was a randomly ascertained set of 636 individuals from 157 US Caucasian nuclear families. Obesity phenotypes tested include BMI, fat mass, and percentage fat mass (PFM). A significant result (P = 0.0056) was observed for linkage with BMI in the sample of the multigenerational pedigrees. Our data support the TNFR2 gene as a quantitative trait locus (QTL) underlying BMI variation in the Caucasian populations.     

Genetic structure and gene flow among European corn borer populations from the Great Plains to the Appalachians of North America

• 1 Earlier population genetic spatial analysis of European corn borer Ostrinia nubilalis (Hübner) indicated no genetic differentiation even between locations separated by 720 km. This result suggests either high dispersal resulting in high gene flow or that populations are not in migration–drift equilibrium subsequent to their invasion of the central U.S.A. in the 1940s.
• 2 To discriminate among these two possibilities, samples were collected at 12 locations in eight states from New York to Colorado, a geographic scale that is three‐fold greater than previously tested. Eight microsatellite markers were employed to estimate genetic differentiation and gene flow among these populations, and to test for isolation‐by‐distance.
• 3 Although pairwise F_ST estimates were very low, there was a significant isolation‐by‐distance relationship.
• 4 Wright's neighbourhood area (i.e. the surface area covered by a panmictic group of individuals within a larger continuous distribution) was calculated as 433 km², and the radius indicates that approximately 13% of O. nubilalis adults disperse a net distance >12 km per generation from their natal source.
• 5 Analyses indicated significant differentiation between the north‐eastern region (New York and Pennsylvania) and the region combining sample locations from Ohio to Colorado, suggesting the potential for isolation of populations by topographic barriers in the Northeast.
• 6 Taken together, the results suggest that O. nubilalis exhibits substantial gene flow over long distances and that the lack of genetic differentiation between populations across hundreds of kilometres is not simply a result of migration–drift disequilibrium arising from the recent range expansion.

     

基于线粒体COI、Cytb和COII基因的中国草地螟不同地理种群遗传分化分析

【目的】揭示中国草地螟Loxostege sticticalis不同地理种群的遗传分化程度。【方法】采用PCR技术扩增中国西北和华北地区草地螟11个地理种群的线粒体 COI, Cytb和COII基因序列,基于其序列变异及单倍型贝叶斯系统发育树和单倍型网络图分析,探讨不同地理种群间的遗传距离、分子系统发生关系及遗传分化程度。【结果】草地螟11个地理种群的线粒体 COI, Cytb和COII基因序列分别有24, 12和69个变异位点(分别占总序列的3.6%, 2.7%和8.8%),检测到的单倍型分别为22, 14和16个,单倍型多样度(Hd)分别为0.7600, 0.5842和0.7341,核苷酸平均差异度(K)分别为1.704, 0.752和3.997,不同单倍型间的遗传距离平均值分别为0.004, 0.005和0.013。总种群的Tajima’s D和Fu’s Fs值皆不显著,表明草地螟不同地理种群间的遗传分化不明显,群体大小稳定。根据各地理种群的单倍型建立的系统发育树和单倍型网络图表明,各单倍型散布在不同的地理种群中,无明显的地理分布格局。【结论】草地螟各地理种群的遗传距离与地理距离间不具有显著的相关性,其遗传分化不明显。     

Variability of HXT2 at the protein and gene level among the Saccharomyces sensu stricto group

Variability of HXT2 at the protein and gene level was investigated among Saccharomyces sensu stricto and other yeast species. Results showed that the HXT2 gene is probably present in yeast genera other than Saccharomyces, suggesting that this gene is widely distributed in the yeast world. Chromosomal analyses indicated the stable location of HXT2 on the same chromosome and with the same copy number throughout the entire sensu stricto group. Results of the immunoblotting assay demonstrated that all strains tested (with the exception of S. cerevisiae DBVPG 6042) exhibited a lower level of Hxt2p expression than that shown by laboratory wild-type. Moreover, Hxt2p expression seems to reinforce the taxonomical differences between the two pairs of species (S. cerevisiae and S. paradoxus vs. S. pastorianus and S. bayanus) within the sensu stricto group of the genus of Saccharomyces that also reflect their different ecological niche.     

The disease resistance gene Dm3 is infrequent in natural populations of Lactuca serriola due to deletions and frequent gene conversions at the RGC2 locus

Resistance genes can exhibit heterogeneous patterns of variation. However, there are few data on their frequency and variation in natural populations. We analysed the frequency and variation of the resistance gene Dm3, which confers resistance to Bremia lactucae (downy mildew) in 1033 accessions of Lactuca serriola (prickly lettuce) from 49 natural populations. Inoculations with an isolate of Bremia lactucae carrying avirulence gene Avr3 indicated that the frequency of Dm3 in natural populations of L. serriola was very low. Molecular analysis demonstrated that Dm3 was present in only one of the 1033 wild accessions analysed. The sequence of the 5' region of Dm3 was either highly conserved among accessions, or absent. In contrast, frequent chimeras were detected in the 3' leucine-rich repeat-encoding region. Therefore low frequency of the Dm3 specificity in natural populations was due to either the recent evolution of Dm3 specificity, or deletions of the whole gene as well as variation in 3' region caused by frequent gene conversions. This is the most extensive analysis of the prevalence of a known disease resistance gene to date, and indicates that the total number of resistance genes in a species may be very high. This has implications for the scales of germplasm conservation and exploitation of sources of resistance.     

Distinct haplotype structure at the innate immune receptor Toll‐like receptor 2 across bank vole populations and lineages in Europe

Parasite‐mediated selection may contribute to the maintenance of genetic variation at host immune genes over long time scales. To date, the best evidence for the long‐term maintenance of immunogenetic variation in natural populations comes from studies on the major histocompatibility complex (MHC) genes, whereas evidence for such processes from other immune genes remains scarce. In the present study, we show that, despite pronounced population differentiation and the occurrence of numerous private alleles within populations, the innate immune gene Toll‐like receptor 2 (TLR2) displays a distinct haplotype structure in 21 bank vole (Myodes glareolus) populations across Europe. Haplotypes from all populations grouped in four clearly differentiated clusters, with the three main clusters co‐occurring in at least three previously described mitochondrial lineages. This pattern indicates that the distinct TLR2 haplotype structure may precede the split of the mitochondrial lineages 0.19–0.56 Mya and suggests that haplotype clusters at this innate immune receptor are maintained over prolonged time in wild bank vole populations.     

Genetic structure in a fragmented Northern Hemisphere rainforest: large effective sizes and high connectivity among populations of the epiphytic lichen Lobaria pulmonaria

An extraordinary diversity of epiphytic lichens is found in the boreal rainforest of central Norway, the highest-latitude rainforest in the world. These rainforest relicts are located in ravine systems, and clear cutting has increased the distance between remaining patches. We hypothesized that the relatively small lichen populations in the remaining forest stands have suffered a depletion of genetic diversity through bottlenecks and founder events. To test this hypothesis, we assessed genetic diversity and structure in the populations of the tripartite lichen Lobaria pulmonaria using eight SSR loci. We sampled thalli growing on Picea abies branches and propagules deposited in snow at three localities. Contrary to expectations, we found high genetic diversity in lichen and snow samples, and high effective sizes of the studied populations. Also, limited genetic differentiation between populations, high historical migration rates, and a high proportion of first generation immigrants were estimated, implying high connectivity across distances <30km. Almost all genetic variation was attributed to variation within sites; spatial genetic structures within populations were absent or appeared on small scales (5-10m). The high genetic diversity in the remaining old boreal rainforests shows that even relict forest patches might be suitable for conservation of genetic diversity.     

Genetic variation and biochemical properties of esterase-18 (ES-18) in the laboratory rat (Rattus norvegicus): A new locus of esterase cluster 2 in linkage group V

A new liver-specific rat carboxylesterase isozyme (EC 3.1.1.1) designated esterase-18 (ES-18) is described. Genetic variation of ES-18 was examined in 93 inbred strains and substrains and a structural locusEs-18 was suggested, coding for either the presence (Es-18 ^a) or the absence (Es-18 ^b) of the isozyme. Linkage studies involving two backcross series revealed thatEs-18 resides in cluster 2 of LGV. No recombination betweenEs-18 and other cluster 2 loci was found in 19 lines of two RI strain sets or in the backcross series.R. K. was supported by the Sonderforschungsbereich 146 (Versuchstierforschung). O.D. was supported by the Deutsche Forschungsgemeinschaft (De 315/2). This is communication No. 65 of a research program devoted to the cellular distribution, regulation, and genetics of nonspecific esterases.     

Natural selection and the genetic differentiation of coastal and Arctic populations of the Atlantic cod in northern Norway: a test involving nucleotide sequence variation at the pantophysin (PanI) locus

To examine the role of contemporary selection in maintaining significant allele frequency differences at the pantophysin (PanI) locus among populations of the Atlantic cod, Gadus morhua, in northern Norway, we sequenced 127 PanIA alleles sampled from six coastal and two Barents Sea populations. The distributions of variable sites segregating within the PanIA allelic class were then compared among the populations. Significant differences were detected in the overall frequencies of PanIA alleles among populations within coastal and Arctic regions that was similar in magnitude to heterogeneity in the distributions of polymorphic sites segregating within the PanIA allelic class. The differentiation observed at silent sites in the PanIA allelic class contradicts the predicted effects of widescale gene flow and suggests that postsettlement selection acting on cohorts cannot be responsible for the genetic differences described between coastal and Arctic populations. Our results suggest that the marked differences observed between coastal and Arctic populations of G. morhua in northern Norway at the PanI locus reflect the action of recent diversifying selection and that populations throughout the region may be more independent than suggested by previous studies.