<Emphasis Type="Italic">KIR</Emphasis> haplotypes defined by segregation analysis in 59 Centre d’Etude Polymorphisme Humain (CEPH) families

The killer cell immunoglobulin-like receptor (KIR) gene cluster exhibits extensive allelic and haplotypic diversity. Variation at the locus is associated with an increasing number of human diseases, reminiscent of the HLA loci. Characterization of diversity at the KIR locus has progressed over the past several years, particularly since the sequence of entire KIR haplotypes have become available. To determine the extent of KIR haplotypic variability among individuals of northern European descent, we genotyped 59 CEPH families for presence/absence of all KIR genes and performed limited allelic subtyping at several KIR loci. A total of 20 unique haplotypes differing in gene content were identified, the most common of which was the previously defined A haplotype (f = 0.52). Several unusual haplotypes that probably arose as a consequence of unequal crossing over events were also identified. Linkage disequilibrium (LD) analysis indicated strong negative and positive LD between several pairs of genes, values that may be useful in determining haplotypic structure when family data are not available. These data provide a resource to aid in the interpretation of disease association data involving individuals of European descent. An erratum to this article can be found at     

<Emphasis Type="Italic">FMR1</Emphasis> haplotype analyses among Indians: a weak founder effect and other findings

This study on allelic/haplotypic fragile X associations evaluated using STR (DXS548, FRAXAC1, FRAXAC2) and SNP (ATL1) markers flanking the (CGG)(n) locus of FMR1is the first report from the large ethnically complex Indian population. Results have been compared with allele/haplotype distributions reported for other major ethnic groups, including White Caucasians, Africans, and Pacific Asians. Though overall allele frequency distributions at the individual loci are more similar to Western Caucasians compared with others, significant differences are observed in haplotypic associations with the mutated X. The striking findings are: (1) high diversity and heterozygosity of haplotypes among fragile X chromosomes ( n=40) and controls ( n=262), including four haplotypes found exclusively in this study sample; (2) weak association of DXS548-FRAXAC1-FRAXAC2 haplotypes, 2-1-3, 6-3-3+ and 7-4-6+ with the disorder, and absence of White Caucasian fragile X haplotypes 6-4-4 and 6-4-5; (3) weak founder effect for the fragile X expansion mutation in the Indians; (4) lack of a continuum of haplotype-based FMR1 alleles between intermediate (CGG)(n) size ranges and expanded alleles; (5) exclusion of ATL1 as a candidate genetic indicator of FMR1 instability. The high STR-based haplotype diversity observed among fragile X lineages, irrespective of ethnic alliances, strongly suggests the inappropriateness of using STR haplotypes to infer predisposition to instability among ethnically separated fragile X pedigrees and may reiterate the need for identifying newer SNPs from this region to not only determine true founder effects for the fragile X mutation, but also decipher possible mechanisms leading to CGG instability.     

贵州三都水族Y染色体上七个STR基因座的遗传多态性分析

采用多重PCR技术, 结合ABI PRISMTM 377 DNA Sequencer四色荧光标记进行基因扫描分型, 对中国贵州三都水族群体进行7个Y-STR基因座的多态性分析, 计算其基因频率、遗传多样性及单倍型多样性, 获取相应的遗传多态信息。结果显示: 在94个无关男性样本中, DYS19、DYS389Ⅰ、DYS389Ⅱ、DYS390、DYS391、DYS392、DYS393等基因座分别检出6, 4, 6, 2, 3, 5, 4种等位基因, 遗传多样性在0.124(DYS389Ⅰ)~0.630(DYS19)之间; 由此组成的单倍型为27种, 单倍型多样性0.868。此7个Y-STR基因座在贵州三都水族群体中具有较好的多态性, 单倍型具有较高的遗传多态。     

Breeding structure of Glossina pallidipes populations evaluated by mitochondrial variation

Mitochondrial DNA diversity was studied at four loci in six natural populations of the tsetse fly Glossina pallidipes from Zimbabwe, Mozambique, Kenya, and Ethiopia. Single-locus diversity varied from 0.39 at 12S to 0.65 at COII. A total of 32 haplotypes was found with a mean of 6.4 +/- 2.9 per locus. To study breeding structure, diversity at two loci, COII and 16S2, was evaluated in 18 populations sampled from an area of approximately 1,611,000 km2 and in three laboratory cultures. Twenty-six haplotypes were detected at the two loci and mean haplotype diversity over all natural populations was 0.63. A high degree of population subdivision was detected within and among the Ethiopian and Kenya populations. The Zimbabwe and Zambia populations showed much less variation and differentiation than the northern populations. A population in Mozambique showed high levels of haplotype variation and affinities closest to populations in eastern Kenya, some 1700 km to the north. Analysis of variance of haplotype frequencies showed that 51.5% of the total lay within populations, 13% among populations within five nested groups, and 35.5% among the five groups. Wright's FST was 0.485, Nei's GST was 0.33, and Weir and Cunningham's theta = 0.45. Ecological data show that G. pallidipes is highly vagile. The large amount of genetic differentiation may be explained by genetic drift that occurred in scattered, relict populations during the rinderpest panzootic of the late 19th and early 20th centuries.     

深圳无偿献血人群中李姓、王姓和张姓无关男性个体Y-STR单倍型遗传多态性

为研究姓氏群体Y染色体特异STR单倍型的遗传多态性, 采用PCR复合扩增和ABI PrismTM 3100基因测序仪荧光检测方法对DYS426等9个Y-STR基因座进行基因分型, 检测深圳地区李姓无关男性个体血样139份、王姓无关男性个体118份、张姓无关男性个体119份。结果在139份李姓群体中, 共检出126种单倍型, 其中118种单倍型仅出现1次, 检出频率最高的1种单倍型出现6次, 单倍型多样性为0.9974; 118份王姓无关男性样本中, 共检出105种单倍型, 其中94种单倍型仅出现1次, 检出频率最高的1种单倍型出现4次, 单倍型多样性为0.9953; 张姓无关男性样本中, 共检出101种单倍型, 其中88种单倍型仅出现1次, 检出频率最高的1种单倍型出现4次, 单倍型多样性为0.9964。结果表明: 深圳地区李、王、张姓氏无关男性个体Y-STR单倍型的遗传多态性丰富, 与以往的汉族无关男性群体遗传资料相比较, 差异不显著。     

Interhomologue sequence variation of alpha satellite DNA from human chromosome 17: Evidence for concerted evolution along haplotypic lineages

Alpha satellite DNA is a family of tandemly repeated DNA found at the centromeres of all primate chromosomes. Different human chromosomes 17 in the population are characterized by distinct alpha satellite haplotypes, distinguished by the presence of variant repeat forms that have precise monomeric deletions. Pairwise comparisons of sequence diversity between variant repeat units from each haplotype show that they are closely related in sequence. Direct sequencing of PCR-amplified alpha satellite reveals heterogeneous positions between the repeat units on a chromosome as two bands at the same position on a sequencing ladder. No variation was detected in the sequence and location of these heterogeneous positions between chromosomes 17 from the same haplotype, but distinct patterns of variation were detected between chromosomes from different haplotypes. Subsequent sequence analysis of individual repeats from each haplotype confirmed the presence of extensive haplotype-specific sequence variation. Phylogenetic inference yielded a tree that suggests these chromosome 17 repeat units evolve principally along haplotypic lineages. These studies allow insight into the relative rates and/or timing of genetic turnover processes that lead to the homogenization of tandem DNA families. Correspondence to: H.F. Willard     

Genetic variation and structure in the expanding moss Pogonatum dentatum (Polytrichaceae) in its area of origin and in a recently colonized area

Genetic variation in the expanding moss species Pogonatum dentatum was studied using intersimple sequence repeat (ISSR) markers. The genetic consequences of range expansion were studied by comparing source populations in a mountain area with populations from a recently colonized lowland area in Sweden. Indices of genetic variation show slightly lower number of alleles per locus in the lowlands and a similar gene diversity in both areas. Three of four lowland populations had evidence of a recently passed bottleneck. Considerably higher haplotype diversity was found in the recently colonized lowlands compared to source populations in the mountains. Patterns of allelic diversity suggest that P. dentatum experiences loss of genetic variation through founder effects and genetic drift when expanding its distribution range. Higher haplotypic diversity, less linkage disequilibrium, and fewer compatible loci indicate that sexual recombination is relatively more important in the lowlands compared to the mountains. A likely explanation is higher success of establishment from spores in the lowlands, while clonal propagation predominates in the mountains. Less genetic differentiation among lowland populations indicates more gene flow in the lowland area, involving more spores and/or fragments moving among populations.     

Genetic Variation of Sclerotinia sclerotiorum from Multiple Crops in the North Central United States

Sclerotinia sclerotiorum is an important pathogen of numerous crops in the North Central region of the United States. The objective of this study was to examine the genetic diversity of 145 isolates of the pathogen from multiple hosts in the region. Mycelial compatibility groups (MCG) and microsatellite haplotypes were determined and analyzed for standard estimates of population genetic diversity and the importance of host and distance for genetic variation was examined. MCG tests indicated there were 49 different MCGs in the population and 52 unique microsatellite haplotypes were identified. There was an association between MCG and haplotype such that isolates belonging to the same MCG either shared identical haplotypes or differed at no more than 2 of the 12 polymorphic loci. For the majority of isolates, there was a one-to-one correspondence between MCG and haplotype. Eleven MCGs shared haplotypes. A single haplotype was found to be prevalent throughout the region. The majority of genetic variation in the isolate collection was found within rather than among host crops, suggesting little genetic divergence of S. sclerotiorum among hosts. There was only weak evidence of isolation by distance. Pairwise population comparisons among isolates from canola, dry bean, soybean and sunflower suggested that gene flow between host-populations is more common for some crops than others. Analysis of linkage disequilibrium in the isolates from the four major crops indicated primarily clonal reproduction, but also evidence of genetic recombination for isolates from canola and sunflower. Accordingly, genetic diversity was highest for populations from canola and sunflower. Distribution of microsatellite haplotypes across the study region strongly suggest that specific haplotypes of S. sclerotiorum are often found on multiple crops, movement of individual haplotypes among crops is common and host identity is not a barrier to gene flow for S. sclerotiorum in the north central United States.     

陕西渭南地区汉族人群17个Y-STR基因座多态性及遗传关系分析

调查陕西渭南地区汉族群体17个Y-STR基因座的多态性,探讨其群体遗传学及法医学应用价值。应用Y-fi ler荧光标记复合扩增系统,对413名陕西渭南地区汉族无关男性个体17个Y-STR基因座进行复合扩增,用ABI3130遗传分析仪进行基因分型,计算各基因座的群体遗传学参数,并结合已经发表的其他10个群体相应基因座的单倍型资料,分析各群体间的遗传距离。413名陕西渭南汉族个体共检出405种单倍型,其中397种单倍型仅出现1次,单倍型多样性达0.9999,基因多样性(GD)为0.4130(DYS391)~0.9734(DYS385a/b),累计GD值为0.9999。遗传距离分析提示,陕西渭南汉族与辽宁满族的遗传距离最小(0.00110),与青海藏族的遗传距离最大(0.22333)。结果表明,17个Y-STR基因座在陕西渭南汉族群体中具有丰富的遗传多态性和较高的非父排除能力,在法医学和人类群体遗传学研究中具有重要价值。     

藏羚Y染色体雄性特异区遗传多样性

Genetic diversity is an important indicator of population health, especially for assessing population recovery of endangered species. To characterize the genetic diversity of Tibetan antelope(Pantholops hodgsonii) populations, we used muscle and placental tissues from accidentally killed Tibetan antelopes in Qinghai and Xinjiang and screened 11 Tibetan antelope Y-SNP-specific loci from 30 published polymorphic Y-SNP loci in bovids, of which AMELY3 (g.723 C > T) and SRYOY1 (g.167 G > A) 2 pairs of primers were polymorphic. Based on the AMELY3 locus, the haplotype diversity of Tibetan antelope Y chromosome was 0.048 ± 0.045 and the nucleotide polymorphism was 0.00006 ± 0.00005. According to the SRYOY1 locus, Tibetan antelope was divided into two haplotypes, of which H1 (g.167 G) was the dominant haplotype. Maximum likelihood tree suggests that Tibetan antelope might have two paternal origins. The haplotype diversity of Tibetan antelope Y chromosome was 0.439 ± 0.050 and the nucleotide polymorphism was 0.0008 ± 0.0004. The genetic differentiation index showed that the F_ST value between the male population of Tibetan antelope in Qinghai and Xinjiang was 0.6846 ± 0.0389, suggesting a strong population genetic differentiation. Therefore, integrated conservation across regions and research on sex chromosomes need more attention in the future conservation of Tibetan antelope.     

Dual origins of Finns revealed by Y chromosome haplotype variation.

The Finnish population has often been viewed as an isolate founded 2, 000 years ago via a route across the Gulf of Finland. The founding event has been characterized as involving a limited number of homogeneous founders, isolation, and subsequent rapid population growth. Despite the purported isolation of the population, levels of gene diversity for the Finns at autosomal and mitochondrial DNA loci are indistinguishable from those of other Europeans. Thus, mixed or dual origins for the Finns have been proposed. Here we present genetic evidence for the dual origins of Finns by evaluating the pattern of Y chromosome variation in 280 unrelated males from nine Finnish provinces. Phylogenetic analysis of 77 haplotype configurations revealed two major star-shaped clusters of Y haplotypes, indicative of a population expansion from two common Y haplotypes. Dramatic and quite significant differences in Y haplotype variation were observed between eastern and western regions of Finland, revealing contributions from different paternal types. The geographic distribution and time of expansion for the two common Y haplotypes correlate well with archeological evidence for two culturally and geographically distinct groups of settlers. Also, a northeastern to southwestern gradient of Y haplotype frequencies provides convincing evidence for recent male migration from rural areas into urban Finland.     

EVOLUTION AT THE MOUSE t COMPLEX: WHY IS THE t HAPLOTYPE PRESERVED AS AN INTEGRAL UNIT?

Abstract Segregation distorters are selfish genetic elements that bias Mendelian segregation in their favor. All well-known segregation distortion systems consist of one or more "distorter" loci that act upon a "responder" locus. At the t complex of the house mouse, segregation distortion is brought about by the harmful effect of t alleles at a number of distorter loci on the wild-type variant of the responder locus. The responder and distorter alleles are closely linked by a number of inversions, thus forming a coherent t haplotype. It has been conjectured that the close integration of the various components into a "complete" t haplotype has been crucial for the evolutionary success of these selfish genetic elements. By means of a population genetical metapopulation model, we show that this intuition may be unfounded. In fact, under most circumstances an "insensitive" t haplotype retaining only the responder did invade and reach a high frequency, despite the fact that this haplotype has a strong segregation disadvantage. For certain population structures, the complete t haplotype was even competitively excluded by partial t haplotypes with lower segregation ratios. Moreover, t haplotypes carrying one or more recessive lethals only prevailed over their nonlethal counterparts if the product of local population size and migration rate ( Nm ) was not much smaller or larger than one. These phenomena occurred for rather realistic fitness, segregation, and recombination values. It is therefore quite puzzling that partial t haplotypes are absent from natural house mousepopulations, and that t haplotypes carrying recessive lethals prevail over nonlethal t haplotypes.     

Chloroplast DNA polymorphism reveals little geographical structure in Castanea sativa Mill. (Fagaceae) throughout southern European countries

The distribution of haplotypic diversity of 38 European chestnut (Castanea sativa Mill.) populations was investigated by PCR/RFLP analysis of regions of the chloroplast and mitochondrial genomes in order to shed light on the history of this heavily managed species. The rapid expansion of chestnut starting from 3000 years ago is strongly related to human activities such as agricultural practice. This demonstrates the importance of human impact, which lasted some thousands of years, on the present-day distribution of the species. No polymorphism was detected for the single mitochondrial analysed region, while a total of 11 different chloroplast (cp) haplotypes were scored. The distribution of the cpDNA haplotypes revealed low geographical structure of the genetic diversity. The value of population subdivision, as measured by GSTc, is strikingly lower than in the other species of the family Fagaceae investigated. The actual distribution of haplotypic diversity may be explained by the strong human impact on this species, particularly during the Roman civilization of the continent, and to the long period of cultivation experienced during the last thousand years.     

Mitochondrial haplotypic diversity of pine cone beetles (Scolytinae: Conophthorus) collected on food sources

Conophthorus Hopkins attack, oviposit, and feed in immature cones of many pine (Pinus) species. They are a serious pest of pine seed orchards and can destroy up to 100% of the cone crop. Beetles can plague orchards over many years because emerging beetles tend to attack cones of the same or a nearby tree. However, fluctuating pine cone production suggests that beetles may disperse from their natal tree stand to find second-year cones for oviposition. These dispersal behaviors may influence population level genetic diversity, that is, populations may exhibit low or high diversity. In this study, we assess the mitochondrial haplotypic diversity among 10 populations of Conophthorus representing four species. Furthermore, the haplotypic diversities are compared with published haplotypic diversities of other scolytine species to assess the influence of fluctuating food resources on Conophthorus haplotype diversity. Conophthorus haplotypic diversity ranged between 13 and 70%, which was similar to population level haplotypic diversities of other scolytines. The tendency of the emerging brood to reinfest the same tree has little influence on haplotype composition of populations and haplotype diversity is likely more influenced by beetles in search of pine cones.     

Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans

An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1*15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.     

Minimal sharing of Y-chromosome STR haplotypes among five endogamous population groups from western and southwestern India

We attempt to address the issue of genetic variation and the pattern of male gene flow among and between five Indian population groups of two different geographic and linguistic affiliations using Y-chromosome markers. We studied 221 males at three Y-chromosome biallelic loci and 184 males for the five Y-chromosome STRs. We observed 111 Y-chromosome STR haplotypes. An analysis of molecular variance (AMOVA) based on Y-chromosome STRs showed that the variation observed between the population groups belonging to two major regions (western and southwestern India) was 0.17%, which was significantly lower than the level of genetic variance among the five populations (0.59%) considered as a single group. Combined haplotype analysis of the five STRs and the biallelic locus 92R7 revealed minimal sharing of haplotypes among these five ethnic groups, irrespective of the similar origin of the linguistic and geographic affiliations; this minimal sharing indicates restricted male gene flow. As a consequence, most of the haplotypes were population specific. Network analysis showed that the haplotypes, which were shared between the populations, seem to have originated from different mutational pathways at different loci. Biallelic markers showed that all five ethnic groups have a similar ancestral origin despite their geographic and linguistic diversity.     

Genetic variation and island biogreography: Microsatellite and mitochondrial DNA variation in island populations of the Australian bush rat, Rattus fuscipes greyii

To understand the impact of various factors on the maintenance of genetic variation in natural populations, we need to focus on situations where at least some of these factors are removed or controlled. In this study, we used highly variable, presumably neutral, microsatellite and mtDNA markers to assess the nature of genetic variation in 14 island and two mainland populations of the Australian bush rat, where there is no migration between islands. Thus we are controlling for selection and gene flow. Both marker sets revealed low levels of diversity within the small island populations and extreme differentiation between populations. For six microsatellite loci, all of the small island populations had less genetic variation than the mainland populations; reduction in allelic diversity was more pronounced than loss of heterozygosity. Kangaroo Island, the large island population, had similar levels of diversity to the mainland populations. A 442 base pair (bp) section of the mtDNA control region was screened for variation by outgroup heteroduplex analysis/temperature gradient gel electrophoresis (OHA/TGGE). Only three of the 13 small island populations showed haplotypic diversity: Gambier (2), Waldegrave (2), and Eyere (3). The level of haplotypic diversity in the small island populations was similar to that on the mainland, most likely reflecting a recent population bottleneck on the mainland. In contrast, Kangaroo Island had 9 mtDNA haplotypes. The dominant factor influencing genetic diversity on the islands was island size. No correlation was detected between genetic diversity and the time since isolation or distance form the mainland. The combination of genetic drift within and complete isolation among the small island populations has resulted in rapid and extreme population divergence. Population pair-wise comparisons of allele frequency distributions showed significant differences for all populations for all loci (F _st = 0.11–0.84, R _st = 0.07–0.99). For the mtDNA control region, 92.6% of variation was apportioned between populations; only the Pearson islands shared a haplotype. Mantel tests of pair-wise genetic distance with pair-wise geographic distance showed no significant geographical clustering of haplotypes. However, population substructuring was detected within populations where sampling was conducted over a broader geographical range, as indicated by departures from Hardy-Weinberg equilibrium. Thus substructuring in the ancestral population cannot be ruled out. The dominant evolutionary forces on the islands, after the initial founder event, are stochastic population processes such as genetic drift and mutation. This revised version was published online in July 2006 with corrections to the Cover Date.     

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。     

Haplotypic QTL mapping in an outbred pedigree

An offspring genome can be viewed as a mosaic of chromosomal segments or haplotypes contributed by multiple founders in any quantitative trait locus (QTL) detection study but tracing these is especially complex to achieve for outbred pedigrees. QTL haplotypes can be traced from offspring back to individual founders in outbred pedigrees by combining founder-origin probabilities with fully informative flanking markers. This haplotypic method was illustrated for QTL detection using a three-generation pedigree for a woody perennial plant, Pinus taeda L. Growth rate was estimated using height measurements from ages 2 to 10 years. Using simulated and actual datasets, power of the experimental design was shown to be efficient for detecting QTLs of large effect. Using interval mapping and fully informative markers, a large QTL accounting for 11.3% of the phenotypic variance in the growth rate was detected. This same QTL was expressed at all ages for height, accounting for 7.9-12.2% of the phenotypic variance. A mixed-model inheritance was more appropriate for describing genetic architecture of growth curves in P. taeda than a strictly polygenic model. The positive QTL haplotype was traced from the offspring to its contributing founder, GP3, then the haplotypic phase for GP3 was determined by assaying haploid megagametophytes. The positive QTL haplotype was a recombinant haplotype contributed by GP3. This study illustrates the combined power of fully informative flanking markers and founder origin probabilities for (1) estimating QTL haplotype magnitude, (2) tracing founder origin and (3) determining haplotypic transmission frequency.