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111.
Iype T Francis J Garmey JC Schisler JC Nesher R Weir GC Becker TC Newgard CB Griffen SC Mirmira RG 《The Journal of biological chemistry》2005,280(17):16798-16807
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We propose a multilocus version of FST and a measure of haplotype diversity using localized haplotype clusters. Specifically, we use haplotype clusters identified with BEAGLE, which is a program implementing a hidden Markov model for localized haplotype clustering and performing several functions including inference of haplotype phase. We apply this methodology to HapMap phase 3 data. With this haplotype-cluster approach, African populations have highest diversity and lowest divergence from the ancestral population, East Asian populations have lowest diversity and highest divergence, and other populations (European, Indian, and Mexican) have intermediate levels of diversity and divergence. These relationships accord with expectation based on other studies and accepted models of human history. In contrast, the population-specific FST estimates obtained directly from single-nucleotide polymorphisms (SNPs) do not reflect such expected relationships. We show that ascertainment bias of SNPs has less impact on the proposed haplotype-cluster-based FST than on the SNP-based version, which provides a potential explanation for these results. Thus, these new measures of FST and haplotype-cluster diversity provide an important new tool for population genetic analysis of high-density SNP data.GENOME-WIDE data sets from worldwide panels of individuals provide an outstanding opportunity to investigate the genetic structure of human populations (Conrad et al. 2006; International Hapmap Consortium 2007; Jakobsson et al. 2008; Auton et al. 2009). Populations around the globe form a continuum rather than discrete units (Serre and Paabo 2004; Weiss and Long 2009). However, notions of discrete populations can be appropriate when, for example, ancestral populations were separated by geographic distance or barriers such that little gene flow occurred.FST (Wright 1951; Weir and Cockerham 1984; Holsinger and Weir 2009) is a measure of population divergence. It measures variation between populations vs. within populations. One can calculate a global measure, assuming that all populations are equally diverged from an ancestral population, or one can calculate FST for specific populations or for pairs of populations while utilizing data from all populations (Weir and Hill 2002). One use of FST is to test for signatures of selection (reviewed in Oleksyk et al. 2010).FST may be calculated for single genetic markers. For multiallelic markers, such as microsatellites, this is useful, but single-nucleotide polymorphisms (SNPs) contain much less information when taken one at a time, and thus it is advantageous to calculate averages over windows of markers (Weir et al. 2005) or even over the whole genome. The advantage of windowed FST is that it can be used to find regions of the genome that show different patterns of divergence, indicative of selective forces at work during human history.Another measure of human evolutionary history is haplotype diversity. Haplotype diversity may be measured using a count of the number of observed haplotypes in a region or by the expected haplotype heterozygosity based on haplotype frequencies in a region. Application of this regional measure to chromosomal data can be achieved by a haplotype block strategy (Patil et al. 2001) or by windowing (Conrad et al. 2006; Auton et al. 2009).One problem with the analysis of population structure based on genome-wide panels of SNPs is that a large proportion of the SNPs were ascertained in Caucasians, potentially biasing the results of the analyses. Analysis based on haplotypes is less susceptible to such bias (Conrad et al. 2006). This is because haplotypes can be represented by multiple patterns of SNPs; thus lack of ascertainment of a particular SNP does not usually prevent observation of the haplotype. On a chromosome-wide scale, one cannot directly use entire haplotypes, because all the haplotypes in the sample will almost certainly be unique, thus providing no information on population structure. Instead one can use haplotypes on a local basis, either by using windows of adjacent markers or by using localized haplotype clusters, for example those obtained from fastPHASE (Scheet and Stephens 2006) or BEAGLE (Browning 2006; Browning and Browning 2007a).Localized haplotype clusters are a clustering of haplotypes on a localized basis. At the position of each genetic marker, haplotypes are clustered according to their similarity in the vicinity of the position. Both fastPHASE and BEAGLE use hidden Markov modeling to perform the clustering, although the specific models used by the two programs differ.Localized haplotype clusters derived from fastPHASE have been used to investigate haplotype diversity, to create neighbor-joining trees of populations, and to create multidimensional scaling (MDS) plots (Jakobsson et al. 2008). It was found that haplotype clusters showed different patterns of diversity to SNPs, while the neighbor-joining and MDS plots were similar between haplotype clusters and SNPs.In this work, we apply windowed FST methods to localized haplotype clusters derived from the BEAGLE program (Browning and Browning 2007a,b, 2009). We consider population-average, population-specific, and pairwise FST estimates (Weir and Hill 2002). Population-average FST''s either assume that all the populations are equally diverged from a common ancestor, which is not realistic, or represent the average of a set of population-specific values. This can be convenient in that the results are summarized by a single statistic; however, information is lost. A common procedure is to calculate FST for each pair of populations, and these values reflect the degree of divergence between the two populations. Different levels of divergence are allowed for each pair of populations but each estimate uses data from only that pair of populations. On the other hand, population-specific FST''s allow unequal levels of divergence in a single analysis that makes use of all the data.We compare results from the localized haplotype clusters to those using SNPs directly. The results of applying localized haplotype clusters to population-specific FST estimation are very striking, showing better separation of populations and a more realistic pattern of divergence than for population-specific FST estimation using SNPs directly. We also use BEAGLE''s haplotype clusters in a haplotype diversity measure and investigate the relationship between this measure of haplotype-cluster diversity and the recombination rate. 相似文献
114.
Weir B 《Genetics》2006,172(2):719-720
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The occurrence of Laboulbeniomycete species consistently on a precise portion of beetle integument was investigated in 13 species of Chitonomyces ectoparasitic on the aquatic diving beetle Laccophilus maculosus (Coleoptera, Dytiscidae). The phenomenon was called "position specificity" by Roland Thaxter in 1896, yet the mechanism has remained unknown. By using molecular analysis of the nucSSU rRNA gene and the 5.8S and partial ITS1 rRNA regions, 13 species of Chitonomyces reported to exhibit position specificity on Laccophilus maculosus were placed neatly into pairs of morphotypes, resulting in synonomies and recognition of six phylogenetic species (one species is a triplet). Each phylogenetic species was located at corresponding positions on male and female beetles that make contact during mating. In addition, ecological data and video footage of the mating behaviors of Laccophilus confirmed that sexual transmission is the mechanism behind this enigmatic phenomenon. 相似文献
118.
Harnessing the rhizosphere microbiome through plant breeding and agricultural management 总被引:2,自引:0,他引:2
Matthew G. Bakker Daniel K. Manter Amy M. Sheflin Tiffany L. Weir Jorge M. Vivanco 《Plant and Soil》2012,360(1-2):1-13
Background
The need to enhance the sustainability of intensive agricultural systems is widely recognized One promising approach is to encourage beneficial services provided by soil microorganisms to decrease the inputs of fertilizers and pesticides. However, limited success of this approach in field applications raises questions as to how this might be best accomplished.Scope
We highlight connections between root exudates and the rhizosphere microbiome, and discuss the possibility of using plant exudation characteristics to selectively enhance beneficial microbial activities and microbiome characteristics. Gaps in our understanding and areas of research that are vital to our ability to more fully exploit the soil microbiome for agroecosystem productivity and sustainability are also discussed.Conclusion
This article outlines strategies for more effectively exploiting beneficial microbial services on agricultural systems, and cals attention to topics that require additional research. 相似文献119.
Carter SL Cibulskis K Helman E McKenna A Shen H Zack T Laird PW Onofrio RC Winckler W Weir BA Beroukhim R Pellman D Levine DA Lander ES Meyerson M Getz G 《Nature biotechnology》2012,30(5):413-421
We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity. 相似文献
120.
Heather J. M. Weir Tracey K. Murray Patrick G. Kehoe Seth Love Eric M. Verdin Michael J. O’Neill Jon D. Lane Nina Balthasar 《PloS one》2012,7(11)
Progressive mitochondrial dysfunction contributes to neuronal degeneration in age-mediated disease. An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3). Here we investigate a role for CNS Sirt3 in mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer’s disease (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition of β-amyloid in an AD mouse model and is also upregulated in AD patient temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress. 相似文献