Development and Applications of a Bovine 50,000 SNP Chip

USDA-ARS?s Scientific Manuscript database

To develop an Illumina iSelect high density single nucleotide polymorphism (SNP) assay for cattle, the collaborative iBMC (Illumina, USDA ARS Beltsville, University of Missouri, USDA ARS Clay Center) Consortium first performed a de novo SNP discovery project in which genomic reduced representation l...

Development and validation of a low-density SNP panel related to prolificacy in sheep

USDA-ARS?s Scientific Manuscript database

High-density SNP panels (e.g., 50,000 and 600,000 markers) have been used in exploratory population genetic studies with commercial and minor breeds of sheep. However, routine genetic diversity evaluations of large numbers of samples with large panels are in general cost-prohibitive for gene banks. ...

High-throughput single nucleotide polymorphism genotyping for breeding applications in rice using the BeadXpress platform

USDA-ARS?s Scientific Manuscript database

Multiplexed single nucleotide polymorphism (SNP) markers have the potential to increase the speed and cost-effectiveness of genotyping, provided that an optimal SNP density is used for each application. To test the efficiency of multiplexed SNP genotyping for diversity, mapping and breeding applicat...

Signatures of selection in five Italian cattle breeds detected by a 54K SNP panel.

PubMed

Mancini, Giordano; Gargani, Maria; Chillemi, Giovanni; Nicolazzi, Ezequiel Luis; Marsan, Paolo Ajmone; Valentini, Alessio; Pariset, Lorraine

2014-02-01

In this study we used a medium density panel of SNP markers to perform population genetic analysis in five Italian cattle breeds. The BovineSNP50 BeadChip was used to genotype a total of 2,935 bulls of Piedmontese, Marchigiana, Italian Holstein, Italian Brown and Italian Pezzata Rossa breeds. To determine a genome-wide pattern of positive selection we mapped the F st values against genome location. The highest F st peaks were obtained on BTA6 and BTA13 where some candidate genes are located. We identified selection signatures peculiar of each breed which suggest selection for genes involved in milk or meat traits. The genetic structure was investigated by using a multidimensional scaling of the genetic distance matrix and a Bayesian approach implemented in the STRUCTURE software. The genotyping data showed a clear partitioning of the cattle genetic diversity into distinct breeds if a number of clusters equal to the number of populations were given. Assuming a lower number of clusters beef breeds group together. Both methods showed all five breeds separated in well defined clusters and the Bayesian approach assigned individuals to the breed of origin. The work is of interest not only because it enriches the knowledge on the process of evolution but also because the results generated could have implications for selective breeding programs.

High Concentration of Benzyladenine Solution Stimulates Anthers for Inducing Callus in Ricinus Communis L.

NASA Astrophysics Data System (ADS)

Liu, Ying; Yan, Shuying; Yang, Fuguang; Li, Dongliang; Tang, Jianian; Liu, Guoxuan; Lin, Shiwan; Niu, Sufang; Yang, Yali

2017-12-01

An high-frequency protocol for induction of callus from anther explants of Ricinus communis was described. When anther explants of R. communis was cultured directly onto medium containing 6-benzylaminopurine (BA) induced formation of only poor quality callus that had a low induction frequency of anther callus (10.67%). However, treating the anther explants with high concentrations (7.5-120 mg/L) of BA solution for short time periods (5-80 min) helped to improve the induction frequency and enhance the quality of the callus formation significantly. The best callus induction (41.25%) was observed when anther explants were treated with 15 mg/L BA solution for 10 min before being inoculated onto hormone-free Murashige and Skoog (MS) medium for 30 days. In order to further optimize the culture system, after treated with 15 mg/L BA for 10 min, anther explants were inoculated on the hormone-free MS medium contained concentrations of sodium nitroprusside (SNP). The results showed that SNP significantly promoted the response of callus induction, especially when 8 mg/L SNP was applied, the the highest percentage of callus induction (60.37%) were gained.

A High-Density Consensus Map of Common Wheat Integrating Four Mapping Populations Scanned by the 90K SNP Array

PubMed Central

Wen, Weie; He, Zhonghu; Gao, Fengmei; Liu, Jindong; Jin, Hui; Zhai, Shengnan; Qu, Yanying; Xia, Xianchun

2017-01-01

A high-density consensus map is a powerful tool for gene mapping, cloning and molecular marker-assisted selection in wheat breeding. The objective of this study was to construct a high-density, single nucleotide polymorphism (SNP)-based consensus map of common wheat (Triticum aestivum L.) by integrating genetic maps from four recombinant inbred line populations. The populations were each genotyped using the wheat 90K Infinium iSelect SNP assay. A total of 29,692 SNP markers were mapped on 21 linkage groups corresponding to 21 hexaploid wheat chromosomes, covering 2,906.86 cM, with an overall marker density of 10.21 markers/cM. Compared with the previous maps based on the wheat 90K SNP chip detected 22,736 (76.6%) of the SNPs with consistent chromosomal locations, whereas 1,974 (6.7%) showed different chromosomal locations, and 4,982 (16.8%) were newly mapped. Alignment of the present consensus map and the wheat expressed sequence tags (ESTs) Chromosome Bin Map enabled assignment of 1,221 SNP markers to specific chromosome bins and 819 ESTs were integrated into the consensus map. The marker orders of the consensus map were validated based on physical positions on the wheat genome with Spearman rank correlation coefficients ranging from 0.69 (4D) to 0.97 (1A, 4B, 5B, and 6A), and were also confirmed by comparison with genetic position on the previously 40K SNP consensus map with Spearman rank correlation coefficients ranging from 0.84 (6D) to 0.99 (6A). Chromosomal rearrangements reported previously were confirmed in the present consensus map and new putative rearrangements were identified. In addition, an integrated consensus map was developed through the combination of five published maps with ours, containing 52,607 molecular markers. The consensus map described here provided a high-density SNP marker map and a reliable order of SNPs, representing a step forward in mapping and validation of chromosomal locations of SNPs on the wheat 90K array. Moreover, it can be used as a reference for quantitative trait loci (QTL) mapping to facilitate exploitation of genes and QTL in wheat breeding. PMID:28848588

Insights Into Upland Cotton (Gossypium hirsutum L.) Genetic Recombination Based on 3 High-Density Single-Nucleotide Polymorphism and a Consensus Map Developed Independently With Common Parents.

PubMed

Ulloa, Mauricio; Hulse-Kemp, Amanda M; De Santiago, Luis M; Stelly, David M; Burke, John J

2017-01-01

High-density linkage maps are vital to supporting the correct placement of scaffolds and gene sequences on chromosomes and fundamental to contemporary organismal research and scientific approaches to genetic improvement, especially in paleopolyploids with exceptionally complex genomes, eg, upland cotton ( Gossypium hirsutum L., "2n = 52"). Three independently developed intraspecific upland mapping populations were analyzed to generate 3 high-density genetic linkage single-nucleotide polymorphism (SNP) maps and a consensus map using the CottonSNP63K array. The populations consisted of a previously reported F 2 , a recombinant inbred line (RIL), and reciprocal RIL population, from "Phytogen 72" and "Stoneville 474" cultivars. The cluster file provided 7417 genotyped SNP markers, resulting in 26 linkage groups corresponding to the 26 chromosomes (c) of the allotetraploid upland cotton (AD) 1 arisen from the merging of 2 genomes ("A" Old World and "D" New World). Patterns of chromosome-specific recombination were largely consistent across mapping populations. The high-density genetic consensus map included 7244 SNP markers that spanned 3538 cM and comprised 3824 SNP bins, of which 1783 and 2041 were in the A t and D t subgenomes with 1825 and 1713 cM map lengths, respectively. Subgenome average distances were nearly identical, indicating that subgenomic differences in bin number arose due to the high numbers of SNPs on the D t subgenome. Examination of expected recombination frequency or crossovers (COs) on the chromosomes within each population of the 2 subgenomes revealed that COs were also not affected by the SNPs or SNP bin number in these subgenomes. Comparative alignment analyses identified historical ancestral A t -subgenomic translocations of c02 and c03, as well as of c04 and c05. The consensus map SNP sequences aligned with high congruency to the NBI assembly of Gossypium hirsutum . However, the genomic comparisons revealed evidence of additional unconfirmed possible duplications, inversions and translocations, and unbalance SNP sequence homology or SNP sequence/loci genomic dominance, or homeolog loci bias of the upland tetraploid A t and D t subgenomes. The alignments indicated that 364 SNP-associated previously unintegrated scaffolds can be placed in pseudochromosomes of the NBI G hirsutum assembly. This is the first intraspecific SNP genetic linkage consensus map assembled in G hirsutum with a core of reproducible mendelian SNP markers assayed on different populations and it provides further knowledge of chromosome arrangement of genic and nongenic SNPs. Together, the consensus map and RIL populations provide a synergistically useful platform for localizing and identifying agronomically important loci for improvement of the cotton crop.

Quantitative analysis of low-density SNP data for parentage assignment and estimation of family contributions to pooled samples.

PubMed

Henshall, John M; Dierens, Leanne; Sellars, Melony J

2014-09-02

While much attention has focused on the development of high-density single nucleotide polymorphism (SNP) assays, the costs of developing and running low-density assays have fallen dramatically. This makes it feasible to develop and apply SNP assays for agricultural species beyond the major livestock species. Although low-cost low-density assays may not have the accuracy of the high-density assays widely used in human and livestock species, we show that when combined with statistical analysis approaches that use quantitative instead of discrete genotypes, their utility may be improved. The data used in this study are from a 63-SNP marker Sequenom® iPLEX Platinum panel for the Black Tiger shrimp, for which high-density SNP assays are not currently available. For quantitative genotypes that could be estimated, in 5% of cases the most likely genotype for an individual at a SNP had a probability of less than 0.99. Matrix formulations of maximum likelihood equations for parentage assignment were developed for the quantitative genotypes and also for discrete genotypes perturbed by an assumed error term. Assignment rates that were based on maximum likelihood with quantitative genotypes were similar to those based on maximum likelihood with perturbed genotypes but, for more than 50% of cases, the two methods resulted in individuals being assigned to different families. Treating genotypes as quantitative values allows the same analysis framework to be used for pooled samples of DNA from multiple individuals. Resulting correlations between allele frequency estimates from pooled DNA and individual samples were consistently greater than 0.90, and as high as 0.97 for some pools. Estimates of family contributions to the pools based on quantitative genotypes in pooled DNA had a correlation of 0.85 with estimates of contributions from DNA-derived pedigree. Even with low numbers of SNPs of variable quality, parentage testing and family assignment from pooled samples are sufficiently accurate to provide useful information for a breeding program. Treating genotypes as quantitative values is an alternative to perturbing genotypes using an assumed error distribution, but can produce very different results. An understanding of the distribution of the error is required for SNP genotyping platforms.

Genomic predictions can accelerate selection for resistance against Piscirickettsia salmonis in Atlantic salmon (Salmo salar).

PubMed

Bangera, Rama; Correa, Katharina; Lhorente, Jean P; Figueroa, René; Yáñez, José M

2017-01-31

Salmon Rickettsial Syndrome (SRS) caused by Piscirickettsia salmonis is a major disease affecting the Chilean salmon industry. Genomic selection (GS) is a method wherein genome-wide markers and phenotype information of full-sibs are used to predict genomic EBV (GEBV) of selection candidates and is expected to have increased accuracy and response to selection over traditional pedigree based Best Linear Unbiased Prediction (PBLUP). Widely used GS methods such as genomic BLUP (GBLUP), SNPBLUP, Bayes C and Bayesian Lasso may perform differently with respect to accuracy of GEBV prediction. Our aim was to compare the accuracy, in terms of reliability of genome-enabled prediction, from different GS methods with PBLUP for resistance to SRS in an Atlantic salmon breeding program. Number of days to death (DAYS), binary survival status (STATUS) phenotypes, and 50 K SNP array genotypes were obtained from 2601 smolts challenged with P. salmonis. The reliability of different GS methods at different SNP densities with and without pedigree were compared to PBLUP using a five-fold cross validation scheme. Heritability estimated from GS methods was significantly higher than PBLUP. Pearson's correlation between predicted GEBV from PBLUP and GS models ranged from 0.79 to 0.91 and 0.79-0.95 for DAYS and STATUS, respectively. The relative increase in reliability from different GS methods for DAYS and STATUS with 50 K SNP ranged from 8 to 25% and 27-30%, respectively. All GS methods outperformed PBLUP at all marker densities. DAYS and STATUS showed superior reliability over PBLUP even at the lowest marker density of 3 K and 500 SNP, respectively. 20 K SNP showed close to maximal reliability for both traits with little improvement using higher densities. These results indicate that genomic predictions can accelerate genetic progress for SRS resistance in Atlantic salmon and implementation of this approach will contribute to the control of SRS in Chile. We recommend GBLUP for routine GS evaluation because this method is computationally faster and the results are very similar with other GS methods. The use of lower density SNP or the combination of low density SNP and an imputation strategy may help to reduce genotyping costs without compromising gain in reliability.

An imputed genotype resource for the laboratory mouse

PubMed Central

Szatkiewicz, Jin P.; Beane, Glen L.; Ding, Yueming; Hutchins, Lucie; de Villena, Fernando Pardo-Manuel; Churchill, Gary A.

2009-01-01

We have created a high-density SNP resource encompassing 7.87 million polymorphic loci across 49 inbred mouse strains of the laboratory mouse by combining data available from public databases and training a hidden Markov model to impute missing genotypes in the combined data. The strong linkage disequilibrium found in dense sets of SNP markers in the laboratory mouse provides the basis for accurate imputation. Using genotypes from eight independent SNP resources, we empirically validated the quality of the imputed genotypes and demonstrate that they are highly reliable for most inbred strains. The imputed SNP resource will be useful for studies of natural variation and complex traits. It will facilitate association study designs by providing high density SNP genotypes for large numbers of mouse strains. We anticipate that this resource will continue to evolve as new genotype data become available for laboratory mouse strains. The data are available for bulk download or query at http://cgd.jax.org/. PMID:18301946

SNP-array reveals genome-wide patterns of geographical and potential adaptive divergence across the natural range of Atlantic salmon (Salmo salar).

PubMed

Bourret, Vincent; Kent, Matthew P; Primmer, Craig R; Vasemägi, Anti; Karlsson, Sten; Hindar, Kjetil; McGinnity, Philip; Verspoor, Eric; Bernatchez, Louis; Lien, Sigbjørn

2013-02-01

Atlantic salmon (Salmo salar) is one of the most extensively studied fish species in the world due to its significance in aquaculture, fisheries and ongoing conservation efforts to protect declining populations. Yet, limited genomic resources have hampered our understanding of genetic architecture in the species and the genetic basis of adaptation to the wide range of natural and artificial environments it occupies. In this study, we describe the development of a medium-density Atlantic salmon single nucleotide polymorphism (SNP) array based on expressed sequence tags (ESTs) and genomic sequencing. The array was used in the most extensive assessment of population genetic structure performed to date in this species. A total of 6176 informative SNPs were successfully genotyped in 38 anadromous and freshwater wild populations distributed across the species natural range. Principal component analysis clearly differentiated European and North American populations, and within Europe, three major regional genetic groups were identified for the first time in a single analysis. We assessed the potential for the array to disentangle neutral and putative adaptive divergence of SNP allele frequencies across populations and among regional groups. In Europe, secondary contact zones were identified between major clusters where endogenous and exogenous barriers could be associated, rendering the interpretation of environmental influence on potentially adaptive divergence equivocal. A small number of markers highly divergent in allele frequencies (outliers) were observed between (multiple) freshwater and anadromous populations, between northern and southern latitudes, and when comparing Baltic populations to all others. We also discuss the potential future applications of the SNP array for conservation, management and aquaculture. © 2012 Blackwell Publishing Ltd.

Polymorphisms in AKT3, FIGF, PRKAG3, and TGF-β genes are associated with myofiber characteristics in chickens.

PubMed

Chen, Sirui; An, Jianyong; Lian, Ling; Qu, Lujiang; Zheng, Jiangxia; Xu, Guiyun; Yang, Ning

2013-02-01

Muscle characteristics such as myofiber diameter, density, and total number are important traits in broiler breeding and production. In the present study, 19 SNP of 13 major genes, which are located in the vicinity of quantitative trait loci affecting breast muscle weight, including INS, IGF2, PIK3C2A, AKT3, PRKAB2, PRKAG3, VEGFA, RPS6KA2/3, FIGF, and TGF-β1/2/3, were chosen to be genotyped by high-throughput matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in a broiler population. One hundred twenty birds were slaughtered at 6 wk of age. Body weight, breast muscle weight, myofiber diameter, density, and total number were determined for each bird. Six SNP with a very low minor allele frequency (<1%) were excluded for further analysis. The remaining 13 SNP were used for the association study with muscle characteristics. The results showed that SNP in TGF-β1/2/3 had significant effects on myofiber diameter. A SNP in PRKAG3 had a significant effect on myofiber density (P < 0.05). A C > G mutation in FIGF was strongly associated with total fiber number (P < 0.05). Additionally, birds with the GG genotype of the C > G mutation in AKT3 had significantly larger myofiber numbers (P < 0.05) than birds with the CC or GC genotype. The SNP identified in the present study might be used as potential markers in broiler breeding.

Fine mapping of copy number variations on two cattle genome assemblies using high density SNP array

USDA-ARS?s Scientific Manuscript database

Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases...

The utility of low-density genotyping for imputation in the Thoroughbred horse

PubMed Central

2014-01-01

Background Despite the dramatic reduction in the cost of high-density genotyping that has occurred over the last decade, it remains one of the limiting factors for obtaining the large datasets required for genomic studies of disease in the horse. In this study, we investigated the potential for low-density genotyping and subsequent imputation to address this problem. Results Using the haplotype phasing and imputation program, BEAGLE, it is possible to impute genotypes from low- to high-density (50K) in the Thoroughbred horse with reasonable to high accuracy. Analysis of the sources of variation in imputation accuracy revealed dependence both on the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and on the underlying linkage disequilibrium structure. Whereas equidistant spacing of the SNPs on the low-density panel worked well, optimising SNP selection to increase their minor allele frequency was advantageous, even when the panel was subsequently used in a population of different geographical origin. Replacing base pair position with linkage disequilibrium map distance reduced the variation in imputation accuracy across SNPs. Whereas a 1K SNP panel was generally sufficient to ensure that more than 80% of genotypes were correctly imputed, other studies suggest that a 2K to 3K panel is more efficient to minimize the subsequent loss of accuracy in genomic prediction analyses. The relationship between accuracy and genotyping costs for the different low-density panels, suggests that a 2K SNP panel would represent good value for money. Conclusions Low-density genotyping with a 2K SNP panel followed by imputation provides a compromise between cost and accuracy that could promote more widespread genotyping, and hence the use of genomic information in horses. In addition to offering a low cost alternative to high-density genotyping, imputation provides a means to combine datasets from different genotyping platforms, which is becoming necessary since researchers are starting to use the recently developed equine 70K SNP chip. However, more work is needed to evaluate the impact of between-breed differences on imputation accuracy. PMID:24495673

SNPchiMp: a database to disentangle the SNPchip jungle in bovine livestock.

PubMed

Nicolazzi, Ezequiel Luis; Picciolini, Matteo; Strozzi, Francesco; Schnabel, Robert David; Lawley, Cindy; Pirani, Ali; Brew, Fiona; Stella, Alessandra

2014-02-11

Currently, six commercial whole-genome SNP chips are available for cattle genotyping, produced by two different genotyping platforms. Technical issues need to be addressed to combine data that originates from the different platforms, or different versions of the same array generated by the manufacturer. For example: i) genome coordinates for SNPs may refer to different genome assemblies; ii) reference genome sequences are updated over time changing the positions, or even removing sequences which contain SNPs; iii) not all commercial SNP ID's are searchable within public databases; iv) SNPs can be coded using different formats and referencing different strands (e.g. A/B or A/C/T/G alleles, referencing forward/reverse, top/bottom or plus/minus strand); v) Due to new information being discovered, higher density chips do not necessarily include all the SNPs present in the lower density chips; and, vi) SNP IDs may not be consistent across chips and platforms. Most researchers and breed associations manage SNP data in real-time and thus require tools to standardise data in a user-friendly manner. Here we present SNPchiMp, a MySQL database linked to an open access web-based interface. Features of this interface include, but are not limited to, the following functions: 1) referencing the SNP mapping information to the latest genome assembly, 2) extraction of information contained in dbSNP for SNPs present in all commercially available bovine chips, and 3) identification of SNPs in common between two or more bovine chips (e.g. for SNP imputation from lower to higher density). In addition, SNPchiMp can retrieve this information on subsets of SNPs, accessing such data either via physical position on a supported assembly, or by a list of SNP IDs, rs or ss identifiers. This tool combines many different sources of information, that otherwise are time consuming to obtain and difficult to integrate. The SNPchiMp not only provides the information in a user-friendly format, but also enables researchers to perform a large number of operations with a few clicks of the mouse. This significantly reduces the time needed to execute the large number of operations required to manage SNP data.

A low-density SNP array for analyzing differential selection in freshwater and marine populations of threespine stickleback (Gasterosteus aculeatus).

PubMed

Ferchaud, Anne-Laure; Pedersen, Susanne H; Bekkevold, Dorte; Jian, Jianbo; Niu, Yongchao; Hansen, Michael M

2014-10-06

The threespine stickleback (Gasterosteus aculeatus) has become an important model species for studying both contemporary and parallel evolution. In particular, differential adaptation to freshwater and marine environments has led to high differentiation between freshwater and marine stickleback populations at the phenotypic trait of lateral plate morphology and the underlying candidate gene Ectodysplacin (EDA). Many studies have focused on this trait and candidate gene, although other genes involved in marine-freshwater adaptation may be equally important. In order to develop a resource for rapid and cost efficient analysis of genetic divergence between freshwater and marine sticklebacks, we generated a low-density SNP (Single Nucleotide Polymorphism) array encompassing markers of chromosome regions under putative directional selection, along with neutral markers for background. RAD (Restriction site Associated DNA) sequencing of sixty individuals representing two freshwater and one marine population led to the identification of 33,993 SNP markers. Ninety-six of these were chosen for the low-density SNP array, among which 70 represented SNPs under putatively directional selection in freshwater vs. marine environments, whereas 26 SNPs were assumed to be neutral. Annotation of these regions revealed several genes that are candidates for affecting stickleback phenotypic variation, some of which have been observed in previous studies whereas others are new. We have developed a cost-efficient low-density SNP array that allows for rapid screening of polymorphisms in threespine stickleback. The array provides a valuable tool for analyzing adaptive divergence between freshwater and marine stickleback populations beyond the well-established candidate gene Ectodysplacin (EDA).

Construction of an SNP-based high-density linkage map for flax (Linum usitatissimum L.) using specific length amplified fragment sequencing (SLAF-seq) technology.

PubMed

Yi, Liuxi; Gao, Fengyun; Siqin, Bateer; Zhou, Yu; Li, Qiang; Zhao, Xiaoqing; Jia, Xiaoyun; Zhang, Hui

2017-01-01

Flax is an important crop for oil and fiber, however, no high-density genetic maps have been reported for this species. Specific length amplified fragment sequencing (SLAF-seq) is a high-resolution strategy for large scale de novo discovery and genotyping of single nucleotide polymorphisms. In this study, SLAF-seq was employed to develop SNP markers in an F2 population to construct a high-density genetic map for flax. In total, 196.29 million paired-end reads were obtained. The average sequencing depth was 25.08 in male parent, 32.17 in the female parent, and 9.64 in each F2 progeny. In total, 389,288 polymorphic SLAFs were detected, from which 260,380 polymorphic SNPs were developed. After filtering, 4,638 SNPs were found suitable for genetic map construction. The final genetic map included 4,145 SNP markers on 15 linkage groups and was 2,632.94 cM in length, with an average distance of 0.64 cM between adjacent markers. To our knowledge, this map is the densest SNP-based genetic map for flax. The SNP markers and genetic map reported in here will serve as a foundation for the fine mapping of quantitative trait loci (QTLs), map-based gene cloning and marker assisted selection (MAS) for flax.

Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis.

PubMed

Loughlin, J; Sinsheimer, J S; Mustafa, Z; Carr, A J; Clipsham, K; Bloomfield, V A; Chitnavis, J; Bailey, A; Sykes, B; Chapman, K

2000-03-01

Evidence has accumulated supporting a role for genes in the etiology of osteoarthritis (OA). Several candidates have been targeted as potential susceptibility loci including genes that are involved in the regulation of bone density. Genetic association analysis has suggested a role for the vitamin D receptor gene (VDR) and the estrogen receptor gene (ER) in susceptibility. Such findings must be tested in additional independent cohorts. We tested for association of these 2 genes, plus a third gene implicated in bone density, COL1A1, with idiopathic OA. A case-control cohort of 371 affected probands and 369 unaffected spouses was used. Association was tested using 4 intragenic single nucleotide polymorphisms (SNP), one each for the VDR and COL1A1 genes, and 2 for the ER gene. The VDR and ER SNP are the same SNP that have been associated with OA. All 4 SNP affect restriction enzyme sites and were genotyped using polymerase chain reaction and enzyme digestion. Allele and genotype distributions for each SNP were compared between cases and controls and analyzed using Fisher's exact test. There was no evidence of association of the VDR or the ER gene SNP to OA. There was weak evidence of association of the COL1A1 SNP in female cases (p = 0.017), reflected by a difference in the distribution of genotypes at this SNP between female cases and controls (p = 0.027). However, when corrected for multiple testing, these results were not significant. If the VDR, ER, or COL1A1 genes do encode predisposition to OA then the 4 SNP tested are not associated with major susceptibility alleles at these 3 loci.

Construction and Annotation of a High Density SNP Linkage Map of the Atlantic Salmon (Salmo salar) Genome.

PubMed

Tsai, Hsin Y; Robledo, Diego; Lowe, Natalie R; Bekaert, Michael; Taggart, John B; Bron, James E; Houston, Ross D

2016-07-07

High density linkage maps are useful tools for fine-scale mapping of quantitative trait loci, and characterization of the recombination landscape of a species' genome. Genomic resources for Atlantic salmon (Salmo salar) include a well-assembled reference genome, and high density single nucleotide polymorphism (SNP) arrays. Our aim was to create a high density linkage map, and to align it with the reference genome assembly. Over 96,000 SNPs were mapped and ordered on the 29 salmon linkage groups using a pedigreed population comprising 622 fish from 60 nuclear families, all genotyped with the 'ssalar01' high density SNP array. The number of SNPs per group showed a high positive correlation with physical chromosome length (r = 0.95). While the order of markers on the genetic and physical maps was generally consistent, areas of discrepancy were identified. Approximately 6.5% of the previously unmapped reference genome sequence was assigned to chromosomes using the linkage map. Male recombination rate was lower than females across the vast majority of the genome, but with a notable peak in subtelomeric regions. Finally, using RNA-Seq data to annotate the reference genome, the mapped SNPs were categorized according to their predicted function, including annotation of ∼2500 putative nonsynonymous variants. The highest density SNP linkage map for any salmonid species has been created, annotated, and integrated with the Atlantic salmon reference genome assembly. This map highlights the marked heterochiasmy of salmon, and provides a useful resource for salmonid genetics and genomics research. Copyright © 2016 Tsai et al.

Analysis and visualization of chromosomal abnormalities in SNP data with SNPscan

PubMed Central

Ting, Jason C; Ye, Ying; Thomas, George H; Ruczinski, Ingo; Pevsner, Jonathan

2006-01-01

Background A variety of diseases are caused by chromosomal abnormalities such as aneuploidies (having an abnormal number of chromosomes), microdeletions, microduplications, and uniparental disomy. High density single nucleotide polymorphism (SNP) microarrays provide information on chromosomal copy number changes, as well as genotype (heterozygosity and homozygosity). SNP array studies generate multiple types of data for each SNP site, some with more than 100,000 SNPs represented on each array. The identification of different classes of anomalies within SNP data has been challenging. Results We have developed SNPscan, a web-accessible tool to analyze and visualize high density SNP data. It enables researchers (1) to visually and quantitatively assess the quality of user-generated SNP data relative to a benchmark data set derived from a control population, (2) to display SNP intensity and allelic call data in order to detect chromosomal copy number anomalies (duplications and deletions), (3) to display uniparental isodisomy based on loss of heterozygosity (LOH) across genomic regions, (4) to compare paired samples (e.g. tumor and normal), and (5) to generate a file type for viewing SNP data in the University of California, Santa Cruz (UCSC) Human Genome Browser. SNPscan accepts data exported from Affymetrix Copy Number Analysis Tool as its input. We validated SNPscan using data generated from patients with known deletions, duplications, and uniparental disomy. We also inspected previously generated SNP data from 90 apparently normal individuals from the Centre d'Étude du Polymorphisme Humain (CEPH) collection, and identified three cases of uniparental isodisomy, four females having an apparently mosaic X chromosome, two mislabelled SNP data sets, and one microdeletion on chromosome 2 with mosaicism from an apparently normal female. These previously unrecognized abnormalities were all detected using SNPscan. The microdeletion was independently confirmed by fluorescence in situ hybridization, and a region of homozygosity in a UPD case was confirmed by sequencing of genomic DNA. Conclusion SNPscan is useful to identify chromosomal abnormalities based on SNP intensity (such as chromosomal copy number changes) and heterozygosity data (including regions of LOH and some cases of UPD). The program and source code are available at the SNPscan website . PMID:16420694

Development and Validation of a High-Density SNP Genotyping Array for African Oil Palm.

PubMed

Kwong, Qi Bin; Teh, Chee Keng; Ong, Ai Ling; Heng, Huey Ying; Lee, Heng Leng; Mohamed, Mohaimi; Low, Joel Zi-Bin; Apparow, Sukganah; Chew, Fook Tim; Mayes, Sean; Kulaveerasingam, Harikrishna; Tammi, Martti; Appleton, David Ross

2016-08-01

High-density single nucleotide polymorphism (SNP) genotyping arrays are powerful tools that can measure the level of genetic polymorphism within a population. To develop a whole-genome SNP array for oil palms, SNP discovery was performed using deep resequencing of eight libraries derived from 132 Elaeis guineensis and Elaeis oleifera palms belonging to 59 origins, resulting in the discovery of >3 million putative SNPs. After SNP filtering, the Illumina OP200K custom array was built with 170 860 successful probes. Phenetic clustering analysis revealed that the array could distinguish between palms of different origins in a way consistent with pedigree records. Genome-wide linkage disequilibrium declined more slowly for the commercial populations (ranging from 120 kb at r(2) = 0.43 to 146 kb at r(2) = 0.50) when compared with the semi-wild populations (19.5 kb at r(2) = 0.22). Genetic fixation mapping comparing the semi-wild and commercial population identified 321 selective sweeps. A genome-wide association study (GWAS) detected a significant peak on chromosome 2 associated with the polygenic component of the shell thickness trait (based on the trait shell-to-fruit; S/F %) in tenera palms. Testing of a genomic selection model on the same trait resulted in good prediction accuracy (r = 0.65) with 42% of the S/F % variation explained. The first high-density SNP genotyping array for oil palm has been developed and shown to be robust for use in genetic studies and with potential for developing early trait prediction to shorten the oil palm breeding cycle. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Development of a 63K SNP Array for Cotton and High-Density Mapping of Intraspecific and Interspecific Populations of Gossypium spp.

PubMed Central

Hulse-Kemp, Amanda M.; Lemm, Jana; Plieske, Joerg; Ashrafi, Hamid; Buyyarapu, Ramesh; Fang, David D.; Frelichowski, James; Giband, Marc; Hague, Steve; Hinze, Lori L.; Kochan, Kelli J.; Riggs, Penny K.; Scheffler, Jodi A.; Udall, Joshua A.; Ulloa, Mauricio; Wang, Shirley S.; Zhu, Qian-Hao; Bag, Sumit K.; Bhardwaj, Archana; Burke, John J.; Byers, Robert L.; Claverie, Michel; Gore, Michael A.; Harker, David B.; Islam, Md S.; Jenkins, Johnie N.; Jones, Don C.; Lacape, Jean-Marc; Llewellyn, Danny J.; Percy, Richard G.; Pepper, Alan E.; Poland, Jesse A.; Mohan Rai, Krishan; Sawant, Samir V.; Singh, Sunil Kumar; Spriggs, Andrew; Taylor, Jen M.; Wang, Fei; Yourstone, Scott M.; Zheng, Xiuting; Lawley, Cindy T.; Ganal, Martin W.; Van Deynze, Allen; Wilson, Iain W.; Stelly, David M.

2015-01-01

High-throughput genotyping arrays provide a standardized resource for plant breeding communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), complex trait dissection, and studying patterns of genomic diversity among cultivars and wild accessions. We have developed the CottonSNP63K, an Illumina Infinium array containing assays for 45,104 putative intraspecific single nucleotide polymorphism (SNP) markers for use within the cultivated cotton species Gossypium hirsutum L. and 17,954 putative interspecific SNP markers for use with crosses of other cotton species with G. hirsutum. The SNPs on the array were developed from 13 different discovery sets that represent a diverse range of G. hirsutum germplasm and five other species: G. barbadense L., G. tomentosum Nuttal × Seemann, G. mustelinum Miers × Watt, G. armourianum Kearny, and G. longicalyx J.B. Hutchinson and Lee. The array was validated with 1,156 samples to generate cluster positions to facilitate automated analysis of 38,822 polymorphic markers. Two high-density genetic maps containing a total of 22,829 SNPs were generated for two F2 mapping populations, one intraspecific and one interspecific, and 3,533 SNP markers were co-occurring in both maps. The produced intraspecific genetic map is the first saturated map that associates into 26 linkage groups corresponding to the number of cotton chromosomes for a cross between two G. hirsutum lines. The linkage maps were shown to have high levels of collinearity to the JGI G. raimondii Ulbrich reference genome sequence. The CottonSNP63K array, cluster file and associated marker sequences constitute a major new resource for the global cotton research community. PMID:25908569

Genomic Heritability of Beef Cattle Growth

USDA-ARS?s Scientific Manuscript database

Calf weights were examined to determine association between high-density SNP genotypes and growth, in order to estimate additive genetic variation explained by SNP. Data taken from Cycle VII of the U.S. Meat Animal Research Center Germplasm Evaluation Project included birth weight (BWT), 205-d adju...

Evaluation of Bovine High-Density SNP Genotyping Array in Indigenous Dairy Cattle Breeds.

PubMed

Dash, S; Singh, A; Bhatia, A K; Jayakumar, S; Sharma, A; Singh, S; Ganguly, I; Dixit, S P

2018-04-03

In total 52 samples of Sahiwal ( 19 ), Tharparkar ( 17 ), and Gir ( 16 ) were genotyped by using BovineHD SNP chip to analyze minor allele frequency (MAF), genetic diversity, and linkage disequilibrium among these cattle. The common SNPs of BovineHD and 54K SNP Chips were also extracted and evaluated for their performance. Only 40%-50% SNPs of these arrays was found informative for genetic analysis in these cattle breeds. The overall mean of MAF for SNPs of BovineHD SNPChip was 0.248 ± 0.006, 0.241 ± 0.007, and 0.242 ± 0.009 in Sahiwal, Tharparkar and Gir, respectively, while that for 54K SNPs was on lower side. The average Reynold's genetic distance between breeds ranged from 0.042 to 0.055 based on BovineHD Beadchip, and from 0.052 to 0.084 based on 54K SNP Chip. The estimates of genetic diversity based on HD and 54K chips were almost same and, hence, low density chip seems to be good enough to decipher genetic diversity of these cattle breeds. The linkage disequilibrium started decaying (r 2  < 0.2) at 140 kb inter-marker distance and, hence, a 20K low density customized SNP array from HD chip could be designed for genomic selection in these cattle else the 54K Bead Chip as such will be useful.

Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology

PubMed Central

Ramos, Antonio M.; Crooijmans, Richard P. M. A.; Affara, Nabeel A.; Amaral, Andreia J.; Archibald, Alan L.; Beever, Jonathan E.; Bendixen, Christian; Churcher, Carol; Clark, Richard; Dehais, Patrick; Hansen, Mark S.; Hedegaard, Jakob; Hu, Zhi-Liang; Kerstens, Hindrik H.; Law, Andy S.; Megens, Hendrik-Jan; Milan, Denis; Nonneman, Danny J.; Rohrer, Gary A.; Rothschild, Max F.; Smith, Tim P. L.; Schnabel, Robert D.; Van Tassell, Curt P.; Taylor, Jeremy F.; Wiedmann, Ralph T.; Schook, Lawrence B.; Groenen, Martien A. M.

2009-01-01

Background The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay. Methodology/Principal Findings A total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274. Conclusions/Significance Overall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs. PMID:19654876

CIDR

Science.gov Websites

NIH CIDR Program Studies For whole exome sequencing projects, we pretest all samples using a high -density SNP array (>200,000 markers). For custom targeted sequencing, we pretest all samples using a 96 pretest samples using a 96 SNP GoldenGate assay. This extensive pretesting allows us to unambiguously tie

An improved consensus linkage map of barley based on flow-sorted chromosomes and SNP markers

USDA-ARS?s Scientific Manuscript database

Recent advances in high-throughput genotyping have made it easier to combine information from different mapping populations into consensus genetic maps, which provide increased marker density and genome coverage compared to individual maps. Previously, a SNP-based genotyping platform was developed a...

Potential and limits to unravel the genetic architecture and predict the variation of Fusarium head blight resistance in European winter wheat (Triticum aestivum L.).

PubMed

Jiang, Y; Zhao, Y; Rodemann, B; Plieske, J; Kollers, S; Korzun, V; Ebmeyer, E; Argillier, O; Hinze, M; Ling, J; Röder, M S; Ganal, M W; Mette, M F; Reif, J C

2015-03-01

Genome-wide mapping approaches in diverse populations are powerful tools to unravel the genetic architecture of complex traits. The main goals of our study were to investigate the potential and limits to unravel the genetic architecture and to identify the factors determining the accuracy of prediction of the genotypic variation of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum L.) based on data collected with a diverse panel of 372 European varieties. The wheat lines were phenotyped in multi-location field trials for FHB resistance and genotyped with 782 simple sequence repeat (SSR) markers, and 9k and 90k single-nucleotide polymorphism (SNP) arrays. We applied genome-wide association mapping in combination with fivefold cross-validations and observed surprisingly high accuracies of prediction for marker-assisted selection based on the detected quantitative trait loci (QTLs). Using a random sample of markers not selected for marker-trait associations revealed only a slight decrease in prediction accuracy compared with marker-based selection exploiting the QTL information. The same picture was confirmed in a simulation study, suggesting that relatedness is a main driver of the accuracy of prediction in marker-assisted selection of FHB resistance. When the accuracy of prediction of three genomic selection models was contrasted for the three marker data sets, no significant differences in accuracies among marker platforms and genomic selection models were observed. Marker density impacted the accuracy of prediction only marginally. Consequently, genomic selection of FHB resistance can be implemented most cost-efficiently based on low- to medium-density SNP arrays.

Efficiency of multi-breed genomic selection for dairy cattle breeds with different sizes of reference population.

PubMed

Hozé, C; Fritz, S; Phocas, F; Boichard, D; Ducrocq, V; Croiseau, P

2014-01-01

Single-breed genomic selection (GS) based on medium single nucleotide polymorphism (SNP) density (~50,000; 50K) is now routinely implemented in several large cattle breeds. However, building large enough reference populations remains a challenge for many medium or small breeds. The high-density BovineHD BeadChip (HD chip; Illumina Inc., San Diego, CA) containing 777,609 SNP developed in 2010 is characterized by short-distance linkage disequilibrium expected to be maintained across breeds. Therefore, combining reference populations can be envisioned. A population of 1,869 influential ancestors from 3 dairy breeds (Holstein, Montbéliarde, and Normande) was genotyped with the HD chip. Using this sample, 50K genotypes were imputed within breed to high-density genotypes, leading to a large HD reference population. This population was used to develop a multi-breed genomic evaluation. The goal of this paper was to investigate the gain of multi-breed genomic evaluation for a small breed. The advantage of using a large breed (Normande in the present study) to mimic a small breed is the large potential validation population to compare alternative genomic selection approaches more reliably. In the Normande breed, 3 training sets were defined with 1,597, 404, and 198 bulls, and a unique validation set included the 394 youngest bulls. For each training set, estimated breeding values (EBV) were computed using pedigree-based BLUP, single-breed BayesC, or multi-breed BayesC for which the reference population was formed by any of the Normande training data sets and 4,989 Holstein and 1,788 Montbéliarde bulls. Phenotypes were standardized by within-breed genetic standard deviation, the proportion of polygenic variance was set to 30%, and the estimated number of SNP with a nonzero effect was about 7,000. The 2 genomic selection (GS) approaches were performed using either the 50K or HD genotypes. The correlations between EBV and observed daughter yield deviations (DYD) were computed for 6 traits and using the different prediction approaches. Compared with pedigree-based BLUP, the average gain in accuracy with GS in small populations was 0.057 for the single-breed and 0.086 for multi-breed approach. This gain was up to 0.193 and 0.209, respectively, with the large reference population. Improvement of EBV prediction due to the multi-breed evaluation was higher for animals not closely related to the reference population. In the case of a breed with a small reference population size, the increase in correlation due to multi-breed GS was 0.141 for bulls without their sire in reference population compared with 0.016 for bulls with their sire in reference population. These results demonstrate that multi-breed GS can contribute to increase genomic evaluation accuracy in small breeds. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genome-Wide QTL Mapping for Wheat Processing Quality Parameters in a Gaocheng 8901/Zhoumai 16 Recombinant Inbred Line Population.

PubMed

Jin, Hui; Wen, Weie; Liu, Jindong; Zhai, Shengnan; Zhang, Yan; Yan, Jun; Liu, Zhiyong; Xia, Xianchun; He, Zhonghu

2016-01-01

Dough rheological and starch pasting properties play an important role in determining processing quality in bread wheat (Triticum aestivum L.). In the present study, a recombinant inbred line (RIL) population derived from a Gaocheng 8901/Zhoumai 16 cross grown in three environments was used to identify quantitative trait loci (QTLs) for dough rheological and starch pasting properties evaluated by Mixograph, Rapid Visco-Analyzer (RVA), and Mixolab parameters using the wheat 90 and 660 K single nucleotide polymorphism (SNP) chip assays. A high-density linkage map constructed with 46,961 polymorphic SNP markers from the wheat 90 and 660 K SNP assays spanned a total length of 4121 cM, with an average chromosome length of 196.2 cM and marker density of 0.09 cM/marker; 6596 new SNP markers were anchored to the bread wheat linkage map, with 1046 and 5550 markers from the 90 and 660 K SNP assays, respectively. Composite interval mapping identified 119 additive QTLs on 20 chromosomes except 4D; among them, 15 accounted for more than 10% of the phenotypic variation across two or three environments. Twelve QTLs for Mixograph parameters, 17 for RVA parameters and 55 for Mixolab parameters were new. Eleven QTL clusters were identified. The closely linked SNP markers can be used in marker-assisted wheat breeding in combination with the Kompetitive Allele Specific PCR (KASP) technique for improvement of processing quality in bread wheat.

Genome-Wide QTL Mapping for Wheat Processing Quality Parameters in a Gaocheng 8901/Zhoumai 16 Recombinant Inbred Line Population

PubMed Central

Jin, Hui; Wen, Weie; Liu, Jindong; Zhai, Shengnan; Zhang, Yan; Yan, Jun; Liu, Zhiyong; Xia, Xianchun; He, Zhonghu

2016-01-01

Dough rheological and starch pasting properties play an important role in determining processing quality in bread wheat (Triticum aestivum L.). In the present study, a recombinant inbred line (RIL) population derived from a Gaocheng 8901/Zhoumai 16 cross grown in three environments was used to identify quantitative trait loci (QTLs) for dough rheological and starch pasting properties evaluated by Mixograph, Rapid Visco-Analyzer (RVA), and Mixolab parameters using the wheat 90 and 660 K single nucleotide polymorphism (SNP) chip assays. A high-density linkage map constructed with 46,961 polymorphic SNP markers from the wheat 90 and 660 K SNP assays spanned a total length of 4121 cM, with an average chromosome length of 196.2 cM and marker density of 0.09 cM/marker; 6596 new SNP markers were anchored to the bread wheat linkage map, with 1046 and 5550 markers from the 90 and 660 K SNP assays, respectively. Composite interval mapping identified 119 additive QTLs on 20 chromosomes except 4D; among them, 15 accounted for more than 10% of the phenotypic variation across two or three environments. Twelve QTLs for Mixograph parameters, 17 for RVA parameters and 55 for Mixolab parameters were new. Eleven QTL clusters were identified. The closely linked SNP markers can be used in marker-assisted wheat breeding in combination with the Kompetitive Allele Specific PCR (KASP) technique for improvement of processing quality in bread wheat. PMID:27486464

Construction of a high density SNP linkage map of kelp (Saccharina japonica) by sequencing Taq I site associated DNA and mapping of a sex determining locus.

PubMed

Zhang, Ning; Zhang, Linan; Tao, Ye; Guo, Li; Sun, Juan; Li, Xia; Zhao, Nan; Peng, Jie; Li, Xiaojie; Zeng, Liang; Chen, Jinsa; Yang, Guanpin

2015-03-15

Kelp (Saccharina japonica) has been intensively cultured in China for almost a century. Its genetic improvement is comparable with that of rice. However, the development of its molecular tools is extremely limited, thus its genes, genetics and genomics. Kelp performs an alternative life cycle during which sporophyte generation alternates with gametophyte generation. The gametophytes of kelp can be cloned and crossed. Due to these characteristics, kelp may serve as a reference for the biological and genetic studies of Volvox, mosses and ferns. We constructed a high density single nucleotide polymorphism (SNP) linkage map for kelp by restriction site associated DNA (RAD) sequencing. In total, 4,994 SNP-containing physical (tag-defined) RAD loci were mapped on 31 linkage groups. The map expanded a total genetic distance of 1,782.75 cM, covering 98.66% of the expected (1,806.94 cM). The length of RAD tags (85 bp) was extended to 400-500 bp with Miseq method, offering us an easiness of developing SNP chips and shifting SNP genotyping to a high throughput track. The number of linkage groups was in accordance with the documented with cytological methods. In addition, we identified a set of microsatellites (99 in total) from the extended RAD tags. A gametophyte sex determining locus was mapped on linkage group 2 in a window about 9.0 cM in width, which was 2.66 cM up to marker_40567 and 6.42 cM down to marker_23595. A high density SNP linkage map was constructed for kelp, an intensively cultured brown alga in China. The RAD tags were also extended so that a SNP chip could be developed. In addition, a set of microsatellites were identified among mapped loci, and a gametophyte sex determining locus was mapped. This map will facilitate the genetic studies of kelp including for example the evaluation of germplasm and the decipherment of the genetic bases of economic traits.

Comparing strategies for selection of low-density SNPs for imputation-mediated genomic prediction in U. S. Holsteins.

PubMed

He, Jun; Xu, Jiaqi; Wu, Xiao-Lin; Bauck, Stewart; Lee, Jungjae; Morota, Gota; Kachman, Stephen D; Spangler, Matthew L

2018-04-01

SNP chips are commonly used for genotyping animals in genomic selection but strategies for selecting low-density (LD) SNPs for imputation-mediated genomic selection have not been addressed adequately. The main purpose of the present study was to compare the performance of eight LD (6K) SNP panels, each selected by a different strategy exploiting a combination of three major factors: evenly-spaced SNPs, increased minor allele frequencies, and SNP-trait associations either for single traits independently or for all the three traits jointly. The imputation accuracies from 6K to 80K SNP genotypes were between 96.2 and 98.2%. Genomic prediction accuracies obtained using imputed 80K genotypes were between 0.817 and 0.821 for daughter pregnancy rate, between 0.838 and 0.844 for fat yield, and between 0.850 and 0.863 for milk yield. The two SNP panels optimized on the three major factors had the highest genomic prediction accuracy (0.821-0.863), and these accuracies were very close to those obtained using observed 80K genotypes (0.825-0.868). Further exploration of the underlying relationships showed that genomic prediction accuracies did not respond linearly to imputation accuracies, but were significantly affected by genotype (imputation) errors of SNPs in association with the traits to be predicted. SNPs optimal for map coverage and MAF were favorable for obtaining accurate imputation of genotypes whereas trait-associated SNPs improved genomic prediction accuracies. Thus, optimal LD SNP panels were the ones that combined both strengths. The present results have practical implications on the design of LD SNP chips for imputation-enabled genomic prediction.

Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar).

PubMed

Houston, Ross D; Taggart, John B; Cézard, Timothé; Bekaert, Michaël; Lowe, Natalie R; Downing, Alison; Talbot, Richard; Bishop, Stephen C; Archibald, Alan L; Bron, James E; Penman, David J; Davassi, Alessandro; Brew, Fiona; Tinch, Alan E; Gharbi, Karim; Hamilton, Alastair

2014-02-06

Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection.

Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar)

PubMed Central

2014-01-01

Background Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. Results SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. Conclusions This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection. PMID:24524230

A powerful tool for genome analysis in maize: development and evaluation of the high density 600 k SNP genotyping array.

PubMed

Unterseer, Sandra; Bauer, Eva; Haberer, Georg; Seidel, Michael; Knaak, Carsten; Ouzunova, Milena; Meitinger, Thomas; Strom, Tim M; Fries, Ruedi; Pausch, Hubert; Bertani, Christofer; Davassi, Alessandro; Mayer, Klaus Fx; Schön, Chris-Carolin

2014-09-29

High density genotyping data are indispensable for genomic analyses of complex traits in animal and crop species. Maize is one of the most important crop plants worldwide, however a high density SNP genotyping array for analysis of its large and highly dynamic genome was not available so far. We developed a high density maize SNP array composed of 616,201 variants (SNPs and small indels). Initially, 57 M variants were discovered by sequencing 30 representative temperate maize lines and then stringently filtered for sequence quality scores and predicted conversion performance on the array resulting in the selection of 1.2 M polymorphic variants assayed on two screening arrays. To identify high-confidence variants, 285 DNA samples from a broad genetic diversity panel of worldwide maize lines including the samples used for sequencing, important founder lines for European maize breeding, hybrids, and proprietary samples with European, US, semi-tropical, and tropical origin were used for experimental validation. We selected 616 k variants according to their performance during validation, support of genotype calls through sequencing data, and physical distribution for further analysis and for the design of the commercially available Affymetrix® Axiom® Maize Genotyping Array. This array is composed of 609,442 SNPs and 6,759 indels. Among these are 116,224 variants in coding regions and 45,655 SNPs of the Illumina® MaizeSNP50 BeadChip for study comparison. In a subset of 45,974 variants, apart from the target SNP additional off-target variants are detected, which show only a minor bias towards intermediate allele frequencies. We performed principal coordinate and admixture analyses to determine the ability of the array to detect and resolve population structure and investigated the extent of LD within a worldwide validation panel. The high density Affymetrix® Axiom® Maize Genotyping Array is optimized for European and American temperate maize and was developed based on a diverse sample panel by applying stringent quality filter criteria to ensure its suitability for a broad range of applications. With 600 k variants it is the largest currently publically available genotyping array in crop species.

Predictive ability of direct genomic values for lifetime net merit of Holstein sires using selected subsets of single nucleotide polymorphism markers.

PubMed

Weigel, K A; de los Campos, G; González-Recio, O; Naya, H; Wu, X L; Long, N; Rosa, G J M; Gianola, D

2009-10-01

The objective of the present study was to assess the predictive ability of subsets of single nucleotide polymorphism (SNP) markers for development of low-cost, low-density genotyping assays in dairy cattle. Dense SNP genotypes of 4,703 Holstein bulls were provided by the USDA Agricultural Research Service. A subset of 3,305 bulls born from 1952 to 1998 was used to fit various models (training set), and a subset of 1,398 bulls born from 1999 to 2002 was used to evaluate their predictive ability (testing set). After editing, data included genotypes for 32,518 SNP and August 2003 and April 2008 predicted transmitting abilities (PTA) for lifetime net merit (LNM$), the latter resulting from progeny testing. The Bayesian least absolute shrinkage and selection operator method was used to regress August 2003 PTA on marker covariates in the training set to arrive at estimates of marker effects and direct genomic PTA. The coefficient of determination (R(2)) from regressing the April 2008 progeny test PTA of bulls in the testing set on their August 2003 direct genomic PTA was 0.375. Subsets of 300, 500, 750, 1,000, 1,250, 1,500, and 2,000 SNP were created by choosing equally spaced and highly ranked SNP, with the latter based on the absolute value of their estimated effects obtained from the training set. The SNP effects were re-estimated from the training set for each subset of SNP, and the 2008 progeny test PTA of bulls in the testing set were regressed on corresponding direct genomic PTA. The R(2) values for subsets of 300, 500, 750, 1,000, 1,250, 1,500, and 2,000 SNP with largest effects (evenly spaced SNP) were 0.184 (0.064), 0.236 (0.111), 0.269 (0.190), 0.289 (0.179), 0.307 (0.228), 0.313 (0.268), and 0.322 (0.291), respectively. These results indicate that a low-density assay comprising selected SNP could be a cost-effective alternative for selection decisions and that significant gains in predictive ability may be achieved by increasing the number of SNP allocated to such an assay from 300 or fewer to 1,000 or more.

Conservation genomics of anadromous Atlantic salmon across its North American range: outlier loci identify the same patterns of population structure as neutral loci.

PubMed

Moore, Jean-Sébastien; Bourret, Vincent; Dionne, Mélanie; Bradbury, Ian; O'Reilly, Patrick; Kent, Matthew; Chaput, Gérald; Bernatchez, Louis

2014-12-01

Anadromous Atlantic salmon (Salmo salar) is a species of major conservation and management concern in North America, where population abundance has been declining over the past 30 years. Effective conservation actions require the delineation of conservation units to appropriately reflect the spatial scale of intraspecific variation and local adaptation. Towards this goal, we used the most comprehensive genetic and genomic database for Atlantic salmon to date, covering the entire North American range of the species. The database included microsatellite data from 9142 individuals from 149 sampling locations and data from a medium-density SNP array providing genotypes for >3000 SNPs for 50 sampling locations. We used neutral and putatively selected loci to integrate adaptive information in the definition of conservation units. Bayesian clustering with the microsatellite data set and with neutral SNPs identified regional groupings largely consistent with previously published regional assessments. The use of outlier SNPs did not result in major differences in the regional groupings, suggesting that neutral markers can reflect the geographic scale of local adaptation despite not being under selection. We also performed assignment tests to compare power obtained from microsatellites, neutral SNPs and outlier SNPs. Using SNP data substantially improved power compared to microsatellites, and an assignment success of 97% to the population of origin and of 100% to the region of origin was achieved when all SNP loci were used. Using outlier SNPs only resulted in minor improvements to assignment success to the population of origin but improved regional assignment. We discuss the implications of these new genetic resources for the conservation and management of Atlantic salmon in North America. © 2014 John Wiley & Sons Ltd.

Polymorphism at the TRIB1 gene modulates plasma lipid levels: insight from the Spanish familial hypercholesterolemia cohort study

USDA-ARS?s Scientific Manuscript database

rs17321515 SNP has been associated with variation in LDL-C, high density lipoprotein cholesterol and triglycerides concentrations. This effect has never been studied in patients with severe hypercholesterolemia. Therefore, our aims were to assess the association of the rs17321515 (TRIB1) SNP with pl...

SNP discovery and genotyping using Genotyping-by-Sequencing in Pekin ducks.

PubMed

Zhu, Feng; Cui, Qian-Qian; Hou, Zhuo-Cheng

2016-11-15

Genomic selection and genome-wide association studies need thousands to millions of SNPs. However, many non-model species do not have reference chips for detecting variation. Our goal was to develop and validate an inexpensive but effective method for detecting SNP variation. Genotyping by sequencing (GBS) can be a highly efficient strategy for genome-wide SNP detection, as an alternative to microarray chips. Here, we developed a GBS protocol for ducks and tested it to genotype 49 Pekin ducks. A total of 169,209 SNPs were identified from all animals, with a mean of 55,920 SNPs per individual. The average SNP density reached 1156 SNPs/MB. In this study, the first application of GBS to ducks, we demonstrate the power and simplicity of this method. GBS can be used for genetic studies in to provide an effective method for genome-wide SNP discovery.

High-density SNP Scan of Production and Product Quality Traits in Beef Cattle

USDA-ARS?s Scientific Manuscript database

Genotypes from the BovineSNP50 BeadChip (50K) were obtained on animals derived from 150 AI sires from seven breeds (22 sires per breed; Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental) as either progeny (F1; 590 steers) or grandprogeny (F1 x F1 = F1**2; 1,306 steers and 707 ...

Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

PubMed

Lee, Kyoung-Young; Kang, Hyun-Sik; Shin, Yun-A

2013-03-10

The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Effect of L-arginine on the relaxation caused by sodium nitroprusside on isolated rat renal artery.

PubMed

Orescanin, Z; Milovanović, S R

2006-12-01

In the present study we investigated the mechanism of nitric oxide induced relaxation of renal arteries, with or without endothelium, taken from normotensive and spontaneously hypertensive (SH) rats. With this purpose in mind, the effects of the nitric oxide donor, sodium nitroprusside (SNP), with and without L-arg in the medium, on isolated rat renal artery relaxation were studied. Relaxing effect of SNP was higher in normotensive (10(-5) M of SNP caused 220% of relaxation in the cases with endothelium and 240% without endothelium), in comparison with SH rats (100% of relaxation with endothelium and 150% without). L-arg antagonized the relaxing effect of SNP in the examined renal arteries, more in normotensive (100-160% with endothelium and 110-195% without) than in hypertensive ones (0-10% with endothelium and 35-75% without) at SNP concentrations 10(-7) - 10(-5) M, respectively (*P < 0.05; **P < 0.001). L-arg did not significantly change relaxing effect of SNP in the isolated renal arteries with endothelium taken from SH rats, which show that L-arg, by modifying the chemical versatility of NO into redox active forms -nitrosonium (NO+) and -nitroxyl (NO-), produces different relaxing effects in normotensive and hypertensive isolated arteries of rats, with or without endothelium, potentiating the role of nitroxyl induced relaxation in SH rats.

Genetic diversity, linkage disequilibrium, population structure and construction of a core collection of Prunus avium L. landraces and bred cultivars.

PubMed

Campoy, José Antonio; Lerigoleur-Balsemin, Emilie; Christmann, Hélène; Beauvieux, Rémi; Girollet, Nabil; Quero-García, José; Dirlewanger, Elisabeth; Barreneche, Teresa

2016-02-24

Depiction of the genetic diversity, linkage disequilibrium (LD) and population structure is essential for the efficient organization and exploitation of genetic resources. The objectives of this study were to (i) to evaluate the genetic diversity and to detect the patterns of LD, (ii) to estimate the levels of population structure and (iii) to identify a 'core collection' suitable for association genetic studies in sweet cherry. A total of 210 genotypes including modern cultivars and landraces from 16 countries were genotyped using the RosBREED cherry 6 K SNP array v1. Two groups, mainly bred cultivars and landraces, respectively, were first detected using STRUCTURE software and confirmed by Principal Coordinate Analysis (PCoA). Further analyses identified nine subgroups using STRUCTURE and Discriminant Analysis of Principal Components (DAPC). Several sub-groups correspond to different eco-geographic regions of landraces distribution. Linkage disequilibrium was evaluated showing lower values than in peach, the reference Prunus species. A 'core collection' containing 156 accessions was selected using the maximum length sub tree method. The present study constitutes the first population genetics analysis in cultivated sweet cherry using a medium-density SNP (single nucleotide polymorphism) marker array. We provided estimations of linkage disequilibrium, genetic structure and the definition of a first INRA's Sweet Cherry core collection useful for breeding programs, germplasm management and association genetics studies.

Influence of adiponectin gene polymorphism SNP276 (G/T) on adiponectin in response to exercise training.

PubMed

Huang, Hu; Tada Iida, Kaoruko; Murakami, Haruka; Saito, Yoko; Otsuki, Takeshi; Iemitsu, Motoyuki; Maeda, Seiji; Sone, Hirohito; Kuno, Shinya; Ajisaka, Ryuichi

2007-12-01

Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P<0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P<0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p<0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.

Tumor Touch Imprints as Source for Whole Genome Analysis of Neuroblastoma Tumors

PubMed Central

Brunner, Clemens; Brunner-Herglotz, Bettina; Ziegler, Andrea; Frech, Christian; Amann, Gabriele; Ladenstein, Ruth; Ambros, Inge M.; Ambros, Peter F.

2016-01-01

Introduction Tumor touch imprints (TTIs) are routinely used for the molecular diagnosis of neuroblastomas by interphase fluorescence in-situ hybridization (I-FISH). However, in order to facilitate a comprehensive, up-to-date molecular diagnosis of neuroblastomas and to identify new markers to refine risk and therapy stratification methods, whole genome approaches are needed. We examined the applicability of an ultra-high density SNP array platform that identifies copy number changes of varying sizes down to a few exons for the detection of genomic changes in tumor DNA extracted from TTIs. Material and Methods DNAs were extracted from TTIs of 46 neuroblastoma and 4 other pediatric tumors. The DNAs were analyzed on the Cytoscan HD SNP array platform to evaluate numerical and structural genomic aberrations. The quality of the data obtained from TTIs was compared to that from randomly chosen fresh or fresh frozen solid tumors (n = 212) and I-FISH validation was performed. Results SNP array profiles were obtained from 48 (out of 50) TTI DNAs of which 47 showed genomic aberrations. The high marker density allowed for single gene analysis, e.g. loss of nine exons in the ATRX gene and the visualization of chromothripsis. Data quality was comparable to fresh or fresh frozen tumor SNP profiles. SNP array results were confirmed by I-FISH. Conclusion TTIs are an excellent source for SNP array processing with the advantage of simple handling, distribution and storage of tumor tissue on glass slides. The minimal amount of tumor tissue needed to analyze whole genomes makes TTIs an economic surrogate source in the molecular diagnostic work up of tumor samples. PMID:27560999

A Bayesian antedependence model for whole genome prediction.

PubMed

Yang, Wenzhao; Tempelman, Robert J

2012-04-01

Hierarchical mixed effects models have been demonstrated to be powerful for predicting genomic merit of livestock and plants, on the basis of high-density single-nucleotide polymorphism (SNP) marker panels, and their use is being increasingly advocated for genomic predictions in human health. Two particularly popular approaches, labeled BayesA and BayesB, are based on specifying all SNP-associated effects to be independent of each other. BayesB extends BayesA by allowing a large proportion of SNP markers to be associated with null effects. We further extend these two models to specify SNP effects as being spatially correlated due to the chromosomally proximal effects of causal variants. These two models, that we respectively dub as ante-BayesA and ante-BayesB, are based on a first-order nonstationary antedependence specification between SNP effects. In a simulation study involving 20 replicate data sets, each analyzed at six different SNP marker densities with average LD levels ranging from r(2) = 0.15 to 0.31, the antedependence methods had significantly (P < 0.01) higher accuracies than their corresponding classical counterparts at higher LD levels (r(2) > 0. 24) with differences exceeding 3%. A cross-validation study was also conducted on the heterogeneous stock mice data resource (http://mus.well.ox.ac.uk/mouse/HS/) using 6-week body weights as the phenotype. The antedependence methods increased cross-validation prediction accuracies by up to 3.6% compared to their classical counterparts (P < 0.001). Finally, we applied our method to other benchmark data sets and demonstrated that the antedependence methods were more accurate than their classical counterparts for genomic predictions, even for individuals several generations beyond the training data.

Extensive population structure in San, Khoe, and mixed ancestry populations from southern Africa revealed by 44 short 5-SNP haplotypes.

PubMed

Schlebusch, Carina M; Soodyall, Himlya

2012-12-01

The San and Khoe people currently represent remnant groups of a much larger and widely distributed population of hunter-gatherers and pastoralists who had exclusive occupation of southern Africa before the arrival of Bantu-speaking groups in the past 1,200 years and sea-borne immigrants within the last 350 years. Genetic studies [mitochondrial deoxyribonucleic acid (DNA) and Y-chromosome] conducted on San and Khoe groups revealed that they harbor some of the most divergent lineages found in living peoples throughout the world. Recently, high-density, autosomal, single-nucleotide polymorphism (SNP)-array studies confirmed the early divergence of Khoe-San population groups from all other human populations. The present study made use of 220 autosomal SNP markers (in the format of both haplotypes and genotypes) to examine the population structure of various San and Khoe groups and their relationship to other neighboring groups. Whereas analyses based on the genotypic SNP data only supported the division of the included populations into three main groups-Khoe-San, Bantu-speakers, and non-African populations-haplotype analyses revealed finer structure within Khoe-San populations. By the use of only 44 short SNP haplotypes (compiled from a total of 220 SNPs), most of the Khoe-San groups could be resolved as separate groups by applying STRUCTURE analyses. Therefore, by carefully selecting a few SNPs and combining them into haplotypes, we were able to achieve the same level of population distinction that was achieved previously in high-density SNP studies on the same population groups. Using haplotypes proved to be a very efficient and cost-effective way to study population structure. Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309.

Effect of increasing the number of single-nucleotide polymorphisms from 60,000 to 85,000 in genomic evaluation of Holsteins

USDA-ARS?s Scientific Manuscript database

The periodic need to restock reagent pools for genotyping chips provides an opportunity to increase the number of single-nucleotide polymorphisms (SNP) on a chip at no increase in cost. A high-density chip with >140,000 SNP has been developed by GeneSeek Inc. (Lincoln, NE) to increase accuracy of ge...

Extent of linkage disequilibrium, consistency of gametic phase, and imputation accuracy within and across Canadian dairy breeds.

PubMed

Larmer, S G; Sargolzaei, M; Schenkel, F S

2014-05-01

Genomic selection requires a large reference population to accurately estimate single nucleotide polymorphism (SNP) effects. In some Canadian dairy breeds, the available reference populations are not large enough for accurate estimation of SNP effects for traits of interest. If marker phase is highly consistent across multiple breeds, it is theoretically possible to increase the accuracy of genomic prediction for one or all breeds by pooling several breeds into a common reference population. This study investigated the extent of linkage disequilibrium (LD) in 5 major dairy breeds using a 50,000 (50K) SNP panel and 3 of the same breeds using the 777,000 (777K) SNP panel. Correlation of pair-wise SNP phase was also investigated on both panels. The level of LD was measured using the squared correlation of alleles at 2 loci (r(2)), and the consistency of SNP gametic phases was correlated using the signed square root of these values. Because of the high cost of the 777K panel, the accuracy of imputation from lower density marker panels [6,000 (6K) or 50K] was examined both within breed and using a multi-breed reference population in Holstein, Ayrshire, and Guernsey. Imputation was carried out using FImpute V2.2 and Beagle 3.3.2 software. Imputation accuracies were then calculated as both the proportion of correct SNP filled in (concordance rate) and allelic R(2). Computation time was also explored to determine the efficiency of the different algorithms for imputation. Analysis showed that LD values >0.2 were found in all breeds at distances at or shorter than the average adjacent pair-wise distance between SNP on the 50K panel. Correlations of r-values, however, did not reach high levels (<0.9) at these distances. High correlation values of SNP phase between breeds were observed (>0.94) when the average pair-wise distances using the 777K SNP panel were examined. High concordance rate (0.968-0.995) and allelic R(2) (0.946-0.991) were found for all breeds when imputation was carried out with FImpute from 50K to 777K. Imputation accuracy for Guernsey and Ayrshire was slightly lower when using the imputation method in Beagle. Computing time was significantly greater when using Beagle software, with all comparable procedures being 9 to 13 times less efficient, in terms of time, compared with FImpute. These findings suggest that use of a multi-breed reference population might increase prediction accuracy using the 777K SNP panel and that 777K genotypes can be efficiently and effectively imputed using the lower density 50K SNP panel. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A comparison of restriction fragment length polymorphism, tetra primer amplification refractory mutation system PCR and unlabeled probe melting analysis for LTA+252 C>T SNP genotyping.

PubMed

Soler, Stephan; Rittore, Cécile; Touitou, Isabelle; Philibert, Laurent

2011-02-20

From the wide range of methods currently available for genotyping, we wished to identify a quick, reliable and affordable approach for routine use in our laboratory for LTA+252 C>T SNP screening. We set up and compared three genotyping methods for SNP detection: restriction fragment length polymorphism (RFLP), tetra primer amplification refractory mutation system PCR (TPAP) and unlabeled probe melting analysis (UPMA). The SNP model used was LTA+252 C>T, a cytokine gene polymorphism that has been associated with response to treatment in rheumatoid arthritis. The study was performed using 46 samples from healthy Caucasian volunteers. Allele and genotype distribution was similar to that previously described in the same population. All three genotyping methods showed good reproducibility and are suitable for a medium scale throughput molecular platform. UPMA was the most cost effective, reliable and safe method since it required the shortest technician time, could be performed in a single closed tube and involved automatic data analysis. This work is the first to compare these three genotyping techniques and provides evidence for UPMA being the method of choice for LTA+252 C>T SNP genotyping. Copyright © 2010 Elsevier B.V. All rights reserved.

Comparative Analysis of CNV Calling Algorithms: Literature Survey and a Case Study Using Bovine High-Density SNP Data.

PubMed

Xu, Lingyang; Hou, Yali; Bickhart, Derek M; Song, Jiuzhou; Liu, George E

2013-06-25

Copy number variations (CNVs) are gains and losses of genomic sequence between two individuals of a species when compared to a reference genome. The data from single nucleotide polymorphism (SNP) microarrays are now routinely used for genotyping, but they also can be utilized for copy number detection. Substantial progress has been made in array design and CNV calling algorithms and at least 10 comparison studies in humans have been published to assess them. In this review, we first survey the literature on existing microarray platforms and CNV calling algorithms. We then examine a number of CNV calling tools to evaluate their impacts using bovine high-density SNP data. Large incongruities in the results from different CNV calling tools highlight the need for standardizing array data collection, quality assessment and experimental validation. Only after careful experimental design and rigorous data filtering can the impacts of CNVs on both normal phenotypic variability and disease susceptibility be fully revealed.

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

PubMed Central

Chagné, David; Crowhurst, Ross N.; Troggio, Michela; Davey, Mark W.; Gilmore, Barbara; Lawley, Cindy; Vanderzande, Stijn; Hellens, Roger P.; Kumar, Satish; Cestaro, Alessandro; Velasco, Riccardo; Main, Dorrie; Rees, Jasper D.; Iezzoni, Amy; Mockler, Todd; Wilhelm, Larry; Van de Weg, Eric; Gardiner, Susan E.; Bassil, Nahla; Peace, Cameron

2012-01-01

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of ‘Golden Delicious’, SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple. PMID:22363718

In Vitro and In Vivo Toxicity Evaluation of Colloidal Silver Nanoparticles Used in Endodontic Treatments.

PubMed

Takamiya, Aline Satie; Monteiro, Douglas Roberto; Bernabé, Daniel Galera; Gorup, Luiz Fernando; Camargo, Emerson Rodrigues; Gomes-Filho, João Eduardo; Oliveira, Sandra Helena Penha; Barbosa, Debora Barros

2016-06-01

Silver nanoparticles have been used for different purposes in dentistry, including endodontic treatments. The aim of this study was to determine the cytotoxicity of different types of silver nanoparticles on mouse fibroblast cell line L929 and the reaction of subcutaneous connective tissue of Wistar rats to these nanoparticles. Silver nanoparticles of an average size of 5 nm were synthesized with ammonia (SNA) or polyvinylpyrrolidone (SNP). L929 was exposed to SNA and SNP (0.1-100 μg/mL), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and enzyme-linked immunosorbent assays were performed after 6, 24, and 48 hours. Culture medium was used as the control. Sixteen rats received, individually, 3 polyethylene tubes filled with a fibrin sponge embedded in 100 μL SNA or SNP (1 μg/mL). A fibrin sponge with no embedding was the control. Tissue reaction was performed qualitatively and quantitatively after 7, 15, 30, and 90 days of implantation in the dorsal connective tissue of Wistar rats. SNA and SNP were cytotoxic to L929 in higher concentrations, with SNA significantly more toxic than SNP. SNA and SNP did not induce significant interleukin-1β and interleukin-6 production. The release of stem cell factor by L929 increased 48 hours after the treatment with SNP at 5 μg/mL. Histologic examination showed that the inflammatory responses caused by SNA and SNP at 1 μg/mL were similar to the control in all experimental periods. It was concluded that SNA and SNP were not cytotoxic at 25 μg/mL or lower concentrations. However, for safe clinical use, further studies establishing others points of its toxicologic profile are recommended. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Practical implementation of cost-effective genomic selection in commercial pig breeding using imputation.

PubMed

Cleveland, M A; Hickey, J M

2013-08-01

Genomic selection can be implemented in pig breeding at a reduced cost using genotype imputation. Accuracy of imputation and the impact on resulting genomic breeding values (gEBV) was investigated. High-density genotype data was available for 4,763 animals from a single pig line. Three low-density genotype panels were constructed with SNP densities of 450 (L450), 3,071 (L3k) and 5,963 (L6k). Accuracy of imputation was determined using 184 test individuals with no genotyped descendants in the data but with parents and grandparents genotyped using the Illumina PorcineSNP60 Beadchip. Alternative genotyping scenarios were created in which parents, grandparents, and individuals that were not direct ancestors of test animals (Other) were genotyped at high density (S1), grandparents were not genotyped (S2), dams and granddams were not genotyped (S3), and dams and granddams were genotyped at low density (S4). Four additional scenarios were created by excluding Other animal genotypes. Test individuals were always genotyped at low density. Imputation was performed with AlphaImpute. Genomic breeding values were calculated using the single-step genomic evaluation. Test animals were evaluated for the information retained in the gEBV, calculated as the correlation between gEBV using imputed genotypes and gEBV using true genotypes. Accuracy of imputation was high for all scenarios but decreased with fewer SNP on the low-density panel (0.995 to 0.965 for S1) and with reduced genotyping of ancestors, where the largest changes were for L450 (0.965 in S1 to 0.914 in S3). Exclusion of genotypes for Other animals resulted in only small accuracy decreases. Imputation accuracy was not consistent across the genome. Information retained in the gEBV was related to genotyping scenario and thus to imputation accuracy. Reducing the number of SNP on the low-density panel reduced the information retained in the gEBV, with the largest decrease observed from L3k to L450. Excluding Other animal genotypes had little impact on imputation accuracy but caused large decreases in the information retained in the gEBV. These results indicate that accuracy of gEBV from imputed genotypes depends on the level of genotyping in close relatives and the size of the genotyped dataset. Fewer high-density genotyped individuals are needed to obtain accurate imputation than are needed to obtain accurate gEBV. Strategies to optimize development of low-density panels can improve both imputation and gEBV accuracy.

Measuring firm size distribution with semi-nonparametric densities

NASA Astrophysics Data System (ADS)

Cortés, Lina M.; Mora-Valencia, Andrés; Perote, Javier

2017-11-01

In this article, we propose a new methodology based on a (log) semi-nonparametric (log-SNP) distribution that nests the lognormal and enables better fits in the upper tail of the distribution through the introduction of new parameters. We test the performance of the lognormal and log-SNP distributions capturing firm size, measured through a sample of US firms in 2004-2015. Taking different levels of aggregation by type of economic activity, our study shows that the log-SNP provides a better fit of the firm size distribution. We also formally introduce the multivariate log-SNP distribution, which encompasses the multivariate lognormal, to analyze the estimation of the joint distribution of the value of the firm's assets and sales. The results suggest that sales are a better firm size measure, as indicated by other studies in the literature.

KinSNP software for homozygosity mapping of disease genes using SNP microarrays

PubMed Central

2010-01-01

Consanguineous families affected with a recessive genetic disease caused by homozygotisation of a mutation offer a unique advantage for positional cloning of rare diseases. Homozygosity mapping of patient genotypes is a powerful technique for the identification of the genomic locus harbouring the causing mutation. This strategy relies on the observation that in these patients a large region spanning the disease locus is also homozygous with high probability. The high marker density in single nucleotide polymorphism (SNP) arrays is extremely advantageous for homozygosity mapping. We present KinSNP, a user-friendly software tool for homozygosity mapping using SNP arrays. The software searches for stretches of SNPs which are homozygous to the same allele in all ascertained sick individuals. User-specified parameters control the number of allowed genotyping 'errors' within homozygous blocks. Candidate disease regions are then reported in a detailed, coloured Excel file, along with genotypes of family members and healthy controls. An interactive genome browser has been included which shows homozygous blocks, individual genotypes, genes and further annotations along the chromosomes, with zooming and scrolling capabilities. The software has been used to identify the location of a mutated gene causing insensitivity to pain in a large Bedouin family. KinSNP is freely available from http://bioinfo.bgu.ac.il/bsu/software/kinSNP. PMID:20846928

Association, effects and validation of polymorphisms within the NCAPG - LCORL locus located on BTA6 with feed intake, gain, meat and carcass traits in beef cattle

USDA-ARS?s Scientific Manuscript database

Background: In a previously reported genome-wide association study based on a high-density bovine SNP genotyping array, 8 SNP were nominally associated (P

Cross-talk interactions of exogenous nitric oxide and sucrose modulates phenylpropanoid metabolism in yellow lupine embryo axes infected with Fusarium oxysporum.

PubMed

Morkunas, Iwona; Formela, Magda; Floryszak-Wieczorek, Jolanta; Marczak, Łukasz; Narożna, Dorota; Nowak, Witold; Bednarski, Waldemar

2013-10-01

The aim of the study was to examine cross-talk of exogenous nitric oxide (NO) and sucrose in the mechanisms of synthesis and accumulation of isoflavonoids in embryo axes of Lupinus luteus L. cv. Juno. It was verified whether the interaction of these molecules can modulate the defense response of axes to infection and development of the pathogenic fungus Fusarium oxysporum f. sp. lupini. Sucrose alone strongly stimulated a high level of genistein glucoside in axes pretreated with exogenous nitric oxide (SNP or GSNO) and non-pretreated axes. As a result of amplification of the signal coming from sucrose and GSNO, high isoflavonoids accumulation was observed (+Sn+GSNO). It needs to be stressed that infection in tissues pretreated with SNP/GSNO and cultured on the medium with sucrose (+Si+SNP/+Si+GSNO) very strongly enhances the accumulation of free isoflavone aglycones. In +Si+SNP axes phenylalanine ammonia-lyase activity was high up to 72h. As early as at 12h in +Si+SNP axes an increase was recorded in gene expression level of the specific isoflavonoid synthesis pathway. At 24h in +Si+SNP axes a very high total antioxidant capacity dependent on the pool of fast antioxidants was noted. Post-infection generation of semiquinone radicals was lower in axes with a high level of sucrose than with a deficit. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Construction of a high-density genetic map for grape using next generation restriction-site associated DNA sequencing

PubMed Central

2012-01-01

Background Genetic mapping and QTL detection are powerful methodologies in plant improvement and breeding. Construction of a high-density and high-quality genetic map would be of great benefit in the production of superior grapes to meet human demand. High throughput and low cost of the recently developed next generation sequencing (NGS) technology have resulted in its wide application in genome research. Sequencing restriction-site associated DNA (RAD) might be an efficient strategy to simplify genotyping. Combining NGS with RAD has proven to be powerful for single nucleotide polymorphism (SNP) marker development. Results An F1 population of 100 individual plants was developed. In-silico digestion-site prediction was used to select an appropriate restriction enzyme for construction of a RAD sequencing library. Next generation RAD sequencing was applied to genotype the F1 population and its parents. Applying a cluster strategy for SNP modulation, a total of 1,814 high-quality SNP markers were developed: 1,121 of these were mapped to the female genetic map, 759 to the male map, and 1,646 to the integrated map. A comparison of the genetic maps to the published Vitis vinifera genome revealed both conservation and variations. Conclusions The applicability of next generation RAD sequencing for genotyping a grape F1 population was demonstrated, leading to the successful development of a genetic map with high density and quality using our designed SNP markers. Detailed analysis revealed that this newly developed genetic map can be used for a variety of genome investigations, such as QTL detection, sequence assembly and genome comparison. PMID:22908993

A high-density intraspecific SNP linkage map of pigeonpea (Cajanas cajan L. Millsp.)

PubMed Central

Mandal, Paritra; Bhutani, Shefali; Dutta, Sutapa; Kumawat, Giriraj; Singh, Bikram Pratap; Chaudhary, A. K.; Yadav, Rekha; Gaikwad, K.; Sevanthi, Amitha Mithra; Datta, Subhojit; Raje, Ranjeet S.; Sharma, Tilak R.; Singh, Nagendra Kumar

2017-01-01

Pigeonpea (Cajanus cajan (L.) Millsp.) is a major food legume cultivated in semi-arid tropical regions including the Indian subcontinent, Africa, and Southeast Asia. It is an important source of protein, minerals, and vitamins for nearly 20% of the world population. Due to high carbon sequestration and drought tolerance, pigeonpea is an important crop for the development of climate resilient agriculture and nutritional security. However, pigeonpea productivity has remained low for decades because of limited genetic and genomic resources, and sparse utilization of landraces and wild pigeonpea germplasm. Here, we present a dense intraspecific linkage map of pigeonpea comprising 932 markers that span a total adjusted map length of 1,411.83 cM. The consensus map is based on three different linkage maps that incorporate a large number of single nucleotide polymorphism (SNP) markers derived from next generation sequencing data, using Illumina GoldenGate bead arrays, and genotyping with restriction site associated DNA (RAD) sequencing. The genotyping-by-sequencing enhanced the marker density but was met with limited success due to lack of common markers across the genotypes of mapping population. The integrated map has 547 bead-array SNP, 319 RAD-SNP, and 65 simple sequence repeat (SSR) marker loci. We also show here correspondence between our linkage map and published genome pseudomolecules of pigeonpea. The availability of a high-density linkage map will help improve the anchoring of the pigeonpea genome to its chromosomes and the mapping of genes and quantitative trait loci associated with useful agronomic traits. PMID:28654689

Protective Effect of Coriolus versicolor Cultivated in Citrus Extract Against Nitric Oxide-Induced Apoptosis in Human Neuroblastoma SK-N-MC Cells

PubMed Central

Kim, Byung-Chul; Kim, Youn-Sub; Lee, Jin-Woo; Seo, Jin-Hee; Ji, Eun-Sang; Lee, Hyejung; Park, Yong-Il

2011-01-01

Nitric oxide (NO) is a reactive free radical and a messenger molecule in many physiological functions. However, excessive NO is believed to be a mediator of neurotoxicity. The medicinal plant Coriolus versicolor is known to possess anti-tumor and immune-potentiating activities. In this study, we investigated whether Coriolus versicolor possesses a protective effect against NO donor sodium nitroprusside (SNP)-induced apoptosis in the human neuroblastoma cell line SK-N-MC. We utilized 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, DNA fragmentation assay, reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and caspase-3 enzyme activity assay in SK-N-MC cells. MTT assay showed that SNP treatment significantly reduces the viability of cells, and the viabilities of cells pre-treated with the aqueous extract of Coriolus versicolor cultivated in citrus extract (CVEcitrus) was increased. However, aqueous extract of Coriolus versicolor cultivated in synthetic medium (CVEsynthetic) showed no protective effect and aqueous citrus extract (CE) had a little protective effect. The cell treated with SNP exhibited several apoptotic features, while those pre-treated for 1 h with CVEcitrus prior to SNP expose showed reduced apoptotic features. The cells pre-treated for 1 h with CVEcitrus prior to SNP expose inhibited p53 and Bax expressions and caspase-3 enzyme activity up-regulated by SNP. We showed that CVEcitrus exerts a protective effect against SNP-induced apoptosis in SK-N-MC cells. Our study suggests that CVEcitrus has therapeutic value in the treatment of a variety of NO-induced brain diseases. PMID:22110367

Protective Effect of Coriolus versicolor Cultivated in Citrus Extract Against Nitric Oxide-Induced Apoptosis in Human Neuroblastoma SK-N-MC Cells.

PubMed

Kim, Byung-Chul; Kim, Youn-Sub; Lee, Jin-Woo; Seo, Jin-Hee; Ji, Eun-Sang; Lee, Hyejung; Park, Yong-Il; Kim, Chang-Ju

2011-06-01

Nitric oxide (NO) is a reactive free radical and a messenger molecule in many physiological functions. However, excessive NO is believed to be a mediator of neurotoxicity. The medicinal plant Coriolus versicolor is known to possess anti-tumor and immune-potentiating activities. In this study, we investigated whether Coriolus versicolor possesses a protective effect against NO donor sodium nitroprusside (SNP)-induced apoptosis in the human neuroblastoma cell line SK-N-MC. We utilized 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, DNA fragmentation assay, reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and caspase-3 enzyme activity assay in SK-N-MC cells. MTT assay showed that SNP treatment significantly reduces the viability of cells, and the viabilities of cells pre-treated with the aqueous extract of Coriolus versicolor cultivated in citrus extract (CVE(citrus)) was increased. However, aqueous extract of Coriolus versicolor cultivated in synthetic medium (CVE(synthetic)) showed no protective effect and aqueous citrus extract (CE) had a little protective effect. The cell treated with SNP exhibited several apoptotic features, while those pre-treated for 1 h with CVE(citrus) prior to SNP expose showed reduced apoptotic features. The cells pre-treated for 1 h with CVE(citrus) prior to SNP expose inhibited p53 and Bax expressions and caspase-3 enzyme activity up-regulated by SNP. We showed that CVE(citrus) exerts a protective effect against SNP-induced apoptosis in SK-N-MC cells. Our study suggests that CVE(citrus) has therapeutic value in the treatment of a variety of NO-induced brain diseases.

Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing

PubMed Central

Wiszniewska, Joanna; Bi, Weimin; Shaw, Chad; Stankiewicz, Pawel; Kang, Sung-Hae L; Pursley, Amber N; Lalani, Seema; Hixson, Patricia; Gambin, Tomasz; Tsai, Chun-hui; Bock, Hans-Georg; Descartes, Maria; Probst, Frank J; Scaglia, Fernando; Beaudet, Arthur L; Lupski, James R; Eng, Christine; Wai Cheung, Sau; Bacino, Carlos; Patel, Ankita

2014-01-01

In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60 000 SNP probes, referred to as Chromosomal Microarray Analysis – Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner. PMID:23695279

High-density single nucleotide polymorphism (SNP) array mapping in Brassica oleracea: identification of QTL associated with carotenoid variation in broccoli florets.

PubMed

Brown, Allan F; Yousef, Gad G; Chebrolu, Kranthi K; Byrd, Robert W; Everhart, Koyt W; Thomas, Aswathy; Reid, Robert W; Parkin, Isobel A P; Sharpe, Andrew G; Oliver, Rebekah; Guzman, Ivette; Jackson, Eric W

2014-09-01

A high-resolution genetic linkage map of B. oleracea was developed from a B. napus SNP array. The work will facilitate genetic and evolutionary studies in Brassicaceae. A broccoli population, VI-158 × BNC, consisting of 150 F2:3 families was used to create a saturated Brassica oleracea (diploid: CC) linkage map using a recently developed rapeseed (Brassica napus) (tetraploid: AACC) Illumina Infinium single nucleotide polymorphism (SNP) array. The map consisted of 547 non-redundant SNP markers spanning 948.1 cM across nine chromosomes with an average interval size of 1.7 cM. As the SNPs are anchored to the genomic reference sequence of the rapid cycling B. oleracea TO1000, we were able to estimate that the map provides 96 % coverage of the diploid genome. Carotenoid analysis of 2 years data identified 3 QTLs on two chromosomes that are associated with up to half of the phenotypic variation associated with the accumulation of total or individual compounds. By searching the genome sequences of the two related diploid species (B. oleracea and B. rapa), we further identified putative carotenoid candidate genes in the region of these QTLs. This is the first description of the use of a B. napus SNP array to rapidly construct high-density genetic linkage maps of one of the constituent diploid species. The unambiguous nature of these markers with regard to genomic sequences provides evidence to the nature of genes underlying the QTL, and demonstrates the value and impact this resource will have on Brassica research.

Insights into the genetic architecture of morphological traits in two passerine bird species.

PubMed

Silva, C N S; McFarlane, S E; Hagen, I J; Rönnegård, L; Billing, A M; Kvalnes, T; Kemppainen, P; Rønning, B; Ringsby, T H; Sæther, B-E; Qvarnström, A; Ellegren, H; Jensen, H; Husby, A

2017-09-01

Knowledge about the underlying genetic architecture of phenotypic traits is needed to understand and predict evolutionary dynamics. The number of causal loci, magnitude of the effects and location in the genome are, however, still largely unknown. Here, we use genome-wide single-nucleotide polymorphism (SNP) data from two large-scale data sets on house sparrows and collared flycatchers to examine the genetic architecture of different morphological traits (tarsus length, wing length, body mass, bill depth, bill length, total and visible badge size and white wing patches). Genomic heritabilities were estimated using relatedness calculated from SNPs. The proportion of variance captured by the SNPs (SNP-based heritability) was lower in house sparrows compared with collared flycatchers, as expected given marker density (6348 SNPs in house sparrows versus 38 689 SNPs in collared flycatchers). Indeed, after downsampling to similar SNP density and sample size, this estimate was no longer markedly different between species. Chromosome-partitioning analyses demonstrated that the proportion of variance explained by each chromosome was significantly positively related to the chromosome size for some traits and, generally, that larger chromosomes tended to explain proportionally more variation than smaller chromosomes. Finally, we found two genome-wide significant associations with very small-effect sizes. One SNP on chromosome 20 was associated with bill length in house sparrows and explained 1.2% of phenotypic variation (V P ), and one SNP on chromosome 4 was associated with tarsus length in collared flycatchers (3% of V P ). Although we cannot exclude the possibility of undetected large-effect loci, our results indicate a polygenic basis for morphological traits.

Prospecting for pig single nucleotide polymorphisms in the human genome: have we struck gold?

PubMed

Grapes, L; Rudd, S; Fernando, R L; Megy, K; Rocha, D; Rothschild, M F

2006-06-01

Gene-to-gene variation in the frequency of single nucleotide polymorphisms (SNPs) has been observed in humans, mice, rats, primates and pigs, but a relationship across species in this variation has not been described. Here, the frequency of porcine coding SNPs (cSNPs) identified by in silico methods, and the frequency of murine cSNPs, were compared with the frequency of human cSNPs across homologous genes. From 150,000 porcine expressed sequence tag (EST) sequences, a total of 452 SNP-containing sequence clusters were found, totalling 1394 putative SNPs. All the clustered porcine EST annotations and SNP data have been made publicly available at http://sputnik.btk.fi/project?name=swine. Human and murine cSNPs were identified from dbSNP and were characterized as either validated or total number of cSNPs (validated plus non-validated) for comparison purposes. The correlation between in silico pig cSNP and validated human cSNP densities was found to be 0.77 (p < 0.00001) for a set of 25 homologous genes, while a correlation of 0.48 (p < 0.0005) was found for a primarily random sample of 50 homologous human and mouse genes. This is the first evidence of conserved gene-to-gene variability in cSNP frequency across species and indicates that site-directed screening of porcine genes that are homologous to cSNP-rich human genes may rapidly advance cSNP discovery in pigs.

Application of genomic selection in farm animal breeding.

PubMed

Tan, Cheng; Bian, Cheng; Yang, Da; Li, Ning; Wu, Zhen-Fang; Hu, Xiao-Xiang

2017-11-20

Genomic selection (GS) has become a widely accepted method in animal breeding to genetically improve economic traits. With the declining costs of high-density SNP chips and next-generation sequencing, GS has been applied in dairy cattle, swine, poultry and other animals and gained varying degrees of success. Currently, major challenges in GS studies include further reducing the cost of genome-wide SNP genotyping and improving the predictive accuracy of genomic estimated breeding value (GEBV). In this review, we summarize various methods for genome-wide SNP genotyping and GEBV prediction, and give a brief introduction of GS in livestock and poultry breeding. This review will provide a reference for further implementation of GS in farm animal breeding.

Development of new SNP derived cleaved amplified polymorphic sequence marker set and its successful utilization in the genetic analysis of seed color variation in barley.

PubMed

Bungartz, Annemarie; Klaus, Marius; Mathew, Boby; Léon, Jens; Naz, Ali Ahmad

2016-03-01

The aim of the present study was to develop a new cost effective PCR based CAPS marker set using advantages of high-throughput SNP genotyping. Initially, SNP survey was made using 20 diverse barley genotypes via 9k iSelect array genotyping that resulted in 6334 polymorphic SNP markers. Principle component analysis using this marker data showed fine differentiation of barley diverse gene pool. Till this end, we developed 200 SNP derived CAPS markers distributed across the genome covering around 991cM with an average marker density of 5.09cM. Further, we genotyped 68 CAPS markers in an F2 population (Cheri×ICB181160) segregating for seed color variation in barley. Genetic mapping of seed color revealed putative linkage of single nuclear gene on chromosome 1H. These findings showed the proof of concept for the development and utility of a newer cost effective genomic tool kit to analyze broader genetic resources of barley worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

Detection of selective sweeps in cattle using genome-wide SNP data

PubMed Central

2013-01-01

Background The domestication and subsequent selection by humans to create breeds and biological types of cattle undoubtedly altered the patterning of variation within their genomes. Strong selection to fix advantageous large-effect mutations underlying domesticability, breed characteristics or productivity created selective sweeps in which variation was lost in the chromosomal region flanking the selected allele. Selective sweeps have now been identified in the genomes of many animal species including humans, dogs, horses, and chickens. Here, we attempt to identify and characterise regions of the bovine genome that have been subjected to selective sweeps. Results Two datasets were used for the discovery and validation of selective sweeps via the fixation of alleles at a series of contiguous SNP loci. BovineSNP50 data were used to identify 28 putative sweep regions among 14 diverse cattle breeds. Affymetrix BOS 1 prescreening assay data for five breeds were used to identify 85 regions and validate 5 regions identified using the BovineSNP50 data. Many genes are located within these regions and the lack of sequence data for the analysed breeds precludes the nomination of selected genes or variants and limits the prediction of the selected phenotypes. However, phenotypes that we predict to have historically been under strong selection include horned-polled, coat colour, stature, ear morphology, and behaviour. Conclusions The bias towards common SNPs in the design of the BovineSNP50 assay led to the identification of recent selective sweeps associated with breed formation and common to only a small number of breeds rather than ancient events associated with domestication which could potentially be common to all European taurines. The limited SNP density, or marker resolution, of the BovineSNP50 assay significantly impacted the rate of false discovery of selective sweeps, however, we found sweeps in common between breeds which were confirmed using an ultra-high-density assay scored in a small number of animals from a subset of the breeds. No sweep regions were shared between indicine and taurine breeds reflecting their divergent selection histories and the very different environmental habitats to which these sub-species have adapted. PMID:23758707

A New Single Nucleotide Polymorphism Database for Rainbow Trout Generated Through Whole Genome Resequencing.

PubMed

Gao, Guangtu; Nome, Torfinn; Pearse, Devon E; Moen, Thomas; Naish, Kerry A; Thorgaard, Gary H; Lien, Sigbjørn; Palti, Yniv

2018-01-01

Single-nucleotide polymorphisms (SNPs) are highly abundant markers, which are broadly distributed in animal genomes. For rainbow trout ( Oncorhynchus mykiss ), SNP discovery has been previously done through sequencing of restriction-site associated DNA (RAD) libraries, reduced representation libraries (RRL) and RNA sequencing. Recently we have performed high coverage whole genome resequencing with 61 unrelated samples, representing a wide range of rainbow trout and steelhead populations, with 49 new samples added to 12 aquaculture samples from AquaGen (Norway) that we previously used for SNP discovery. Of the 49 new samples, 11 were double-haploid lines from Washington State University (WSU) and 38 represented wild and hatchery populations from a wide range of geographic distribution and with divergent migratory phenotypes. We then mapped the sequences to the new rainbow trout reference genome assembly (GCA_002163495.1) which is based on the Swanson YY doubled haploid line. Variant calling was conducted with FreeBayes and SAMtools mpileup , followed by filtering of SNPs based on quality score, sequence complexity, read depth on the locus, and number of genotyped samples. Results from the two variant calling programs were compared and genotypes of the double haploid samples were used for detecting and filtering putative paralogous sequence variants (PSVs) and multi-sequence variants (MSVs). Overall, 30,302,087 SNPs were identified on the rainbow trout genome 29 chromosomes and 1,139,018 on unplaced scaffolds, with 4,042,723 SNPs having high minor allele frequency (MAF > 0.25). The average SNP density on the chromosomes was one SNP per 64 bp, or 15.6 SNPs per 1 kb. Results from the phylogenetic analysis that we conducted indicate that the SNP markers contain enough population-specific polymorphisms for recovering population relationships despite the small sample size used. Intra-Population polymorphism assessment revealed high level of polymorphism and heterozygosity within each population. We also provide functional annotation based on the genome position of each SNP and evaluate the use of clonal lines for filtering of PSVs and MSVs. These SNPs form a new database, which provides an important resource for a new high density SNP array design and for other SNP genotyping platforms used for genetic and genomics studies of this iconic salmonid fish species.

Characterization of polyploid wheat genomic diversity using a high-density 90 000 single nucleotide polymorphism array

USDA-ARS?s Scientific Manuscript database

High-density single nucleotide polymorphism (SNP) genotyping chips are a powerful tool for studying genomic patterns of diversity, inferring ancestral relationships among individuals in populations and studying marker-trait associations in mapping experiments. We developed a genotyping array includ...

Design and characterization of a 52K SNP chip for goats.

PubMed

Tosser-Klopp, Gwenola; Bardou, Philippe; Bouchez, Olivier; Cabau, Cédric; Crooijmans, Richard; Dong, Yang; Donnadieu-Tonon, Cécile; Eggen, André; Heuven, Henri C M; Jamli, Saadiah; Jiken, Abdullah Johari; Klopp, Christophe; Lawley, Cynthia T; McEwan, John; Martin, Patrice; Moreno, Carole R; Mulsant, Philippe; Nabihoudine, Ibouniyamine; Pailhoux, Eric; Palhière, Isabelle; Rupp, Rachel; Sarry, Julien; Sayre, Brian L; Tircazes, Aurélie; Jun Wang; Wang, Wen; Zhang, Wenguang

2014-01-01

The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50-60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years.

Design and Characterization of a 52K SNP Chip for Goats

PubMed Central

Tosser-Klopp, Gwenola; Bardou, Philippe; Bouchez, Olivier; Cabau, Cédric; Crooijmans, Richard; Dong, Yang; Donnadieu-Tonon, Cécile; Eggen, André; Heuven, Henri C. M.; Jamli, Saadiah; Jiken, Abdullah Johari; Klopp, Christophe; Lawley, Cynthia T.; McEwan, John; Martin, Patrice; Moreno, Carole R.; Mulsant, Philippe; Nabihoudine, Ibouniyamine; Pailhoux, Eric; Palhière, Isabelle; Rupp, Rachel; Sarry, Julien; Sayre, Brian L.; Tircazes, Aurélie; Jun Wang; Wang, Wen; Zhang, Wenguang

2014-01-01

The success of Genome Wide Association Studies in the discovery of sequence variation linked to complex traits in humans has increased interest in high throughput SNP genotyping assays in livestock species. Primary goals are QTL detection and genomic selection. The purpose here was design of a 50–60,000 SNP chip for goats. The success of a moderate density SNP assay depends on reliable bioinformatic SNP detection procedures, the technological success rate of the SNP design, even spacing of SNPs on the genome and selection of Minor Allele Frequencies (MAF) suitable to use in diverse breeds. Through the federation of three SNP discovery projects consolidated as the International Goat Genome Consortium, we have identified approximately twelve million high quality SNP variants in the goat genome stored in a database together with their biological and technical characteristics. These SNPs were identified within and between six breeds (meat, milk and mixed): Alpine, Boer, Creole, Katjang, Saanen and Savanna, comprising a total of 97 animals. Whole genome and Reduced Representation Library sequences were aligned on >10 kb scaffolds of the de novo goat genome assembly. The 60,000 selected SNPs, evenly spaced on the goat genome, were submitted for oligo manufacturing (Illumina, Inc) and published in dbSNP along with flanking sequences and map position on goat assemblies (i.e. scaffolds and pseudo-chromosomes), sheep genome V2 and cattle UMD3.1 assembly. Ten breeds were then used to validate the SNP content and 52,295 loci could be successfully genotyped and used to generate a final cluster file. The combined strategy of using mainly whole genome Next Generation Sequencing and mapping on a contig genome assembly, complemented with Illumina design tools proved to be efficient in producing this GoatSNP50 chip. Advances in use of molecular markers are expected to accelerate goat genomic studies in coming years. PMID:24465974

Breeding value prediction for production traits in layer chickens using pedigree or genomic relationships in a reduced animal model.

PubMed

Wolc, Anna; Stricker, Chris; Arango, Jesus; Settar, Petek; Fulton, Janet E; O'Sullivan, Neil P; Preisinger, Rudolf; Habier, David; Fernando, Rohan; Garrick, Dorian J; Lamont, Susan J; Dekkers, Jack C M

2011-01-21

Genomic selection involves breeding value estimation of selection candidates based on high-density SNP genotypes. To quantify the potential benefit of genomic selection, accuracies of estimated breeding values (EBV) obtained with different methods using pedigree or high-density SNP genotypes were evaluated and compared in a commercial layer chicken breeding line. The following traits were analyzed: egg production, egg weight, egg color, shell strength, age at sexual maturity, body weight, albumen height, and yolk weight. Predictions appropriate for early or late selection were compared. A total of 2,708 birds were genotyped for 23,356 segregating SNP, including 1,563 females with records. Phenotypes on relatives without genotypes were incorporated in the analysis (in total 13,049 production records).The data were analyzed with a Reduced Animal Model using a relationship matrix based on pedigree data or on marker genotypes and with a Bayesian method using model averaging. Using a validation set that consisted of individuals from the generation following training, these methods were compared by correlating EBV with phenotypes corrected for fixed effects, selecting the top 30 individuals based on EBV and evaluating their mean phenotype, and by regressing phenotypes on EBV. Using high-density SNP genotypes increased accuracies of EBV up to two-fold for selection at an early age and by up to 88% for selection at a later age. Accuracy increases at an early age can be mostly attributed to improved estimates of parental EBV for shell quality and egg production, while for other egg quality traits it is mostly due to improved estimates of Mendelian sampling effects. A relatively small number of markers was sufficient to explain most of the genetic variation for egg weight and body weight.

Evaluation of ERα and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women.

PubMed

Kurt, Ozlem; Yilmaz-Aydogan, Hulya; Uyar, Mehmet; Isbir, Turgay; Seyhan, Mehmet Fatih; Can, Ayse

2012-06-01

It has been suggested that the estrogen receptor alpha (ERα) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERα PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERα (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERα PvuII "PP" and ERα XbaI "XX" genotypes than in those with "Pp/pp" genotypes and "xx" genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI "FF" genotype had lower BMD values of femoral neck and total hip compared to those with "Ff" genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI "FF" genotypes, BMI ≤ 27.5, age ≥ 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERα PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women.

SNP Data Quality Control in a National Beef and Dairy Cattle System and Highly Accurate SNP Based Parentage Verification and Identification

PubMed Central

McClure, Matthew C.; McCarthy, John; Flynn, Paul; McClure, Jennifer C.; Dair, Emma; O'Connell, D. K.; Kearney, John F.

2018-01-01

A major use of genetic data is parentage verification and identification as inaccurate pedigrees negatively affect genetic gain. Since 2012 the international standard for single nucleotide polymorphism (SNP) verification in Bos taurus cattle has been the ISAG SNP panels. While these ISAG panels provide an increased level of parentage accuracy over microsatellite markers (MS), they can validate the wrong parent at ≤1% misconcordance rate levels, indicating that more SNP are needed if a more accurate pedigree is required. With rapidly increasing numbers of cattle being genotyped in Ireland that represent 61 B. taurus breeds from a wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred, and large to small herd size the Irish Cattle Breeding Federation (ICBF) analyzed different SNP densities to determine that at a minimum ≥500 SNP are needed to consistently predict only one set of parents at a ≤1% misconcordance rate. For parentage validation and prediction ICBF uses 800 SNP (ICBF800) selected based on SNP clustering quality, ISAG200 inclusion, call rate (CR), and minor allele frequency (MAF) in the Irish cattle population. Large datasets require sample and SNP quality control (QC). Most publications only deal with SNP QC via CR, MAF, parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We report here parentage, SNP QC, and a genomic sample QC pipelines to deal with the unique challenges of >1 million genotypes from a national herd such as SNP genotype errors from mis-tagging of animals, lab errors, farm errors, and multiple other issues that can arise. We divide the pipeline into two parts: a Genotype QC and an Animal QC pipeline. The Genotype QC identifies samples with low call rate, missing or mixed genotype classes (no BB genotype or ABTG alleles present), and low genotype frequencies. The Animal QC handles situations where the genotype might not belong to the listed individual by identifying: >1 non-matching genotypes per animal, SNP duplicates, sex and breed prediction mismatches, parentage and progeny validation results, and other situations. The Animal QC pipeline make use of ICBF800 SNP set where appropriate to identify errors in a computationally efficient yet still highly accurate method. PMID:29599798

Dissecting tocopherols content in maize (Zea mays L.), using two segregating populations and high-density single nucleotide polymorphism markers

PubMed Central

2012-01-01

Background Tocopherols, which are vitamin E compounds, play an important role in maintaining human health. Compared with other staple foods, maize grains contain high level of tocopherols. Results Two F2 populations (K22/CI7 and K22/Dan340, referred to as POP-1 and POP-2, respectively), which share a common parent (K22), were developed and genotyped using a GoldenGate assay containing 1,536 single nucleotide polymorphism (SNP) markers. An integrated genetic linkage map was constructed using 619 SNP markers, spanning a total of 1649.03 cM of the maize genome with an average interval of 2.67 cM. Seventeen quantitative trait loci (QTLs) for all the traits were detected in the first map and 13 in the second. In these two maps, QTLs for different traits were localized to the same genomic regions and some were co-located with candidate genes in the tocopherol biosynthesis pathway. Single QTL was responsible for 3.03% to 52.75% of the phenotypic variation and the QTLs in sum explained23.4% to 66.52% of the total phenotypic variation. A major QTL (qc5-1/qd5-1) affecting α-tocopherol (αT) was identified on chromosome 5 between the PZA03161.1 and PZA02068.1 in the POP-2. The QTL region was narrowed down from 18.7 Mb to 5.4 Mb by estimating the recombination using high-density markers of the QTL region. This allowed the identification of the candidate gene VTE4 which encodes γ-tocopherol methyltransferase, an enzyme that transforms γ-tocopherol (γT)to αT. Conclusions These results demonstrate that a few QTLs with major effects and several QTLs with medium to minor effects might contribute to the natural variation of tocopherols in maize grain. The high-density markers will help to fine map and identify the QTLs with major effects even in the preliminary segregating populations. Furthermore, this study provides a simple guide line for the breeders to improve traits that minimize the risk of malnutrition, especially in developing countries. PMID:23122295

KinSNP software for homozygosity mapping of disease genes using SNP microarrays.

PubMed

Amir, El-Ad David; Bartal, Ofer; Morad, Efrat; Nagar, Tal; Sheynin, Jony; Parvari, Ruti; Chalifa-Caspi, Vered

2010-08-01

Consanguineous families affected with a recessive genetic disease caused by homozygotisation of a mutation offer a unique advantage for positional cloning of rare diseases. Homozygosity mapping of patient genotypes is a powerful technique for the identification of the genomic locus harbouring the causing mutation. This strategy relies on the observation that in these patients a large region spanning the disease locus is also homozygous with high probability. The high marker density in single nucleotide polymorphism (SNP) arrays is extremely advantageous for homozygosity mapping. We present KinSNP, a user-friendly software tool for homozygosity mapping using SNP arrays. The software searches for stretches of SNPs which are homozygous to the same allele in all ascertained sick individuals. User-specified parameters control the number of allowed genotyping 'errors' within homozygous blocks. Candidate disease regions are then reported in a detailed, coloured Excel file, along with genotypes of family members and healthy controls. An interactive genome browser has been included which shows homozygous blocks, individual genotypes, genes and further annotations along the chromosomes, with zooming and scrolling capabilities. The software has been used to identify the location of a mutated gene causing insensitivity to pain in a large Bedouin family. KinSNP is freely available from.

Association between ABCG1 polymorphism rs1893590 and high-density lipoprotein (HDL) in an asymptomatic Brazilian population.

PubMed

Zago, V H S; Scherrer, D Z; Parra, E S; Panzoldo, N B; Alexandre, F; Nakandakare, E R; Quintão, E C R; de Faria, E C

2015-03-01

ATP binding cassette transporter G1 (ABCG1) promotes lipidation of nascent high-density lipoprotein (HDL) particles, acting as an intracellular transporter. SNP rs1893590 (c.-204A > C) of ABCG1 gene has been previously studied and reported as functional over plasma HDL-C and lipoprotein lipase activity. This study aimed to investigate the relationships of SNP rs1893590 with plasma lipids and lipoproteins in a large Brazilian population. Were selected 654 asymptomatic and normolipidemic volunteers from both genders. Clinical and anthropometrical data were taken and blood samples were drawn after 12 h fasting. Plasma lipids and lipoproteins, as well as HDL particle size and volume were determined. Genomic DNA was isolated for SNP rs1893590 detection by TaqMan(®) OpenArray(®) Real-Time PCR Plataform (Applied Biosystems). Mann-Whitney U, Chi square and two-way ANOVA were the used statistical tests. No significant differences were found in the comparison analyses between the allele groups for all studied parameters. Conversely, significant interactions were observed between SNP and age over plasma HDL-C, were volunteers under 60 years with AA genotype had increased HDL-C (p = 0.048). Similar results were observed in the group with body mass index (BMI) < 25 kg/m(2), where volunteers with AA genotype had higher HDL-C levels (p = 0.0034), plus an increased HDL particle size (p = 0.01). These findings indicate that SNP rs1893590 of ABCG1 has a significant impact over HDL-C under asymptomatic clinical conditions in an age and BMI dependent way.

Use of partial least squares regression to impute SNP genotypes in Italian cattle breeds.

PubMed

Dimauro, Corrado; Cellesi, Massimo; Gaspa, Giustino; Ajmone-Marsan, Paolo; Steri, Roberto; Marras, Gabriele; Macciotta, Nicolò P P

2013-06-05

The objective of the present study was to test the ability of the partial least squares regression technique to impute genotypes from low density single nucleotide polymorphisms (SNP) panels i.e. 3K or 7K to a high density panel with 50K SNP. No pedigree information was used. Data consisted of 2093 Holstein, 749 Brown Swiss and 479 Simmental bulls genotyped with the Illumina 50K Beadchip. First, a single-breed approach was applied by using only data from Holstein animals. Then, to enlarge the training population, data from the three breeds were combined and a multi-breed analysis was performed. Accuracies of genotypes imputed using the partial least squares regression method were compared with those obtained by using the Beagle software. The impact of genotype imputation on breeding value prediction was evaluated for milk yield, fat content and protein content. In the single-breed approach, the accuracy of imputation using partial least squares regression was around 90 and 94% for the 3K and 7K platforms, respectively; corresponding accuracies obtained with Beagle were around 85% and 90%. Moreover, computing time required by the partial least squares regression method was on average around 10 times lower than computing time required by Beagle. Using the partial least squares regression method in the multi-breed resulted in lower imputation accuracies than using single-breed data. The impact of the SNP-genotype imputation on the accuracy of direct genomic breeding values was small. The correlation between estimates of genetic merit obtained by using imputed versus actual genotypes was around 0.96 for the 7K chip. Results of the present work suggested that the partial least squares regression imputation method could be useful to impute SNP genotypes when pedigree information is not available.

The impact of training strategies on the accuracy of genomic predictors in United States Red Angus cattle.

PubMed

Lee, J; Kachman, S D; Spangler, M L

2017-08-01

Genomic selection (GS) has become an integral part of genetic evaluation methodology and has been applied to all major livestock species, including beef and dairy cattle, pigs, and chickens. Significant contributions in increased accuracy of selection decisions have been clearly illustrated in dairy cattle after practical application of GS. In the majority of U.S. beef cattle breeds, similar efforts have also been made to increase the accuracy of genetic merit estimates through the inclusion of genomic information into routine genetic evaluations using a variety of methods. However, prediction accuracies can vary relative to panel density, the number of folds used for folds cross-validation, and the choice of dependent variables (e.g., EBV, deregressed EBV, adjusted phenotypes). The aim of this study was to evaluate the accuracy of genomic predictors for Red Angus beef cattle with different strategies used in training and evaluation. The reference population consisted of 9,776 Red Angus animals whose genotypes were imputed to 2 medium-density panels consisting of over 50,000 (50K) and approximately 80,000 (80K) SNP. Using the imputed panels, we determined the influence of marker density, exclusion (deregressed EPD adjusting for parental information [DEPD-PA]) or inclusion (deregressed EPD without adjusting for parental information [DEPD]) of parental information in the deregressed EPD used as the dependent variable, and the number of clusters used to partition training animals (3, 5, or 10). A BayesC model with π set to 0.99 was used to predict molecular breeding values (MBV) for 13 traits for which EPD existed. The prediction accuracies were measured as genetic correlations between MBV and weighted deregressed EPD. The average accuracies across all traits were 0.540 and 0.552 when using the 50K and 80K SNP panels, respectively, and 0.538, 0.541, and 0.561 when using 3, 5, and 10 folds, respectively, for cross-validation. Using DEPD-PA as the response variable resulted in higher accuracies of MBV than those obtained by DEPD for growth and carcass traits. When DEPD were used as the response variable, accuracies were greater for threshold traits and those that are sex limited, likely due to the fact that these traits suffer from a lack of information content and excluding animals in training with only parental information substantially decreases the training population size. It is recommended that the contribution of parental average to deregressed EPD should be removed in the construction of genomic prediction equations. The difference in terms of prediction accuracies between the 2 SNP panels or the number of folds compared herein was negligible.

Mechanism of S100b release from rat cortical slices determined under basal and stimulated conditions.

PubMed

Gürsoy, Murat; Büyükuysal, R Levent

2010-03-01

Incubation of rat cortical slices in a medium that was not containing oxygen and glucose (oxygen-glucose deprivation, OGD) caused a 200% increase in the release of S100B. However, when slices were transferred to a medium containing oxygen and glucose (reoxygenation conditions, or REO), S100B release reached 500% of its control value. Neither inhibition of nitric oxide (NO) synthase by L-NAME nor addition of the NO donors sodium nitroprussid (SNP) or hydroxylamine (HA) to the medium altered basal S100B release. Similarly, the presence of SNP, HA or NO precursor L: -arginine in the medium, or inhibition of NO synthase by L-NAME also failed to alter OGD- and REO-induced S100B outputs. Moreover, individual inhibition of PKC, PLA(2) or PLC all failed to attenuate the S100B release determined under control condition or enhanced by either OGD or REO. Blockade of calcium channels with verapamil, chelating the Ca(+2) ions with BAPTA or blockade of sodium channels with tetrodotoxin (TTX) did not alter OGD- and REO-induced S100B release. In contrast to the pharmacologic manipulations mentioned above, glutamate and alpha-ketoglutarate added at high concentrations to the medium prevented both OGD- and REO-induced S100B outputs. These results indicate that neither NO nor the activation of PKC, PLA(2) or PLC seem to be involved in basal or OGD- and REO-induced S100B outputs. Additionally, calcium and sodium currents that are sensitive to verapamil and TTX, respectively, are unlikely to contribute to the enhanced S100B release observed under these conditions.

Genetics of Bone Mass in Childhood and Adolescence: Effects of Sex and Maturation Interactions.

PubMed

Mitchell, Jonathan A; Chesi, Alessandra; Elci, Okan; McCormack, Shana E; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Kelly, Andrea; Zemel, Babette S; Grant, Struan F A

2015-09-01

We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study (n = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between an SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex • SNP interaction, revealing a significant association only in females (b = -0.32, p = 1.8 × 10(-6)). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 × 10(-5)). In contrast, the sex • SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, p = 4.4 × 10(-4)) and distal radius aBMD (b = 0.27, p = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex • SNP interactions were found at 15 loci; pubertal stage • SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation. © 2015 American Society for Bone and Mineral Research.

Nitroprusside inhibits calcium-induced impairment of red blood cell deformability.

PubMed

Barodka, Viachaslau; Mohanty, Joy G; Mustafa, Asif K; Santhanam, Lakshmi; Nyhan, Aoibhinn; Bhunia, Anil K; Sikka, Gautam; Nyhan, Daniel; Berkowitz, Dan E; Rifkind, Joseph M

2014-02-01

Red blood cell (RBC) deformation is critical for microvascular perfusion and oxygen delivery to tissues. Abnormalities in RBC deformability have been observed in aging, sickle cell disease, diabetes, and preeclampsia. Although nitric oxide (NO) prevents decreases in RBC deformability, the underlying mechanism is unknown. As an experimental model, we used ionophore A23187-mediated calcium influx in RBCs to reduce their deformability and investigated the role of NO donor sodium nitroprusside (SNP) and KCa3.1 (Gardos) channel blockers on RBC deformability (measured as elongation index [EI] by microfluidic ektacytometry). RBC intracellular Ca(2+) and extracellular K(+) were measured by inductively coupled plasma mass spectrometry and potassium ion selective electrode, respectively. SNP treatment of RBCs blocked the Ca(2+) (approx. 10 μmol/L)-induced decrease in RBC deformability (EI 0.34 ± 0.02 vs. 0.09 ± 0.01, control vs. Ca(2+) loaded, p < 0.001; and EI 0.37 ± 0.02 vs. 0.30 ± 0.01, SNP vs. SNP plus Ca(2+) loaded) as well as Ca(2+) influx and K(+) efflux. The SNP effect was similar to that observed after pharmacologic blockade of the KCa3.1 channel (with charybdotoxin or extracellular medium containing isotonic K(+) concentration). In RBCs from KCa3.1(-/-) mice, 10 μmol/L Ca(2+) loading did not decrease cellular deformability. A preliminary attempt to address the molecular mechanism of SNP protection suggests the involvement of cell surface thiols. Our results suggest that nitroprusside treatment of RBCs may protect them from intracellular calcium increase-mediated stiffness, which may occur during microvascular perfusion in diseased states, as well as during RBC storage. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

A high-density, SNP-based consensus map of tetraploid wheat as a bridge to integrate durum and bread wheat genomics and breeding

USDA-ARS?s Scientific Manuscript database

Consensus linkage maps are important tools in crop genomics. We have assembled a high-density tetraploid wheat consensus map by integrating 13 datasets from independent biparental populations involving durum wheat cultivars (Triticum turgidum ssp. durum), cultivated emmer (T. turgidum ssp. dicoccum...

Design of a bovine low-density SNP array optimized for imputation

USDA-ARS?s Scientific Manuscript database

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where de...

Association of ADRB2 polymorphism with triglyceride levels in Tongans.

PubMed

Naka, Izumi; Ohashi, Jun; Kimura, Ryosuke; Inaoka, Tsukasa; Matsumura, Yasuhiro

2013-07-23

Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.

The contribution of individual and pairwise combinations of SNPs in the APOA1 and APOC3 genes to interindividual HDL-C variability.

PubMed

Brown, C M; Rea, T J; Hamon, S C; Hixson, J E; Boerwinkle, E; Clark, A G; Sing, C F

2006-07-01

Apolipoproteins (apo) A-I and C-III are components of high-density lipoprotein-cholesterol (HDL-C), a quantitative trait negatively correlated with risk of cardiovascular disease (CVD). We analyzed the contribution of individual and pairwise combinations of single nucleotide polymorphisms (SNPs) in the APOA1/APOC3 genes to HDL-C variability to evaluate (1) consistency of published single-SNP studies with our single-SNP analyses; (2) consistency of single-SNP and two-SNP phenotype-genotype relationships across race-, gender-, and geographical location-dependent contexts; and (3) the contribution of single SNPs and pairs of SNPs to variability beyond that explained by plasma apo A-I concentration. We analyzed 45 SNPs in 3,831 young African-American (N=1,858) and European-American (N=1,973) females and males ascertained by the Coronary Artery Risk Development in Young Adults (CARDIA) study. We found three SNPs that significantly impact HDL-C variability in both the literature and the CARDIA sample. Single-SNP analyses identified only one of five significant HDL-C SNP genotype relationships in the CARDIA study that was consistent across all race-, gender-, and geographical location-dependent contexts. The other four were consistent across geographical locations for a particular race-gender context. The portion of total phenotypic variance explained by single-SNP genotypes and genotypes defined by pairs of SNPs was less than 3%, an amount that is miniscule compared to the contribution explained by variability in plasma apo A-I concentration. Our findings illustrate the impact of context-dependence on SNP selection for prediction of CVD risk factor variability.

SNPchiMp v.3: integrating and standardizing single nucleotide polymorphism data for livestock species.

PubMed

Nicolazzi, Ezequiel L; Caprera, Andrea; Nazzicari, Nelson; Cozzi, Paolo; Strozzi, Francesco; Lawley, Cindy; Pirani, Ali; Soans, Chandrasen; Brew, Fiona; Jorjani, Hossein; Evans, Gary; Simpson, Barry; Tosser-Klopp, Gwenola; Brauning, Rudiger; Williams, John L; Stella, Alessandra

2015-04-10

In recent years, the use of genomic information in livestock species for genetic improvement, association studies and many other fields has become routine. In order to accommodate different market requirements in terms of genotyping cost, manufacturers of single nucleotide polymorphism (SNP) arrays, private companies and international consortia have developed a large number of arrays with different content and different SNP density. The number of currently available SNP arrays differs among species: ranging from one for goats to more than ten for cattle, and the number of arrays available is increasing rapidly. However, there is limited or no effort to standardize and integrate array- specific (e.g. SNP IDs, allele coding) and species-specific (i.e. past and current assemblies) SNP information. Here we present SNPchiMp v.3, a solution to these issues for the six major livestock species (cow, pig, horse, sheep, goat and chicken). Original data was collected directly from SNP array producers and specific international genome consortia, and stored in a MySQL database. The database was then linked to an open-access web tool and to public databases. SNPchiMp v.3 ensures fast access to the database (retrieving within/across SNP array data) and the possibility of annotating SNP array data in a user-friendly fashion. This platform allows easy integration and standardization, and it is aimed at both industry and research. It also enables users to easily link the information available from the array producer with data in public databases, without the need of additional bioinformatics tools or pipelines. In recognition of the open-access use of Ensembl resources, SNPchiMp v.3 was officially credited as an Ensembl E!mpowered tool. Availability at http://bioinformatics.tecnoparco.org/SNPchimp.

Pharmacogenetics.

PubMed

Roses, A D

2001-10-01

Pharmacogenetics is the variability of drug response due to inherited characteristics in individuals. Drug metabolizing enzymes have been studied for decades, first as chemical reactions and, more recently, as specific polymorphisms of known molecules. With the availability of whole-genome single-nucleotide polymorphism (SNP) maps, it will soon be possible to create an SNP profile for patients who experience adverse events (AEs) or who respond clinically to the medicine (efficacy). Proof-of-principle experiments have demonstrated that high density SNP maps in chromosomal regions of genetic linkage facilitate the identification of susceptibility disease genes. Whole-genome SNP mapping analyses aimed at determining linkage disequilibrium (LD) profiles along an ordered human genome backbone are in progress. SNP 'fingerprints' or SNP PRINTs(sm) will be used to identify patients at greater risk of an AE, or those patients with a greater chance of responding to a medicine. As LD maps for various ethnic populations are constructed, the number of SNPs necessary to measure for an individual will decrease. Standardized pharmacogenetic maps for drug registration and post-marketing surveillance will result in safer, more effective and more cost-efficient medicines. The timing of these pharmacogenetic applications will occur over the next 5 years. In contrast, the benefits of pharmacogenomic applications such as the identification of new tractable targets will not be visible as new medicines for 7-12 years, due to the lengthy drug development and registration processes.

Enhancing the stability of colloidal silver nanoparticles using polyhydroxyalkanoates (PHA) from Bacillus circulans (MTCC 8167) isolated from crude oil contaminated soil.

PubMed

Phukon, Pinkee; Saikia, Jyoti Prasad; Konwar, Bolin Kumar

2011-09-01

Polyhydroxyalkanoate (PHA) was produced by growing Bacillus circulans (MTCC 8167) in the specific detection medium. The identification of the polymer as PHA was confirmed by fluorescence microscopy. The PHA was purified and characterized using FT-IR. The silver nanoparticles (SNP) were synthesized from AgNO3 in the dispersed colloids of PHA (0.085%) using NaBH4 (sodium borohydrate as reducing agent). The stability was tested using wave length scanning with a UV-Vis spectrophotometer and finally with transmission electron microscopy. The PHA stabilized solution was found to be stable for 30 days as against the low stability of silver nanoparticles (SNP) solution alone. Copyright © 2011 Elsevier B.V. All rights reserved.

Assumption-free estimation of the genetic contribution to refractive error across childhood.

PubMed

Guggenheim, Jeremy A; St Pourcain, Beate; McMahon, George; Timpson, Nicholas J; Evans, David M; Williams, Cathy

2015-01-01

Studies in relatives have generally yielded high heritability estimates for refractive error: twins 75-90%, families 15-70%. However, because related individuals often share a common environment, these estimates are inflated (via misallocation of unique/common environment variance). We calculated a lower-bound heritability estimate for refractive error free from such bias. Between the ages 7 and 15 years, participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent non-cycloplegic autorefraction at regular research clinics. At each age, an estimate of the variance in refractive error explained by single nucleotide polymorphism (SNP) genetic variants was calculated using genome-wide complex trait analysis (GCTA) using high-density genome-wide SNP genotype information (minimum N at each age=3,404). The variance in refractive error explained by the SNPs ("SNP heritability") was stable over childhood: Across age 7-15 years, SNP heritability averaged 0.28 (SE=0.08, p<0.001). The genetic correlation for refractive error between visits varied from 0.77 to 1.00 (all p<0.001) demonstrating that a common set of SNPs was responsible for the genetic contribution to refractive error across this period of childhood. Simulations suggested lack of cycloplegia during autorefraction led to a small underestimation of SNP heritability (adjusted SNP heritability=0.35; SE=0.09). To put these results in context, the variance in refractive error explained (or predicted) by the time participants spent outdoors was <0.005 and by the time spent reading was <0.01, based on a parental questionnaire completed when the child was aged 8-9 years old. Genetic variation captured by common SNPs explained approximately 35% of the variation in refractive error between unrelated subjects. This value sets an upper limit for predicting refractive error using existing SNP genotyping arrays, although higher-density genotyping in larger samples and inclusion of interaction effects is expected to raise this figure toward twin- and family-based heritability estimates. The same SNPs influenced refractive error across much of childhood. Notwithstanding the strong evidence of association between time outdoors and myopia, and time reading and myopia, less than 1% of the variance in myopia at age 15 was explained by crude measures of these two risk factors, indicating that their effects may be limited, at least when averaged over the whole population.

Development of a 63K SNP array for Gossypium and high-density mapping of intra- and inter-specific populations of cotton (G. hirsutum L.)

USDA-ARS?s Scientific Manuscript database

High-throughput genotyping arrays provide a standardized resource for crop research communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), candidate marker and quantitative trait loci (QTL) ide...

Development and evaluation of a high density genotyping 'Axiom_Arachis' array with 58K SNPs for accelerating genetics and breeding in groundnut

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are the most abundant DNA sequence variation in the genomes which can be used to associate genotypic variation to the phenotype. Therefore, availability of a high-density SNP array with uniform genome coverage can advance genetic studies and breeding applicatio...

Sn4+x P3 @ amorphous Sn-P composites as anodes for sodium-ion batteries with low cost, high capacity, long life, and superior rate capability.

PubMed

Li, Weijie; Chou, Shu-Lei; Wang, Jia-Zhao; Kim, Jung Ho; Liu, Hua-Kun; Dou, Shi-Xue

2014-06-25

Sn4+x P3 @ amorphous Sn-P composites are a promising cheap anode material for sodium-ion batteries with high capacity (502 mA h g(-1) at a current density of 100 mA g(-1)), long cycling stability (92.6% capacity retention up to 100 cycles), and high rate capability (165 mA h g(-1) at the 10C rate). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High Density Single Nucleotide Polymorphism (SNP) Mapping and Quantitative Trait Loci (QTL) Analysis in a Biparental Spring Triticale Population Localized Major and Minor Effect Fusarium Head Blight Resistance and Associated Traits QTL

PubMed Central

Dhariwal, Raman; Fedak, George; Dion, Yves; Pozniak, Curtis; Laroche, André; Eudes, François; Randhawa, Harpinder Singh

2018-01-01

Triticale (xTriticosecale Wittmack) is an important feed crop which suffers severe yield, grade and end-use quality losses due to Fusarium head blight (FHB). Development of resistant triticale cultivars is hindered by lack of effective genetic resistance sources. To dissect FHB resistance, a doubled haploid spring triticale population produced from the cross TMP16315/AC Ultima using a microspore culture method, was phenotyped for FHB incidence, severity, visual rating index (VRI), deoxynivalenol (DON) and some associated traits (ergot, grain protein content, test weight, yield, plant height and lodging) followed by single nucleotide polymorphism (SNP) genotyping. A high-density map consisting of 5274 SNPs, mapped on all 21 chromosomes with a map density of 0.48 cM/SNP, was constructed. Together, 17 major quantitative trait loci were identified for FHB on chromosomes 1A, 2B, 3A, 4A, 4R, 5A, 5R and 6B; two of incidence loci (on 2B and 5R) also co-located with loci for severity and VRI, and two other loci of VRI (on 1A and 4R) with DON accumulation. Major and minor loci were also identified for all other traits in addition to many epistasis loci. This study provides new insight into the genetic basis of FHB resistance and their association with other traits in triticale. PMID:29304028

Effect of the medium's density on the hydrocyclonic separation of waste plastics with different densities.

PubMed

Fu, Shuangcheng; Fang, Yong; Yuan, Huixin; Tan, Wanjiang; Dong, Yiwen

2017-09-01

Hydrocyclones can be applied to recycle waste plastics with different densities through separating plastics based on their differences in densities. In the process, the medium density is one of key parameters and the value of the medium's density is not just the average of the density of two kinds of plastics separated. Based on the force analysis and establishing the equation of motion of particles in the hydrocyclone, a formula to calculate the optimum separation medium density has been deduced. This value of the medium's density is a function of various parameters including the diameter, density, radial position and tangential velocity of particles, and viscosity of the medium. Tests on the separation performance of the hydrocyclone has been conducted with PET and PVC particles. The theoretical result appeared to be in good agreement with experimental results. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-throughput SNP genotyping in the highly heterozygous genome of Eucalyptus: assay success, polymorphism and transferability across species

PubMed Central

2011-01-01

Background High-throughput SNP genotyping has become an essential requirement for molecular breeding and population genomics studies in plant species. Large scale SNP developments have been reported for several mainstream crops. A growing interest now exists to expand the speed and resolution of genetic analysis to outbred species with highly heterozygous genomes. When nucleotide diversity is high, a refined diagnosis of the target SNP sequence context is needed to convert queried SNPs into high-quality genotypes using the Golden Gate Genotyping Technology (GGGT). This issue becomes exacerbated when attempting to transfer SNPs across species, a scarcely explored topic in plants, and likely to become significant for population genomics and inter specific breeding applications in less domesticated and less funded plant genera. Results We have successfully developed the first set of 768 SNPs assayed by the GGGT for the highly heterozygous genome of Eucalyptus from a mixed Sanger/454 database with 1,164,695 ESTs and the preliminary 4.5X draft genome sequence for E. grandis. A systematic assessment of in silico SNP filtering requirements showed that stringent constraints on the SNP surrounding sequences have a significant impact on SNP genotyping performance and polymorphism. SNP assay success was high for the 288 SNPs selected with more rigorous in silico constraints; 93% of them provided high quality genotype calls and 71% of them were polymorphic in a diverse panel of 96 individuals of five different species. SNP reliability was high across nine Eucalyptus species belonging to three sections within subgenus Symphomyrtus and still satisfactory across species of two additional subgenera, although polymorphism declined as phylogenetic distance increased. Conclusions This study indicates that the GGGT performs well both within and across species of Eucalyptus notwithstanding its nucleotide diversity ≥2%. The development of a much larger array of informative SNPs across multiple Eucalyptus species is feasible, although strongly dependent on having a representative and sufficiently deep collection of sequences from many individuals of each target species. A higher density SNP platform will be instrumental to undertake genome-wide phylogenetic and population genomics studies and to implement molecular breeding by Genomic Selection in Eucalyptus. PMID:21492434

The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

PubMed

Steinbacher, Peter; Feichtinger, René G; Kedenko, Lyudmyla; Kedenko, Igor; Reinhardt, Sandra; Schönauer, Anna-Lena; Leitner, Isabella; Sänger, Alexandra M; Stoiber, Walter; Kofler, Barbara; Förster, Holger; Paulweber, Bernhard; Ring-Dimitriou, Susanne

2015-01-01

PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

Rs219780 SNP of Claudin 14 Gene is not Related to Clinical Expression in Primary Hyperparathyroidism.

PubMed

Piedra, María; Berja, Ana; García-Unzueta, María Teresa; Ramos, Laura; Valero, Carmen; Amado, José Antonio

2015-01-01

The CLDN14 gene encodes a protein involved in the regulation of paracellular permeability or ion transport at epithelial tight junctions as in the nephron. The C allele of the rs219780 SNP (single nucleotide polymorphism) of CLDN14 has been associated with renal lithiasis, high levels of parathormone (PTH), and with low bone mineral density (BMD) in healthy women. Our aim is to study the relationship between rs219780 SNP of CLDN14 and renal lithiasis, fractures, and BMD in patients with primary hyperparathyroidism (PHPT). We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analysed anthropometric data, history of fractures or kidney stones, biochemical parameters including markers for bone remodelling, abdominal ultrasound, and BMD and genotyping for the rs219780 SNP of CLDN14. We did not find any difference in the frequency of fractures or renal lithiasis between the genotype groups in PHPT patients. Moreover, we did not find any relationship between the T or C alleles and BMD or biochemical parameters. rs219780 SNP of CLDN14 does not appear to be a risk factor for the development of PHPT nor does it seem to influence the clinical expression of PHPT.

The Single Nucleotide Polymorphism Gly482Ser in the PGC-1α Gene Impairs Exercise-Induced Slow-Twitch Muscle Fibre Transformation in Humans

PubMed Central

Steinbacher, Peter; Feichtinger, René G.; Kedenko, Lyudmyla; Kedenko, Igor; Reinhardt, Sandra; Schönauer, Anna-Lena; Leitner, Isabella; Sänger, Alexandra M.; Stoiber, Walter; Kofler, Barbara; Förster, Holger; Paulweber, Bernhard; Ring-Dimitriou, Susanne

2015-01-01

PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation. PMID:25886402

Common genetic variation and novel loci associated with volumetric mammographic density.

PubMed

Brand, Judith S; Humphreys, Keith; Li, Jingmei; Karlsson, Robert; Hall, Per; Czene, Kamila

2018-04-17

Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h 2 SNP ]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P < 5 × 10 - 8 ): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h 2 SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h 2 SNP to previously observed narrow-sense h 2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h 2 SNP /h 2 ratios varying between dense and nondense MD components.

Genome-wide SNP identification and QTL mapping for black rot resistance in cabbage.

PubMed

Lee, Jonghoon; Izzah, Nur Kholilatul; Jayakodi, Murukarthick; Perumal, Sampath; Joh, Ho Jun; Lee, Hyeon Ju; Lee, Sang-Choon; Park, Jee Young; Yang, Ki-Woung; Nou, Il-Sup; Seo, Joodeok; Yoo, Jaeheung; Suh, Youngdeok; Ahn, Kyounggu; Lee, Ji Hyun; Choi, Gyung Ja; Yu, Yeisoo; Kim, Heebal; Yang, Tae-Jin

2015-02-03

Black rot is a destructive bacterial disease causing large yield and quality losses in Brassica oleracea. To detect quantitative trait loci (QTL) for black rot resistance, we performed whole-genome resequencing of two cabbage parental lines and genome-wide SNP identification using the recently published B. oleracea genome sequences as reference. Approximately 11.5 Gb of sequencing data was produced from each parental line. Reference genome-guided mapping and SNP calling revealed 674,521 SNPs between the two cabbage lines, with an average of one SNP per 662.5 bp. Among 167 dCAPS markers derived from candidate SNPs, 117 (70.1%) were validated as bona fide SNPs showing polymorphism between the parental lines. We then improved the resolution of a previous genetic map by adding 103 markers including 87 SNP-based dCAPS markers. The new map composed of 368 markers and covers 1467.3 cM with an average interval of 3.88 cM between adjacent markers. We evaluated black rot resistance in the mapping population in three independent inoculation tests using F2:3 progenies and identified one major QTL and three minor QTLs. We report successful utilization of whole-genome resequencing for large-scale SNP identification and development of molecular markers for genetic map construction. In addition, we identified novel QTLs for black rot resistance. The high-density genetic map will promote QTL analysis for other important agricultural traits and marker-assisted breeding of B. oleracea.

Identification of Pyrus single nucleotide polymorphisms (SNPs) and evaluation for genetic mapping in European pear and interspecific Pyrus hybrids.

PubMed

Montanari, Sara; Saeed, Munazza; Knäbel, Mareike; Kim, YoonKyeong; Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E; Crowhurst, Ross N; Chagné, David

2013-01-01

We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear ('Old Home'×'Louise Bon Jersey') and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality.

Materials Data on SnP (SG:107) by Materials Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristin Persson

2016-07-14

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on SnP (SG:225) by Materials Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristin Persson

2016-04-23

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

A high density linkage map of the ancestral diploid strawberry F. iinumae using SNP markers from the ISTRAW90 array and GBS

USDA-ARS?s Scientific Manuscript database

Fragaria iinumae is recognized as an ancestor of the octoploid strawberry species, including the cultivated strawberry, Fragaria ×ananassa. Here we report the construction of the first high density linkage map for F. iinumae. The map is based on two high-throughput techniques of single nucleotide p...

Association of ADRB2 polymorphism with triglyceride levels in Tongans

PubMed Central

2013-01-01

Background Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. Methods To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. Results A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index. PMID:23875540

Development and dissection of diagnostic SNP markers for the downy mildew resistance genes Pl Arg and Pl 8 and maker-assisted gene pyramiding in sunflower (Helianthus annuus L.).

PubMed

Qi, L L; Talukder, Z I; Hulke, B S; Foley, M E

2017-06-01

Diagnostic DNA markers are an invaluable resource in breeding programs for successful introgression and pyramiding of disease resistance genes. Resistance to downy mildew (DM) disease in sunflower is mediated by Pl genes which are known to be effective against the causal fungus, Plasmopara halstedii. Two DM resistance genes, Pl Arg and Pl 8 , are highly effective against P. halstedii races in the USA, and have been previously mapped to the sunflower linkage groups (LGs) 1 and 13, respectively, using simple sequence repeat (SSR) markers. In this study, we developed high-density single nucleotide polymorphism (SNP) maps encompassing the Pl arg and Pl 8 genes and identified diagnostic SNP markers closely linked to these genes. The specificity of the diagnostic markers was validated in a highly diverse panel of 548 sunflower lines. Dissection of a large marker cluster co-segregated with Pl Arg revealed that the closest SNP markers NSA_007595 and NSA_001835 delimited Pl Arg to an interval of 2.83 Mb on the LG1 physical map. The SNP markers SFW01497 and SFW06597 delimited Pl 8 to an interval of 2.85 Mb on the LG13 physical map. We also developed sunflower lines with homozygous, three gene pyramids carrying Pl Arg , Pl 8 , and the sunflower rust resistance gene R 12 using the linked SNP markers from a segregating F 2 population of RHA 340 (carrying Pl 8 )/RHA 464 (carrying Pl Arg and R 12 ). The high-throughput diagnostic SNP markers developed in this study will facilitate marker-assisted selection breeding, and the pyramided sunflower lines will provide durable resistance to downy mildew and rust diseases.

Genotype imputation in a tropical crossbred dairy cattle population.

PubMed

Oliveira Júnior, Gerson A; Chud, Tatiane C S; Ventura, Ricardo V; Garrick, Dorian J; Cole, John B; Munari, Danísio P; Ferraz, José B S; Mullart, Erik; DeNise, Sue; Smith, Shannon; da Silva, Marcos Vinícius G B

2017-12-01

The objective of this study was to investigate different strategies for genotype imputation in a population of crossbred Girolando (Gyr × Holstein) dairy cattle. The data set consisted of 478 Girolando, 583 Gyr, and 1,198 Holstein sires genotyped at high density with the Illumina BovineHD (Illumina, San Diego, CA) panel, which includes ∼777K markers. The accuracy of imputation from low (20K) and medium densities (50K and 70K) to the HD panel density and from low to 50K density were investigated. Seven scenarios using different reference populations (RPop) considering Girolando, Gyr, and Holstein breeds separately or combinations of animals of these breeds were tested for imputing genotypes of 166 randomly chosen Girolando animals. The population genotype imputation were performed using FImpute. Imputation accuracy was measured as the correlation between observed and imputed genotypes (CORR) and also as the proportion of genotypes that were imputed correctly (CR). This is the first paper on imputation accuracy in a Girolando population. The sample-specific imputation accuracies ranged from 0.38 to 0.97 (CORR) and from 0.49 to 0.96 (CR) imputing from low and medium densities to HD, and 0.41 to 0.95 (CORR) and from 0.50 to 0.94 (CR) for imputation from 20K to 50K. The CORR anim exceeded 0.96 (for 50K and 70K panels) when only Girolando animals were included in RPop (S1). We found smaller CORR anim when Gyr (S2) was used instead of Holstein (S3) as RPop. The same behavior was observed between S4 (Gyr + Girolando) and S5 (Holstein + Girolando) because the target animals were more related to the Holstein population than to the Gyr population. The highest imputation accuracies were observed for scenarios including Girolando animals in the reference population, whereas using only Gyr animals resulted in low imputation accuracies, suggesting that the haplotypes segregating in the Girolando population had a greater effect on accuracy than the purebred haplotypes. All chromosomes had similar imputation accuracies (CORR snp ) within each scenario. Crossbred animals (Girolando) must be included in the reference population to provide the best imputation accuracies. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Characterization of Insect Resistance Loci in the USDA Soybean Germplasm Collection Using Genome-Wide Association Studies

PubMed Central

Chang, Hao-Xun; Hartman, Glen L.

2017-01-01

Management of insects that cause economic damage to yields of soybean mainly rely on insecticide applications. Sources of resistance in soybean plant introductions (PIs) to different insect pests have been reported, and some of these sources, like for the soybean aphid (SBA), have been used to develop resistant soybean cultivars. With the availability of SoySNP50K and the statistical power of genome-wide association studies, we integrated phenotypic data for beet armyworm, Mexican bean beetle (MBB), potato leafhopper (PLH), SBA, soybean looper (SBL), velvetbean caterpillar (VBC), and chewing damage caused by unspecified insects for a comprehensive understanding of insect resistance in the United States Department of Agriculture Soybean Germplasm Collection. We identified significant single nucleotide (SNP) polymorphic markers for MBB, PLH, SBL, and VBC, and we highlighted several leucine-rich repeat-containing genes and myeloblastosis transcription factors within the high linkage disequilibrium region surrounding significant SNP markers. Specifically for soybean resistance to PLH, we found the PLH locus is close but distinct to a locus for soybean pubescence density on chromosome 12. The results provide genetic support that pubescence density may not directly link to PLH resistance. This study offers a novel insight of soybean resistance to four insect pests and reviews resistance mapping studies for major soybean insects. PMID:28555141

Parentage Reconstruction in Eucalyptus nitens Using SNPs and Microsatellite Markers: A Comparative Analysis of Marker Data Power and Robustness.

PubMed

Telfer, Emily J; Stovold, Grahame T; Li, Yongjun; Silva-Junior, Orzenil B; Grattapaglia, Dario G; Dungey, Heidi S

2015-01-01

Pedigree reconstruction using molecular markers enables efficient management of inbreeding in open-pollinated breeding strategies, replacing expensive and time-consuming controlled pollination. This is particularly useful in preferentially outcrossed, insect pollinated Eucalypts known to suffer considerable inbreeding depression from related matings. A single nucleotide polymorphism (SNP) marker panel consisting of 106 markers was selected for pedigree reconstruction from the recently developed high-density Eucalyptus Infinium SNP chip (EuCHIP60K). The performance of this SNP panel for pedigree reconstruction in open-pollinated progenies of two Eucalyptus nitens seed orchards was compared with that of two microsatellite panels with 13 and 16 markers respectively. The SNP marker panel out-performed one of the microsatellite panels in the resolution power to reconstruct pedigrees and out-performed both panels with respect to data quality. Parentage of all but one offspring in each clonal seed orchard was correctly matched to the expected seed parent using the SNP marker panel, whereas parentage assignment to less than a third of the expected seed parents were supported using the 13-microsatellite panel. The 16-microsatellite panel supported all but one of the recorded seed parents, one better than the SNP panel, although there was still a considerable level of missing and inconsistent data. SNP marker data was considerably superior to microsatellite data in accuracy, reproducibility and robustness. Although microsatellites and SNPs data provide equivalent resolution for pedigree reconstruction, microsatellite analysis requires more time and experience to deal with the uncertainties of allele calling and faces challenges for data transferability across labs and over time. While microsatellite analysis will continue to be useful for some breeding tasks due to the high information content, existing infrastructure and low operating costs, the multi-species SNP resource available with the EuCHIP60k, opens a whole new array of opportunities for high-throughput, genome-wide or targeted genotyping in species of Eucalyptus.

A journey from a SSR-based low density map to a SNP-based high density map for identification of disease resistance quantitative trait loci in peanut

USDA-ARS?s Scientific Manuscript database

Mapping and identification of quantitative trait loci (QTLs) are important for efficient marker-assisted breeding. Diseases such as leaf spots and Tomato spotted wilt virus (TSWV) cause significant loses to peanut growers. The U.S. Peanut Genome Initiative (PGI) was launched in 2004, and expanded to...

Genotype imputation from various low-density SNP panels and its impact on accuracy of genomic breeding values in pigs.

PubMed

Grossi, D A; Brito, L F; Jafarikia, M; Schenkel, F S; Feng, Z

2018-04-30

The uptake of genomic selection (GS) by the swine industry is still limited by the costs of genotyping. A feasible alternative to overcome this challenge is to genotype animals using an affordable low-density (LD) single nucleotide polymorphism (SNP) chip panel followed by accurate imputation to a high-density panel. Therefore, the main objective of this study was to screen incremental densities of LD panels in order to systematically identify one that balances the tradeoffs among imputation accuracy, prediction accuracy of genomic estimated breeding values (GEBVs), and genotype density (directly associated with genotyping costs). Genotypes using the Illumina Porcine60K BeadChip were available for 1378 Duroc (DU), 2361 Landrace (LA) and 3192 Yorkshire (YO) pigs. In addition, pseudo-phenotypes (de-regressed estimated breeding values) for five economically important traits were provided for the analysis. The reference population for genotyping imputation consisted of 931 DU, 1631 LA and 2103 YO animals and the remainder individuals were included in the validation population of each breed. A LD panel of 3000 evenly spaced SNPs (LD3K) yielded high imputation accuracy rates: 93.78% (DU), 97.07% (LA) and 97.00% (YO) and high correlations (>0.97) between the predicted GEBVs using the actual 60 K SNP genotypes and the imputed 60 K SNP genotypes for all traits and breeds. The imputation accuracy was influenced by the reference population size as well as the amount of parental genotype information available in the reference population. However, parental genotype information became less important when the LD panel had at least 3000 SNPs. The correlation of the GEBVs directly increased with an increase in imputation accuracy. When genotype information for both parents was available, a panel of 300 SNPs (imputed to 60 K) yielded GEBV predictions highly correlated (⩾0.90) with genomic predictions obtained based on the true 60 K panel, for all traits and breeds. For a small reference population size with no parents on reference population, it is recommended the use of a panel at least as dense as the LD3K and, when there are two parents in the reference population, a panel as small as the LD300 might be a feasible option. These findings are of great importance for the development of LD panels for swine in order to reduce genotyping costs, increase the uptake of GS and, therefore, optimize the profitability of the swine industry.

Effect of diabetes and elevated glucose on nitric oxide-mediated neurotransmission in rat anococcygeus muscle.

PubMed Central

Way, K. J.; Reid, J. J.

1995-01-01

1. Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus muscle from 8-week streptozotocin-induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been investigated on NO-mediated relaxations, in muscles from untreated rats. 2. Relaxant responses to field stimulation (0.5-5 Hz, 10s train), sodium nitroprusside (SNP; 5 and 10 nM) and NO (1 and 3 microM) were significantly impaired in anococcygeus muscles from 8-week diabetic rats, compared to responses from control rats. Insulin treatment (5 u Lente day-1, s.c.) of diabetic rats prevented the development of this impairment. 3. Consistent with findings in 8-week diabetic rats, relaxation induced by field stimulation, SNP and NO were attenuated in tissues from 2-week and 4-week diabetic rats compared to corresponding control responses, whereas relaxations to papaverine (3 and 10 microM) were not reduced. In contrast, diabetes of 3-days duration did not affect relaxations to field stimulation, SNP or NO. 4. Incubation of anococcygeus muscles from untreated rats in medium containing elevated glucose (44.1 mM) for 6 h, significantly impaired relaxations to field stimulation compared to responses obtained after normal glucose (11.1 mM) incubation. Relaxations to SNP and to NO were not affected by 6 h exposure to elevated glucose. Similarly, incubation in hyperosmolar solutions containing mannose or sucrose for 6 h, impaired relaxations to field stimulation, but not to SNP or NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582450

Materials Data on Sr5(SnP3)2 (SG:55) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Materials Data on Ba3(SnP2)2 (SG:14) by Materials Project

DOE Data Explorer

Kristin Persson

2014-11-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Efficient selection of tagging single-nucleotide polymorphisms in multiple populations.

PubMed

Howie, Bryan N; Carlson, Christopher S; Rieder, Mark J; Nickerson, Deborah A

2006-08-01

Common genetic polymorphism may explain a portion of the heritable risk for common diseases, so considerable effort has been devoted to finding and typing common single-nucleotide polymorphisms (SNPs) in the human genome. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), suggesting that only a subset of all SNPs (known as tagging SNPs, or tagSNPs) need to be genotyped for disease association studies. Based on the genetic differences that exist among human populations, most tagSNP sets are defined in a single population and applied only in populations that are closely related. To improve the efficiency of multi-population analyses, we have developed an algorithm called MultiPop-TagSelect that finds a near-minimal union of population-specific tagSNP sets across an arbitrary number of populations. We present this approach as an extension of LD-select, a tagSNP selection method that uses a greedy algorithm to group SNPs into bins based on their pairwise association patterns, although the MultiPop-TagSelect algorithm could be used with any SNP tagging approach that allows choices between nearly equivalent SNPs. We evaluate the algorithm by considering tagSNP selection in candidate-gene resequencing data and lower density whole-chromosome data. Our analysis reveals that an exhaustive search is often intractable, while the developed algorithm can quickly and reliably find near-optimal solutions even for difficult tagSNP selection problems. Using populations of African, Asian, and European ancestry, we also show that an optimal multi-population set of tagSNPs can be substantially smaller (up to 44%) than a typical set obtained through independent or sequential selection.

Identification of Pyrus Single Nucleotide Polymorphisms (SNPs) and Evaluation for Genetic Mapping in European Pear and Interspecific Pyrus Hybrids

PubMed Central

Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E.; Crowhurst, Ross N.; Chagné, David

2013-01-01

We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (‘Old Home’בLouise Bon Jersey’) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. PMID:24155917

SNP Discovery in the Transcriptome of White Pacific Shrimp Litopenaeus vannamei by Next Generation Sequencing

PubMed Central

Yu, Yang; Wei, Jiankai; Zhang, Xiaojun; Liu, Jingwen; Liu, Chengzhang; Li, Fuhua; Xiang, Jianhai

2014-01-01

The application of next generation sequencing technology has greatly facilitated high throughput single nucleotide polymorphism (SNP) discovery and genotyping in genetic research. In the present study, SNPs were discovered based on two transcriptomes of Litopenaeus vannamei (L. vannamei) generated from Illumina sequencing platform HiSeq 2000. One transcriptome of L. vannamei was obtained through sequencing on the RNA from larvae at mysis stage and its reference sequence was de novo assembled. The data from another transcriptome were downloaded from NCBI and the reads of the two transcriptomes were mapped separately to the assembled reference by BWA. SNP calling was performed using SAMtools. A total of 58,717 and 36,277 SNPs with high quality were predicted from the two transcriptomes, respectively. SNP calling was also performed using the reads of two transcriptomes together, and a total of 96,040 SNPs with high quality were predicted. Among these 96,040 SNPs, 5,242 and 29,129 were predicted as non-synonymous and synonymous SNPs respectively. Characterization analysis of the predicted SNPs in L. vannamei showed that the estimated SNP frequency was 0.21% (one SNP per 476 bp) and the estimated ratio for transition to transversion was 2.0. Fifty SNPs were randomly selected for validation by Sanger sequencing after PCR amplification and 76% of SNPs were confirmed, which indicated that the SNPs predicted in this study were reliable. These SNPs will be very useful for genetic study in L. vannamei, especially for the high density linkage map construction and genome-wide association studies. PMID:24498047

G-Protein Genomic Association With Normal Variation in Gray Matter Density

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Arias-Vasquez, Alejandro; Zwiers, Marcel P.; van Hulzen, Kimm; Fernández, Guillén; Fisher, Simon E.; Franke, Barbara; Turner, Jessica A.; Liu, Jingyu

2017-01-01

While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = −0.16, P = 2.34 × 10−8), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = −0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions. PMID:26248772

Heuristic aspect of the lateral root initiation index: A case study of the role of nitric oxide in root branching.

PubMed

Lira-Ruan, Verónica; Mendivil, Selene Napsucialy; Dubrovsky, Joseph G

2013-10-01

Lateral root (LR) initiation (LRI) is a central process in root branching. Based on LR and/or LR primordium densities, it has been shown that nitric oxide (NO) promotes LRI. However, because NO inhibits primary root growth, we hypothesized that NO may have an opposite effect if the analysis is performed on a cellular basis. Using a previously proposed parameter, the LRI index (which measures how many LRI events take place along a root portion equivalent to the length of a single file of 100 cortical cells of average length), we addressed this hypothesis and illustrate here that the LRI index provides a researcher with a tool to uncover hidden but important information about root initiation. • Arabidopsis thaliana roots were treated with an NO donor (sodium nitroprusside [SNP]) and/or an NO scavenger (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide [cPTIO]). LRI was analyzed separately in the root portions formed before and during the treatment. In the latter, SNP caused root growth inhibition and an increase in the LR density accompanied by a decrease in LRI index, indicating overall inhibitory outcome of the NO donor on branching. The inhibitory effect of SNP was reversed by cPTIO, showing the NO-specific action of SNP on LRI. • Analysis of the LRI index permits the discovery of otherwise unknown modes of action of a substance on the root system formation. NO has a dual action on root branching, slightly promoting it in the root portion formed before the treatment and strongly inhibiting it in the root portion formed during the treatment.

MADD-FOLH1 Polymorphisms and Their Haplotypes with Serum Lipid Levels and the Risk of Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population.

PubMed

Wu, Dong-Feng; Yin, Rui-Xing; Cao, Xiao-Li; Huang, Feng; Wu, Jin-Zhen; Chen, Wu-Xian

2016-04-08

This study aimed to detect the association of the MADD-FOLH1 single nucleotide polymorphisms (SNPs) and their haplotypes with the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Chinese Han population. Six SNPs of rs7395662, rs326214, rs326217, rs1051006, rs3736101, and rs7120118 were genotyped in 584 CHD and 555 IS patients, and 596 healthy controls. The genotypic and allelic frequencies of the rs7395662 SNP were different between controls and patients, and the genotypes of the rs7395662 SNP were associated with the risk of CHD and IS in different genetic models. Six main haplotypes among the rs1051006, rs326214, rs326217, rs3736101, and rs7120118 SNPs were detected in our study population, the haplotypes of G-G-T-G-C and G-A-T-G-T were associated with an increased risk of CHD and IS, respectively. The subjects with rs7395662GG genotype in controls had higher triglyceride (TG) and lower high-density lipoprotein cholesterol (HDL-C) levels than the subjects with AA/AG genotypes. Several SNPs interacted with alcohol consumption to influence serum TG (rs326214, rs326217, and rs7120118) and HDL-C (rs7395662) levels. The SNP of rs3736101 interacted with cigarette smoking to modify serum HDL-C levels. The SNP of rs1051006 interacted with body mass index ≥24 kg/m² to modulate serum low-density lipoprotein cholesterol levels. The interactions of several haplotypes and alcohol consumption on the risk of CHD and IS were also observed.

Genomic prediction of the polled and horned phenotypes in Merino sheep.

PubMed

Duijvesteijn, Naomi; Bolormaa, Sunduimijid; Daetwyler, Hans D; van der Werf, Julius H J

2018-05-22

In horned sheep breeds, breeding for polledness has been of interest for decades. The objective of this study was to improve prediction of the horned and polled phenotypes using horn scores classified as polled, scurs, knobs or horns. Derived phenotypes polled/non-polled (P/NP) and horned/non-horned (H/NH) were used to test four different strategies for prediction in 4001 purebred Merino sheep. These strategies include the use of single 'single nucleotide polymorphism' (SNP) genotypes, multiple-SNP haplotypes, genome-wide and chromosome-wide genomic best linear unbiased prediction and information from imputed sequence variants from the region including the RXFP2 gene. Low-density genotypes of these animals were imputed to the Illumina Ovine high-density (600k) chip and the 1.78-kb insertion polymorphism in RXFP2 was included in the imputation process to whole-genome sequence. We evaluated the mode of inheritance and validated models by a fivefold cross-validation and across- and between-family prediction. The most significant SNPs for prediction of P/NP and H/NH were OAR10_29546872.1 and OAR10_29458450, respectively, located on chromosome 10 close to the 1.78-kb insertion at 29.5 Mb. The mode of inheritance included an additive effect and a sex-dependent effect for dominance for P/NP and a sex-dependent additive and dominance effect for H/NH. Models with the highest prediction accuracies for H/NH used either single SNPs or 3-SNP haplotypes and included a polygenic effect estimated based on traditional pedigree relationships. Prediction accuracies for H/NH were 0.323 for females and 0.725 for males. For predicting P/NP, the best models were the same as for H/NH but included a genomic relationship matrix with accuracies of 0.713 for females and 0.620 for males. Our results show that prediction accuracy is high using a single SNP, but does not reach 1 since the causative mutation is not genotyped. Incomplete penetrance or allelic heterogeneity, which can influence expression of the phenotype, may explain why prediction accuracy did not approach 1 with any of the genetic models tested here. Nevertheless, a breeding program to eradicate horns from Merino sheep can be effective by selecting genotypes GG of SNP OAR10_29458450 or TT of SNP OAR10_29546872.1 since all sheep with these genotypes will be non-horned.

High-throughput SNP genotyping in Cucurbita pepo for map construction and quantitative trait loci mapping

PubMed Central

2012-01-01

Background Cucurbita pepo is a member of the Cucurbitaceae family, the second- most important horticultural family in terms of economic importance after Solanaceae. The "summer squash" types, including Zucchini and Scallop, rank among the highest-valued vegetables worldwide. There are few genomic tools available for this species. The first Cucurbita transcriptome, along with a large collection of Single Nucleotide Polymorphisms (SNP), was recently generated using massive sequencing. A set of 384 SNP was selected to generate an Illumina GoldenGate assay in order to construct the first SNP-based genetic map of Cucurbita and map quantitative trait loci (QTL). Results We herein present the construction of the first SNP-based genetic map of Cucurbita pepo using a population derived from the cross of two varieties with contrasting phenotypes, representing the main cultivar groups of the species' two subspecies: Zucchini (subsp. pepo) × Scallop (subsp. ovifera). The mapping population was genotyped with 384 SNP, a set of selected EST-SNP identified in silico after massive sequencing of the transcriptomes of both parents, using the Illumina GoldenGate platform. The global success rate of the assay was higher than 85%. In total, 304 SNP were mapped, along with 11 SSR from a previous map, giving a map density of 5.56 cM/marker. This map was used to infer syntenic relationships between C. pepo and cucumber and to successfully map QTL that control plant, flowering and fruit traits that are of benefit to squash breeding. The QTL effects were validated in backcross populations. Conclusion Our results show that massive sequencing in different genotypes is an excellent tool for SNP discovery, and that the Illumina GoldenGate platform can be successfully applied to constructing genetic maps and performing QTL analysis in Cucurbita. This is the first SNP-based genetic map in the Cucurbita genus and is an invaluable new tool for biological research, especially considering that most of these markers are located in the coding regions of genes involved in different physiological processes. The platform will also be useful for future mapping and diversity studies, and will be essential in order to accelerate the process of breeding new and better-adapted squash varieties. PMID:22356647

A fine structure genetic analysis evaluating ecoregional adaptability of a Bos taurus breed (Hereford)

PubMed Central

Krehbiel, B.; Ericsson, S. A.; Wilson, C.; Caetano, A. R.; Paiva, S. R.

2017-01-01

Ecoregional differences contribute to genetic environmental interactions and impact animal performance. These differences may become more important under climate change scenarios. Utilizing genetic diversity within a species to address such problems has not been fully explored. In this study Hereford cattle were genotyped with 50K Bead Chip or 770K Bovine Bead Chip to test the existence of genetic structure in five U.S. ecoregions characterized by precipitation, temperature and humidity and designated: cool arid (CA), cool humid (CH), transition zone (TZ), warm arid (WA), and warm humid (WH). SNP data were analyzed in three sequential analyses. Broad genetic structure was evaluated with STRUCTURE, and ADMIXTURE software using 14,312 SNPs after passing quality control variables. The second analysis was performed using principal coordinate analysis with 66 Tag SNPs associated in the literature with various aspects of environmental stressors (e.g., heat tolerance) or production (e.g., milk production). In the third analysis TreeSelect was used with the 66 SNPs to evaluate if ecoregional allelic frequencies deviated from a central frequency and by so doing are indicative of directional selection. The three analyses suggested subpopulation structures associated with ecoregions from where animals were derived. ADMIXTURE and PCA results illustrated the importance of temperature and humidity and confirm subpopulation assignments. Comparisons of allele frequencies with TreeSelect showed ecoregion differences, in particular the divergence between arid and humid regions. Patterns of genetic variability obtained by medium and high density SNP chips can be used to acclimatize a temperately derived breed to various ecoregions. As climate change becomes an important factor in cattle production, this study should be used as a proof of concept to review future breeding and conservation schemes aimed at adaptation to climatic events. PMID:28459870

Materials Data on Si3Ag3(SnP3)2 (SG:217) by Materials Project

DOE Data Explorer

Kristin Persson

2016-05-02

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Exogenous nitric oxide donor protects Artemisia annua from oxidative stress generated by boron and aluminium toxicity.

PubMed

Aftab, Tariq; Khan, M Masroor A; Naeem, M; Idrees, Mohd; Moinuddin; Teixeira da Silva, Jaime A; Ram, M

2012-06-01

Nitric oxide (NO) is an important signal molecule modulating the response of plants to environmental stress. Here we report the effects of boron (B) and aluminium (Al) contamination in soil, carried out with or without application of exogenous SNP (NO donor), on various plant processes in Artemisia annua, including changes in artemisinin content. The addition of B or Al to soil medium significantly reduced the yield and growth of plants and lowered the values of net photosynthetic rate, stomatal conductance, internal CO(2) concentration and total chlorophyll content. The follow-up treatment of NO donor favoured growth and improved the photosynthetic efficiency in stressed as well as non-stressed plants. Artemisinin content was enhanced by 24.6% and 43.8% at 1mmole of soil-applied B or Al. When SNP was applied at 2mmole concentration together with either 1mmole of B and/or Al, it further stimulated artemisinin biosynthesis compared to the control. Application of B+Al+SNP proved to be the best treatment combination for the artemisinin content in Artemisia annua leaves. Copyright © 2012 Elsevier Inc. All rights reserved.

Large-Scale SNP Discovery and Genotyping for Constructing a High-Density Genetic Map of Tea Plant Using Specific-Locus Amplified Fragment Sequencing (SLAF-seq)

PubMed Central

Ma, Chun-Lei; Jin, Ji-Qiang; Li, Chun-Fang; Wang, Rong-Kai; Zheng, Hong-Kun; Yao, Ming-Zhe; Chen, Liang

2015-01-01

Genetic maps are important tools in plant genomics and breeding. The present study reports the large-scale discovery of single nucleotide polymorphisms (SNPs) for genetic map construction in tea plant. We developed a total of 6,042 valid SNP markers using specific-locus amplified fragment sequencing (SLAF-seq), and subsequently mapped them into the previous framework map. The final map contained 6,448 molecular markers, distributing on fifteen linkage groups corresponding to the number of tea plant chromosomes. The total map length was 3,965 cM, with an average inter-locus distance of 1.0 cM. This map is the first SNP-based reference map of tea plant, as well as the most saturated one developed to date. The SNP markers and map resources generated in this study provide a wealth of genetic information that can serve as a foundation for downstream genetic analyses, such as the fine mapping of quantitative trait loci (QTL), map-based cloning, marker-assisted selection, and anchoring of scaffolds to facilitate the process of whole genome sequencing projects for tea plant. PMID:26035838

Rapid Detection of Rare Deleterious Variants by Next Generation Sequencing with Optional Microarray SNP Genotype Data

PubMed Central

Watson, Christopher M.; Crinnion, Laura A.; Gurgel‐Gianetti, Juliana; Harrison, Sally M.; Daly, Catherine; Antanavicuite, Agne; Lascelles, Carolina; Markham, Alexander F.; Pena, Sergio D. J.; Bonthron, David T.

2015-01-01

ABSTRACT Autozygosity mapping is a powerful technique for the identification of rare, autosomal recessive, disease‐causing genes. The ease with which this category of disease gene can be identified has greatly increased through the availability of genome‐wide SNP genotyping microarrays and subsequently of exome sequencing. Although these methods have simplified the generation of experimental data, its analysis, particularly when disparate data types must be integrated, remains time consuming. Moreover, the huge volume of sequence variant data generated from next generation sequencing experiments opens up the possibility of using these data instead of microarray genotype data to identify disease loci. To allow these two types of data to be used in an integrated fashion, we have developed AgileVCFMapper, a program that performs both the mapping of disease loci by SNP genotyping and the analysis of potentially deleterious variants using exome sequence variant data, in a single step. This method does not require microarray SNP genotype data, although analysis with a combination of microarray and exome genotype data enables more precise delineation of disease loci, due to superior marker density and distribution. PMID:26037133

Surface invasive cleavage assay on a maskless light-directed diamond DNA microarray for genome-wide human SNP mapping.

PubMed

Nie, Bei; Yang, Min; Fu, Weiling; Liang, Zhiqing

2015-07-07

The surface invasive cleavage assay, because of its innate accuracy and ability for self-signal amplification, provides a potential route for the mapping of hundreds of thousands of human SNP sites. However, its performance on a high density DNA array has not yet been established, due to the unusual "hairpin" probe design on the microarray and the lack of chemical stability of commercially available substrates. Here we present an applicable method to implement a nanocrystalline diamond thin film as an alternative substrate for fabricating an addressable DNA array using maskless light-directed photochemistry, producing the most chemically stable and biocompatible system for genetic analysis and enzymatic reactions. The surface invasive cleavage reaction, followed by degenerated primer ligation and post-rolling circle amplification is consecutively performed on the addressable diamond DNA array, accurately mapping SNP sites from PCR-amplified human genomic target DNA. Furthermore, a specially-designed DNA array containing dual probes in the same pixel is fabricated by following a reverse light-directed DNA synthesis protocol. This essentially enables us to decipher thousands of SNP alleles in a single-pot reaction by the simple addition of enzyme, target and reaction buffers.

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus.

PubMed

Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L; Kreiner, Eskil; Chesi, Alessandra; Zemel, Babette S; Bønnelykke, Klaus; Boer, Cindy G; Ahluwalia, Tarunveer S; Bisgaard, Hans; Evangelou, Evangelos; Heppe, Denise H M; Bonewald, Lynda F; Gorski, Jeffrey P; Ghanbari, Mohsen; Demissie, Serkalem; Duque, Gustavo; Maurano, Matthew T; Kiel, Douglas P; Hsu, Yi-Hsiang; C J van der Eerden, Bram; Ackert-Bicknell, Cheryl; Reppe, Sjur; Gautvik, Kaare M; Raastad, Truls; Karasik, David; van de Peppel, Jeroen; Jaddoe, Vincent W V; Uitterlinden, André G; Tobias, Jonathan H; Grant, Struan F A; Bagos, Pantelis G; Evans, David M; Rivadeneira, Fernando

2017-07-25

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.

Lack of effect of bone morphogenetic protein 2 and 4 gene polymorphisms on bone density in postmenopausal Turkish women.

PubMed

Ozkan, Z S; Deveci, D; Onalan Etem, E; Yüce, H

2010-11-30

We investigated the effect of bone morphogenetic protein 2 and 4 (BMP-2 and -4) gene polymorphisms on bone density in postmenopausal Turkish women with osteoporosis. The frequency of single-nucleotide polymorphisms (SNPs) of BMP-2 and -4 genes was analyzed in 101 osteoporotic-postmenopausal women and 52 postmenopausal women with positive bone mineral density scores. We evaluated the frequency of the thymine→cytosine nucleotide variation at position 538 for BMP-4 and the transposition of adenine→thymine at codon 190 for BMP-2, with PCR. The proportions of genotypes observed for the BMP-2 SNP in the osteoporotic group were AA (47.5%), AT (39.6%), TT (12.9%), and in the non-osteoporotic group they were AA (48.1%), AT (40.4%), TT (11.5%). The corresponding frequencies for the BMP-4 SNP in the osteoporotic group were TT (30.7%), TC (45.5%), CC (23.8%), and in the non-osteoporotic group they were TT (26.9%), TC (40.4%), CC (32.7%). There were no significant differences in the frequencies of these genotypes between the patient and control groups. We conclude that genetic variations in BMP-2 and -4 do not substantially contribute to lumbar spine bone mineral density in postmenopausal Turkish women.

Solar Radiation-Associated Adaptive SNP Genetic Differentiation in Wild Emmer Wheat, Triticum dicoccoides.

PubMed

Ren, Jing; Chen, Liang; Jin, Xiaoli; Zhang, Miaomiao; You, Frank M; Wang, Jirui; Frenkel, Vladimir; Yin, Xuegui; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

2017-01-01

Whole-genome scans with large number of genetic markers provide the opportunity to investigate local adaptation in natural populations and identify candidate genes under positive selection. In the present study, adaptation genetic differentiation associated with solar radiation was investigated using 695 polymorphic SNP markers in wild emmer wheat originated in a micro-site at Yehudiyya, Israel. The test involved two solar radiation niches: (1) sun, in-between trees; and (2) shade, under tree canopy, separated apart by a distance of 2-4 m. Analysis of molecular variance showed a small (0.53%) but significant portion of overall variation between the sun and shade micro-niches, indicating a non-ignorable genetic differentiation between sun and shade habitats. Fifty SNP markers showed a medium (0.05 ≤ F ST ≤ 0.15) or high genetic differentiation ( F ST > 0.15). A total of 21 outlier loci under positive selection were identified by using four different F ST -outlier testing algorithms. The markers and genome locations under positive selection are consistent with the known patterns of selection. These results suggested that genetic differentiation between sun and shade habitats is substantial, radiation-associated, and therefore ecologically determined. Hence, the results of this study reflected effects of natural selection through solar radiation on EST-related SNP genetic diversity, resulting presumably in different adaptive complexes at a micro-scale divergence. The present work highlights the evolutionary theory and application significance of solar radiation-driven natural selection in wheat improvement.

Analysis of operational requirements for medium density air transportation. Volume 1: Summary

NASA Technical Reports Server (NTRS)

1975-01-01

The medium density air travel market was studied to determine the aircraft design and operational requirements. The impact of operational characteristics on the air travel system and the economic viability of the study aircraft were also evaluated. Medium density is defined in terms of numbers of people transported (20 to 500 passengers per day on round trip routes), and frequency of service ( a minumium of two and maximum of eight round trips per day) for 10 regional carriers. The operational characteristics of aircraft best suited to serve the medium density air transportation market are determined and a basepoint aircraft is designed from which tradeoff studies and parametric variations could be conducted. The impact of selected aircraft on the medium density market, economics, and operations is ascertained. Research and technology objectives for future programs in medium density air transportation are identified and ranked.

[Single nucleotide polymorphism and its application in allogeneic hematopoietic stem cell transplantation--review].

PubMed

Li, Su-Xia

2004-12-01

Single nucleotide polymorphism (SNP) is the third genetic marker after restriction fragment length polymorphism (RFLP) and short tandem repeat. It represents the most density genetic variability in the human genome and has been widely used in gene location, cloning, and research of heredity variation, as well as parenthood identification in forensic medicine. As steady heredity polymorphism, single nucleotide polymorphism is becoming the focus of attention in monitoring chimerism and minimal residual disease in the patients after allogeneic hematopoietic stem cell transplantation. The article reviews SNP heredity characterization, analysis techniques and its applications in allogeneic stem cell transplantation and other fields.

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

PubMed Central

Nunes, José de Ribamar da Silva; Liu, Shikai; Pértille, Fábio; Perazza, Caio Augusto; Villela, Priscilla Marqui Schmidt; de Almeida-Val, Vera Maria Fonseca; Hilsdorf, Alexandre Wagner Silva; Liu, Zhanjiang; Coutinho, Luiz Lehmann

2017-01-01

Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs. PMID:28387238

Is there any relation between IL-6 gene -174 G>C polymorphism and postmenopausal osteoporosis?

PubMed

Deveci, Derya; Ozkan, Zehra Sema; Yuce, Huseyin

2012-09-01

IL-6 gene single nucleotide polymorphisms (SNPs) have been reported to have a protective effect against bone resorption. We aimed to investigate the association between bone mineral density and IL-6 promoter region -174 G>C SNP. This study included 356 postmenopausal Turkish women, of whom 201 were osteoporotic (lumbar spine T score<-2.5 SD) and 155 non-osteoporotic (lumbar spine T score>-1.5 SD). Bone mineral density (BMD) measures were obtained using dual-energy X-ray absorptiometry. SNP of the IL-6 gene (-174 G>C) was examined by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of the variant C allele (24% vs. 30%, p=0.074) and mutant CC genotype (12% vs. 20%, p=0.094) were higher in non-osteoporotic women. Lumbar spine and total hip BMD values were lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype. The GG (p=0.022) and GC (p=0.037) genotypes were covariates which approached statistical significance in the regression model fitting of BMD. IL-6 promoter region SNP showed an association with BMD in this postmenopausal Turkish population and these data suggest that the wild GG genotype influences the phenotype. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

SNP discovery by high-throughput sequencing in soybean

PubMed Central

2010-01-01

Background With the advance of new massively parallel genotyping technologies, quantitative trait loci (QTL) fine mapping and map-based cloning become more achievable in identifying genes for important and complex traits. Development of high-density genetic markers in the QTL regions of specific mapping populations is essential for fine-mapping and map-based cloning of economically important genes. Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic variation existing between any diverse genotypes that are usually used for QTL mapping studies. The massively parallel sequencing technologies (Roche GS/454, Illumina GA/Solexa, and ABI/SOLiD), have been widely applied to identify genome-wide sequence variations. However, it is still remains unclear whether sequence data at a low sequencing depth are enough to detect the variations existing in any QTL regions of interest in a crop genome, and how to prepare sequencing samples for a complex genome such as soybean. Therefore, with the aims of identifying SNP markers in a cost effective way for fine-mapping several QTL regions, and testing the validation rate of the putative SNPs predicted with Solexa short sequence reads at a low sequencing depth, we evaluated a pooled DNA fragment reduced representation library and SNP detection methods applied to short read sequences generated by Solexa high-throughput sequencing technology. Results A total of 39,022 putative SNPs were identified by the Illumina/Solexa sequencing system using a reduced representation DNA library of two parental lines of a mapping population. The validation rates of these putative SNPs predicted with low and high stringency were 72% and 85%, respectively. One hundred sixty four SNP markers resulted from the validation of putative SNPs and have been selectively chosen to target a known QTL, thereby increasing the marker density of the targeted region to one marker per 42 K bp. Conclusions We have demonstrated how to quickly identify large numbers of SNPs for fine mapping of QTL regions by applying massively parallel sequencing combined with genome complexity reduction techniques. This SNP discovery approach is more efficient for targeting multiple QTL regions in a same genetic population, which can be applied to other crops. PMID:20701770

Genome-wide association studies identified novel loci for non-high-density lipoprotein cholesterol and its postprandial lipemic response.

PubMed

An, Ping; Straka, Robert J; Pollin, Toni I; Feitosa, Mary F; Wojczynski, Mary K; Daw, E Warwick; O'Connell, Jeffrey R; Gibson, Quince; Ryan, Kathleen A; Hopkins, Paul N; Tsai, Michael Y; Lai, Chao-Qiang; Province, Michael A; Ordovas, Jose M; Shuldiner, Alan R; Arnett, Donna K; Borecki, Ingrid B

2014-07-01

Non-high-density lipoprotein cholesterol(NHDL) is an independent and superior predictor of CVD risk as compared to low-density lipoprotein alone. It represents a spectrum of atherogenic lipid fractions with possibly a distinct genomic signature. We performed genome-wide association studies (GWAS) to identify loci influencing baseline NHDL and its postprandial lipemic (PPL) response. We carried out GWAS in 4,241 participants of European descent. Our discovery cohort included 928 subjects from the Genetics of Lipid-Lowering Drugs and Diet Network Study. Our replication cohorts included 3,313 subjects from the Heredity and Phenotype Intervention Heart Study and Family Heart Study. A linear mixed model using the kinship matrix was used for association tests. The best association signal was found in a tri-genic region at RHOQ-PIGF-CRIPT for baseline NHDL (lead SNP rs6544903, discovery p = 7e-7, MAF = 2 %; validation p = 6e-4 at 0.1 kb upstream neighboring SNP rs3768725, and 5e-4 at 0.7 kb downstream neighboring SNP rs6733143, MAF = 10 %). The lead and neighboring SNPs were not perfect surrogate proxies to each other (D' = 1, r (2) = 0.003) but they seemed to be partially dependent (likelihood ration test p = 0.04). Other suggestive loci (discovery p < 1e-6) included LOC100419812 and LOC100288337 for baseline NHDL, and LOC100420502 and CDH13 for NHDL PPL response that were not replicated (p > 0.01). The current and first GWAS of NHDL yielded an interesting common variant in RHOQ-PIGF-CRIPT influencing baseline NHDL levels. Another common variant in CDH13 for NHDL response to dietary high-fat intake challenge was also suggested. Further validations for both loci from large independent studies, especially interventional studies, are warranted.

High-Density SNP Genotyping to Define β-Globin Locus Haplotypes

PubMed Central

Liu, Li; Muralidhar, Shalini; Singh, Manisha; Sylvan, Caprice; Kalra, Inderdeep S.; Quinn, Charles T.; Onyekwere, Onyinye C.; Pace, Betty S.

2014-01-01

Five major β-globin locus haplotypes have been established in individuals with sickle cell disease (SCD) from the Benin, Bantu, Senegal, Cameroon, and Arab-Indian populations. Historically, β-haplotypes were established using restriction fragment length polymorphism (RFLP) analysis across the β-locus, which consists of five functional β-like globin genes located on chromosome 11. Previous attempts to correlate these haplotypes as robust predictors of clinical phenotypes observed in SCD have not been successful. We speculate that the coverage and distribution of the RFLP sites located proximal to or within the globin genes are not sufficiently dense to accurately reflect the complexity of this region. To test our hypothesis, we performed RFLP analysis and high-density single nucleotide polymorphism (SNP) genotyping across the β-locus using DNA samples from either healthy African Americans with normal hemoglobin A (HbAA) or individuals with homozygous SS (HbSS) disease. Using the genotyping data from 88 SNPs and Haploview analysis, we generated a greater number of haplotypes than that observed with RFLP analysis alone. Furthermore, a unique pattern of long-range linkage disequilibrium between the locus control region and the β-like globin genes was observed in the HbSS group. Interestingly, we observed multiple SNPs within the HindIII restriction site located in the Gγ-globin intervening sequence II which produced the same RFLP pattern. These findings illustrated the inability of RFLP analysis to decipher the complexity of sequence variations that impacts genomic structure in this region. Our data suggest that high density SNP mapping may be required to accurately define β-haplotypes that correlate with the different clinical phenotypes observed in SCD. PMID:18829352

The construction of a high-density linkage map for identifying SNP markers that are tightly linked to a nuclear-recessive major gene for male sterility in Cryptomeria japonica D. Don

PubMed Central

2012-01-01

Background High-density linkage maps facilitate the mapping of target genes and the construction of partial linkage maps around target loci to develop markers for marker-assisted selection (MAS). MAS is quite challenging in conifers because of their large, complex, and poorly-characterized genomes. Our goal was to construct a high-density linkage map to facilitate the identification of markers that are tightly linked to a major recessive male-sterile gene (ms1) for MAS in C. japonica, a species that is important in Japanese afforestation but which causes serious social pollinosis problems. Results We constructed a high-density saturated genetic linkage map for C. japonica using expressed sequence-derived co-dominant single nucleotide polymorphism (SNP) markers, most of which were genotyped using the GoldenGate genotyping assay. A total of 1261 markers were assigned to 11 linkage groups with an observed map length of 1405.2 cM and a mean distance between two adjacent markers of 1.1 cM; the number of linkage groups matched the basic chromosome number in C. japonica. Using this map, we located ms1 on the 9th linkage group and constructed a partial linkage map around the ms1 locus. This enabled us to identify a marker (hrmSNP970_sf) that is closely linked to the ms1 gene, being separated from it by only 0.5 cM. Conclusions Using the high-density map, we located the ms1 gene on the 9th linkage group and constructed a partial linkage map around the ms1 locus. The map distance between the ms1 gene and the tightly linked marker was only 0.5 cM. The identification of markers that are tightly linked to the ms1 gene will facilitate the early selection of male-sterile trees, which should expedite C. japonica breeding programs aimed at alleviating pollinosis problems without harming productivity. PMID:22424262

SNP Discovery by Illumina-Based Transcriptome Sequencing of the Olive and the Genetic Characterization of Turkish Olive Genotypes Revealed by AFLP, SSR and SNP Markers

PubMed Central

Kaya, Hilal Betul; Cetin, Oznur; Kaya, Hulya; Sahin, Mustafa; Sefer, Filiz; Kahraman, Abdullah; Tanyolac, Bahattin

2013-01-01

Background The olive tree (Olea europaea L.) is a diploid (2n = 2x = 46) outcrossing species mainly grown in the Mediterranean area, where it is the most important oil-producing crop. Because of its economic, cultural and ecological importance, various DNA markers have been used in the olive to characterize and elucidate homonyms, synonyms and unknown accessions. However, a comprehensive characterization and a full sequence of its transcriptome are unavailable, leading to the importance of an efficient large-scale single nucleotide polymorphism (SNP) discovery in olive. The objectives of this study were (1) to discover olive SNPs using next-generation sequencing and to identify SNP primers for cultivar identification and (2) to characterize 96 olive genotypes originating from different regions of Turkey. Methodology/Principal Findings Next-generation sequencing technology was used with five distinct olive genotypes and generated cDNA, producing 126,542,413 reads using an Illumina Genome Analyzer IIx. Following quality and size trimming, the high-quality reads were assembled into 22,052 contigs with an average length of 1,321 bases and 45 singletons. The SNPs were filtered and 2,987 high-quality putative SNP primers were identified. The assembled sequences and singletons were subjected to BLAST similarity searches and annotated with a Gene Ontology identifier. To identify the 96 olive genotypes, these SNP primers were applied to the genotypes in combination with amplified fragment length polymorphism (AFLP) and simple sequence repeats (SSR) markers. Conclusions/Significance This study marks the highest number of SNP markers discovered to date from olive genotypes using transcriptome sequencing. The developed SNP markers will provide a useful source for molecular genetic studies, such as genetic diversity and characterization, high density quantitative trait locus (QTL) analysis, association mapping and map-based gene cloning in the olive. High levels of genetic variation among Turkish olive genotypes revealed by SNPs, AFLPs and SSRs allowed us to characterize the Turkish olive genotype. PMID:24058483

International Collaboration on Genomics of Economically Relevant Traits

USDA-ARS?s Scientific Manuscript database

An international collaboration is attempting to make better use of high density SNP information by combining each contributor’s results. The initial group of collaborators are from Australia (CRC for Beef Genetic Technologies), Canada (a joint contribution from the Universities of Alberta and Guelp...

High-density marker imputation accuracy in sixteen French cattle breeds.

PubMed

Hozé, Chris; Fouilloux, Marie-Noëlle; Venot, Eric; Guillaume, François; Dassonneville, Romain; Fritz, Sébastien; Ducrocq, Vincent; Phocas, Florence; Boichard, Didier; Croiseau, Pascal

2013-09-03

Genotyping with the medium-density Bovine SNP50 BeadChip® (50K) is now standard in cattle. The high-density BovineHD BeadChip®, which contains 777,609 single nucleotide polymorphisms (SNPs), was developed in 2010. Increasing marker density increases the level of linkage disequilibrium between quantitative trait loci (QTL) and SNPs and the accuracy of QTL localization and genomic selection. However, re-genotyping all animals with the high-density chip is not economically feasible. An alternative strategy is to genotype part of the animals with the high-density chip and to impute high-density genotypes for animals already genotyped with the 50K chip. Thus, it is necessary to investigate the error rate when imputing from the 50K to the high-density chip. Five thousand one hundred and fifty three animals from 16 breeds (89 to 788 per breed) were genotyped with the high-density chip. Imputation error rates from the 50K to the high-density chip were computed for each breed with a validation set that included the 20% youngest animals. Marker genotypes were masked for animals in the validation population in order to mimic 50K genotypes. Imputation was carried out using the Beagle 3.3.0 software. Mean allele imputation error rates ranged from 0.31% to 2.41% depending on the breed. In total, 1980 SNPs had high imputation error rates in several breeds, which is probably due to genome assembly errors, and we recommend to discard these in future studies. Differences in imputation accuracy between breeds were related to the high-density-genotyped sample size and to the genetic relationship between reference and validation populations, whereas differences in effective population size and level of linkage disequilibrium showed limited effects. Accordingly, imputation accuracy was higher in breeds with large populations and in dairy breeds than in beef breeds. More than 99% of the alleles were correctly imputed if more than 300 animals were genotyped at high-density. No improvement was observed when multi-breed imputation was performed. In all breeds, imputation accuracy was higher than 97%, which indicates that imputation to the high-density chip was accurate. Imputation accuracy depends mainly on the size of the reference population and the relationship between reference and target populations.

High-density marker imputation accuracy in sixteen French cattle breeds

PubMed Central

2013-01-01

Background Genotyping with the medium-density Bovine SNP50 BeadChip® (50K) is now standard in cattle. The high-density BovineHD BeadChip®, which contains 777 609 single nucleotide polymorphisms (SNPs), was developed in 2010. Increasing marker density increases the level of linkage disequilibrium between quantitative trait loci (QTL) and SNPs and the accuracy of QTL localization and genomic selection. However, re-genotyping all animals with the high-density chip is not economically feasible. An alternative strategy is to genotype part of the animals with the high-density chip and to impute high-density genotypes for animals already genotyped with the 50K chip. Thus, it is necessary to investigate the error rate when imputing from the 50K to the high-density chip. Methods Five thousand one hundred and fifty three animals from 16 breeds (89 to 788 per breed) were genotyped with the high-density chip. Imputation error rates from the 50K to the high-density chip were computed for each breed with a validation set that included the 20% youngest animals. Marker genotypes were masked for animals in the validation population in order to mimic 50K genotypes. Imputation was carried out using the Beagle 3.3.0 software. Results Mean allele imputation error rates ranged from 0.31% to 2.41% depending on the breed. In total, 1980 SNPs had high imputation error rates in several breeds, which is probably due to genome assembly errors, and we recommend to discard these in future studies. Differences in imputation accuracy between breeds were related to the high-density-genotyped sample size and to the genetic relationship between reference and validation populations, whereas differences in effective population size and level of linkage disequilibrium showed limited effects. Accordingly, imputation accuracy was higher in breeds with large populations and in dairy breeds than in beef breeds. More than 99% of the alleles were correctly imputed if more than 300 animals were genotyped at high-density. No improvement was observed when multi-breed imputation was performed. Conclusion In all breeds, imputation accuracy was higher than 97%, which indicates that imputation to the high-density chip was accurate. Imputation accuracy depends mainly on the size of the reference population and the relationship between reference and target populations. PMID:24004563

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis.

PubMed

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I; Padyukov, Leonid; Toes, Rene E M; Huizinga, Tom W J; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I W; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert M; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-12-01

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

PubMed Central

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-01-01

Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

An ultra-high density linkage map and QTL mapping for sex and growth-related traits of common carp (Cyprinus carpio)

PubMed Central

Peng, Wenzhu; Xu, Jian; Zhang, Yan; Feng, Jianxin; Dong, Chuanju; Jiang, Likun; Feng, Jingyan; Chen, Baohua; Gong, Yiwen; Chen, Lin; Xu, Peng

2016-01-01

High density genetic linkage maps are essential for QTL fine mapping, comparative genomics and high quality genome sequence assembly. In this study, we constructed a high-density and high-resolution genetic linkage map with 28,194 SNP markers on 14,146 distinct loci for common carp based on high-throughput genotyping with the carp 250 K single nucleotide polymorphism (SNP) array in a mapping family. The genetic length of the consensus map was 10,595.94 cM with an average locus interval of 0.75 cM and an average marker interval of 0.38 cM. Comparative genomic analysis revealed high level of conserved syntenies between common carp and the closely related model species zebrafish and medaka. The genome scaffolds were anchored to the high-density linkage map, spanning 1,357 Mb of common carp reference genome. QTL mapping and association analysis identified 22 QTLs for growth-related traits and 7 QTLs for sex dimorphism. Candidate genes underlying growth-related traits were identified, including important regulators such as KISS2, IGF1, SMTLB, NPFFR1 and CPE. Candidate genes associated with sex dimorphism were also identified including 3KSR and DMRT2b. The high-density and high-resolution genetic linkage map provides an important tool for QTL fine mapping and positional cloning of economically important traits, and improving common carp genome assembly. PMID:27225429

Genomic signatures reveal geographic adaption and human selection in cattle

USDA-ARS?s Scientific Manuscript database

We investigated geographic adaptation and human selection using high-density SNP data of five diverse cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-k...

Assessment of inbreeding depression in Nellore cows (Bos indicus) through high-density SNP genotypes

USDA-ARS?s Scientific Manuscript database

Inbreeding has been incriminated as a cause of decrease in reproductive performance in cattle. This negative correlation is known as ‘inbreeding depression’, and evidence supporting this hypothesis was generated from association studies between reproductive traits and estimates of inbreeding coeffic...

Tin phosphide-based anodes for sodium-ion batteries: synthesis via solvothermal transformation of Sn metal and phase-dependent Na storage performance

PubMed Central

Shin, Hyun-Seop; Jung, Kyu-Nam; Jo, Yong Nam; Park, Min-Sik; Kim, Hansung; Lee, Jong-Won

2016-01-01

There is a great deal of current interest in the development of rechargeable sodium (Na)-ion batteries (SIBs) for low-cost, large-scale stationary energy storage systems. For the commercial success of this technology, significant progress should be made in developing robust anode (negative electrode) materials with high capacity and long cycle life. Sn-P compounds are considered promising anode materials that have considerable potential to meet the required performance of SIBs, and they have been typically prepared by high-energy mechanical milling. Here, we report Sn-P-based anodes synthesised through solvothermal transformation of Sn metal and their electrochemical Na storage properties. The temperature and time period used for solvothermal treatment play a crucial role in determining the phase, microstructure, and composition of the Sn-P compound and thus its electrochemical performance. The Sn-P compound prepared under an optimised solvothermal condition shows excellent electrochemical performance as an SIB anode, as evidenced by a high reversible capacity of ~560 mAh g−1 at a current density of 100 mA g−1 and cycling stability for 100 cycles. The solvothermal route provides an effective approach to synthesising Sn-P anodes with controlled phases and compositions, thus tailoring their Na storage behaviour. PMID:27189834

Construction and analysis of a high-density genetic linkage map in cabbage (Brassica oleracea L. var. capitata)

PubMed Central

2012-01-01

Background Brassica oleracea encompass a family of vegetables and cabbage that are among the most widely cultivated crops. In 2009, the B. oleracea Genome Sequencing Project was launched using next generation sequencing technology. None of the available maps were detailed enough to anchor the sequence scaffolds for the Genome Sequencing Project. This report describes the development of a large number of SSR and SNP markers from the whole genome shotgun sequence data of B. oleracea, and the construction of a high-density genetic linkage map using a double haploid mapping population. Results The B. oleracea high-density genetic linkage map that was constructed includes 1,227 markers in nine linkage groups spanning a total of 1197.9 cM with an average of 0.98 cM between adjacent loci. There were 602 SSR markers and 625 SNP markers on the map. The chromosome with the highest number of markers (186) was C03, and the chromosome with smallest number of markers (99) was C09. Conclusions This first high-density map allowed the assembled scaffolds to be anchored to pseudochromosomes. The map also provides useful information for positional cloning, molecular breeding, and integration of information of genes and traits in B. oleracea. All the markers on the map will be transferable and could be used for the construction of other genetic maps. PMID:23033896

Two-component scattering model and the electron density spectrum

NASA Astrophysics Data System (ADS)

Zhou, A. Z.; Tan, J. Y.; Esamdin, A.; Wu, X. J.

2010-02-01

In this paper, we discuss a rigorous treatment of the refractive scintillation caused by a two-component interstellar scattering medium and a Kolmogorov form of density spectrum. It is assumed that the interstellar scattering medium is composed of a thin-screen interstellar medium (ISM) and an extended interstellar medium. We consider the case that the scattering of the thin screen concentrates in a thin layer represented by a δ function distribution and that the scattering density of the extended irregular medium satisfies the Gaussian distribution. We investigate and develop equations for the flux density structure function corresponding to this two-component ISM geometry in the scattering density distribution and compare our result with the observations. We conclude that the refractive scintillation caused by this two-component ISM scattering gives a more satisfactory explanation for the observed flux density variation than does the single extended medium model. The level of refractive scintillation is strongly sensitive to the distribution of scattering material along the line of sight (LOS). The theoretical modulation indices are comparatively less sensitive to the scattering strength of the thin-screen medium, but they critically depend on the distance from the observer to the thin screen. The logarithmic slope of the structure function is sensitive to the scattering strength of the thin-screen medium, but is relatively insensitive to the thin-screen location. Therefore, the proposed model can be applied to interpret the structure functions of flux density observed in pulsar PSR B2111 + 46 and PSR B0136 + 57. The result suggests that the medium consists of a discontinuous distribution of plasma turbulence embedded in the interstellar medium. Thus our work provides some insight into the distribution of the scattering along the LOS to the pulsar PSR B2111 + 46 and PSR B0136 + 57.

Genome-wide association study of fertility traits in dairy cattle using high-density single nucleotide polymorphism marker panels

USDA-ARS?s Scientific Manuscript database

Unfavorable genetic correlations between production and fertility traits are well documented. Genetic selection for fertility traits is slow, however, due to low heritabilities. Identification of single nucleotide polymorphisms (SNP) involved in reproduction could improve reliability of genomic esti...

Population analysis of 60 worldwide cattle breeds using high-density (700k)SNP genotyping

USDA-ARS?s Scientific Manuscript database

Genetic differences associated with speciation, breed formation, or local adaptation can help inform efforts to preserve and to effectively utilize individuals in selection programs as well as assist in accurately identifying genomic region’s importance through genome-wide association studies. To th...

OPG, RANKL, and RANK gene polymorphisms and the bone mineral density response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia.

PubMed

Zheng, Hui; Wang, Chun; He, Jin-Wei; Fu, Wen-Zhen; Zhang, Zhen-Lin

2016-01-01

The aim of the study was to explore the association between OPG, RANKL, and RANK gene variations and the bone mineral density (BMD) response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia. In the present study, 40 single-nucleotide polymorphisms (SNPs) in the OPG, RANKL, and RANK genes were genotyped in 501 postmenopausal Chinese women with osteoporosis or osteopenia who were given alendronate (70 mg weekly) orally for 1 year. The BMD at the lumbar spine 1-4 (L1-L4), femoral neck, and total hip was measured. A total of 442 patients completed 1 year of alendronate therapy. The rs7239261 SNP of the RANK gene was significantly associated with baseline L1-L4 BMD (P=0.0004) after correction for age and BMI. Participants with the SNP A allele (C/A and A/A) had a higher BMD than those with the C/C genotype (C/A vs. C/C, P=0.001; A/A vs. C/C, P=0.025). Haplotypes AG of rs7239261-rs12969154, GG of rs3826619-rs11877530, and CACG of rs1805034-rs8083511-rs17069895-rs7231887 in the RANK gene were genetic protective factors toward a higher baseline L1-L4 BMD. No association was observed between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy. The RANK gene might contribute to genetic variability in L1-L4 BMD in postmenopausal Chinese women with osteoporosis or osteopenia. No evidence of an association between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy was found in postmenopausal Chinese women with osteoporosis or osteopenia.

The recombination landscape around forensic STRs: Accurate measurement of genetic distances between syntenic STR pairs using HapMap high density SNP data.

PubMed

Phillips, C; Ballard, D; Gill, P; Court, D Syndercombe; Carracedo, A; Lareu, M V

2012-05-01

Family studies can be used to measure the genetic distance between same-chromosome (syntenic) STRs in order to detect physical linkage or linkage disequilibrium. However, family studies are expensive and time consuming, in many cases uninformative, and lack a reliable means to infer the phase of the diplotypes obtained. HapMap provides a more comprehensive and fine-scale estimation of recombination rates using high density multi-point SNP data (average inter-SNP distance: 900 nucleotides). Data at this fine scale detects sub-kilobase genetic distances across the whole recombining human genome. We have used the most recent HapMap SNP data release 22 to measure and compare genetic distances, and by inference fine-scale recombination rates, between 29 syntenic STR pairs identified from 39 validated STRs currently available for forensic use. The 39 STRs comprise 23 core loci: SE33, Penta D & E, 13 CODIS and 7 non-CODIS European Standard Set STRs, plus supplementary STRs in the recently released Promega CS-7™ and Qiagen Investigator HDplex™ kits. Also included were D9S1120, a marker we developed for forensic use unique to chromosome 9, and the novel D6S1043 component STR of SinoFiler™ (Applied Biosystems). The data collated provides reliable estimates of recombination rates between each STR pair, that can then be placed into haplotype frequency calculators for short pedigrees with multiple meiotic inputs and which just requires the addition of allele frequencies. This allows all current STR sets or their combinations to be used in supplemented paternity analyses without the need for further adjustment for physical linkage. The detailed analysis of recombination rates made for autosomal forensic STRs was extended to the more than 50 X chromosome STRs established or in development for complex kinship analyses. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Genome-wide linkage mapping of yield-related traits in three Chinese bread wheat populations using high-density SNP markers.

PubMed

Li, Faji; Wen, Weie; He, Zhonghu; Liu, Jindong; Jin, Hui; Cao, Shuanghe; Geng, Hongwei; Yan, Jun; Zhang, Pingzhi; Wan, Yingxiu; Xia, Xianchun

2018-06-01

We identified 21 new and stable QTL, and 11 QTL clusters for yield-related traits in three bread wheat populations using the wheat 90 K SNP assay. Identification of quantitative trait loci (QTL) for yield-related traits and closely linked molecular markers is important in order to identify gene/QTL for marker-assisted selection (MAS) in wheat breeding. The objectives of the present study were to identify QTL for yield-related traits and dissect the relationships among different traits in three wheat recombinant inbred line (RIL) populations derived from crosses Doumai × Shi 4185 (D × S), Gaocheng 8901 × Zhoumai 16 (G × Z) and Linmai 2 × Zhong 892 (L × Z). Using the available high-density linkage maps previously constructed with the wheat 90 K iSelect single nucleotide polymorphism (SNP) array, 65, 46 and 53 QTL for 12 traits were identified in the three RIL populations, respectively. Among them, 34, 23 and 27 were likely to be new QTL. Eighteen common QTL were detected across two or three populations. Eleven QTL clusters harboring multiple QTL were detected in different populations, and the interval 15.5-32.3 cM around the Rht-B1 locus on chromosome 4BS harboring 20 QTL is an important region determining grain yield (GY). Thousand-kernel weight (TKW) is significantly affected by kernel width and plant height (PH), whereas flag leaf width can be used to select lines with large kernel number per spike. Eleven candidate genes were identified, including eight cloned genes for kernel, heading date (HD) and PH-related traits as well as predicted genes for TKW, spike length and HD. The closest SNP markers of stable QTL or QTL clusters can be used for MAS in wheat breeding using kompetitive allele-specific PCR or semi-thermal asymmetric reverse PCR assays for improvement of GY.

Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression

PubMed Central

Darabi, Hatef; McCue, Karen; Beesley, Jonathan; Michailidou, Kyriaki; Nord, Silje; Kar, Siddhartha; Humphreys, Keith; Thompson, Deborah; Ghoussaini, Maya; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Canisius, Sander; Scott, Christopher G.; Apicella, Carmel; Hopper, John L.; Southey, Melissa C.; Stone, Jennifer; Broeks, Annegien; Schmidt, Marjanka K.; Scott, Rodney J.; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W.; Ekici, Arif B.; Fasching, Peter A.; Heusinger, Katharina; dos-Santos-Silva, Isabel; Peto, Julian; Tomlinson, Ian; Sawyer, Elinor J.; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L.; Arndt, Volker; Brenner, Hermann; Engel, Christoph; Meindl, Alfons; Schmutzler, Rita K.; Arnold, Norbert; Brauch, Hiltrud; Hamann, Ute; Chang-Claude, Jenny; Khan, Sofia; Nevanlinna, Heli; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-chen; Wu, Anna H.; Floris, Giuseppe; Lambrechts, Diether; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Couch, Fergus J.; Vachon, Celine; Giles, Graham G.; McLean, Catriona; Milne, Roger L.; Dugué, Pierre-Antoine; Haiman, Christopher A.; Maskarinec, Gertraud; Woolcott, Christy; Henderson, Brian E.; Goldberg, Mark S.; Simard, Jacques; Teo, Soo H.; Mariapun, Shivaani; Helland, Åslaug; Haakensen, Vilde; Zheng, Wei; Beeghly-Fadiel, Alicia; Tamimi, Rulla; Jukkola-Vuorinen, Arja; Winqvist, Robert; Andrulis, Irene L.; Knight, Julia A.; Devilee, Peter; Tollenaar, Robert A.E.M.; Figueroa, Jonine; García-Closas, Montserrat; Czene, Kamila; Hooning, Maartje J.; Tilanus-Linthorst, Madeleine; Li, Jingmei; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S.; Luben, Robert; Khaw, Kay-Tee; Choi, Ji-Yeob; Kang, Daehee; Hartman, Mikael; Lim, Wei Yen; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; McKay, James; Sangrajrang, Suleeporn; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen-Yang; Yu, Jyh-Cherng; Ziogas, Argyrios; Schoemaker, Minouk J.; Swerdlow, Anthony; Borresen-Dale, Anne-Lise; Kristensen, Vessela; French, Juliet D.; Edwards, Stacey L.; Dunning, Alison M.; Easton, Douglas F.; Hall, Per; Chenevix-Trench, Georgia

2015-01-01

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82–0.88]) and ER-negative (OR = 0.87 [0.82–0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91–0.95] and OR = 1.06 [1.03–1.09]) and ER-negative (OR = 0.95 [0.91–0.98] and OR = 1.08 [1.04–1.13]) disease. There was weaker evidence for iCHAV4, located 5′ of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90–0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1–4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer. PMID:26073781

A combined long-range phasing and long haplotype imputation method to impute phase for SNP genotypes

PubMed Central

2011-01-01

Background Knowing the phase of marker genotype data can be useful in genome-wide association studies, because it makes it possible to use analysis frameworks that account for identity by descent or parent of origin of alleles and it can lead to a large increase in data quantities via genotype or sequence imputation. Long-range phasing and haplotype library imputation constitute a fast and accurate method to impute phase for SNP data. Methods A long-range phasing and haplotype library imputation algorithm was developed. It combines information from surrogate parents and long haplotypes to resolve phase in a manner that is not dependent on the family structure of a dataset or on the presence of pedigree information. Results The algorithm performed well in both simulated and real livestock and human datasets in terms of both phasing accuracy and computation efficiency. The percentage of alleles that could be phased in both simulated and real datasets of varying size generally exceeded 98% while the percentage of alleles incorrectly phased in simulated data was generally less than 0.5%. The accuracy of phasing was affected by dataset size, with lower accuracy for dataset sizes less than 1000, but was not affected by effective population size, family data structure, presence or absence of pedigree information, and SNP density. The method was computationally fast. In comparison to a commonly used statistical method (fastPHASE), the current method made about 8% less phasing mistakes and ran about 26 times faster for a small dataset. For larger datasets, the differences in computational time are expected to be even greater. A computer program implementing these methods has been made available. Conclusions The algorithm and software developed in this study make feasible the routine phasing of high-density SNP chips in large datasets. PMID:21388557

Short communication: Improving the accuracy of genomic prediction of body conformation traits in Chinese Holsteins using markers derived from high-density marker panels.

PubMed

Song, H; Li, L; Ma, P; Zhang, S; Su, G; Lund, M S; Zhang, Q; Ding, X

2018-06-01

This study investigated the efficiency of genomic prediction with adding the markers identified by genome-wide association study (GWAS) using a data set of imputed high-density (HD) markers from 54K markers in Chinese Holsteins. Among 3,056 Chinese Holsteins with imputed HD data, 2,401 individuals born before October 1, 2009, were used for GWAS and a reference population for genomic prediction, and the 220 younger cows were used as a validation population. In total, 1,403, 1,536, and 1,383 significant single nucleotide polymorphisms (SNP; false discovery rate at 0.05) associated with conformation final score, mammary system, and feet and legs were identified, respectively. About 2 to 3% genetic variance of 3 traits was explained by these significant SNP. Only a very small proportion of significant SNP identified by GWAS was included in the 54K marker panel. Three new marker sets (54K+) were herein produced by adding significant SNP obtained by linear mixed model for each trait into the 54K marker panel. Genomic breeding values were predicted using a Bayesian variable selection (BVS) model. The accuracies of genomic breeding value by BVS based on the 54K+ data were 2.0 to 5.2% higher than those based on the 54K data. The imputed HD markers yielded 1.4% higher accuracy on average (BVS) than the 54K data. Both the 54K+ and HD data generated lower bias of genomic prediction, and the 54K+ data yielded the lowest bias in all situations. Our results show that the imputed HD data were not very useful for improving the accuracy of genomic prediction and that adding the significant markers derived from the imputed HD marker panel could improve the accuracy of genomic prediction and decrease the bias of genomic prediction. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Fast and Accurate Approximation to Significance Tests in Genome-Wide Association Studies

PubMed Central

Zhang, Yu; Liu, Jun S.

2011-01-01

Genome-wide association studies commonly involve simultaneous tests of millions of single nucleotide polymorphisms (SNP) for disease association. The SNPs in nearby genomic regions, however, are often highly correlated due to linkage disequilibrium (LD, a genetic term for correlation). Simple Bonferonni correction for multiple comparisons is therefore too conservative. Permutation tests, which are often employed in practice, are both computationally expensive for genome-wide studies and limited in their scopes. We present an accurate and computationally efficient method, based on Poisson de-clumping heuristics, for approximating genome-wide significance of SNP associations. Compared with permutation tests and other multiple comparison adjustment approaches, our method computes the most accurate and robust p-value adjustments for millions of correlated comparisons within seconds. We demonstrate analytically that the accuracy and the efficiency of our method are nearly independent of the sample size, the number of SNPs, and the scale of p-values to be adjusted. In addition, our method can be easily adopted to estimate false discovery rate. When applied to genome-wide SNP datasets, we observed highly variable p-value adjustment results evaluated from different genomic regions. The variation in adjustments along the genome, however, are well conserved between the European and the African populations. The p-value adjustments are significantly correlated with LD among SNPs, recombination rates, and SNP densities. Given the large variability of sequence features in the genome, we further discuss a novel approach of using SNP-specific (local) thresholds to detect genome-wide significant associations. This article has supplementary material online. PMID:22140288

Aerogel Fingerprint Media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Fred S.; Andresen, Brian D.

1999-09-21

A fingerprint medium which is made of an aerogel having a predetermined density. The fingerprint medium may have a midrange density for forming plates or may be crushed forming a powder. The fingerprint medium may further include at least one of a metal and metal oxide to enhance characteristics desirable in a fingerprint medium.

Time resolved interferometric study of the plasma plume induced shock wave in confined geometry: Two-dimensional mapping of the ambient and plasma density

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choudhury, Kaushik; Singh, R. K.; Kumar, Ajai, E-mail: ajai@ipr.res.in

2016-04-15

An experimental investigation of the laser produced plasma induced shock wave in the presence of confining walls placed along the axial as well as the lateral direction has been performed. A time resolved Mach Zehnder interferometer is set up to track the primary as well as the reflected shock waves and its effect on the evolving plasma plume has been studied. An attempt has been made to discriminate the electronic and medium density contributions towards the changes in the refractive index of the medium. Two dimensional spatial distributions for both ambient medium density and plasma density (electron density) have beenmore » obtained by employing customised inversion technique and algorithm on the recorded interferograms. The observed density pattern of the surrounding medium in the presence of confining walls is correlated with the reflected shock wave propagation in the medium. Further, the shock wave plasma interaction and the subsequent changes in the shape and density of the plasma plume in confined geometry are briefly described.« less

Revisiting demographic processes in cattle with genome-wide population genetic analysis

PubMed Central

Orozco-terWengel, Pablo; Barbato, Mario; Nicolazzi, Ezequiel; Biscarini, Filippo; Milanesi, Marco; Davies, Wyn; Williams, Don; Stella, Alessandra; Ajmone-Marsan, Paolo; Bruford, Michael W.

2015-01-01

The domestication of the aurochs took place approximately 10,000 years ago giving rise to the two main types of domestic cattle known today, taurine (Bos taurus) domesticated somewhere on or near the Fertile Crescent, and indicine (Bos indicus) domesticated in the Indus Valley. However, although cattle have historically played a prominent role in human society the exact origin of many extant breeds is not well known. Here we used a combination of medium and high-density Illumina Bovine SNP arrays (i.e., ~54,000 and ~770,000 SNPs, respectively), genotyped for over 1300 animals representing 56 cattle breeds, to describe the relationships among major European cattle breeds and detect patterns of admixture among them. Our results suggest modern cross-breeding and ancient hybridisation events have both played an important role, including with animals of indicine origin. We use these data to identify signatures of selection reflecting both domestication (hypothesized to produce a common signature across breeds) and local adaptation (predicted to exhibit a signature of selection unique to a single breed or group of related breeds with a common history) to uncover additional demographic complexity of modern European cattle. PMID:26082794

Nuclear and mitochondrial genetic structure in the Eurasian beaver (Castor fiber) – implications for future reintroductions

PubMed Central

Senn, Helen; Ogden, Rob; Frosch, Christiane; Syrůčková, Alena; Campbell-Palmer, Roisin; Munclinger, Pavel; Durka, Walter; Kraus, Robert H S; Saveljev, Alexander P; Nowak, Carsten; Stubbe, Annegret; Stubbe, Michael; Michaux, Johan; Lavrov, Vladimir; Samiya, Ravchig; Ulevicius, Alius; Rosell, Frank

2014-01-01

Many reintroduction projects for conservation fail, and there are a large number of factors that may contribute to failure. Genetic analysis can be used to help stack the odds of a reintroduction in favour of success, by conducting assessment of source populations to evaluate the possibility of inbreeding and outbreeding depression and by conducting postrelease monitoring. In this study, we use a panel of 306 SNP (single nucleotide polymorphism) markers and 487–489 base pairs of mitochondrial DNA control region sequence data to examine 321 individuals from possible source populations of the Eurasian beaver for a reintroduction to Scotland. We use this information to reassess the phylogenetic history of the Eurasian beavers, to examine the genetic legacy of past reintroductions on the Eurasian landmass and to assess the future power of the genetic markers to conduct ongoing monitoring via parentage analysis and individual identification. We demonstrate the capacity of medium density genetic data (hundreds of SNPs) to provide information suitable for applied conservation and discuss the difficulty of balancing the need for high genetic diversity against phylogenetic best fit when choosing source population(s) for reintroduction. PMID:25067948

Genomic signatures of adaptive introgression from European mouflon into domestic sheep.

PubMed

Barbato, Mario; Hailer, Frank; Orozco-terWengel, Pablo; Kijas, James; Mereu, Paolo; Cabras, Pierangela; Mazza, Raffaele; Pirastru, Monica; Bruford, Michael W

2017-08-08

Mouflon (Ovis aries musimon) became extinct from mainland Europe after the Neolithic, but remnant populations from the Mediterranean islands of Corsica and Sardinia have been used for reintroductions across Europe since the 19 th -century. Mouflon x sheep hybrids are larger-bodied than mouflon, potentially showing increased male reproductive success, but little is known about genomic levels of admixture, or about the adaptive significance of introgression between resident mouflon and local sheep breeds. Here we analysed Ovine medium-density SNP array genotypes of 92 mouflon from six geographic regions, along with data from 330 individuals of 16 domestic sheep breeds. We found lower levels of genetic diversity in mouflon than in domestic sheep, consistent with past bottlenecks in mouflon. Introgression signals were bidirectional and affected most mouflon and sheep populations, being strongest in one Sardinian mouflon population. Developing and using a novel approach to identify chromosomal regions with consistent introgression signals, we infer adaptive introgression from mouflon to domestic sheep related to immunity mechanisms, but not in the opposite direction. Further, we infer that Soay and Sarda sheep carry introgressed mouflon alleles involved in bitter taste perception and/or innate immunity. Our results illustrate the potential for adaptive introgression even among recently diverged populations.

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Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array.

PubMed

Antanaviciute, Laima; Fernández-Fernández, Felicidad; Jansen, Johannes; Banchi, Elisa; Evans, Katherine M; Viola, Roberto; Velasco, Riccardo; Dunwell, Jim M; Troggio, Michela; Sargent, Daniel J

2012-05-25

A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the 'Golden Delicious' genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the 'Golden Delicious' pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the 'Golden Delicious' reference sequence will assist in the continued improvement of the genome sequence assembly for that variety.

A high-density genetic map and QTL analysis of agronomic traits in foxtail millet [Setaria italica (L.) P. Beauv.] using RAD-seq.

PubMed

Wang, Jun; Wang, Zhilan; Du, Xiaofen; Yang, Huiqing; Han, Fang; Han, Yuanhuai; Yuan, Feng; Zhang, Linyi; Peng, Shuzhong; Guo, Erhu

2017-01-01

Foxtail millet (Setaria italica), a very important grain crop in China, has become a new model plant for cereal crops and biofuel grasses. Although its reference genome sequence was released recently, quantitative trait loci (QTLs) controlling complex agronomic traits remains limited. The development of massively parallel genotyping methods and next-generation sequencing technologies provides an excellent opportunity for developing single-nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of complex quantitative traits. In this study, a high-throughput and cost-effective RAD-seq approach was employed to generate a high-density genetic map for foxtail millet. A total of 2,668,587 SNP loci were detected according to the reference genome sequence; meanwhile, 9,968 SNP markers were used to genotype 124 F2 progenies derived from the cross between Hongmiaozhangu and Changnong35; a high-density genetic map spanning 1648.8 cM, with an average distance of 0.17 cM between adjacent markers was constructed; 11 major QTLs for eight agronomic traits were identified; five co-dominant DNA markers were developed. These findings will be of value for the identification of candidate genes and marker-assisted selection in foxtail millet.

A high-density genetic map and QTL analysis of agronomic traits in foxtail millet [Setaria italica (L.) P. Beauv.] using RAD-seq

PubMed Central

Wang, Zhilan; Du, Xiaofen; Yang, Huiqing; Han, Fang; Han, Yuanhuai; Yuan, Feng; Zhang, Linyi; Peng, Shuzhong; Guo, Erhu

2017-01-01

Foxtail millet (Setaria italica), a very important grain crop in China, has become a new model plant for cereal crops and biofuel grasses. Although its reference genome sequence was released recently, quantitative trait loci (QTLs) controlling complex agronomic traits remains limited. The development of massively parallel genotyping methods and next-generation sequencing technologies provides an excellent opportunity for developing single-nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of complex quantitative traits. In this study, a high-throughput and cost-effective RAD-seq approach was employed to generate a high-density genetic map for foxtail millet. A total of 2,668,587 SNP loci were detected according to the reference genome sequence; meanwhile, 9,968 SNP markers were used to genotype 124 F2 progenies derived from the cross between Hongmiaozhangu and Changnong35; a high-density genetic map spanning 1648.8 cM, with an average distance of 0.17 cM between adjacent markers was constructed; 11 major QTLs for eight agronomic traits were identified; five co-dominant DNA markers were developed. These findings will be of value for the identification of candidate genes and marker-assisted selection in foxtail millet. PMID:28644843

Improving accuracy of genomic predictions within and between dairy cattle breeds with imputed high-density single nucleotide polymorphism panels.

PubMed

Erbe, M; Hayes, B J; Matukumalli, L K; Goswami, S; Bowman, P J; Reich, C M; Mason, B A; Goddard, M E

2012-07-01

Achieving accurate genomic estimated breeding values for dairy cattle requires a very large reference population of genotyped and phenotyped individuals. Assembling such reference populations has been achieved for breeds such as Holstein, but is challenging for breeds with fewer individuals. An alternative is to use a multi-breed reference population, such that smaller breeds gain some advantage in accuracy of genomic estimated breeding values (GEBV) from information from larger breeds. However, this requires that marker-quantitative trait loci associations persist across breeds. Here, we assessed the gain in accuracy of GEBV in Jersey cattle as a result of using a combined Holstein and Jersey reference population, with either 39,745 or 624,213 single nucleotide polymorphism (SNP) markers. The surrogate used for accuracy was the correlation of GEBV with daughter trait deviations in a validation population. Two methods were used to predict breeding values, either a genomic BLUP (GBLUP_mod), or a new method, BayesR, which used a mixture of normal distributions as the prior for SNP effects, including one distribution that set SNP effects to zero. The GBLUP_mod method scaled both the genomic relationship matrix and the additive relationship matrix to a base at the time the breeds diverged, and regressed the genomic relationship matrix to account for sampling errors in estimating relationship coefficients due to a finite number of markers, before combining the 2 matrices. Although these modifications did result in less biased breeding values for Jerseys compared with an unmodified genomic relationship matrix, BayesR gave the highest accuracies of GEBV for the 3 traits investigated (milk yield, fat yield, and protein yield), with an average increase in accuracy compared with GBLUP_mod across the 3 traits of 0.05 for both Jerseys and Holsteins. The advantage was limited for either Jerseys or Holsteins in using 624,213 SNP rather than 39,745 SNP (0.01 for Holsteins and 0.03 for Jerseys, averaged across traits). Even this limited and nonsignificant advantage was only observed when BayesR was used. An alternative panel, which extracted the SNP in the transcribed part of the bovine genome from the 624,213 SNP panel (to give 58,532 SNP), performed better, with an increase in accuracy of 0.03 for Jerseys across traits. This panel captures much of the increased genomic content of the 624,213 SNP panel, with the advantage of a greatly reduced number of SNP effects to estimate. Taken together, using this panel, a combined breed reference and using BayesR rather than GBLUP_mod increased the accuracy of GEBV in Jerseys from 0.43 to 0.52, averaged across the 3 traits. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Association of the rs7395662 SNP in the MADD-FOLH1 and Several Environmental Factors with Serum Lipid Levels in the Mulao and Han Populations

PubMed Central

Huang, Ke-Ke; Yin, Rui-Xing; Zeng, Xiao-Na; Huang, Ping; Lin, Quan-Zhen; Wu, Jian; Guo, Tao; Wang, Wei; Yang, De-Zhai; Lin, Wei-Xiong

2013-01-01

Background: The rs7395662 single nucleotide polymorphism (SNP) in the MADD-FOLH1 has been associated with serum lipid traits, but the results are inconsistent in different populations. The present study was undertaken to investigate the association of rs7395662 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations. Method: A total of 721 subjects of Mulao and 727 subjects of Han Chinese were randomly selected from our previous stratified randomized samples. Genotyping of the SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and confirmed by direct sequencing. Results: Serum apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.01). The allelic and genotypic frequencies in Han were different between males and females (P < 0.05 for each), but there was no difference between Mulao and Han or between Mulao males and females. The levels of low-density lipoprotein cholesterol (LDL-C) and ApoB in Mulao females were different among the genotypes (P < 0.05), the G allele carriers had higher LDL-C and ApoB levels than the G allele non-carriers. The levels of total cholesterol (TC), triglyceride (TG), LDL-C and ApoB in Han males and TC, TG and high-density lipoprotein cholesterol (HDL-C) in Han females were different among the genotypes (P < 0.05-0.01), the subjects with GG genotype in Han males had higher TC, TG, and ApoB and lower LDL-C levels than the subjects with AA or AG genotype, and the G allele carriers in Han females had lower TC and HDL-C levels than the G allele non-carriers. The levels of LDL-C and ApoB in Mulao females were correlated with the genotypes (P < 0.05 for each). The levels of HDL-C and ApoAI in Han males and HDL-C in Han females were correlated with genotypes (P < 0.05-0.001). Serum lipid parameters were also correlated with several environmental factors in both ethnic groups (P < 0.05-0.01). Conclusion: The association of rs7395662 SNP and serum lipid levels is different between the Mulao and Han populations, and between males and females in both ethnic groups. PMID:24046529

Genetic tests for estimating dairy breed proportion and parentage assignment in East African crossbred cattle.

PubMed

Strucken, Eva M; Al-Mamun, Hawlader A; Esquivelzeta-Rabell, Cecilia; Gondro, Cedric; Mwai, Okeyo A; Gibson, John P

2017-09-12

Smallholder dairy farming in much of the developing world is based on the use of crossbred cows that combine local adaptation traits of indigenous breeds with high milk yield potential of exotic dairy breeds. Pedigree recording is rare in such systems which means that it is impossible to make informed breeding decisions. High-density single nucleotide polymorphism (SNP) assays allow accurate estimation of breed composition and parentage assignment but are too expensive for routine application. Our aim was to determine the level of accuracy achieved with low-density SNP assays. We constructed subsets of 100 to 1500 SNPs from the 735k-SNP Illumina panel by selecting: (a) on high minor allele frequencies (MAF) in a crossbred population; (b) on large differences in allele frequency between ancestral breeds; (c) at random; or (d) with a differential evolution algorithm. These panels were tested on a dataset of 1933 crossbred dairy cattle from Kenya/Uganda and on crossbred populations from Ethiopia (N = 545) and Tanzania (N = 462). Dairy breed proportions were estimated by using the ADMIXTURE program, a regression approach, and SNP-best linear unbiased prediction, and tested against estimates obtained by ADMIXTURE based on the 735k-SNP panel. Performance for parentage assignment was based on opposing homozygotes which were used to calculate the separation value (sv) between true and false assignments. Panels of SNPs based on the largest differences in allele frequency between European dairy breeds and a combined Nelore/N'Dama population gave the best predictions of dairy breed proportion (r 2  = 0.962 to 0.994 for 100 to 1500 SNPs) with an average absolute bias of 0.026. Panels of SNPs based on the highest MAF in the crossbred population (Kenya/Uganda) gave the most accurate parentage assignments (sv = -1 to 15 for 100 to 1500 SNPs). Due to the different required properties of SNPs, panels that did well for breed composition did poorly for parentage assignment and vice versa. A combined panel of 400 SNPs was not able to assign parentages correctly, thus we recommend the use of 200 SNPs either for breed proportion prediction or parentage assignment, independently.

Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids

PubMed Central

McKay, Gareth J; Loane, Edward; Nolan, John M; Patterson, Christopher C; Meyers, Kristin J; Mares, Julie A; Yonova-Doing, Ekaterina; Hammond, Christopher J; Beatty, Stephen; Silvestri, Giuliana

2013-01-01

Objective To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). Design A cross-sectional study of healthy adults aged 20-70. Participants 302 participants recruited following local advertisement. Methods MPOD was measured by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by HPLC and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and CAREDS cohorts. Main outcome measures Odds ratios (ORs) for macular pigment optical density area, serum lutein and zeaxanthin concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and sex. Results Following multiple regression analysis with adjustment for age, body mass index, sex, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, smoking, dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P=0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P=2×10−4), a SNP in high linkage disequilibrium with rs11057841 (r2=0.93). No significant interactions by sex were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. Conclusions Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of AMD risk through combating the effects of oxidative stress within the retina. PMID:23562302

A Large Maize (Zea mays L.) SNP Genotyping Array: Development and Germplasm Genotyping, and Genetic Mapping to Compare with the B73 Reference Genome

PubMed Central

Ganal, Martin W.; Durstewitz, Gregor; Polley, Andreas; Bérard, Aurélie; Buckler, Edward S.; Charcosset, Alain; Clarke, Joseph D.; Graner, Eva-Maria; Hansen, Mark; Joets, Johann; Le Paslier, Marie-Christine; McMullen, Michael D.; Montalent, Pierre; Rose, Mark; Schön, Chris-Carolin; Sun, Qi; Walter, Hildrun; Martin, Olivier C.; Falque, Matthieu

2011-01-01

SNP genotyping arrays have been useful for many applications that require a large number of molecular markers such as high-density genetic mapping, genome-wide association studies (GWAS), and genomic selection. We report the establishment of a large maize SNP array and its use for diversity analysis and high density linkage mapping. The markers, taken from more than 800,000 SNPs, were selected to be preferentially located in genes and evenly distributed across the genome. The array was tested with a set of maize germplasm including North American and European inbred lines, parent/F1 combinations, and distantly related teosinte material. A total of 49,585 markers, including 33,417 within 17,520 different genes and 16,168 outside genes, were of good quality for genotyping, with an average failure rate of 4% and rates up to 8% in specific germplasm. To demonstrate this array's use in genetic mapping and for the independent validation of the B73 sequence assembly, two intermated maize recombinant inbred line populations – IBM (B73×Mo17) and LHRF (F2×F252) – were genotyped to establish two high density linkage maps with 20,913 and 14,524 markers respectively. 172 mapped markers were absent in the current B73 assembly and their placement can be used for future improvements of the B73 reference sequence. Colinearity of the genetic and physical maps was mostly conserved with some exceptions that suggest errors in the B73 assembly. Five major regions containing non-colinearities were identified on chromosomes 2, 3, 6, 7 and 9, and are supported by both independent genetic maps. Four additional non-colinear regions were found on the LHRF map only; they may be due to a lower density of IBM markers in those regions or to true structural rearrangements between lines. Given the array's high quality, it will be a valuable resource for maize genetics and many aspects of maize breeding. PMID:22174790

Improving accuracy of genomic prediction in Brangus cattle by adding animals with imputed low-density SNP genotypes.

PubMed

Lopes, F B; Wu, X-L; Li, H; Xu, J; Perkins, T; Genho, J; Ferretti, R; Tait, R G; Bauck, S; Rosa, G J M

2018-02-01

Reliable genomic prediction of breeding values for quantitative traits requires the availability of sufficient number of animals with genotypes and phenotypes in the training set. As of 31 October 2016, there were 3,797 Brangus animals with genotypes and phenotypes. These Brangus animals were genotyped using different commercial SNP chips. Of them, the largest group consisted of 1,535 animals genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to the SNP content of the GGP-LDV4 chip, so that the number of animals available for training the genomic prediction models was more than doubled. The present study showed that the pooling of animals with both original or imputed 40K SNP genotypes substantially increased genomic prediction accuracies on the ten traits. By supplementing imputed genotypes, the relative gains in genomic prediction accuracies on estimated breeding values (EBV) were from 12.60% to 31.27%, and the relative gain in genomic prediction accuracies on de-regressed EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the performance of five genomic prediction models and two cross-validation methods. The five genomic models predicted EBV and de-regressed EBV of the ten traits similarly well. Of the two cross-validation methods, leave-one-out cross-validation maximized the number of animals at the stage of training for genomic prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was validated in 1,106 newly genotyped Brangus animals based on the SNP effects estimated in the previous set of 3,797 Brangus animals, and they were slightly lower than GPA in the original data. The present study was the first to leverage currently available genotype and phenotype resources in order to harness genomic prediction in Brangus beef cattle. © 2018 Blackwell Verlag GmbH.

Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification

PubMed Central

Faye, Laura L.; Machiela, Mitchell J.; Kraft, Peter; Bull, Shelley B.; Sun, Lei

2013-01-01

Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-use of GWAS data for fine-mapping exploits previous findings to ensure genome-wide significance in GWAS-associated regions. However, using GWAS findings to inform fine-mapping analysis can bias evidence away from the causal SNP toward the tag SNP and SNPs in high LD with the tag. Together these factors can reduce power to localize the causal SNP by more than half. Other strategies commonly employed to increase power to detect association, namely increasing sample size and using higher density genotyping arrays, can, in certain common scenarios, actually exacerbate these effects and further decrease power to localize causal variants. We develop a re-ranking procedure that accounts for these adverse effects and substantially improves the accuracy of causal SNP identification, often doubling the probability that the causal SNP is top-ranked. Application to the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis identified a new top SNP at 2 of 3 associated loci and several additional possible causal SNPs at these loci that may have otherwise been overlooked. This method is simple to implement using R scripts provided on the author's website. PMID:23950724

Gender-dependent association of a β(2)-adrenergic gene variant with obesity parameters in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Ming, Moy Foong; Rampal, Sanjay; Bulgiba, Awang; Mohamed, Zahurin

2015-03-01

Recent findings have shown that the rs1042714 (Gln27Glu) single-nucleotide polymorphism (SNP) on the β2-adrenoceptor gene may predispose to obesity. The findings from other studies carried on different populations, however, have been inconsistent. The authors investigated the association between the rs1042714 SNP with obesity-related parameters. DNA of 672 Malaysian Malays was analyzed using real-time polymerase chain reaction. Univariate and multivariate linear regression analyses revealed significant associations between rs1042714 and diastolic blood pressure in the pooled Malaysian Malay subjects under additive and recessive models. After gender stratification, however, a significant association was found between the rs1042714 and triglyceride and the rs1042714 and log-transformed high-density lipoprotein cholesterol levels in Malaysian Malay men. No significant association was found between the SNP and log-transformed body mass index. This polymorphism may have an important role in the development of obesity-related traits in Malaysian Malays. Gender is an effect modifier for the effect of the rs1042714 polymorphism on obesity-related traits in Malaysian Malays. © 2011 APJPH.

Lack of Association of Bone Morphogenetic Protein 2 Gene Haplotypes with Bone Mineral Density, Bone Loss, or Risk of Fractures in Men

PubMed Central

Varanasi, Satya S.; Tuck, Stephen P.; Mastana, Sarabjit S.; Dennison, Elaine; Cooper, Cyrus; Vila, Josephine; Francis, Roger M.; Datta, Harish K.

2011-01-01

Introduction. The association of bone morphogenetic protein 2 (BMP2) with BMD and risk of fracture was suggested by a recent linkage study, but subsequent studies have been contradictory. We report the results of a study of the relationship between BMP2 genotypes and BMD, annual change in BMD, and risk of fracture in male subjects. Materials and Methods. We tested three single-nucleotide polymorphisms (SNPs) across the BMP2 gene, including Ser37Ala SNP, in 342 Caucasian Englishmen, comprising 224 control and 118 osteoporotic subjects. Results. BMP2 SNP1 (Ser37Ala) genotypes were found to have similar low frequency in control subjects and men with osteoporosis. The major informative polymorphism, BMP2 SNP3 (Arg190Ser), showed no statistically significant association with weight, height, BMD, change in BMD at hip or lumbar spine, and risk of fracture. Conclusion. There were no genotypic or haplotypic effects of the BMP2 candidate gene on BMD, change in BMD, or fracture risk identified in this cohort. PMID:22013543

ITALICS: an algorithm for normalization and DNA copy number calling for Affymetrix SNP arrays.

PubMed

Rigaill, Guillem; Hupé, Philippe; Almeida, Anna; La Rosa, Philippe; Meyniel, Jean-Philippe; Decraene, Charles; Barillot, Emmanuel

2008-03-15

Affymetrix SNP arrays can be used to determine the DNA copy number measurement of 11 000-500 000 SNPs along the genome. Their high density facilitates the precise localization of genomic alterations and makes them a powerful tool for studies of cancers and copy number polymorphism. Like other microarray technologies it is influenced by non-relevant sources of variation, requiring correction. Moreover, the amplitude of variation induced by non-relevant effects is similar or greater than the biologically relevant effect (i.e. true copy number), making it difficult to estimate non-relevant effects accurately without including the biologically relevant effect. We addressed this problem by developing ITALICS, a normalization method that estimates both biological and non-relevant effects in an alternate, iterative manner, accurately eliminating irrelevant effects. We compared our normalization method with other existing and available methods, and found that ITALICS outperformed these methods for several in-house datasets and one public dataset. These results were validated biologically by quantitative PCR. The R package ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) has been submitted to Bioconductor.

Genome-Wide Association Mapping of Barley Yellow Dwarf Virus Tolerance in Spring Oat (Avena sativa L.)

PubMed Central

Foresman, Bradley J.; Oliver, Rebekah E.; Jackson, Eric W.; Chao, Shiaoman; Arruda, Marcio P.; Kolb, Frederic L.

2016-01-01

Barley yellow dwarf viruses (BYDVs) are responsible for the disease barley yellow dwarf (BYD) and affect many cereals including oat (Avena sativa L.). Until recently, the molecular marker technology in oat has not allowed for many marker-trait association studies to determine the genetic mechanisms for tolerance. A genome-wide association study (GWAS) was performed on 428 spring oat lines using a recently developed high-density oat single nucleotide polymorphism (SNP) array as well as a SNP-based consensus map. Marker-trait associations were performed using a Q-K mixed model approach to control for population structure and relatedness. Six significant SNP-trait associations representing two QTL were found on chromosomes 3C (Mrg17) and 18D (Mrg04). This is the first report of BYDV tolerance QTL on chromosome 3C (Mrg17) and 18D (Mrg04). Haplotypes using the two QTL were evaluated and distinct classes for tolerance were identified based on the number of favorable alleles. A large number of lines carrying both favorable alleles were observed in the panel. PMID:27175781

Remote Sensing of Cryosphere: Estimation of Mass Balance Change in Himalayan Glaciers

NASA Astrophysics Data System (ADS)

Ambinakudige, Shrinidhi; Joshi, Kabindra

2012-07-01

Glacial changes are an important indicator of climate change. Our understanding mass balance change in Himalayan glaciers is limited. This study estimates mass balance of some major glaciers in the Sagarmatha National Park (SNP) in Nepal using remote sensing applications. Remote sensing technique to measure mass balance of glaciers is an important methodological advance in the highly rugged Himalayan terrain. This study uses ASTER VNIR, 3N (nadir view) and 3B (backward view) bands to generate Digital Elevation Models (DEMs) for the SNP area for the years 2002, 2003, 2004 and 2005. Glacier boundaries were delineated using combination of boundaries available in the Global land ice measurement (GLIMS) database and various band ratios derived from ASTER images. Elevation differences, glacial area, and ice densities were used to estimate the change in mass balance. The results indicated that the rate of glacier mass balance change was not uniform across glaciers. While there was a decrease in mass balance of some glaciers, some showed increase. This paper discusses how each glacier in the SNP area varied in its annual mass balance measurement during the study period.

Genome-wide association studies identify 25 genetic loci associated with resistance to Bacterial Cold Water Disease in rainbow trout

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant mortality and economic losses in salmonids aquaculture. In previous studies we have identified moderate-large effect QTL for BCWD resistance in rainbow trout (Oncorhynchus mykiss). However, the recent availability of a high density SNP array and...

Integration of genomic resources to uncover pleiotropic regions associated with age at puberty and reproductive longevity in sows

USDA-ARS?s Scientific Manuscript database

Commercial and experimental genetic resources were used to investigate genetic pleiotropic factors that influence age at puberty, litter-size and reproductive longevity. The phenotypes were complemented by high-density genotyping and whole genome and RNA sequencing. The SNPs from Porcine SNP60 BeadA...

Distribution and Location of Genetic Effects for Dairy Traits

USDA-ARS?s Scientific Manuscript database

Genetic effects for many dairy traits and for total economic merit are fairly evenly distributed across all chromosomes. A high-density scan using 38,416 SNP markers for 5,285 bulls confirmed two previously-known major genes on Bos taurus autosomes (BTA) 6 and 14 but revealed few other large effects...

Determination of Metastatic Potential in Breast Tumors by Global Molecular Characterization Using Multiple Modalities

DTIC Science & Technology

2010-10-01

5 Results ...to disease prognosis and in determining the course of treatment for the patient (2) . Breast cancer is a highly heterogeneous and complex disease...progression is a challenge. Introduction of high density single nucleotide polymorphism (SNP) genotyping arrays has helped not only for whole genome

Effect of Co-segregating Markers on High-Density Genetic Maps and Prediction of Map Expansion Using Machine Learning Algorithms.

PubMed

N'Diaye, Amidou; Haile, Jemanesh K; Fowler, D Brian; Ammar, Karim; Pozniak, Curtis J

2017-01-01

Advances in sequencing and genotyping methods have enable cost-effective production of high throughput single nucleotide polymorphism (SNP) markers, making them the choice for linkage mapping. As a result, many laboratories have developed high-throughput SNP assays and built high-density genetic maps. However, the number of markers may, by orders of magnitude, exceed the resolution of recombination for a given population size so that only a minority of markers can accurately be ordered. Another issue attached to the so-called 'large p, small n' problem is that high-density genetic maps inevitably result in many markers clustering at the same position (co-segregating markers). While there are a number of related papers, none have addressed the impact of co-segregating markers on genetic maps. In the present study, we investigated the effects of co-segregating markers on high-density genetic map length and marker order using empirical data from two populations of wheat, Mohawk × Cocorit (durum wheat) and Norstar × Cappelle Desprez (bread wheat). The maps of both populations consisted of 85% co-segregating markers. Our study clearly showed that excess of co-segregating markers can lead to map expansion, but has little effect on markers order. To estimate the inflation factor (IF), we generated a total of 24,473 linkage maps (8,203 maps for Mohawk × Cocorit and 16,270 maps for Norstar × Cappelle Desprez). Using seven machine learning algorithms, we were able to predict with an accuracy of 0.7 the map expansion due to the proportion of co-segregating markers. For example in Mohawk × Cocorit, with 10 and 80% co-segregating markers the length of the map inflated by 4.5 and 16.6%, respectively. Similarly, the map of Norstar × Cappelle Desprez expanded by 3.8 and 11.7% with 10 and 80% co-segregating markers. With the increasing number of markers on SNP-chips, the proportion of co-segregating markers in high-density maps will continue to increase making map expansion unavoidable. Therefore, we suggest developers improve linkage mapping algorithms for efficient analysis of high-throughput data. This study outlines a practical strategy to estimate the IF due to the proportion of co-segregating markers and outlines a method to scale the length of the map accordingly.

Effect of Co-segregating Markers on High-Density Genetic Maps and Prediction of Map Expansion Using Machine Learning Algorithms

PubMed Central

N’Diaye, Amidou; Haile, Jemanesh K.; Fowler, D. Brian; Ammar, Karim; Pozniak, Curtis J.

2017-01-01

Advances in sequencing and genotyping methods have enable cost-effective production of high throughput single nucleotide polymorphism (SNP) markers, making them the choice for linkage mapping. As a result, many laboratories have developed high-throughput SNP assays and built high-density genetic maps. However, the number of markers may, by orders of magnitude, exceed the resolution of recombination for a given population size so that only a minority of markers can accurately be ordered. Another issue attached to the so-called ‘large p, small n’ problem is that high-density genetic maps inevitably result in many markers clustering at the same position (co-segregating markers). While there are a number of related papers, none have addressed the impact of co-segregating markers on genetic maps. In the present study, we investigated the effects of co-segregating markers on high-density genetic map length and marker order using empirical data from two populations of wheat, Mohawk × Cocorit (durum wheat) and Norstar × Cappelle Desprez (bread wheat). The maps of both populations consisted of 85% co-segregating markers. Our study clearly showed that excess of co-segregating markers can lead to map expansion, but has little effect on markers order. To estimate the inflation factor (IF), we generated a total of 24,473 linkage maps (8,203 maps for Mohawk × Cocorit and 16,270 maps for Norstar × Cappelle Desprez). Using seven machine learning algorithms, we were able to predict with an accuracy of 0.7 the map expansion due to the proportion of co-segregating markers. For example in Mohawk × Cocorit, with 10 and 80% co-segregating markers the length of the map inflated by 4.5 and 16.6%, respectively. Similarly, the map of Norstar × Cappelle Desprez expanded by 3.8 and 11.7% with 10 and 80% co-segregating markers. With the increasing number of markers on SNP-chips, the proportion of co-segregating markers in high-density maps will continue to increase making map expansion unavoidable. Therefore, we suggest developers improve linkage mapping algorithms for efficient analysis of high-throughput data. This study outlines a practical strategy to estimate the IF due to the proportion of co-segregating markers and outlines a method to scale the length of the map accordingly. PMID:28878789

Construction of a High-Density Genetic Map from RNA-Seq Data for an Arabidopsis Bay-0 × Shahdara RIL Population

PubMed Central

Serin, Elise A. R.; Snoek, L. B.; Nijveen, Harm; Willems, Leo A. J.; Jiménez-Gómez, Jose M.; Hilhorst, Henk W. M.; Ligterink, Wilco

2017-01-01

High-density genetic maps are essential for high resolution mapping of quantitative traits. Here, we present a new genetic map for an Arabidopsis Bayreuth × Shahdara recombinant inbred line (RIL) population, built on RNA-seq data. RNA-seq analysis on 160 RILs of this population identified 30,049 single-nucleotide polymorphisms (SNPs) covering the whole genome. Based on a 100-kbp window SNP binning method, 1059 bin-markers were identified, physically anchored on the genome. The total length of the RNA-seq genetic map spans 471.70 centimorgans (cM) with an average marker distance of 0.45 cM and a maximum marker distance of 4.81 cM. This high resolution genotyping revealed new recombination breakpoints in the population. To highlight the advantages of such high-density map, we compared it to two publicly available genetic maps for the same population, comprising 69 PCR-based markers and 497 gene expression markers derived from microarray data, respectively. In this study, we show that SNP markers can effectively be derived from RNA-seq data. The new RNA-seq map closes many existing gaps in marker coverage, saturating the previously available genetic maps. Quantitative trait locus (QTL) analysis for published phenotypes using the available genetic maps showed increased QTL mapping resolution and reduced QTL confidence interval using the RNA-seq map. The new high-density map is a valuable resource that facilitates the identification of candidate genes and map-based cloning approaches. PMID:29259624

Accuracy of estimation of genomic breeding values in pigs using low-density genotypes and imputation.

PubMed

Badke, Yvonne M; Bates, Ronald O; Ernst, Catherine W; Fix, Justin; Steibel, Juan P

2014-04-16

Genomic selection has the potential to increase genetic progress. Genotype imputation of high-density single-nucleotide polymorphism (SNP) genotypes can improve the cost efficiency of genomic breeding value (GEBV) prediction for pig breeding. Consequently, the objectives of this work were to: (1) estimate accuracy of genomic evaluation and GEBV for three traits in a Yorkshire population and (2) quantify the loss of accuracy of genomic evaluation and GEBV when genotypes were imputed under two scenarios: a high-cost, high-accuracy scenario in which only selection candidates were imputed from a low-density platform and a low-cost, low-accuracy scenario in which all animals were imputed using a small reference panel of haplotypes. Phenotypes and genotypes obtained with the PorcineSNP60 BeadChip were available for 983 Yorkshire boars. Genotypes of selection candidates were masked and imputed using tagSNP in the GeneSeek Genomic Profiler (10K). Imputation was performed with BEAGLE using 128 or 1800 haplotypes as reference panels. GEBV were obtained through an animal-centric ridge regression model using de-regressed breeding values as response variables. Accuracy of genomic evaluation was estimated as the correlation between estimated breeding values and GEBV in a 10-fold cross validation design. Accuracy of genomic evaluation using observed genotypes was high for all traits (0.65-0.68). Using genotypes imputed from a large reference panel (accuracy: R(2) = 0.95) for genomic evaluation did not significantly decrease accuracy, whereas a scenario with genotypes imputed from a small reference panel (R(2) = 0.88) did show a significant decrease in accuracy. Genomic evaluation based on imputed genotypes in selection candidates can be implemented at a fraction of the cost of a genomic evaluation using observed genotypes and still yield virtually the same accuracy. On the other side, using a very small reference panel of haplotypes to impute training animals and candidates for selection results in lower accuracy of genomic evaluation.

A high-density, multi-parental SNP genetic map on apple validates a new mapping approach for outcrossing species.

PubMed

Di Pierro, Erica A; Gianfranceschi, Luca; Di Guardo, Mario; Koehorst-van Putten, Herma Jj; Kruisselbrink, Johannes W; Longhi, Sara; Troggio, Michela; Bianco, Luca; Muranty, Hélène; Pagliarani, Giulia; Tartarini, Stefano; Letschka, Thomas; Lozano Luis, Lidia; Garkava-Gustavsson, Larisa; Micheletti, Diego; Bink, Marco Cam; Voorrips, Roeland E; Aziz, Ebrahimi; Velasco, Riccardo; Laurens, François; van de Weg, W Eric

2016-01-01

Quantitative trait loci (QTL) mapping approaches rely on the correct ordering of molecular markers along the chromosomes, which can be obtained from genetic linkage maps or a reference genome sequence. For apple ( Malus domestica Borkh), the genome sequence v1 and v2 could not meet this need; therefore, a novel approach was devised to develop a dense genetic linkage map, providing the most reliable marker-loci order for the highest possible number of markers. The approach was based on four strategies: (i) the use of multiple full-sib families, (ii) the reduction of missing information through the use of HaploBlocks and alternative calling procedures for single-nucleotide polymorphism (SNP) markers, (iii) the construction of a single backcross-type data set including all families, and (iv) a two-step map generation procedure based on the sequential inclusion of markers. The map comprises 15 417 SNP markers, clustered in 3 K HaploBlock markers spanning 1 267 cM, with an average distance between adjacent markers of 0.37 cM and a maximum distance of 3.29 cM. Moreover, chromosome 5 was oriented according to its homoeologous chromosome 10. This map was useful to improve the apple genome sequence, design the Axiom Apple 480 K SNP array and perform multifamily-based QTL studies. Its collinearity with the genome sequences v1 and v3 are reported. To our knowledge, this is the shortest published SNP map in apple, while including the largest number of markers, families and individuals. This result validates our methodology, proving its value for the construction of integrated linkage maps for any outbreeding species.

Consistency between cross-sectional and longitudinal SNP: blood lipid associations.

PubMed

Costanza, Michael C; Beer-Borst, Sigrid; James, Richard W; Gaspoz, Jean-Michel; Morabia, Alfredo

2012-02-01

Various studies have linked different genetic single nucleotide polymorphisms (SNPs) to different blood lipids (BL), but whether these "connections" were identified using cross-sectional or longitudinal (i.e., changes over time) designs has received little attention. Cross-sectional and longitudinal assessments of BL [total, high-, low-density lipoprotein cholesterol (TC, HDL, LDL), triglycerides (TG)] and non-genetic factors (body mass index, smoking, alcohol intake) were measured for 2,002 Geneva, Switzerland, adults during 1999-2008 (two measurements, median 6 years apart), and 20 SNPs in 13 BL metabolism-related genes. Fixed and mixed effects repeated measures linear regression models, respectively, were employed to identify cross-sectional and longitudinal SNP:BL associations among the 1,516 (76%) study participants who reported not being treated for hypercholesterolemia at either measurement time. One-third more (12 vs. 9) longitudinal than cross-sectional associations were found [Bonferroni-adjusted two-tailed p < 0.00125 (=0.05/2)/20) for each of the four ensembles of 20 SNP:individual BL associations tested under the two study designs]. There was moderate consistency between the cross-sectional and longitudinal findings, with eight SNP:BL associations consistently identified across both study designs: [APOE.2 and APOE.4 (rs7412 and rs429358)]:TC; HL/LIPC (rs2070895):HDL; [APOB (rs1367117), APOE.2 and APOE.4 (rs7412 and rs429358)]:LDL; [APOA5 (rs2072560) and APOC III (rs5128)]:TG. The results suggest that cross-sectional studies, which include most genome-wide association studies (GWAS), can assess the large majority of SNP:BL associations. In the present analysis, which was much less powered than a GWAS, the cross-sectional study was around 2/3 (67%) as efficient as the longitudinal study.

A high-density, multi-parental SNP genetic map on apple validates a new mapping approach for outcrossing species

PubMed Central

Di Pierro, Erica A; Gianfranceschi, Luca; Di Guardo, Mario; Koehorst-van Putten, Herma JJ; Kruisselbrink, Johannes W; Longhi, Sara; Troggio, Michela; Bianco, Luca; Muranty, Hélène; Pagliarani, Giulia; Tartarini, Stefano; Letschka, Thomas; Lozano Luis, Lidia; Garkava-Gustavsson, Larisa; Micheletti, Diego; Bink, Marco CAM; Voorrips, Roeland E; Aziz, Ebrahimi; Velasco, Riccardo; Laurens, François; van de Weg, W Eric

2016-01-01

Quantitative trait loci (QTL) mapping approaches rely on the correct ordering of molecular markers along the chromosomes, which can be obtained from genetic linkage maps or a reference genome sequence. For apple (Malus domestica Borkh), the genome sequence v1 and v2 could not meet this need; therefore, a novel approach was devised to develop a dense genetic linkage map, providing the most reliable marker-loci order for the highest possible number of markers. The approach was based on four strategies: (i) the use of multiple full-sib families, (ii) the reduction of missing information through the use of HaploBlocks and alternative calling procedures for single-nucleotide polymorphism (SNP) markers, (iii) the construction of a single backcross-type data set including all families, and (iv) a two-step map generation procedure based on the sequential inclusion of markers. The map comprises 15 417 SNP markers, clustered in 3 K HaploBlock markers spanning 1 267 cM, with an average distance between adjacent markers of 0.37 cM and a maximum distance of 3.29 cM. Moreover, chromosome 5 was oriented according to its homoeologous chromosome 10. This map was useful to improve the apple genome sequence, design the Axiom Apple 480 K SNP array and perform multifamily-based QTL studies. Its collinearity with the genome sequences v1 and v3 are reported. To our knowledge, this is the shortest published SNP map in apple, while including the largest number of markers, families and individuals. This result validates our methodology, proving its value for the construction of integrated linkage maps for any outbreeding species. PMID:27917289

A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies

PubMed Central

McCue, Molly E.; Bannasch, Danika L.; Petersen, Jessica L.; Gurr, Jessica; Bailey, Ernie; Binns, Matthew M.; Distl, Ottmar; Guérin, Gérard; Hasegawa, Telhisa; Hill, Emmeline W.; Leeb, Tosso; Lindgren, Gabriella; Penedo, M. Cecilia T.; Røed, Knut H.; Ryder, Oliver A.; Swinburne, June E.; Tozaki, Teruaki; Valberg, Stephanie J.; Vaudin, Mark; Lindblad-Toh, Kerstin

2012-01-01

An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species. More than 54,000 polymorphic SNPs provided an average inter-SNP spacing of ∼43 kb. The mean minor allele frequency across domestic horse breeds was 0.23, and the number of polymorphic SNPs within breeds ranged from 43,287 to 52,085. Genome-wide linkage disequilibrium (LD) in most breeds declined rapidly over the first 50–100 kb and reached background levels within 1–2 Mb. The extent of LD and the level of inbreeding were highest in the Thoroughbred and lowest in the Mongolian and Quarter Horse. Multidimensional scaling (MDS) analyses demonstrated the tight grouping of individuals within most breeds, close proximity of related breeds, and less tight grouping in admixed breeds. The close relationship between the Przewalski's Horse and the domestic horse was demonstrated by pair-wise genetic distance and MDS. Genotyping of other Perissodactyla (zebras, asses, tapirs, and rhinoceros) was variably successful, with call rates and the number of polymorphic loci varying across taxa. Parsimony analysis placed the modern horse as sister taxa to Equus przewalski. The utility of the SNP array in genome-wide association was confirmed by mapping the known recessive chestnut coat color locus (MC1R) and defining a conserved haplotype of ∼750 kb across all breeds. These results demonstrate the high quality of this SNP genotyping resource, its usefulness in diverse genome analyses of the horse, and potential use in related species. PMID:22253606

A Candidate Gene Association Study of Bone Mineral Density in an Iranian Population.

PubMed

Dastgheib, Seyed Alireza; Gartland, Alison; Tabei, Seyed Mohammad Bagher; Omrani, Gholamhossein Ranjbar; Teare, Marion Dawn

2016-01-01

The genetic epidemiology of variation in bone mineral density (BMD) and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross-sectional study of 501 males and females sampled from the Iranian Multi-Centre Osteoporosis Study, Shiraz, Iran. We selected to study the association with 21 single nucleotide polymorphisms (SNPs) located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR , and ESR1 . BMD was measured at the three sites L2-L4, neck of femur, and total hip. Association between BMD and each SNP was assessed using multiple linear regression assuming an allele dose (additive effect) on BMD (adjusted for age and sex). Statistically significant (at the unadjusted 5% level) associations were seen with seven SNPs in five of the candidate genes. Two SNPs showed statistically significant association with more than one BMD site. Significant association was seen between BMD at all the three sites with the VDR SNP rs731246 (L2-L4 p  = 0.038; neck of femur p  = 0.001; and total hip p  < 0.001). The T allele was consistently associated with lower BMD than the C allele. Significant association was also seen for the P2RX7 SNP rs3751143, where the G allele was consistently associated with lower BMD than the T allele (L2-L4 p  = 0.069; neck of femur p  = 0.024; and total hip p  = 0.045).

Emulsions Containing Perfluorocarbon Support Cell Cultures

NASA Technical Reports Server (NTRS)

Ju, Lu-Kwang; Lee, Jaw Fang; Armiger, William B.

1990-01-01

Addition of emulsion containing perfluorocarbon liquid to aqueous cell-culture medium increases capacity of medium to support mammalian cells. FC-40 Fluorinert (or equivalent) - increases average density of medium so approximately equal to that of cells. Cells stay suspended in medium without mechanical stirring, which damages them. Increases density enough to prevent cells from setting, and increases viscosity of medium so oxygen bubbled through it and nutrients stirred in with less damage to delicate cells.

The effect of the external medium on the gravity-induced polarity of cytoplasmic streaming in Chara corallina (Characeae).

PubMed

Staves, M P; Wayne, R; Leopold, A C

1997-11-01

Gravity induces a polarity of cytoplasmic streaming in vertical internodal cells of Chara such that the downwardly directed stream moves faster than the upwardly directed stream. In order to determine whether the statolith theory (in which intracellular sedimenting particles are responsible for gravity sensing) or the gravitational pressure theory (in which the entire protoplast acts as the gravity sensor) best explain the gravity response in Chara internodal cells, we controlled the physical properties of the external medium, including density and osmolarity, with impermeant solutes and examined the effect on the polarity of cytoplasmic streaming. As the density of the external medium is increased, the polarity of cytoplasmic streaming decreases and finally disappears when the density of the external medium is equal to that of the cell (1015 kg/m3). A further increase in the density of the external medium causes a reversal of the gravity response. These results are consistent with the gravitational pressure theory of gravity sensing since the buoyancy of the protoplast is dependent on the difference between the density of the protoplast and the external medium, and are inconsistent with the statolith theory since the buoyancy of intracellular particles are unaffected by changes in the external medium.

The effect of the external medium on the gravity-induced polarity of cytoplasmic streaming in Chara corallina (Characeae)

NASA Technical Reports Server (NTRS)

Staves, M. P.; Wayne, R.; Leopold, A. C.

1997-01-01

Gravity induces a polarity of cytoplasmic streaming in vertical internodal cells of Chara such that the downwardly directed stream moves faster than the upwardly directed stream. In order to determine whether the statolith theory (in which intracellular sedimenting particles are responsible for gravity sensing) or the gravitational pressure theory (in which the entire protoplast acts as the gravity sensor) best explain the gravity response in Chara internodal cells, we controlled the physical properties of the external medium, including density and osmolarity, with impermeant solutes and examined the effect on the polarity of cytoplasmic streaming. As the density of the external medium is increased, the polarity of cytoplasmic streaming decreases and finally disappears when the density of the external medium is equal to that of the cell (1015 kg/m3). A further increase in the density of the external medium causes a reversal of the gravity response. These results are consistent with the gravitational pressure theory of gravity sensing since the buoyancy of the protoplast is dependent on the difference between the density of the protoplast and the external medium, and are inconsistent with the statolith theory since the buoyancy of intracellular particles are unaffected by changes in the external medium.

Properties of medium-density fiberboard produced in an oil-heated laboratory press

Treesearch

O. Suchsland; G.E. Woodson

1976-01-01

Medium-density fiberboards from pressurized double-disk refined fibers have a close correlation between layer density and layer dynamic modulus of elasticity. Density distribution over the thickness was readily controlled by manipulating platen temperature and applied pressure. Thus, overall modulus of elasticity could be adjusted. In contrast to modulus of elasticity...

Genetic dissection of Al tolerance QTLs in the maize genome by high density SNP scan

USDA-ARS?s Scientific Manuscript database

Aluminum (Al) toxicity is an important limitation to food security in the tropical and subtropical regions. High Al saturation in acid soils limits root development and its ability to uptake water and nutrients. In this study, we present a genome scan for Al tolerance loci with over 50,000 GBS-based...

Discovery of 20,000 RAD-SNPs and development of a 52-SNP array for monitoring river otters

Treesearch

Jeffrey B. Stetz; Seth Smith; Michael A. Sawaya; Alan B. Ramsey; Stephen J. Amish; Michael K. Schwartz; Gordon Luikart

2016-01-01

Many North American river otter (Lontra canadensis) populations are threatened or recovering but are difficult to study because they occur at low densities, it is difficult to visually identify individuals, and they inhabit aquatic environments that accelerate degradation of biological samples. Single nucleotide polymorphisms (SNPs) can improve our ability to...

Associations between breast density and a panel of single nucleotide polymorphisms linked to breast cancer risk: a cohort study with digital mammography.

PubMed

Keller, Brad M; McCarthy, Anne Marie; Chen, Jinbo; Armstrong, Katrina; Conant, Emily F; Domchek, Susan M; Kontos, Despina

2015-03-18

Breast density and single-nucleotide polymorphisms (SNPs) have both been associated with breast cancer risk. To determine the extent to which these two breast cancer risk factors are associated, we investigate the association between a panel of validated SNPs related to breast cancer and quantitative measures of mammographic density in a cohort of Caucasian and African-American women. In this IRB-approved, HIPAA-compliant study, we analyzed a screening population of 639 women (250 African American and 389 Caucasian) who were tested with a validated panel assay of 12 SNPs previously associated to breast cancer risk. Each woman underwent digital mammography as part of routine screening and all were interpreted as negative. Both absolute and percent estimates of area and volumetric density were quantified on a per-woman basis using validated software. Associations between the number of risk alleles in each SNP and the density measures were assessed through a race-stratified linear regression analysis, adjusted for age, BMI, and Gail lifetime risk. The majority of SNPs were not found to be associated with any measure of breast density. SNP rs3817198 (in LSP1) was significantly associated with both absolute area (p = 0.004) and volumetric (p = 0.019) breast density in Caucasian women. In African-American women, SNPs rs3803662 (in TNRC9/TOX3) and rs4973768 (in NEK10) were significantly associated with absolute (p = 0.042) and percent (p = 0.028) volume density respectively. The majority of SNPs investigated in our study were not found to be significantly associated with breast density, even when accounting for age, BMI, and Gail risk, suggesting that these two different risk factors contain potentially independent information regarding a woman's risk to develop breast cancer. Additionally, the few statistically significant associations between breast density and SNPs were different for Caucasian versus African American women. Larger prospective studies are warranted to validate our findings and determine potential implications for breast cancer risk assessment.

Effects of panel density and mat moisture content on processing medium density fiberboard

Treesearch

Zhiyong Cai; James H. Muehl; Jerrold E. Winandy

2006-01-01

Development of a fundamental understanding of heat transfer and resin curing during hot- pressing will help to optimize the manufacturing process of medium density fiberboard (MDF) allowing increased productivity, improved product quality, and enhanced durability. Effect of mat moisture content (MC) and panel density on performance of MDF panels, heat transfer,...

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array

PubMed Central

2012-01-01

Background A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Results Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the ‘Golden Delicious’ genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the ‘Golden Delicious’ pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. Conclusions We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the ‘Golden Delicious’ reference sequence will assist in the continued improvement of the genome sequence assembly for that variety. PMID:22631220

Joint genome-wide association study for milk fatty acid traits in Chinese and Danish Holstein populations.

PubMed

Li, X; Buitenhuis, A J; Lund, M S; Li, C; Sun, D; Zhang, Q; Poulsen, N A; Su, G

2015-11-01

The identification of causal genes or genomic regions associated with fatty acids (FA) will enhance our understanding of the pathways underlying FA synthesis and provide opportunities for changing milk fat composition through a genetic approach. The linkage disequilibrium between adjacent markers is highly consistent between the Chinese and Danish Holstein populations, such that a joint genome-wide association study (GWAS) can be performed. In this study, a joint GWAS was performed for 16 milk FA traits based on data of 784 Chinese and 371 Danish Holstein cows genotyped by a high-density bovine single nucleotide polymorphism (SNP) array. A total of 486,464 SNP markers on 29 bovine autosomes were used. Bonferroni corrections were applied to adjust the significance thresholds for multiple testing at the genome- and chromosome-wide levels. According to the analysis of either the Chinese or Danish data individually, the total numbers of overlapping SNP that were significant at the chromosome level were 94 for C14:1, 208 for the C14 index, and 1 for C18:0. Joint analysis using the combined data of the 2 populations detected greater numbers of significant SNP compared with either of the individual populations alone for 7 and 10 traits at the genome- and chromosome-wide significance levels, respectively. Greater numbers of significant SNP were detected for C18:0 and the C18 index in the Chinese population compared with the joint analysis. Sixty-five significant SNP across all traits had significantly different effects in the 2 populations. Ten FA were influenced by a quantitative trait loci (QTL) region including DGAT1. Both C14:1 and the C14 index were influenced by a QTL region including SCD1 in the combined population. Other QTL regions also showed significant associations with the studied FA. A large region (14.9-24.9 Mbp) in BTA26 significantly influenced C14:1 and the C14 index in both populations, mostly likely due to the SNP in SCD1. A QTL region (69.97-73.69 Mbp) on BTA9 showed a significantly different effect on C18:0 between the 2 populations. Detection of these important SNP and the corresponding QTL regions will be helpful for follow-up studies to identify causal mutations and their interaction with environments for milk FA in dairy cattle. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Characterization of polyploid wheat genomic diversity using a high-density 90 000 single nucleotide polymorphism array

PubMed Central

Wang, Shichen; Wong, Debbie; Forrest, Kerrie; Allen, Alexandra; Chao, Shiaoman; Huang, Bevan E; Maccaferri, Marco; Salvi, Silvio; Milner, Sara G; Cattivelli, Luigi; Mastrangelo, Anna M; Whan, Alex; Stephen, Stuart; Barker, Gary; Wieseke, Ralf; Plieske, Joerg; International Wheat Genome Sequencing Consortium; Lillemo, Morten; Mather, Diane; Appels, Rudi; Dolferus, Rudy; Brown-Guedira, Gina; Korol, Abraham; Akhunova, Alina R; Feuillet, Catherine; Salse, Jerome; Morgante, Michele; Pozniak, Curtis; Luo, Ming-Cheng; Dvorak, Jan; Morell, Matthew; Dubcovsky, Jorge; Ganal, Martin; Tuberosa, Roberto; Lawley, Cindy; Mikoulitch, Ivan; Cavanagh, Colin; Edwards, Keith J; Hayden, Matthew; Akhunov, Eduard

2014-01-01

High-density single nucleotide polymorphism (SNP) genotyping arrays are a powerful tool for studying genomic patterns of diversity, inferring ancestral relationships between individuals in populations and studying marker–trait associations in mapping experiments. We developed a genotyping array including about 90 000 gene-associated SNPs and used it to characterize genetic variation in allohexaploid and allotetraploid wheat populations. The array includes a significant fraction of common genome-wide distributed SNPs that are represented in populations of diverse geographical origin. We used density-based spatial clustering algorithms to enable high-throughput genotype calling in complex data sets obtained for polyploid wheat. We show that these model-free clustering algorithms provide accurate genotype calling in the presence of multiple clusters including clusters with low signal intensity resulting from significant sequence divergence at the target SNP site or gene deletions. Assays that detect low-intensity clusters can provide insight into the distribution of presence–absence variation (PAV) in wheat populations. A total of 46 977 SNPs from the wheat 90K array were genetically mapped using a combination of eight mapping populations. The developed array and cluster identification algorithms provide an opportunity to infer detailed haplotype structure in polyploid wheat and will serve as an invaluable resource for diversity studies and investigating the genetic basis of trait variation in wheat. PMID:24646323

QTL meta-analysis of root traits in Brassica napus under contrasting phosphorus supply in two growth systems

PubMed Central

Zhang, Ying; Thomas, Catherine L.; Xiang, Jinxia; Long, Yan; Wang, Xiaohua; Zou, Jun; Luo, Ziliang; Ding, Guangda; Cai, Hongmei; Graham, Neil S.; Hammond, John P.; King, Graham J.; White, Philip J.; Xu, Fangsen; Broadley, Martin R.; Shi, Lei; Meng, Jinling

2016-01-01

A high-density SNP-based genetic linkage map was constructed and integrated with a previous map in the Tapidor x Ningyou7 (TNDH) Brassica napus population, giving a new map with a total of 2041 molecular markers and an average marker density which increased from 0.39 to 0.97 (0.82 SNP bin) per cM. Root and shoot traits were screened under low and ‘normal’ phosphate (Pi) supply using a ‘pouch and wick’ system, and had been screened previously in an agar based system. The P-efficient parent Ningyou7 had a shorter primary root length (PRL), greater lateral root density (LRD) and a greater shoot biomass than the P-inefficient parent Tapidor under both treatments and growth systems. Quantitative trait loci (QTL) analysis identified a total of 131 QTL, and QTL meta-analysis found four integrated QTL across the growth systems. Integration reduced the confidence interval by ~41%. QTL for root and shoot biomass were co-located on chromosome A3 and for lateral root emergence were co-located on chromosomes A4/C4 and C8/C9. There was a major QTL for LRD on chromosome C9 explaining ~18% of the phenotypic variation. QTL underlying an increased LRD may be a useful breeding target for P uptake efficiency in Brassica. PMID:27624881

The use of genomic information increases the accuracy of breeding value predictions for sea louse (Caligus rogercresseyi) resistance in Atlantic salmon (Salmo salar).

PubMed

Correa, Katharina; Bangera, Rama; Figueroa, René; Lhorente, Jean P; Yáñez, José M

2017-01-31

Sea lice infestations caused by Caligus rogercresseyi are a main concern to the salmon farming industry due to associated economic losses. Resistance to this parasite was shown to have low to moderate genetic variation and its genetic architecture was suggested to be polygenic. The aim of this study was to compare accuracies of breeding value predictions obtained with pedigree-based best linear unbiased prediction (P-BLUP) methodology against different genomic prediction approaches: genomic BLUP (G-BLUP), Bayesian Lasso, and Bayes C. To achieve this, 2404 individuals from 118 families were measured for C. rogercresseyi count after a challenge and genotyped using 37 K single nucleotide polymorphisms. Accuracies were assessed using fivefold cross-validation and SNP densities of 0.5, 1, 5, 10, 25 and 37 K. Accuracy of genomic predictions increased with increasing SNP density and was higher than pedigree-based BLUP predictions by up to 22%. Both Bayesian and G-BLUP methods can predict breeding values with higher accuracies than pedigree-based BLUP, however, G-BLUP may be the preferred method because of reduced computation time and ease of implementation. A relatively low marker density (i.e. 10 K) is sufficient for maximal increase in accuracy when using G-BLUP or Bayesian methods for genomic prediction of C. rogercresseyi resistance in Atlantic salmon.

SNP ID-info: SNP ID searching and visualization platform.

PubMed

Yang, Cheng-Hong; Chuang, Li-Yeh; Cheng, Yu-Huei; Wen, Cheng-Hao; Chang, Phei-Lang; Chang, Hsueh-Wei

2008-09-01

Many association studies provide the relationship between single nucleotide polymorphisms (SNPs), diseases and cancers, without giving a SNP ID, however. Here, we developed the SNP ID-info freeware to provide the SNP IDs within inputting genetic and physical information of genomes. The program provides an "SNP-ePCR" function to generate the full-sequence using primers and template inputs. In "SNPosition," sequence from SNP-ePCR or direct input is fed to match the SNP IDs from SNP fasta-sequence. In "SNP search" and "SNP fasta" function, information of SNPs within the cytogenetic band, contig position, and keyword input are acceptable. Finally, the SNP ID neighboring environment for inputs is completely visualized in the order of contig position and marked with SNP and flanking hits. The SNP identification problems inherent in NCBI SNP BLAST are also avoided. In conclusion, the SNP ID-info provides a visualized SNP ID environment for multiple inputs and assists systematic SNP association studies. The server and user manual are available at http://bio.kuas.edu.tw/snpid-info.

Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.

PubMed

Darabi, Hatef; McCue, Karen; Beesley, Jonathan; Michailidou, Kyriaki; Nord, Silje; Kar, Siddhartha; Humphreys, Keith; Thompson, Deborah; Ghoussaini, Maya; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Canisius, Sander; Scott, Christopher G; Apicella, Carmel; Hopper, John L; Southey, Melissa C; Stone, Jennifer; Broeks, Annegien; Schmidt, Marjanka K; Scott, Rodney J; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Ekici, Arif B; Fasching, Peter A; Heusinger, Katharina; Dos-Santos-Silva, Isabel; Peto, Julian; Tomlinson, Ian; Sawyer, Elinor J; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L; Arndt, Volker; Brenner, Hermann; Engel, Christoph; Meindl, Alfons; Schmutzler, Rita K; Arnold, Norbert; Brauch, Hiltrud; Hamann, Ute; Chang-Claude, Jenny; Khan, Sofia; Nevanlinna, Heli; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natalia V; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-Chen; Wu, Anna H; Floris, Giuseppe; Lambrechts, Diether; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Couch, Fergus J; Vachon, Celine; Giles, Graham G; McLean, Catriona; Milne, Roger L; Dugué, Pierre-Antoine; Haiman, Christopher A; Maskarinec, Gertraud; Woolcott, Christy; Henderson, Brian E; Goldberg, Mark S; Simard, Jacques; Teo, Soo H; Mariapun, Shivaani; Helland, Åslaug; Haakensen, Vilde; Zheng, Wei; Beeghly-Fadiel, Alicia; Tamimi, Rulla; Jukkola-Vuorinen, Arja; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Tollenaar, Robert A E M; Figueroa, Jonine; García-Closas, Montserrat; Czene, Kamila; Hooning, Maartje J; Tilanus-Linthorst, Madeleine; Li, Jingmei; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Luben, Robert; Khaw, Kay-Tee; Choi, Ji-Yeob; Kang, Daehee; Hartman, Mikael; Lim, Wei Yen; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; McKay, James; Sangrajrang, Suleeporn; Toland, Amanda E; Yannoukakos, Drakoulis; Shen, Chen-Yang; Yu, Jyh-Cherng; Ziogas, Argyrios; Schoemaker, Minouk J; Swerdlow, Anthony; Borresen-Dale, Anne-Lise; Kristensen, Vessela; French, Juliet D; Edwards, Stacey L; Dunning, Alison M; Easton, Douglas F; Hall, Per; Chenevix-Trench, Georgia

2015-07-02

Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Density-dependent regulation of growth of BSC-1 cells in cell culture: growth inhibitors formed by the cells.

PubMed Central

Holley, R W; Armour, R; Baldwin, J H

1978-01-01

Inhibitors formed by a monkey epithelial cell line, BSC-1, play an important role in limiting growth at high cell densities. At least three inhibitors are formed: lactic acid, ammonia, and an unidentified inhibitor that may be an unstable protein. The unidentified inhibitor is destroyed by shaking the conditioned medium, by bubbling gas through the medium, or by heating or storing the medium in the absence of cells. The concentrations of lactic acid and ammonia that accumulate in conditioned medium inhibit growth when added to fresh medium. These results, together with earlier studies, indicate that density-dependent regulation of growth of BSC-1 cells results from the combined effects of (a) inhibitors formed by the cells, (b) decreased availability of receptor sites for serum growth factors as the cells become crowded, and (c) limiting concentrations of low molecular weight nutrients in the medium. In contrast, density-dependent regulation of growth in 3T3 mouse embryo fibroblasts results almost entirely from inactivation of serum factors. PMID:273914

Coverage and efficiency in current SNP chips

PubMed Central

Ha, Ngoc-Thuy; Freytag, Saskia; Bickeboeller, Heike

2014-01-01

To answer the question as to which commercial high-density SNP chip covers most of the human genome given a fixed budget, we compared the performance of 12 chips of different sizes released by Affymetrix and Illumina for the European, Asian, and African populations. These include Affymetrix' relatively new population-optimized arrays, whose SNP sets are each tailored toward a specific ethnicity. Our evaluation of the chips included the use of two measures, efficiency and cost–benefit ratio, which we developed as supplements to genetic coverage. Unlike coverage, these measures factor in the price of a chip or its substitute size (number of SNPs on chip), allowing comparisons to be drawn between differently priced chips. In this fashion, we identified the Affymetrix population-optimized arrays as offering the most cost-effective coverage for the Asian and African population. For the European population, we established the Illumina Human Omni 2.5-8 as the preferred choice. Interestingly, the Affymetrix chip tailored toward an Eastern Asian subpopulation performed well for all three populations investigated. However, our coverage estimates calculated for all chips proved much lower than those advertised by the producers. All our analyses were based on the 1000 Genome Project as reference population. PMID:24448550

Genome wide analysis of flowering time trait in multiple environments via high-throughput genotyping technique in Brassica napus L.

PubMed

Li, Lun; Long, Yan; Zhang, Libin; Dalton-Morgan, Jessica; Batley, Jacqueline; Yu, Longjiang; Meng, Jinling; Li, Maoteng

2015-01-01

The prediction of the flowering time (FT) trait in Brassica napus based on genome-wide markers and the detection of underlying genetic factors is important not only for oilseed producers around the world but also for the other crop industry in the rotation system in China. In previous studies the low density and mixture of biomarkers used obstructed genomic selection in B. napus and comprehensive mapping of FT related loci. In this study, a high-density genome-wide SNP set was genotyped from a double-haploid population of B. napus. We first performed genomic prediction of FT traits in B. napus using SNPs across the genome under ten environments of three geographic regions via eight existing genomic predictive models. The results showed that all the models achieved comparably high accuracies, verifying the feasibility of genomic prediction in B. napus. Next, we performed a large-scale mapping of FT related loci among three regions, and found 437 associated SNPs, some of which represented known FT genes, such as AP1 and PHYE. The genes tagged by the associated SNPs were enriched in biological processes involved in the formation of flowers. Epistasis analysis showed that significant interactions were found between detected loci, even among some known FT related genes. All the results showed that our large scale and high-density genotype data are of great practical and scientific values for B. napus. To our best knowledge, this is the first evaluation of genomic selection models in B. napus based on a high-density SNP dataset and large-scale mapping of FT loci.

Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol

PubMed Central

Bodhini, Dhanasekaran; Gaal, Szilvia; Shatwan, Israa; Ramya, Kandaswamy; Ellahi, Basma; Surendran, Shelini; Sudha, Vasudevan; Anjana, Mohan R.; Mohan, Viswanathan; Lovegrove, Julie A.; Radha, Venkatesan

2017-01-01

Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n = 861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES). A validated food frequency questionnaire (FFQ) was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high-density lipoprotein cholesterol (HDL-C), where the ‘T’ allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day) (Pinteraction<0.0001) on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024) and those in the highest PUFA tertile had lower HDL-C (P = 0.028) than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day) on HDL-C (Pinteraction<0.0001). None of the other interactions between the SNPs and lifestyle factors were statistically significant after correction for multiple testing. Our findings indicate that the association between TCF7L2 SNP rs12255372 and HDL-C may be modified by dietary fat intake in this Asian Indian population. PMID:29182660

Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology

USDA-ARS?s Scientific Manuscript database

The dissection of complex traits of economic importance for the pig industry requires the availability of a significant number of genetic markers, such as SNPs. This study was conducted in order to discover thousands of porcine SNPs using next generation sequencing technologies and use those SNPs, a...

Dissection of genetic factors underlying wheat kernel shape and size in an elite x nonadapted cross using a high density SNP linkage map

USDA-ARS?s Scientific Manuscript database

Wheat kernel shape and size has been under selection since early domestication. Kernel morphology is a major consideration in wheat breeding, as it impacts grain yield and quality. A population of 160 recombinant inbred lines (RIL), developed using an elite (ND 705) and a nonadapted genotype (PI 414...

A high density integrated genetic linkage map of soybean and the development of a 1,536 Universal Soy Linkage Panel for QTL mapping

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are the marker of choice for many researchers due to their abundance and the high-throughput methods available for their multiplex analysis. Only recently have SNP markers been available to researchers in soybean [Glycine max (L.) Merr.] with the release of th...

Mosquito density, biting rate and cage size effects on repellent tests.

PubMed

Barnard, D R; Posey, K H; Smith, D; Schreck, C E

1998-01-01

Mosquito biting rates and the mean duration of protection (in hours) from bites (MDPB) of Aedes aegypti and Anopheles quadrimaculatus, using the repellent 'deet' (N,N-diethyl-3-methylbenzamide) on a 50 cm2 area of healthy human skin, were observed in small (27 l), medium (approximately 65 l) and large (125 l) cages containing low, medium or high densities of mosquitoes: respectively, 640, 128 or 49 cm3 of cage volume per female. At the initial treatment rate of approximately 0.4 microliter/cm2 (1 ml of 25% deet in ethanol on 650 cm2 of skin), the MDPB for deet against Ae. aegypti ranged from 4.5 to 6.5 h and was significantly less (5.0 +/- 0.8 h) in large cages compared with medium (6.2 +/- 0.9 h) and small (6.2 +/- 0.8 h) cages, regardless of the density. Against An. quadrimaculatus the MDPB for deet 0.4 microliter/cm2 was 1.5-8.0 h, less in small (3.7 +/- 2.3 h) and large (2.2 +/- 1.1 h) cages at medium (3.7 +/- 2.3 h) and high (2.5 +/- 1.7 h) mosquito densities, and was longest in medium cages (6.2 +/- 2.6 h) at low mosquito densities (5.8 +/- 2.8 h). With equinoxial photoperiodicity (light on 06.00-18.00 hours) the biting rate was influenced by the time of observation (08.00, 12.00, 16.00 hours) for Ae. aegypti but not for An. quadrimaculatus. For both species, the biting rate was inversely proportional to mosquito density and the MDPB. The shortest MDPBs were obtained in large cages with high densities of mosquitoes and longest protection times occurred in medium sized cages with low mosquito densities.

High-density genetic map construction and comparative genome analysis in asparagus bean.

PubMed

Huang, Haitao; Tan, Huaqiang; Xu, Dongmei; Tang, Yi; Niu, Yisong; Lai, Yunsong; Tie, Manman; Li, Huanxiu

2018-03-19

Genetic maps are a prerequisite for quantitative trait locus (QTL) analysis, marker-assisted selection (MAS), fine gene mapping, and assembly of genome sequences. So far, several asparagus bean linkage maps have been established using various kinds of molecular markers. However, these maps were all constructed by gel- or array-based markers. No maps based on sequencing method have been reported. In this study, an NGS-based strategy, SLAF-seq, was applied to create a high-density genetic map for asparagus bean. Through SLAF library construction and Illumina sequencing of two parents and 100 F2 individuals, a total of 55,437 polymorphic SLAF markers were developed and mined for SNP markers. The map consisted of 5,225 SNP markers in 11 LGs, spanning a total distance of 1,850.81 cM, with an average distance between markers of 0.35 cM. Comparative genome analysis with four other legume species, soybean, common bean, mung bean and adzuki bean showed that asparagus bean is genetically more related to adzuki bean. The results will provide a foundation for future genomic research, such as QTL fine mapping, comparative mapping in pulses, and offer support for assembling asparagus bean genome sequence.

Interspecies synteny mapping identifies a quantitative trait locus for bone mineral density on human chromosome Xp22.

PubMed

Parsons, Claire A; Mroczkowski, H Joel; McGuigan, Fiona E A; Albagha, Omar M E; Manolagas, Stavros; Reid, David M; Ralston, Stuart H; Shmookler Reis, Robert J

2005-11-01

Bone mineral density (BMD) is a complex trait with a strong genetic component and an important predictor of osteoporotic fracture risk. Here we report the use of a cross-species strategy to identify genes that regulate BMD, proceeding from quantitative trait mapping in mice to association mapping of the syntenic region in the human genome. We identified a quantitative trait locus (QTL) on the mouse X-chromosome for post-maturity change in spine BMD in a cross of SAMP6 and AKR/J mice and conducted association mapping of the syntenic region on human chromosome Xp22. We studied 76 single nucleotide polymorphisms (SNP) from the human region in two sets of DNA pools prepared from individuals with lumbar spine-BMD (LS-BMD) values falling into the top and bottom 13th percentiles of a population-based study of 3100 post-menopausal women. This procedure identified a region of significant association for two adjacent SNP (rs234494 and rs234495) within the Xp22 locus (P<0.001). Individual genotyping for rs234494 in the BMD pools confirmed the presence of an association for alleles (P=0.018) and genotypes (P=0.008). Analysis of rs234494 and rs234495 in 1053 women derived from the same population who were not selected for BMD values showed an association with LS-BMD for rs234495 (P=0.01) and for haplotypes defined by both SNP (P=0.002). Our study illustrates that interspecies synteny can be used to identify and refine QTL for complex traits and represents the first example where a human QTL for BMD regulation has been mapped using this approach.

Sex-dependent Association of a Common Low Density Lipoprotein Receptor Polymorphism with RNA Splicing Efficiency in the Brain and Alzheimers Disease

PubMed Central

Zou, Fanggeng; Gopalraj, Rangaraj K.; Lok, Johann; Zhu, Haiyan; Ling, I-Fang; Simpson, James F.; Tucker, H. Michael; Kelly, Jeremiah F.; Younkin, Samuel G.; Dickson, Dennis W.; Petersen, Ronald C; Graff-Radford, Neill R.; Bennett, David A.; Crook, Julia E.; G.Younkin, Steven; Estus, Steven

2008-01-01

Since apoE allele status is the predominant Alzheimers disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNP)s in brain apoE receptors represent excellent candidates for association with AD. Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in the female human liver and in minigene transfected HepG2 cells. Moreover, the rs688T minor allele associated with significantly higher LDL and total cholesterol in women in the Framingham Offspring Study. Since LDLR is a major apoE receptor in the brain, we hypothesized that rs688 modulates LDLR splicing in neural tissues and associates with AD. To evaluate this hypothesis, we first transfected LDLR minigenes into SH-SY5Y neuroblastoma cells and found that rs688T reduces exon 12 inclusion in this neural model. We then evaluated rs688 association with exon 12 splicing efficiency in vivo by quantifying LDLR splicing in human anterior cingulate tissue obtained at autopsy; the rs688T allele associated with decreased LDLR exon 12 splicing efficiency in aged men but not women. Lastly, we evaluated whether rs688 associates with AD by genotyping DNA from 1,457 men and 2,055 women drawn from three case-control series. The rs688T/T genotype was associated with increased AD odds in males (recessive model, odds ratio (OR) of 1.49, 95% confidence interval (CI) of 1.13−1.97, uncorrected p=0.005), but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion. PMID:18065781

Germline variation in the MTHFR and MTRR genes determines the nadir of bone density in pediatric acute lymphoblastic leukemia: a prospective study.

PubMed

te Winkel, M L; de Muinck Keizer-Schrama, S M P F; de Jonge, R; van Beek, R D; van der Sluis, I M; Hop, W C J; Pieters, R; van den Heuvel-Eibrink, M M

2011-03-01

This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment. We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C) and methionine synthase reductase (MTRR 66A > G) single nucleotide polymorphisms (SNPs) on total body BMD (BMD(TB)) and lumbar spine BMD (BMD(LS)) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥ 4 years (n = 68). Carriers of the MTHFR 677 T-allele showed a lower baseline BMD(TB) than non-carriers (-0.38 SDS vs. +0.55 SDS, p = 0.01) and BMD(TB) remained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMD(TB) (p = 0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMD(TB) compared with non-carriers. Combining these two SNPs, patients carrying ≥ 2 risk alleles had a significantly lower BMD(TB) (-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A > C had higher homocysteine levels, this SNP was not related to BMD(TB). BMD(LS) of carriers was similar to non-carriers of the investigated SNPs. The MTHFR 677C>T SNP and the MTRR 66A >G SNP were identified as determinants of impaired BMD(TB) in childhood ALL patients. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Genome wide association study and genomic prediction for fatty acid composition in Chinese Simmental beef cattle using high density SNP array.

PubMed

Zhu, Bo; Niu, Hong; Zhang, Wengang; Wang, Zezhao; Liang, Yonghu; Guan, Long; Guo, Peng; Chen, Yan; Zhang, Lupei; Guo, Yong; Ni, Heming; Gao, Xue; Gao, Huijiang; Xu, Lingyang; Li, Junya

2017-06-14

Fatty acid composition of muscle is an important trait contributing to meat quality. Recently, genome-wide association study (GWAS) has been extensively used to explore the molecular mechanism underlying important traits in cattle. In this study, we performed GWAS using high density SNP array to analyze the association between SNPs and fatty acids and evaluated the accuracy of genomic prediction for fatty acids in Chinese Simmental cattle. Using the BayesB method, we identified 35 and 7 regions in Chinese Simmental cattle that displayed significant associations with individual fatty acids and fatty acid groups, respectively. We further obtained several candidate genes which may be involved in fatty acid biosynthesis including elongation of very long chain fatty acids protein 5 (ELOVL5), fatty acid synthase (FASN), caspase 2 (CASP2) and thyroglobulin (TG). Specifically, we obtained strong evidence of association signals for one SNP located at 51.3 Mb for FASN using Genome-wide Rapid Association Mixed Model and Regression-Genomic Control (GRAMMAR-GC) approaches. Also, region-based association test identified multiple SNPs within FASN and ELOVL5 for C14:0. In addition, our result revealed that the effectiveness of genomic prediction for fatty acid composition using BayesB was slightly superior over GBLUP in Chinese Simmental cattle. We identified several significantly associated regions and loci which can be considered as potential candidate markers for genomics-assisted breeding programs. Using multiple methods, our results revealed that FASN and ELOVL5 are associated with fatty acids with strong evidence. Our finding also suggested that it is feasible to perform genomic selection for fatty acids in Chinese Simmental cattle.

Development and evaluation of high-density Axiom® CicerSNP Array for high-resolution genetic mapping and breeding applications in chickpea.

PubMed

Roorkiwal, Manish; Jain, Ankit; Kale, Sandip M; Doddamani, Dadakhalandar; Chitikineni, Annapurna; Thudi, Mahendar; Varshney, Rajeev K

2018-04-01

To accelerate genomics research and molecular breeding applications in chickpea, a high-throughput SNP genotyping platform 'Axiom ® CicerSNP Array' has been designed, developed and validated. Screening of whole-genome resequencing data from 429 chickpea lines identified 4.9 million SNPs, from which a subset of 70 463 high-quality nonredundant SNPs was selected using different stringent filter criteria. This was further narrowed down to 61 174 SNPs based on p-convert score ≥0.3, of which 50 590 SNPs could be tiled on array. Among these tiled SNPs, a total of 11 245 SNPs (22.23%) were from the coding regions of 3673 different genes. The developed Axiom ® CicerSNP Array was used for genotyping two recombinant inbred line populations, namely ICCRIL03 (ICC 4958 × ICC 1882) and ICCRIL04 (ICC 283 × ICC 8261). Genotyping data reflected high success and polymorphic rate, with 15 140 (29.93%; ICCRIL03) and 20 018 (39.57%; ICCRIL04) polymorphic SNPs. High-density genetic maps comprising 13 679 SNPs spanning 1033.67 cM and 7769 SNPs spanning 1076.35 cM were developed for ICCRIL03 and ICCRIL04 populations, respectively. QTL analysis using multilocation, multiseason phenotyping data on these RILs identified 70 (ICCRIL03) and 120 (ICCRIL04) main-effect QTLs on genetic map. Higher precision and potential of this array is expected to advance chickpea genetics and breeding applications. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

A medium density genetic map and QTL for behavioral and production traits in Japanese quail.

PubMed

Recoquillay, Julien; Pitel, Frédérique; Arnould, Cécile; Leroux, Sophie; Dehais, Patrice; Moréno, Carole; Calandreau, Ludovic; Bertin, Aline; Gourichon, David; Bouchez, Olivier; Vignal, Alain; Fariello, Maria Ines; Minvielle, Francis; Beaumont, Catherine; Leterrier, Christine; Le Bihan-Duval, Elisabeth

2015-01-22

Behavioral traits such as sociability, emotional reactivity and aggressiveness are major factors in animal adaptation to breeding conditions. In order to investigate the genetic control of these traits as well as their relationships with production traits, a study was undertaken on a large second generation cross (F2) between two lines of Japanese Quail divergently selected on their social reinstatement behavior. All the birds were measured for several social behaviors (social reinstatement, response to social isolation, sexual motivation, aggression), behaviors measuring the emotional reactivity of the birds (reaction to an unknown object, tonic immobility reaction), and production traits (body weight and egg production). We report the results of the first genome-wide QTL detection based on a medium density SNP panel obtained from whole genome sequencing of a pool of individuals from each divergent line. A genetic map was constructed using 2145 markers among which 1479 could be positioned on 28 different linkage groups. The sex-averaged linkage map spanned a total of 3057 cM with an average marker spacing of 2.1 cM. With the exception of a few regions, the marker order was the same in Japanese Quail and the chicken, which confirmed a well conserved synteny between the two species. The linkage analyses performed using QTLMAP software revealed a total of 45 QTLs related either to behavioral (23) or production (22) traits. The most numerous QTLs (15) concerned social motivation traits. Interestingly, our results pinpointed putative pleiotropic regions which controlled emotional reactivity and body-weight of birds (on CJA5 and CJA8) or their social motivation and the onset of egg laying (on CJA19). This study identified several QTL regions for social and emotional behaviors in the Quail. Further research will be needed to refine the QTL and confirm or refute the role of candidate genes, which were suggested by bioinformatics analysis. It can be hoped that the identification of genes and polymorphisms related to behavioral traits in the quail will have further applications for other poultry species (especially the chicken) and will contribute to solving animal welfare issues in poultry production.

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans

PubMed Central

Evans, Daniel S.; Avery, Christy L.; Nalls, Mike A.; Li, Guo; Barnard, John; Smith, Erin N.; Tanaka, Toshiko; Butler, Anne M.; Buxbaum, Sarah G.; Alonso, Alvaro; Arking, Dan E.; Berenson, Gerald S.; Bis, Joshua C.; Buyske, Steven; Carty, Cara L.; Chen, Wei; Chung, Mina K.; Cummings, Steven R.; Deo, Rajat; Eaton, Charles B.; Fox, Ervin R.; Heckbert, Susan R.; Heiss, Gerardo; Hindorff, Lucia A.; Hsueh, Wen-Chi; Isaacs, Aaron; Jamshidi, Yalda; Kerr, Kathleen F.; Liu, Felix; Liu, Yongmei; Lohman, Kurt K.; Magnani, Jared W.; Maher, Joseph F.; Mehra, Reena; Meng, Yan A.; Musani, Solomon K.; Newton-Cheh, Christopher; North, Kari E.; Psaty, Bruce M.; Redline, Susan; Rotter, Jerome I.; Schnabel, Renate B.; Schork, Nicholas J.; Shohet, Ralph V.; Singleton, Andrew B.; Smith, Jonathan D.; Soliman, Elsayed Z.; Srinivasan, Sathanur R.; Taylor, Herman A.; Van Wagoner, David R.; Wilson, James G.; Young, Taylor; Zhang, Zhu-Ming; Zonderman, Alan B.; Evans, Michele K.; Ferrucci, Luigi; Murray, Sarah S.; Tranah, Gregory J.; Whitsel, Eric A.; Reiner, Alex P.; Sotoodehnia, Nona

2016-01-01

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10−14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10−4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10−8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10−9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10−7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS–SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved. PMID:27577874

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.

PubMed

Evans, Daniel S; Avery, Christy L; Nalls, Mike A; Li, Guo; Barnard, John; Smith, Erin N; Tanaka, Toshiko; Butler, Anne M; Buxbaum, Sarah G; Alonso, Alvaro; Arking, Dan E; Berenson, Gerald S; Bis, Joshua C; Buyske, Steven; Carty, Cara L; Chen, Wei; Chung, Mina K; Cummings, Steven R; Deo, Rajat; Eaton, Charles B; Fox, Ervin R; Heckbert, Susan R; Heiss, Gerardo; Hindorff, Lucia A; Hsueh, Wen-Chi; Isaacs, Aaron; Jamshidi, Yalda; Kerr, Kathleen F; Liu, Felix; Liu, Yongmei; Lohman, Kurt K; Magnani, Jared W; Maher, Joseph F; Mehra, Reena; Meng, Yan A; Musani, Solomon K; Newton-Cheh, Christopher; North, Kari E; Psaty, Bruce M; Redline, Susan; Rotter, Jerome I; Schnabel, Renate B; Schork, Nicholas J; Shohet, Ralph V; Singleton, Andrew B; Smith, Jonathan D; Soliman, Elsayed Z; Srinivasan, Sathanur R; Taylor, Herman A; Van Wagoner, David R; Wilson, James G; Young, Taylor; Zhang, Zhu-Ming; Zonderman, Alan B; Evans, Michele K; Ferrucci, Luigi; Murray, Sarah S; Tranah, Gregory J; Whitsel, Eric A; Reiner, Alex P; Sotoodehnia, Nona

2016-10-01

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10 -14 ) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10 -4 ). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10 -8 ) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10 -9 ). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10 -7 ), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS-SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A high-density SNP genetic linkage map for the silver-lipped pearl oyster, Pinctada maxima: a valuable resource for gene localisation and marker-assisted selection.

PubMed

Jones, David B; Jerry, Dean R; Khatkar, Mehar S; Raadsma, Herman W; Zenger, Kyall R

2013-11-20

The silver-lipped pearl oyster, Pinctada maxima, is an important tropical aquaculture species extensively farmed for the highly sought "South Sea" pearls. Traditional breeding programs have been initiated for this species in order to select for improved pearl quality, but many economic traits under selection are complex, polygenic and confounded with environmental factors, limiting the accuracy of selection. The incorporation of a marker-assisted selection (MAS) breeding approach would greatly benefit pearl breeding programs by allowing the direct selection of genes responsible for pearl quality. However, before MAS can be incorporated, substantial genomic resources such as genetic linkage maps need to be generated. The construction of a high-density genetic linkage map for P. maxima is not only essential for unravelling the genomic architecture of complex pearl quality traits, but also provides indispensable information on the genome structure of pearl oysters. A total of 1,189 informative genome-wide single nucleotide polymorphisms (SNPs) were incorporated into linkage map construction. The final linkage map consisted of 887 SNPs in 14 linkage groups, spans a total genetic distance of 831.7 centimorgans (cM), and covers an estimated 96% of the P. maxima genome. Assessment of sex-specific recombination across all linkage groups revealed limited overall heterochiasmy between the sexes (i.e. 1.15:1 F/M map length ratio). However, there were pronounced localised differences throughout the linkage groups, whereby male recombination was suppressed near the centromeres compared to female recombination, but inflated towards telomeric regions. Mean values of LD for adjacent SNP pairs suggest that a higher density of markers will be required for powerful genome-wide association studies. Finally, numerous nacre biomineralization genes were localised providing novel positional information for these genes. This high-density SNP genetic map is the first comprehensive linkage map for any pearl oyster species. It provides an essential genomic tool facilitating studies investigating the genomic architecture of complex trait variation and identifying quantitative trait loci for economically important traits useful in genetic selection programs within the P. maxima pearling industry. Furthermore, this map provides a foundation for further research aiming to improve our understanding of the dynamic process of biomineralization, and pearl oyster evolution and synteny.

Potential of electrical resistivity tomography and muon density imaging to study spatio-temporal variations in the sub-surface

NASA Astrophysics Data System (ADS)

Lesparre, Nolwenn; Cabrera, Justo; Courbet, Christelle

2015-04-01

We explore the capacity of electrical resistivity tomography and muon density imaging to detect spatio-temporal variations of the medium surrounding a regional fault crossing the underground platform of Tournemire (Aveyron, France). The studied Cernon fault is sub-vertical and intersects perpendicularly the tunnel of Tournemire and extends to surface. The fault separates clay and limestones layers of the Dogger from limestones layers of the Lias. The Cernon fault presents a thickness of a ten of meters and drives water from an aquifer circulating at the top of the Dogger clay layer to the tunnel. An experiment combining electrical resistivity imaging and muon density imaging was setup taking advantage of the tunnel presence. A specific array of electrodes were set up, adapted for the characterization of the fault. Electrodes were placed along the tunnel as well as at the surface above the tunnel on both sides of the fault in order to acquire data in transmission across the massif to better cover the sounded medium. Electrical resistivity is particularly sensitive to water presence in the medium and thus carry information on the main water flow paths and on the pore space saturation. At the same time a muon sensor was placed in the tunnel under the fault region to detect muons coming from the sky after their crossing of the rock medium. Since the muon flux is attenuated as function of the quantity of matter crossed, muons flux measurements supply information on the medium average density along muons paths. The sensor presents 961 angles of view so measurements performed from one station allows a comparison of the muon flux temporal variations along the fault as well as in the medium surrounding the fault. As the water saturation of the porous medium fluctuates through time the medium density might indeed present sensible variations as shown by gravimetric studies. During the experiment important rainfalls occurred leading variations of the medium properties affecting density and electrical resistivity physical parameters. We show with data sets acquired before and after an important rainfall event how muon density and electrical resistivity imaging may complementary characterize variations of the medium properties. The development of such innovative experiments for hydrogeophysical studies presents then the ability to supply new information on fluid dynamics in the sub-surface.

Effects of Energy Density and Shielding Medium on Performance of Laser Beam Welding (LBW) Joints on SAF2205 Duplex Stainless Steel

NASA Astrophysics Data System (ADS)

Zhang, W. W.; Cong, S.; Luo, S. B.; Fang, J. H.

2018-05-01

The corrosion resistance performance of SAF2205 duplex stainless steel depends on the amount of ferrite to austenite transformation, but the ferrite content after power beam welding is always excessively high. To obtain laser beam welding joints with better mechanical and corrosion resistance performance, the effects of the energy density and shielding medium on the austenite content, hardness distribution, and shear strength were investigated. The results showed that ferrite to austenite transformation was realized with increase in the energy density. When the energy density was increased from 120 J/mm to 200 J/mm, the austenite content of the welding joint changed from 2.6% to 38.5%. Addition of nitrogen gas to the shielding medium could promote formation of austenite. When the shielding medium contained 50% and 100% nitrogen gas, the austenite content of the welding joint was 42.7% and 47.2%, respectively. The hardness and shear strength were significantly improved by increase in the energy density. However, the shielding medium had less effect on the mechanical performance. Use of the optimal welding process parameters resulted in peak hardness of 375 HV and average shear strength of 670 MPa.

Nucleon properties in the Polyakov quark-meson model

NASA Astrophysics Data System (ADS)

Li, Yingying; Hu, Jinniu; Mao, Hong

2018-05-01

We study the nucleon as a nontopological soliton in a quark medium as well as in a nucleon medium in terms of the Polyakov quark-meson (PQM) model with two flavors at finite temperature and density. The constituent quark masses evolving with the temperature at various baryon chemical potentials are calculated and the equations of motion are solved according to the proper boundary conditions. The PQM model predicts an increasing size of the nucleon and a reduction of the nucleon mass in both hot environment. However, the phase structure is different from each other in quark and nucleon mediums. There is a crossover in the low-density region and a first-order phase transition in the high-density region in quark medium, whereas there exists a crossover characterized by the overlap of the nucleons in nucleon medium.

Density-dependent regulation of growth of BSC-1 cells in cell culture: Control of growth by low molecular weight nutrients

PubMed Central

Holley, Robert W.; Armour, Rosemary; Baldwin, Julia H.

1978-01-01

BSC-1 cells, epithelial cells of African green monkey kidney origin, show pronounced density-dependent regulation of growth in cell culture. Growth of the cells is rapid to a density of approximately 1.5 × 105 cells/per cm2 in Dulbecco-modified Eagle's medium supplemented with 10% calf serum. Above this “saturation density,” growth is much slower. It has been found that the glucose concentration in the culture medium is important in determining the “saturation density.” If the glucose concentration is increased 4-fold, the “saturation density” increases approximately 50%. Reduction of the “saturation density” of BSC-1 cells is also possible by decreasing the concentrations of low molecular weight nutrients in the culture medium. In medium supplemented with 0.1% calf serum, decreasing the concentrations of all of the organic constituents of the medium, from the high levels present in Dulbecco-modified Eagle's medium to concentrations near physiological levels, decreases the “saturation density” by approximately half. The decreased “saturation density” is not the result of lowering the concentration of any single nutrient but rather results from reduction of the concentrations of several nutrients. When the growth of BSC-1 cells is limited by low concentrations of all of the nutrients, some stimulation of growth results from increasing, separately, the concentrations of individual groups of nutrients, but the best growth stimulation is obtained by increasing the concentrations of all of the nutrients. The “wound healing” phenomenon, one manifestation of density-dependent regulation of growth in cell culture, is abolished by lowering the concentration of glutamine in the medium. Density-dependent regulation of growth of BSC-1 cells in cell culture thus appears to be a complex phenomenon that involves an interaction of nutrient concentrations with other regulatory factors. PMID:272650

Investigation of mitomycin-C-treated fibroblasts in 3-D collagen gel and conditioned medium for keratinocyte proliferation.

PubMed

Huang, Yi-Chau; Wang, Tzu-Wei; Sun, Jui-Sheng; Lin, Feng-Huei

2006-03-01

Fibroblasts produce a spectrum of necessary growth factors essential for growth and proliferation of a variety of cell types. In this study, the paracrine effect of mitomycin-C-treated fibroblasts with various densities in collagen gel for keratinocyte proliferation was investigated from which an optimum cell density and optimum conditioned medium would be determined to expand keratinocyte without further differentiation for skin equivalent tissue engineering. The optimum cell density in collagen feeder gel for optimum collected medium preparation will be determined by checking the level of keratinocyte growth factor and granulocyte macrophage colony-stimulating factor in conventional medium. The results showed that the cell density of 1 x 10(5) cells/gel in the feeder gel is better to produce optimum collected medium. The conditioned medium is prepared by mixing together the optimum collected medium and molecular cellular and developmental biology (MCDB) 153 medium in different ratios for keratinocyte growth. The keratinocyte viability will be measured by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to determine the optimum conditioned medium. From the study, 67% conditioned medium was supposed as the better medium for keratinocyte proliferation. In this experiment, the optimum cell density in feeder gel to coculture with keratinocytes is also determined as 1 x 10(5) cells/gel. Keratin 10 (K10) and Terminal Deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling stain will be used to check the cell differentiation and apoptosis, respectively. The results suggest that keratinocytes should not be cultured in postconfluent conditions due to undesired apoptosis and differentiation. The result of cell viability from passages to passages shows that the optimum feeder gel plays a more important role to the keratinocyte proliferation than that of optimum conditioned medium. Keratinocytes cultured with optimum feeder gel in 67% conditioned medium could effectively promote proliferation, inhibit apoptosis, and prevent differentiation. The combination of conditioned media and feeder gel to culture keratinocytes without external supplements can provide an inexpensive way for keratinocyte proliferation and construct an environment for real-time communication between the two cells. The results conclude that keratinocyte cultivation in feeder gel with modified medium should be feasible in the production of high quality keratinocytes for skin equivalents preparation.

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

PubMed Central

Scherrer, Daniel Zanetti; Zago, Vanessa Helena de Souza; Vieira, Isabela Calanca; Parra, Eliane Soler; Panzoldo, Natália Baratella; Alexandre, Fernanda; Secolin, Rodrigo; Baracat, Jamal; Quintão, Eder Carlos Rocha; de Faria, Eliana Cotta

2015-01-01

Background Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). Objective To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. Methods We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). Results The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. Conclusion In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis. PMID:26039660

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample.

PubMed

Scherrer, Daniel Zanetti; Zago, Vanessa Helena de Souza; Vieira, Isabela Calanca; Parra, Eliane Soler; Panzoldo, Natália Baratella; Alexandre, Fernanda; Secolin, Rodrigo; Baracat, Jamal; Quintão, Eder Carlos Rocha; Faria, Eliana Cotta de

2015-07-01

Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Environmental Response and Genomic Regions Correlated with Rice Root Growth and Yield under Drought in the OryzaSNP Panel across Multiple Study Systems

PubMed Central

Wade, Len J.; Bartolome, Violeta; Mauleon, Ramil; Vasant, Vivek Deshmuck; Prabakar, Sumeet Mankar; Chelliah, Muthukumar; Kameoka, Emi; Nagendra, K.; Reddy, K. R. Kamalnath; Varma, C. Mohan Kumar; Patil, Kalmeshwar Gouda; Shrestha, Roshi; Al-Shugeairy, Zaniab; Al-Ogaidi, Faez; Munasinghe, Mayuri; Gowda, Veeresh; Semon, Mande; Suralta, Roel R.; Shenoy, Vinay; Vadez, Vincent; Serraj, Rachid; Shashidhar, H. E.; Yamauchi, Akira; Babu, Ranganathan Chandra; Price, Adam; McNally, Kenneth L.; Henry, Amelia

2015-01-01

The rapid progress in rice genotyping must be matched by advances in phenotyping. A better understanding of genetic variation in rice for drought response, root traits, and practical methods for studying them are needed. In this study, the OryzaSNP set (20 diverse genotypes that have been genotyped for SNP markers) was phenotyped in a range of field and container studies to study the diversity of rice root growth and response to drought. Of the root traits measured across more than 20 root experiments, root dry weight showed the most stable genotypic performance across studies. The environment (E) component had the strongest effect on yield and root traits. We identified genomic regions correlated with root dry weight, percent deep roots, maximum root depth, and grain yield based on a correlation analysis with the phenotypes and aus, indica, or japonica introgression regions using the SNP data. Two genomic regions were identified as hot spots in which root traits and grain yield were co-located; on chromosome 1 (39.7–40.7 Mb) and on chromosome 8 (20.3–21.9 Mb). Across experiments, the soil type/ growth medium showed more correlations with plant growth than the container dimensions. Although the correlations among studies and genetic co-location of root traits from a range of study systems points to their potential utility to represent responses in field studies, the best correlations were observed when the two setups had some similar properties. Due to the co-location of the identified genomic regions (from introgression block analysis) with QTL for a number of previously reported root and drought traits, these regions are good candidates for detailed characterization to contribute to understanding rice improvement for response to drought. This study also highlights the utility of characterizing a small set of 20 genotypes for root growth, drought response, and related genomic regions. PMID:25909711

High-Density SNP Map Construction and QTL Identification for the Apetalous Character in Brassica napus L.

PubMed Central

Wang, Xiaodong; Yu, Kunjiang; Li, Hongge; Peng, Qi; Chen, Feng; Zhang, Wei; Chen, Song; Hu, Maolong; Zhang, Jiefu

2015-01-01

The apetalous genotype is a morphological ideotype for increasing seed yield and should be of considerable agricultural use; however, only a few studies have focused on the genetic control of this trait in Brassica napus. In the present study, a recombinant inbred line, the AH population, containing 189 individuals was derived from a cross between an apetalous line ‘APL01’ and a normally petalled variety ‘Holly’. The Brassica 60 K Infinium BeadChip Array harboring 52,157 single nucleotide polymorphism (SNP) markers was used to genotype the AH individuals. A high-density genetic linkage map was constructed based on 2,755 bins involving 11,458 SNPs and 57 simple sequence repeats, and was used to identify loci associated with petalous degree (PDgr). The linkage map covered 2,027.53 cM, with an average marker interval of 0.72 cM. The AH map had good collinearity with the B. napus reference genome, indicating its high quality and accuracy. After phenotypic analyses across five different experiments, a total of 19 identified quantitative trait loci (QTLs) distributed across chromosomes A3, A5, A6, A9 and C8 were obtained, and these QTLs were further integrated into nine consensus QTLs by a meta-analysis. Interestingly, the major QTL qPD.C8-2 was consistently detected in all five experiments, and qPD.A9-2 and qPD.C8-3 were stably expressed in four experiments. Comparative mapping between the AH map and the B. napus reference genome suggested that there were 328 genes underlying the confidence intervals of the three steady QTLs. Based on the Gene Ontology assignments of 52 genes to the regulation of floral development in published studies, 146 genes were considered as potential candidate genes for PDgr. The current study carried out a QTL analysis for PDgr using a high-density SNP map in B. napus, providing novel targets for improving seed yield. These results advanced our understanding of the genetic control of PDgr regulation in B. napus. PMID:26779193

High-Density SNP Map Construction and QTL Identification for the Apetalous Character in Brassica napus L.

PubMed

Wang, Xiaodong; Yu, Kunjiang; Li, Hongge; Peng, Qi; Chen, Feng; Zhang, Wei; Chen, Song; Hu, Maolong; Zhang, Jiefu

2015-01-01

The apetalous genotype is a morphological ideotype for increasing seed yield and should be of considerable agricultural use; however, only a few studies have focused on the genetic control of this trait in Brassica napus. In the present study, a recombinant inbred line, the AH population, containing 189 individuals was derived from a cross between an apetalous line 'APL01' and a normally petalled variety 'Holly'. The Brassica 60 K Infinium BeadChip Array harboring 52,157 single nucleotide polymorphism (SNP) markers was used to genotype the AH individuals. A high-density genetic linkage map was constructed based on 2,755 bins involving 11,458 SNPs and 57 simple sequence repeats, and was used to identify loci associated with petalous degree (PDgr). The linkage map covered 2,027.53 cM, with an average marker interval of 0.72 cM. The AH map had good collinearity with the B. napus reference genome, indicating its high quality and accuracy. After phenotypic analyses across five different experiments, a total of 19 identified quantitative trait loci (QTLs) distributed across chromosomes A3, A5, A6, A9 and C8 were obtained, and these QTLs were further integrated into nine consensus QTLs by a meta-analysis. Interestingly, the major QTL qPD.C8-2 was consistently detected in all five experiments, and qPD.A9-2 and qPD.C8-3 were stably expressed in four experiments. Comparative mapping between the AH map and the B. napus reference genome suggested that there were 328 genes underlying the confidence intervals of the three steady QTLs. Based on the Gene Ontology assignments of 52 genes to the regulation of floral development in published studies, 146 genes were considered as potential candidate genes for PDgr. The current study carried out a QTL analysis for PDgr using a high-density SNP map in B. napus, providing novel targets for improving seed yield. These results advanced our understanding of the genetic control of PDgr regulation in B. napus.

High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster).

PubMed

Plomion, C; Bartholomé, J; Lesur, I; Boury, C; Rodríguez-Quilón, I; Lagraulet, H; Ehrenmann, F; Bouffier, L; Gion, J M; Grivet, D; de Miguel, M; de María, N; Cervera, M T; Bagnoli, F; Isik, F; Vendramin, G G; González-Martínez, S C

2016-03-01

Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism (SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred (F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies. © 2015 John Wiley & Sons Ltd.

Population-genetic nature of copy number variations in the human genome.

PubMed

Kato, Mamoru; Kawaguchi, Takahisa; Ishikawa, Shumpei; Umeda, Takayoshi; Nakamichi, Reiichiro; Shapero, Michael H; Jones, Keith W; Nakamura, Yusuke; Aburatani, Hiroyuki; Tsunoda, Tatsuhiko

2010-03-01

Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000-4000 CNVs (4-6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV-SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV-SNP linkage disequilibrium (LD) for 500-900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP-SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs.

Genomic analyses of tropical beef cattle fertility based on genotyping pools of Brahman cows with unknown pedigree.

PubMed

Reverter, A; Porto-Neto, L R; Fortes, M R S; McCulloch, R; Lyons, R E; Moore, S; Nicol, D; Henshall, J; Lehnert, S A

2016-10-01

We introduce an innovative approach to lowering the overall cost of obtaining genomic EBV (GEBV) and encourage their use in commercial extensive herds of Brahman beef cattle. In our approach, the DNA genotyping of cow herds from 2 independent properties was performed using a high-density bovine SNP chip on DNA from pooled blood samples, grouped according to the result of a pregnancy test following their first and second joining opportunities. For the DNA pooling strategy, 15 to 28 blood samples from the same phenotype and contemporary group were allocated to pools. Across the 2 properties, a total of 183 pools were created representing 4,164 cows. In addition, blood samples from 309 bulls from the same properties were also taken. After genotyping and quality control, 74,584 remaining SNP were used for analyses. Pools and individual DNA samples were related by means of a "hybrid" genomic relationship matrix. The pooled genotyping analysis of 2 large and independent commercial populations of tropical beef cattle was able to recover significant and plausible associations between SNP and pregnancy test outcome. We discuss 24 SNP with significant association ( < 1.0 × 10) and mapped within 40 kb of an annotated gene. We have established a method to estimate the GEBV in young herd bulls for a trait that is currently unable to be predicted at all. In summary, our novel approach allowed us to conduct genomic analyses of fertility in 2 large commercial Brahman herds managed under extensive pastoral conditions.

High-frequency and hot-platen curing of medium-density fiberboards

Treesearch

Robert R. Stevens; George E. Woodson

1977-01-01

The effects of two curing methods-high-frequencey heating and hot-platen heating-on the properties of a ureaformaldehyde-bonded medium-density fiberboard prepared with a southern-hardwoods furnish (50% southern read oak, 25% mockernut hickory, and 25% sweetgum) were studied. Boards of three densities-38, 44, and 50 lb./ft3-were cured by the two...

The impact of different interstellar medium structures on the dynamical evolution of supernova remnants

NASA Astrophysics Data System (ADS)

Wang, Yueyang; Bao, Biwen; Yang, Chuyuan; Zhang, Li

2018-05-01

The dynamical properties of supernova remnants (SNRs) evolving with different interstellar medium structures are investigated through performing extensive two-dimensional magnetohydrodynamic (MHD) simulations in the cylindrical symmetry. Three cases of different interstellar medium structures are considered: the uniform medium, the turbulent medium and the cloudy medium. Large-scale density and magnetic fluctuations are calculated and mapped into the computational domain before simulations. The clouds are set by random distribution in advance. The above configuration allows us to study the time-dependent dynamical properties and morphological evolution of the SNR evolving with different ambient structures, along with the development of the instabilities at the contact discontinuity. Our simulation results indicate that remnant morphology deviates from symmetry if the interstellar medium contains clouds or turbulent density fluctuations. In the cloudy medium case, interactions between the shock wave and clouds lead to clouds' fragmentation. The magnetic field can be greatly enhanced by stretching field lines with a combination of instabilities while the width of amplification region is quite different among the three cases. Moreover, both the width of amplification region and the maximum magnetic-field strength are closely related to the clouds' density.

Gallium plasmonic nanoparticles for label-free DNA and single nucleotide polymorphism sensing

NASA Astrophysics Data System (ADS)

Marín, Antonio García; García-Mendiola, Tania; Bernabeu, Cristina Navio; Hernández, María Jesús; Piqueras, Juan; Pau, Jose Luis; Pariente, Félix; Lorenzo, Encarnación

2016-05-01

A label-free DNA and single nucleotide polymorphism (SNP) sensing method is described. It is based on the use of the pseudodielectric function of gallium plasmonic nanoparticles (GaNPs) deposited on Si (100) substrates under reversal of the polarization handedness condition. Under this condition, the pseudodielectric function is extremely sensitive to changes in the surrounding medium of the nanoparticle surface providing an excellent sensing platform competitive to conventional surface plasmon resonance. DNA sensing has been carried out by immobilizing a thiolated capture probe sequence from Helicobacter pylori onto GaNP/Si substrates; complementary target sequences of Helicobacter pylori can be quantified over the range of 10 pM to 3.0 nM with a detection limit of 6.0 pM and a linear correlation coefficient of R2 = 0.990. The selectivity of the device allows the detection of a single nucleotide polymorphism (SNP) in a specific sequence of Helicobacter pylori, without the need for a hybridization suppressor in solution such as formamide. Furthermore, it also allows the detection of this sequence in the presence of other pathogens, such as Escherichia coli in the sample. The broad applicability of the system was demonstrated by the detection of a specific gene mutation directly associated with cystic fibrosis in large genomic DNA isolated from blood cells.A label-free DNA and single nucleotide polymorphism (SNP) sensing method is described. It is based on the use of the pseudodielectric function of gallium plasmonic nanoparticles (GaNPs) deposited on Si (100) substrates under reversal of the polarization handedness condition. Under this condition, the pseudodielectric function is extremely sensitive to changes in the surrounding medium of the nanoparticle surface providing an excellent sensing platform competitive to conventional surface plasmon resonance. DNA sensing has been carried out by immobilizing a thiolated capture probe sequence from Helicobacter pylori onto GaNP/Si substrates; complementary target sequences of Helicobacter pylori can be quantified over the range of 10 pM to 3.0 nM with a detection limit of 6.0 pM and a linear correlation coefficient of R2 = 0.990. The selectivity of the device allows the detection of a single nucleotide polymorphism (SNP) in a specific sequence of Helicobacter pylori, without the need for a hybridization suppressor in solution such as formamide. Furthermore, it also allows the detection of this sequence in the presence of other pathogens, such as Escherichia coli in the sample. The broad applicability of the system was demonstrated by the detection of a specific gene mutation directly associated with cystic fibrosis in large genomic DNA isolated from blood cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00926c

Mercury Slovenian soils: High, medium and low sample density geochemical maps

NASA Astrophysics Data System (ADS)

Gosar, Mateja; Šajn, Robert; Teršič, Tamara

2017-04-01

Regional geochemical survey was conducted in whole territory of Slovenia (20273 km2). High, medium and low sample density surveys were compared. High sample density represented the regional geochemical data set supplemented by local high-density sampling data (irregular grid, n=2835). Medium-density soil sampling was performed in a 5 x 5 km grid (n=817) and low-density geochemical survey was conducted in a sampling grid 25 x 25 km (n=54). Mercury distribution in Slovenian soils was determined with models of mercury distribution in soil using all three data sets. A distinct Hg anomaly in western part of Slovenia is evident on all three models. It is a consequence of 500-years of mining and ore processing in the second largest mercury mine in the world, the Idrija mine. The determined mercury concentrations revealed an important difference between the western and the eastern parts of the country. For the medium scale geochemical mapping is the median value (0.151 mg /kg) for western Slovenia almost 2-fold higher than the median value (0.083 mg/kg) in eastern Slovenia. Besides the Hg median for the western part of Slovenia exceeds the Hg median for European soil by a factor of 4 (Gosar et al., 2016). Comparing these sample density surveys, it was shown that high sampling density allows the identification and characterization of anthropogenic influences on a local scale, while medium- and low-density sampling reveal general trends in the mercury spatial distribution, but are not appropriate for identifying local contamination in industrial regions and urban areas. The resolution of the pattern generated is the best when the high-density survey on a regional scale is supplemented with the geochemical data of the high-density surveys on a local scale. References: Gosar, M, Šajn, R, Teršič, T. Distribution pattern of mercury in the Slovenian soil: geochemical mapping based on multiple geochemical datasets. Journal of geochemical exploration, 2016, 167/38-48.

High-frequency and hot-platen curing of medium-density fiberboards

Treesearch

R.R. Stevens; G.E. Woodson

1977-01-01

The effects of two curing methods- high-frequency heating and hot-platen heating- on the properties of a ure-formaldehyd-bonded medium-density fiberboard prepared with a southern-hardwoods furnish (50% southern red oak, 25% mockernut hickory, and 25% sweetgum) were studied. Boards of three densities- 38, 44, and 50 lb./ft.3- were cured by the two...

Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

PubMed Central

Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca e; Mundim, Gabriel Borges

2016-01-01

Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits.

PubMed

Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca E; Mundim, Gabriel Borges

2016-03-01

The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis.

Analysis of LDLR mutations in familial hypercholesterolemia patients in Greece by use of the NanoChip microelectronic array technology.

PubMed

Laios, Eleftheria; Drogari, Euridiki

2006-12-01

Three mutations in the low density lipoprotein receptor (LDLR) gene account for 49% of familial hypercholesterolemia (FH) cases in Greece. We used the microelectronic array technology of the NanoChip Molecular Biology Workstation to develop a multiplex method to analyze these single-nucleotide polymorphisms (SNPs). Primer pairs amplified the region encompassing each SNP. The biotinylated PCR amplicon was electronically addressed to streptavidin-coated microarray sites. Allele-specific fluorescently labeled oligonucleotide reporters were designed and used for detection of wild-type and SNP sequences. Genotypes were compared to PCR-restriction fragment length polymorphism (PCR-RFLP). We developed three monoplex assays (1 SNP/site) and an optimized multiplex assay (3SNPs/site). We performed 92 Greece II, 100 Genoa, and 98 Afrikaner-2 NanoChip monoplex assays (addressed to duplicate sites and analyzed separately). Of the 580 monoplex genotypings (290 samples), 579 agreed with RFLP. Duplicate sites of one sample were not in agreement with each other. Of the 580 multiplex genotypings, 576 agreed with the monoplex results. Duplicate sites of three samples were not in agreement with each other, indicating requirement for repetition upon which discrepancies were resolved. The multiplex assay detects common LDLR mutations in Greek FH patients and can be extended to accommodate additional mutations.

Cloaks for suppression or enhancement of scattering of diffuse photon density waves

NASA Astrophysics Data System (ADS)

Renthlei, Lalruatfela; Ramakrishna, S. Anantha; Wanare, Harshawardhan

2018-07-01

Enhancement of wave-like characteristics of heavily damped diffuse photon density waves in a random medium by amplification can induce strongly localised resonances. These resonances can be used to either suppress or enhance scattering from an inhomogeneity in the random medium by cloaking the inhomogeneous region by a shell of random medium with the correct levels of absorption or amplification. A spherical core-shell structure consisting of a shell of a random amplifying medium is shown to enhance or suppress specific resonant modes. A shell with an absorbing random medium is also shown to suppress scattering which can also be used for cloaking the core region.

Interplanetary density models as inferred from solar Type III bursts

NASA Astrophysics Data System (ADS)

Oppeneiger, Lucas; Boudjada, Mohammed Y.; Lammer, Helmut; Lichtenegger, Herbert

2016-04-01

We report on the density models derived from spectral features of solar Type III bursts. They are generated by beams of electrons travelling outward from the Sun along open magnetic field lines. Electrons generate Langmuir waves at the plasma frequency along their ray paths through the corona and the interplanetary medium. A large frequency band is covered by the Type III bursts from several MHz down to few kHz. In this analysis, we consider the previous empirical density models proposed to describe the electron density in the interplanetary medium. We show that those models are mainly based on the analysis of Type III bursts generated in the interplanetary medium and observed by satellites (e.g. RAE, HELIOS, VOYAGER, ULYSSES,WIND). Those models are confronted to stereoscopic observations of Type III bursts recorded by WIND, ULYSSES and CASSINI spacecraft. We discuss the spatial evolution of the electron beam along the interplanetary medium where the trajectory is an Archimedean spiral. We show that the electron beams and the source locations are depending on the choose of the empirical density models.

Linear reduction methods for tag SNP selection.

PubMed

He, Jingwu; Zelikovsky, Alex

2004-01-01

It is widely hoped that constructing a complete human haplotype map will help to associate complex diseases with certain SNP's. Unfortunately, the number of SNP's is huge and it is very costly to sequence many individuals. Therefore, it is desirable to reduce the number of SNP's that should be sequenced to considerably small number of informative representatives, so called tag SNP's. In this paper, we propose a new linear algebra based method for selecting and using tag SNP's. Our method is purely combinatorial and can be combined with linkage disequilibrium (LD) and block based methods. We measure the quality of our tag SNP selection algorithm by comparing actual SNP's with SNP's linearly predicted from linearly chosen tag SNP's. We obtain an extremely good compression and prediction rates. For example, for long haplotypes (>25000 SNP's), knowing only 0.4% of all SNP's we predict the entire unknown haplotype with 2% accuracy while the prediction method is based on a 10% sample of the population.

DNA polymorphisms and transcript abundance of PRKAG2 and phosphorylated AMP-activated protein kinase in the rumen are associated with gain and feed intake in beef steers

USDA-ARS?s Scientific Manuscript database

Beef steers with variation in feed efficiency phenotypes were evaluated previously on a high density SNP panel. Ten markers from rs110125325-rs41652818 on bovine chromosome 4 were associated with average daily gain (ADG). To identify the gene(s) in this 1.2Mb region responsible for variation in AD...

Association of PvuII and XbaI polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of post-menopausal women: Effects of aging, body mass index and breast cancer incidence

PubMed Central

Gomes-Rochette, Neuza Felix; Souza, Letícia Soncini; Tommasi, Bruno Otoni; Pedrosa, Diego França; Fin, Irani do Carmo Francischetto; Vieira, Fernando Luiz Herkenhoff; Graceli, Jones Bernardes; Rangel, Letícia Batista Azevedo; Silva, Ian Victor

2017-01-01

Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010–2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations associated to SNP XbaI c454-351A>G on ESR1 gene is enhanced in both obese (higher BMI) and elder women. Taken together, these results suggested that XbaI c454-351A>G SNP is associated to changes in lipid profile, particularly in serum TG and TL, in this cohort of post-menopausal woman. Also, this paper shows another link between obesity and BC corroborating the current thesis that both diseases are interlinked. PMID:28199328

Association of PvuII and XbaI polymorphisms on estrogen receptor alpha (ESR1) gene to changes into serum lipid profile of post-menopausal women: Effects of aging, body mass index and breast cancer incidence.

PubMed

Gomes-Rochette, Neuza Felix; Souza, Letícia Soncini; Tommasi, Bruno Otoni; Pedrosa, Diego França; Eis, Sérgio Ragi; Fin, Irani do Carmo Francischetto; Vieira, Fernando Luiz Herkenhoff; Graceli, Jones Bernardes; Rangel, Letícia Batista Azevedo; Silva, Ian Victor

2017-01-01

Estrogen is a steroidal hormone involved in several physiological functions in the female body including regulation of serum lipid metabolism and breast cancer (BC). Estrogen actions on serum lipids mostly occur through its binding to intracellular Estrogen Receptor alpha (ERalpha) isoform, expressed in most of tissues. This gene (ESR1) exhibit many polymorphic sites (SNPs) located either on translated and non-translated regions that regulate ERalpha protein expression and function. This paper aimed to investigate the association of two intronic SNPs of ESR1 gene, namely c454-397T>C (PvuII) and c454-351A>G (XbaI) to alterations in serum levels of total cholesterol (T-chol), total lipid (TL), low density lipoprotein cholesterol (LDL), high density lipoprotein (HDL), and triglycerides (TG) in a cohort of post-menopausal women. In addition, we aimed to associate presence of these SNPs to development of BC along 5 years period. To do so, a group of healthy 499, highly miscigenated, post-menopausal Brazilian women, were carried using PCR-FRLP technique and further confirmed by automatic sequence analysis as well followed through 5 years for BC incidence. Measurements of serum lipid profile by standard commercial methods were carried individually whereas Dual Energy X-ray Absorciometry (DXA) measured Body Mass Indexes (BMI), Fat Mass (FM), Lean Body Mass (LBM), and Body Water Content (BWC). No effects of PvuII SNP on ESR1 gene were observed on patient´s serum T-chol, TL, LDL, HDL, and TG. However, c454-397T>C PvuII SNP is associated to lower body fat and higher levels of lean mass and body water and lower incidence of BC. On the other hand, statistically significant effect of XbaI c454-351A>G SNP on serum TG and TL levels. Patients homozygous for X allele were followed up from 2010-2015. They showed higher incidence of breast cancer (BC) when compared to either heterozygous and any P allele combination. Moreover, the increasing of TG and TL serum concentrations associated to SNP XbaI c454-351A>G on ESR1 gene is enhanced in both obese (higher BMI) and elder women. Taken together, these results suggested that XbaI c454-351A>G SNP is associated to changes in lipid profile, particularly in serum TG and TL, in this cohort of post-menopausal woman. Also, this paper shows another link between obesity and BC corroborating the current thesis that both diseases are interlinked.

Genes with stable DNA methylation levels show higher evolutionary conservation than genes with fluctuant DNA methylation levels.

PubMed

Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai

2015-11-24

Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.

Inhibitory effect of hot-water extract from dried fruit of Crataegus pinnatifida on low-density lipoprotein (LDL) oxidation in cell and cell-free systems.

PubMed

Chu, Chia-Yih; Lee, Miao-Jane; Liao, Chuen-Lan; Lin, Wea-Lung; Yin, Yu-Fang; Tseng, Tsui-Hwa

2003-12-17

The dried fruit of Crataegus pinnatifida, a local soft drink material and medical herb, was found to possess potential against oxidative stress. In the preliminary study, the antioxidant potential of a hot-water extract obtained from the dried fruit of C. pinnatifida (CF-H) was evaluated in terms of its capacity of quenching 1,1-diphenyl-2-picrylhydrazyl free radicals (EC(50) = 0.118 mg/mL). After content analysis, it was found that CF-H is mainly composed of polyphenols including flavonoids (6.9%), procyanidins (2.2%), (+)-catechin (0.5%), and (-)-epicatechin (0.2%). The antioxidative bioactivity of CF-H had been assess previously using the models of CuSO(4) as cell-free system and sodium nitroprusside (SNP) plus macrophage RAW 264.7 cells as cell system to induce human low-density lipoprotein oxidation. CF-H was found to inhibit relative electrophoretic mobility and thiobarbituric acid reactive substances at the concentration of 0.5-1.0 mg/mL in the cell-free system and at 0.01-0.10 mg/mL in the cell system. Furthermore, it was found that CF-H decreased the SNP-induced cell lipid peroxidation and reduced glutathione depletion.

WNT16 Influences Bone Mineral Density, Cortical Bone Thickness, Bone Strength, and Osteoporotic Fracture Risk

PubMed Central

Eriksson, Joel; Paternoster, Lavinia; Yerges-Armstrong, Laura M.; Lehtimäki, Terho; Bergström, Ulrica; Kähönen, Mika; Leo, Paul J.; Raitakari, Olli; Laaksonen, Marika; Nicholson, Geoffrey C.; Viikari, Jorma; Ladouceur, Martin; Lyytikäinen, Leo-Pekka; Medina-Gomez, Carolina; Rivadeneira, Fernando; Prince, Richard L.; Sievanen, Harri; Leslie, William D.; Mellström, Dan; Eisman, John A.; Movérare-Skrtic, Sofia; Goltzman, David; Hanley, David A.; Jones, Graeme; St. Pourcain, Beate; Xiao, Yongjun; Timpson, Nicholas J.; Smith, George Davey; Reid, Ian R.; Ring, Susan M.; Sambrook, Philip N.; Karlsson, Magnus; Dennison, Elaine M.; Kemp, John P.; Danoy, Patrick; Sayers, Adrian; Wilson, Scott G.; Nethander, Maria; McCloskey, Eugene; Vandenput, Liesbeth; Eastell, Richard; Liu, Jeff; Spector, Tim; Mitchell, Braxton D.; Streeten, Elizabeth A.; Brommage, Robert; Pettersson-Kymmer, Ulrika; Brown, Matthew A.; Ohlsson, Claes; Richards, J. Brent; Lorentzon, Mattias

2012-01-01

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of −0.11 standard deviations [SD] per C allele, P = 6.2×10−9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (−0.14 SD per C allele, P = 2.3×10−12, and −0.16 SD per G allele, P = 1.2×10−15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10−9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10−6 and rs2707466: OR = 1.22, P = 7.2×10−6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16−/− mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%–61% (6.5×10−13

A genome-wide association study of production traits in a commercial population of Large White pigs: evidence of haplotypes affecting meat quality

PubMed Central

2014-01-01

Background Numerous quantitative trait loci (QTL) have been detected in pigs over the past 20 years using microsatellite markers. However, due to the low density of these markers, the accuracy of QTL location has generally been poor. Since 2009, the dense genome coverage provided by the Illumina PorcineSNP60 BeadChip has made it possible to more accurately map QTL using genome-wide association studies (GWAS). Our objective was to perform high-density GWAS in order to identify genomic regions and corresponding haplotypes associated with production traits in a French Large White population of pigs. Methods Animals (385 Large White pigs from 106 sires) were genotyped using the PorcineSNP60 BeadChip and evaluated for 19 traits related to feed intake, growth, carcass composition and meat quality. Of the 64 432 SNPs on the chip, 44 412 were used for GWAS with an animal mixed model that included a regression coefficient for the tested SNPs and a genomic kinship matrix. SNP haplotype effects in QTL regions were then tested for association with phenotypes following phase reconstruction based on the Sscrofa10.2 pig genome assembly. Results Twenty-three QTL regions were identified on autosomes and their effects ranged from 0.25 to 0.75 phenotypic standard deviation units for feed intake and feed efficiency (four QTL), carcass (12 QTL) and meat quality traits (seven QTL). The 10 most significant QTL regions had effects on carcass (chromosomes 7, 10, 16, 17 and 18) and meat quality traits (two regions on chromosome 1 and one region on chromosomes 8, 9 and 13). Thirteen of the 23 QTL regions had not been previously described. A haplotype block of 183 kb on chromosome 1 (six SNPs) was identified and displayed three distinct haplotypes with significant (0.0001 < P < 0.03) associations with all evaluated meat quality traits. Conclusions GWAS analyses with the PorcineSNP60 BeadChip enabled the detection of 23 QTL regions that affect feed consumption, carcass and meat quality traits in a LW population, of which 13 were novel QTL. The proportionally larger number of QTL found for meat quality traits suggests a specific opportunity for improving these traits in the pig by genomic selection. PMID:24528607

Primary stability and self-tapping blades: biomechanical assessment of dental implants in medium-density bone.

PubMed

Kim, Yung-Soo; Lim, Young-Jun

2011-10-01

The aim of this biomechanical study was to assess the influence of self-tapping blades in terms of primary implant stability between implants with self-tapping blades and implants without self-tapping blades using five different analytic methods, especially in medium-density bone. Two different types of dental implants (4 × 10 mm) were tested: self-tapping and non-self-tapping. The fixture design including thread profiles was exactly the same between the two groups; the only difference was the presence of cutting blades on one half of the apical portion of the implant body. Solid rigid polyurethane blocks with corresponding densities were selected to simulate medium-density bone. Five mechanical assessments (insertion torque, resonance frequency analysis [RFA], reverse torque, pull-out and push in test) were performed for primary stability. Implants without self-tapping blades showed significantly higher values (P<0.001) in four biomechanical assessments, except RFA (P=0.684). However, a statistically significant correlation could not be detected between insertion torque values with the four different outcome variables (P>0.05). The outcomes of the present study indicate that the implant body design without self-tapping blades has a good primary stability compared with that with self-tapping blades in medium-density bone. Considering the RFA, a distinct layer of cortical bone on marginal bone will yield implant stability quotient values similar to those in medium-bone density when implants have the same diameter. © 2011 John Wiley & Sons A/S.

Decay of correlations between cross-polarized electromagnetic waves in a two-dimensional random medium.

PubMed

Gorodnichev, E E

2018-04-01

The problem of multiple scattering of polarized light in a two-dimensional medium composed of fiberlike inhomogeneities is studied. The attenuation lengths for the density matrix elements are calculated. For a highly absorbing medium it is found that, as the sample thickness increases, the intensity of waves polarized along the fibers decays faster than the other density matrix elements. With further increase in the sample thickness, the off-diagonal elements which are responsible for correlations between the cross-polarized waves disappear. In the asymptotic limit of very thick samples the scattered light proves to be polarized perpendicular to the fibers. The difference in the attenuation lengths between the density matrix elements results in a nonmonotonic depth dependence of the degree of polarization. In the opposite case of a weakly absorbing medium, the off-diagonal element of the density matrix and, correspondingly, the correlations between the cross-polarized fields are shown to decay faster than the intensity of waves polarized along and perpendicular to the fibers.

Population distribution and ancestry of the cancer protective MDM2 SNP285 (rs117039649).

PubMed

Knappskog, Stian; Gansmo, Liv B; Dibirova, Khadizha; Metspalu, Andres; Cybulski, Cezary; Peterlongo, Paolo; Aaltonen, Lauri; Vatten, Lars; Romundstad, Pål; Hveem, Kristian; Devilee, Peter; Evans, Gareth D; Lin, Dongxin; Van Camp, Guy; Manolopoulos, Vangelis G; Osorio, Ana; Milani, Lili; Ozcelik, Tayfun; Zalloua, Pierre; Mouzaya, Francis; Bliznetz, Elena; Balanovska, Elena; Pocheshkova, Elvira; Kučinskas, Vaidutis; Atramentova, Lubov; Nymadawa, Pagbajabyn; Titov, Konstantin; Lavryashina, Maria; Yusupov, Yuldash; Bogdanova, Natalia; Koshel, Sergey; Zamora, Jorge; Wedge, David C; Charlesworth, Deborah; Dörk, Thilo; Balanovsky, Oleg; Lønning, Per E

2014-09-30

The MDM2 promoter SNP285C is located on the SNP309G allele. While SNP309G enhances Sp1 transcription factor binding and MDM2 transcription, SNP285C antagonizes Sp1 binding and reduces the risk of breast-, ovary- and endometrial cancer. Assessing SNP285 and 309 genotypes across 25 different ethnic populations (>10.000 individuals), the incidence of SNP285C was 6-8% across European populations except for Finns (1.2%) and Saami (0.3%). The incidence decreased towards the Middle-East and Eastern Russia, and SNP285C was absent among Han Chinese, Mongolians and African Americans. Interhaplotype variation analyses estimated SNP285C to have originated about 14,700 years ago (95% CI: 8,300 - 33,300). Both this estimate and the geographical distribution suggest SNP285C to have arisen after the separation between Caucasians and modern day East Asians (17,000 - 40,000 years ago). We observed a strong inverse correlation (r = -0.805; p < 0.001) between the percentage of SNP309G alleles harboring SNP285C and the MAF for SNP309G itself across different populations suggesting selection and environmental adaptation with respect to MDM2 expression in recent human evolution. In conclusion, we found SNP285C to be a pan-Caucasian variant. Ethnic variation regarding distribution of SNP285C needs to be taken into account when assessing the impact of MDM2 SNPs on cancer risk.

SU-E-T-791: Validation of a Determinant Based Photon Transport Solver in Dose Perturbed By Diverse Media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuo, H; Tome, W; Yaparpalvi, R

Purpose: To validate a determinant based photon transport solver in dose imparted within different transition zone between different medium. Methods: Thickness (.2cm,.5cm, 1cm, 3cm) from various materials (Air - density=0.0012g/cm3, Cork-0.19g/cm3, Lung-0.26g/cm3, Bone-1.85g/cm3, Aluminum (Al)-2.7g/cm3, Titanium (Ti)-4.42g/cm3, Iron (Fe)-8g/cm3) were sandwiched by 10cm solid water. 6MV were used to study the calculation difference between a superposition photon beam model (AAA) and the determinant based Boltzmann photon transport solver (XB) at the upstream (I) and downstream boarder (II) of the medium, within the medium (III), and at far distance downstream away from medium (IV). Calculation was validated with available thickness ofmore » Air, Cork, Lung, Al, Ti and Fe. Results are presented as the ratio of the dose at the point with medium perturbation to the same point dose without perturbation. Results: Zone I showed different backscatter enhancement from high-density materials within the 5mm of the upstream border. AAA showed no backscatter at all, XB showed good agreement beyond 1mm upstream (1.18 vs 1.14, 1.09 vs 1.10, and 1.04 vs 1.05 for Fe, Ti, and Fe, respectively). Zone II showed a re-buildup after exiting high-density medium and Air but no build up for density close to water in both of the measurement and XB. AAA yielded the opposite results in Zone II. XB and AAA showed in Zone III very different absorption in high density medium and the Air. XB and measurement had high concordance regarding photon attenuation in Zone IV. AAA showed less agreement especially when the medium was Air or Fe. Conclusion: XB compared well with measurement in regions 1mm away from the interface. Planning using XB should be beneficial for External Beam Planning in situations with large air cavity, very low lung density, compact bone, and any kind of metal implant.« less

Response of a thin airfoil encountering strong density discontinuity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marble, F.E.

1993-12-01

Airfoil theory for unsteady motion has been developed extensively assuming the undisturbed medium to be of uniform density, a restriction accurate for motion in the atmosphere. In some instances, notably for airfoil comprising fan, compressor and turbine blade rows, the undisturbed medium may carry density variations or ``spots``, resulting from non-uniformities in temperature or composition, of a size comparable to the blade chord. This condition exists for turbine blades, immediately downstream of the main burner of a gas turbine engine where the density fluctuations of the order of 50 percent may occur. Disturbances of a somewhat smaller magnitude arise frommore » the ingestion of hot boundary layers into fans, and exhaust into hovercraft. Because these regions of non-uniform density convect with the moving medium, the airfoil experiences a time varying load and moment which the authors calculate.« less

Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach.

PubMed

Spencer, Amy V; Cox, Angela; Lin, Wei-Yu; Easton, Douglas F; Michailidou, Kyriaki; Walters, Kevin

2016-04-01

There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples. © 2016 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

Genetic Linkage Mapping of Economically Important Traits in Cultivated Tetraploid Potato (Solanum tuberosum L.).

PubMed

Massa, Alicia N; Manrique-Carpintero, Norma C; Coombs, Joseph J; Zarka, Daniel G; Boone, Anne E; Kirk, William W; Hackett, Christine A; Bryan, Glenn J; Douches, David S

2015-09-14

The objective of this study was to construct a single nucleotide polymorphism (SNP)-based genetic map at the cultivated tetraploid level to locate quantitative trait loci (QTL) contributing to economically important traits in potato (Solanum tuberosum L.). The 156 F1 progeny and parents of a cross (MSL603) between "Jacqueline Lee" and "MSG227-2" were genotyped using the Infinium 8303 Potato Array. Furthermore, the progeny and parents were evaluated for foliar late blight reaction to isolates of the US-8 genotype of Phytophthora infestans (Mont.) de Bary and vine maturity. Linkage analyses and QTL mapping were performed using a novel approach that incorporates allele dosage information. The resulting genetic maps contained 1972 SNP markers with an average density of 1.36 marker per cM. QTL mapping identified the major source of late blight resistance in "Jacqueline Lee." The best SNP marker mapped ~0.54 Mb from a resistance hotspot on the long arm of chromosome 9. For vine maturity, the major-effect QTL was located on chromosome 5 with allelic effects from both parents. A candidate SNP marker for this trait mapped ~0.25 Mb from the StCDF1 gene, which is a candidate gene for the maturity trait. The identification of markers for P. infestans resistance will enable the introgression of multiple sources of resistance through marker-assisted selection. Moreover, the discovery of a QTL for late blight resistance not linked to the QTL for vine maturity provides the opportunity to use marker-assisted selection for resistance independent of the selection for vine maturity classifications. Copyright © 2015 Massa et al.

Genetic Linkage Mapping of Economically Important Traits in Cultivated Tetraploid Potato (Solanum tuberosum L.)

PubMed Central

Massa, Alicia N.; Manrique-Carpintero, Norma C.; Coombs, Joseph J.; Zarka, Daniel G.; Boone, Anne E.; Kirk, William W.; Hackett, Christine A.; Bryan, Glenn J.; Douches, David S.

2015-01-01

The objective of this study was to construct a single nucleotide polymorphism (SNP)-based genetic map at the cultivated tetraploid level to locate quantitative trait loci (QTL) contributing to economically important traits in potato (Solanum tuberosum L.). The 156 F1 progeny and parents of a cross (MSL603) between “Jacqueline Lee” and “MSG227-2” were genotyped using the Infinium 8303 Potato Array. Furthermore, the progeny and parents were evaluated for foliar late blight reaction to isolates of the US-8 genotype of Phytophthora infestans (Mont.) de Bary and vine maturity. Linkage analyses and QTL mapping were performed using a novel approach that incorporates allele dosage information. The resulting genetic maps contained 1972 SNP markers with an average density of 1.36 marker per cM. QTL mapping identified the major source of late blight resistance in “Jacqueline Lee.” The best SNP marker mapped ∼0.54 Mb from a resistance hotspot on the long arm of chromosome 9. For vine maturity, the major-effect QTL was located on chromosome 5 with allelic effects from both parents. A candidate SNP marker for this trait mapped ∼0.25 Mb from the StCDF1 gene, which is a candidate gene for the maturity trait. The identification of markers for P. infestans resistance will enable the introgression of multiple sources of resistance through marker-assisted selection. Moreover, the discovery of a QTL for late blight resistance not linked to the QTL for vine maturity provides the opportunity to use marker-assisted selection for resistance independent of the selection for vine maturity classifications. PMID:26374597

Exploiting sequence similarity to validate the sensitivity of SNP arrays in detecting fine-scaled copy number variations.

PubMed

Wong, Gerard; Leckie, Christopher; Gorringe, Kylie L; Haviv, Izhak; Campbell, Ian G; Kowalczyk, Adam

2010-04-15

High-density single nucleotide polymorphism (SNP) genotyping arrays are efficient and cost effective platforms for the detection of copy number variation (CNV). To ensure accuracy in probe synthesis and to minimize production costs, short oligonucleotide probe sequences are used. The use of short probe sequences limits the specificity of binding targets in the human genome. The specificity of these short probeset sequences has yet to be fully analysed against a normal reference human genome. Sequence similarity can artificially elevate or suppress copy number measurements, and hence reduce the reliability of affected probe readings. For the purpose of detecting narrow CNVs reliably down to the width of a single probeset, sequence similarity is an important issue that needs to be addressed. We surveyed the Affymetrix Human Mapping SNP arrays for probeset sequence similarity against the reference human genome. Utilizing sequence similarity results, we identified a collection of fine-scaled putative CNVs between gender from autosomal probesets whose sequence matches various loci on the sex chromosomes. To detect these variations, we utilized our statistical approach, Detecting REcurrent Copy number change using rank-order Statistics (DRECS), and showed that its performance was superior and more stable than the t-test in detecting CNVs. Through the application of DRECS on the HapMap population datasets with multi-matching probesets filtered, we identified biologically relevant SNPs in aberrant regions across populations with known association to physical traits, such as height, covered by the span of a single probe. This provided empirical confirmation of the existence of naturally occurring narrow CNVs as well as the sensitivity of the Affymetrix SNP array technology in detecting them. The MATLAB implementation of DRECS is available at http://ww2.cs.mu.oz.au/ approximately gwong/DRECS/index.html.

Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis

PubMed Central

Corbin, Karen D.; Abdelmalek, Manal F.; Spencer, Melanie D.; da Costa, Kerry-Ann; Galanko, Joseph A.; Sha, Wei; Suzuki, Ayako; Guy, Cynthia D.; Cardona, Diana M.; Torquati, Alfonso; Diehl, Anna Mae; Zeisel, Steven H.

2013-01-01

Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleotide polymorphisms (SNPs) across genes of choline/1-carbon metabolism and functionally related pathways increase susceptibility to developing hepatic steatosis. In biopsy-characterized cases of nonalcoholic fatty liver disease and controls, we assessed 260 SNPs across 21 genes in choline/1-carbon metabolism. When SNPs were examined individually, using logistic regression, we only identified a single SNP (PNPLA3 rs738409) that was significantly associated with severity of hepatic steatosis after adjusting for confounders and multiple comparisons (P=0.02). However, when groupings of SNPs in similar metabolic pathways were defined using unsupervised hierarchical clustering, we identified groups of subjects with shared SNP signatures that were significantly correlated with steatosis burden (P=0.0002). The lowest and highest steatosis clusters could also be differentiated by ethnicity. However, unique SNP patterns defined steatosis burden irrespective of ethnicity. Our results suggest that analysis of SNP patterns in genes of choline/1-carbon metabolism may be useful for prediction of severity of steatosis in specific subsets of people, and the metabolic inefficiencies caused by these SNPs should be examined further.—Corbin, K. D., Abdelmalek, M. F., Spencer, M. D., da Costa, K.-A., Galanko, J. A., Sha, W., Suzuki, A., Guy, C. D., Cardona, D. M., Torquati, A., Diehl, A. M., Zeisel, S. H. Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis. PMID:23292069

Genome-wide population structure and evolutionary history of the Frizarta dairy sheep.

PubMed

Kominakis, A; Hager-Theodorides, A L; Saridaki, A; Antonakos, G; Tsiamis, G

2017-10-01

In the present study, we used genomic data, generated with a medium density single nucleotide polymorphisms (SNP) array, to acquire more information on the population structure and evolutionary history of the synthetic Frizarta dairy sheep. First, two typical measures of linkage disequilibrium (LD) were estimated at various physical distances that were then used to make inferences on the effective population size at key past time points. Population structure was also assessed by both multidimensional scaling analysis and k-means clustering on the distance matrix obtained from the animals' genomic relationships. The Wright's fixation F ST index was also employed to assess herds' genetic homogeneity and to indirectly estimate past migration rates. The Wright's fixation F IS index and genomic inbreeding coefficients based on the genomic relationship matrix as well as on runs of homozygosity were also estimated. The Frizarta breed displays relatively low LD levels with r 2 and |D'| equal to 0.18 and 0.50, respectively, at an average inter-marker distance of 31 kb. Linkage disequilibrium decayed rapidly by distance and persisted over just a few thousand base pairs. Rate of LD decay (β) varied widely among the 26 autosomes with larger values estimated for shorter chromosomes (e.g. β=0.057, for OAR6) and smaller values for longer ones (e.g. β=0.022, for OAR2). The inferred effective population size at the beginning of the breed's formation was as high as 549, was then reduced to 463 in 1981 (end of the breed's formation) and further declined to 187, one generation ago. Multidimensional scaling analysis and k-means clustering suggested a genetically homogenous population, F ST estimates indicated relatively low genetic differentiation between herds, whereas a heat map of the animals' genomic kinship relationships revealed a stratified population, at a herd level. Estimates of genomic inbreeding coefficients suggested that most recent parental relatedness may have been a major determinant of the current effective population size. A denser than the 50k SNP panel may be more beneficial when performing genome wide association studies in the breed.

Influence of atomic densities on propagation property for ultrashort pulses in a two-level medium

NASA Astrophysics Data System (ADS)

Liu, Bingxin; Gong, Shangqing; Song, Xiaohong; Jin, Shiqi

2005-05-01

The influence of atomic densities on the propagation property for ultrashort pulses in a two-level atom (TLA) medium is investigated. With higher atomic densities, the self-induced transparency (SIT) cannot be recovered even for 2? ultrashort pulses. New features such as pulse splitting, red-shift and blue-shift of the corresponding spectra arise, and the component of central frequency gradually disappears.

Genotype by environment interactions on culling rates and 305-day milk yield of Holstein cows in 3 US regions.

PubMed

Tsuruta, S; Lourenco, D A L; Misztal, I; Lawlor, T J

2015-08-01

The objective of this study was to investigate genotype by environment interactions for culling rates and milk production in large and small dairy herds in 3 US regions, using genotypes, pedigree, and phenotypes. Single nucleotide polymorphism (SNP) marker variances were also estimated in these different environments. Culling rates including cow mortality were based on 6 Dairy Herd Improvement termination codes reported by dairy producers. Separate data sets for culling rates and 305-d milk yield were created for large and small dairy herds in the US regions of the Southeast (SE), Southwest (SW), and Northeast (NE) for the first 3 lactation cows that calved between 1999 and 2008. Genomic information from 42,503 SNP markers on 34,506 bulls was included in the analysis to predict genomic estimated breeding value (GEBV) of culling rates and 305-d milk yield with a single-step genomic BLUP using a bivariate threshold-linear model. Cow replacement rates in large SE and NE herds were higher. Heritability estimates of culling rates ranged from 0.03 to 0.11, but the differences were small between large and small herds and among the 3 US regions. Genetic correlations between culling rates and 305-d milk yield were medium to high for cows sold for poor production and reproduction problems. Correlations of GEBV for culling rates among the 3 US regions ranged from 0.34 to 0.92 and were lower between the SW and the other regions, especially in small herds. Correlations of GEBV between large and small herds ranged from 0.44 to 0.90 and were lower in the SW. These results indicate genotype by environment interactions of cow culling rate between the US regions and between large and small herds. Correlations of top 30 SNP marker effects for culling rates between 2 US regions ranged from 0.64 to 0.98 and were higher than those of more SNP marker effects except for a culling reason "sold for dairy purpose." Those correlations between large and small herds ranged from 0.67 to 0.98. High correlations of top SNP marker effects on culling reasons between the US regions and between large and small herds suggest that major markers can be useful for selection in different environments. The SNP variance shown in a marker gene segment on chromosome 14 was strongly associated with milk production in large and small herds in the NE but not in the SE and SW. Marker genes on chromosome 14 also showed a strong association with cow culling rates due to poor production and mortality in large herds in the NE. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Construction of a High-Density American Cranberry (Vaccinium macrocarpon Ait.) Composite Map Using Genotyping-by-Sequencing for Multi-pedigree Linkage Mapping

PubMed Central

Schlautman, Brandon; Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Iorizzo, Massimo; Polashock, James; Grygleski, Edward; Vorsa, Nicholi; Zalapa, Juan

2017-01-01

The American cranberry (Vaccinium macrocarpon Ait.) is a recently domesticated, economically important, fruit crop with limited molecular resources. New genetic resources could accelerate genetic gain in cranberry through characterization of its genomic structure and by enabling molecular-assisted breeding strategies. To increase the availability of cranberry genomic resources, genotyping-by-sequencing (GBS) was used to discover and genotype thousands of single nucleotide polymorphisms (SNPs) within three interrelated cranberry full-sib populations. Additional simple sequence repeat (SSR) loci were added to the SNP datasets and used to construct bin maps for the parents of the populations, which were then merged to create the first high-density cranberry composite map containing 6073 markers (5437 SNPs and 636 SSRs) on 12 linkage groups (LGs) spanning 1124 cM. Interestingly, higher rates of recombination were observed in maternal than paternal gametes. The large number of markers in common (mean of 57.3) and the high degree of observed collinearity (mean Pair-wise Spearman rank correlations >0.99) between the LGs of the parental maps demonstrates the utility of GBS in cranberry for identifying polymorphic SNP loci that are transferable between pedigrees and populations in future trait-association studies. Furthermore, the high-density of markers anchored within the component maps allowed identification of segregation distortion regions, placement of centromeres on each of the 12 LGs, and anchoring of genomic scaffolds. Collectively, the results represent an important contribution to the current understanding of cranberry genomic structure and to the availability of molecular tools for future genetic research and breeding efforts in cranberry. PMID:28250016

Genome-wide patterns of recombination, linkage disequilibrium and nucleotide diversity from pooled resequencing and single nucleotide polymorphism genotyping unlock the evolutionary history of Eucalyptus grandis.

PubMed

Silva-Junior, Orzenil B; Grattapaglia, Dario

2015-11-01

We used high-density single nucleotide polymorphism (SNP) data and whole-genome pooled resequencing to examine the landscape of population recombination (ρ) and nucleotide diversity (ϴw ), assess the extent of linkage disequilibrium (r(2) ) and build the highest density linkage maps for Eucalyptus. At the genome-wide level, linkage disequilibrium (LD) decayed within c. 4-6 kb, slower than previously reported from candidate gene studies, but showing considerable variation from absence to complete LD up to 50 kb. A sharp decrease in the estimate of ρ was seen when going from short to genome-wide inter-SNP distances, highlighting the dependence of this parameter on the scale of observation adopted. Recombination was correlated with nucleotide diversity, gene density and distance from the centromere, with hotspots of recombination enriched for genes involved in chemical reactions and pathways of the normal metabolic processes. The high nucleotide diversity (ϴw = 0.022) of E. grandis revealed that mutation is more important than recombination in shaping its genomic diversity (ρ/ϴw = 0.645). Chromosome-wide ancestral recombination graphs allowed us to date the split of E. grandis (1.7-4.8 million yr ago) and identify a scenario for the recent demographic history of the species. Our results have considerable practical importance to Genome Wide Association Studies (GWAS), while indicating bright prospects for genomic prediction of complex phenotypes in eucalypt breeding. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Ti nanorod arrays with a medium density significantly promote osteogenesis and osteointegration

PubMed Central

Ning, Chengyun; Wang, Shuangying; Zhu, Ye; Zhong, Meiling; Lin, Xi; Zhang, Yu; Tan, Guoxin; Li, Mei; Yin, Zhaoyi; Yu, Peng; Wang, Xiaolan; Li, Ying; He, Tianrui; Chen, Wei; Wang, Yingjun; Mao, Chuanbin

2016-01-01

Ti implants are good candidates in bone repair. However, how to promote bone formation on their surface and their consequent perfect integration with the surrounding tissue is still a challenge. To overcome such challenge, we propose to form Ti nanorods on their surface to promote the new bone formation around the implants. Here Ti nanorod arrays (TNrs) with different densities were produced on pure Ti surfaces using an anodizing method. The influence of TNr density on the protein adsorption as well as on the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 pre-osteoblastic cells were assessed. The TNrs were also implanted into the bone defects in rabbits to test their application in promoting bone formation and osteointegration at the implant-bone interface. TNrs with the medium density were found to show the best capability in promoting the protein adsorption from surrounding medium, which in turn efficiently enhanced osteogenic differentiation in vitro and osteointegration in vivo. Our work suggests that growing TNrs with a medium density on the surface of traditional Ti implants is an efficient and facile method for promoting bone formation and osteointegration in bone repair. PMID:26743328

Ti nanorod arrays with a medium density significantly promote osteogenesis and osteointegration

NASA Astrophysics Data System (ADS)

Ning, Chengyun; Wang, Shuangying; Zhu, Ye; Zhong, Meiling; Lin, Xi; Zhang, Yu; Tan, Guoxin; Li, Mei; Yin, Zhaoyi; Yu, Peng; Wang, Xiaolan; Li, Ying; He, Tianrui; Chen, Wei; Wang, Yingjun; Mao, Chuanbin

2016-01-01

Ti implants are good candidates in bone repair. However, how to promote bone formation on their surface and their consequent perfect integration with the surrounding tissue is still a challenge. To overcome such challenge, we propose to form Ti nanorods on their surface to promote the new bone formation around the implants. Here Ti nanorod arrays (TNrs) with different densities were produced on pure Ti surfaces using an anodizing method. The influence of TNr density on the protein adsorption as well as on the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 pre-osteoblastic cells were assessed. The TNrs were also implanted into the bone defects in rabbits to test their application in promoting bone formation and osteointegration at the implant-bone interface. TNrs with the medium density were found to show the best capability in promoting the protein adsorption from surrounding medium, which in turn efficiently enhanced osteogenic differentiation in vitro and osteointegration in vivo. Our work suggests that growing TNrs with a medium density on the surface of traditional Ti implants is an efficient and facile method for promoting bone formation and osteointegration in bone repair.

Influence of stocking density on growth, body composition and energy budget of Atlantic salmon Salmo salar L. in recirculating aquaculture systems

NASA Astrophysics Data System (ADS)

Liu, Baoliang; Liu, Ying; Liu, Ziyi; Qiu, Denggao; Sun, Guoxiang; Li, Xian

2014-09-01

Atlantic salmon Salmo salar were reared at four stocking densities—high density D 1 (final density ˜39 kg/m3), medium densities D 2 (˜29 kg/m3) and D 3 (˜19 kg/m3), and low density D 4 (˜12 kg/m3)—for 40 days to investigate the effect of stocking density on their growth performance, body composition and energy budgets. Stocking density did not significantly affect specific growth rate in terms of weight (SGRw) but did affect specific growth rate in terms of energy (SGRe). Stocking density significantly influenced the ration level (RLw and RLe), feed conversion ratio (FCRw and FCRe) and apparent digestibility rate (ADR). Ration level and FCRw tended to increase with increasing density. Fish at the highest density D 1 and lowest density D 4 showed lower FCRe and higher ADR than at medium densities. Stocking density significantly affected protein and energy contents of the body but did not affect its moisture, lipid, or ash contents. The expenditure of energy for metabolism in the low-density and high-density groups was lower than that in the medium-density groups. Stocking density affected energy utilization from the feces but had no effect on excretion rate. The greater energy allocation to growth at high density and low density may be attributed to reduced metabolic rate and increased apparent digestibility rate. These findings provide information that will assist selection of suitable stocking densities in the Atlantic-salmon-farming industry.

Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics.

PubMed

Gamwell, Lisa F; Gambaro, Karen; Merziotis, Maria; Crane, Colleen; Arcand, Suzanna L; Bourada, Valerie; Davis, Christopher; Squire, Jeremy A; Huntsman, David G; Tonin, Patricia N; Vanderhyden, Barbara C

2013-02-21

The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by > 75% after infection with oncolytic viruses. These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53 mutations. Although BIN-67 cells are resistant to standard chemotherapeutic agents, their sensitivity to oncolytic viruses suggests that their therapeutic use in SCCOHT should be considered.

Genome-wide linkage mapping of QTL for black point reaction in bread wheat (Triticum aestivum L.).

PubMed

Liu, Jindong; He, Zhonghu; Wu, Ling; Bai, Bin; Wen, Weie; Xie, Chaojie; Xia, Xianchun

2016-11-01

Nine QTL for black point resistance in wheat were identified using a RIL population derived from a Linmai 2/Zhong 892 cross and 90K SNP assay. Black point, discoloration of the embryo end of the grain, downgrades wheat grain quality leading to significant economic losses to the wheat industry. The availability of molecular markers will accelerate improvement of black point resistance in wheat breeding. The aims of this study were to identify quantitative trait loci (QTL) for black point resistance and tightly linked molecular markers, and to search for candidate genes using a high-density genetic linkage map of wheat. A recombinant inbred line (RIL) population derived from the cross Linmai 2/Zhong 892 was evaluated for black point reaction during the 2011-2012, 2012-2013 and 2013-2014 cropping seasons, providing data for seven environments. A high-density linkage map was constructed by genotyping the RILs with the wheat 90K single nucleotide polymorphism (SNP) chip. Composite interval mapping detected nine QTL on chromosomes 2AL, 2BL, 3AL, 3BL, 5AS, 6A, 7AL (2) and 7BS, designated as QBp.caas-2AL, QBp.caas-2BL, QBp.caas-3AL, QBp.caas-3BL, QBp.caas-5AS, QBp.caas-6A, QBp.caas-7AL.1, QBp.caas-7AL.2 and QBp.caas-7BS, respectively. All resistance alleles, except for QBp.caas-7AL.1 from Linmai 2, were contributed by Zhong 892. QBp.caas-3BL, QBp.caas-5AS, QBp.caas-7AL.1, QBp.caas-7AL.2 and QBp.caas-7BS probably represent new loci for black point resistance. Sequences of tightly linked SNPs were used to survey wheat and related cereal genomes identifying three candidate genes for black point resistance. The tightly linked SNP markers can be used in marker-assisted breeding in combination with the kompetitive allele specific PCR technique to improve black point resistance.

Congruence as a measurement of extended haplotype structure across the genome

PubMed Central

2012-01-01

Background Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC) for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we developed software for studying extended haplotypes. Methods The software, called ExHap (Extended Haplotype), uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project. Results Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes. Conclusions Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies. PMID:22369243

Apolipoprotein A1 genotype affects the change in high density lipoprotein cholesterol subfractions with exercise training.

PubMed

Ruaño, Gualberto; Seip, Richard L; Windemuth, Andreas; Zöllner, Stefan; Tsongalis, Gregory J; Ordovas, Jose; Otvos, James; Bilbie, Cherie; Miles, Mary; Zoeller, Robert; Visich, Paul; Gordon, Paul; Angelopoulos, Theodore J; Pescatello, Linda; Moyna, Niall; Thompson, Paul D

2006-03-01

High density lipoprotein cholesterol (HDL-C) is a primary risk factor for cardiovascular disease. Apolipoprotein A-1 (apoA1) is the major HDL-associated apolipoprotein. The -75G/A single nucleotide polymorphism (SNP) in the apolipoprotein A1 gene (APOA1) promoter has been reported to be associated with HDL-C concentrations as well as HDL-C response to dietary changes in polyunsaturated fat intake. We examined the effect of this APOA1 SNP on exercise-induced changes in HDL subfraction distribution. From a cohort of healthy normolipidemic adults who volunteered for 6 months of supervised aerobic exercise, 75 subjects were genotyped for the -75G/A SNP. Of these, 53 subjects were G homozygotes (G/G) and 22 were A carriers (A/G and A/A). HDL subfractions were measured by nuclear magnetic resonance (NMR) spectroscopy by adding categories HDL-C 1+2 for the small subfraction, and HDL-C 3+4+5 for the large. The change in total HDL-C after exercise was 0.8+/-7.2 mg/dL (+1.7%), and was not statistically significant. HDL subfraction amounts also did not significantly change with exercise training in the total cohort or in G homozygotes or A carriers. The amount of the large HDL subfraction increased in the G homozygotes and decreased in the A carriers (mean+/-S.E.M., 1.8+/-6.6 mg/dL versus -6.1+/-2.3 mg/dL, p<0.0005). In contrast, the amount of the small HDL subfraction decreased in G homozygotes and increased in A carriers (-1.3+/-6.6 mg/dL versus 4.7+/-1.2 mg/dL, p<0.005). These results show that genetic variation at the APOA1 gene promoter is associated with HDL subfraction redistribution resulting from exercise training.

Aggressive and foraging behavioral interactions among ruffe

USGS Publications Warehouse

Savino, Jacqueline F.; Kostich, Melissa J.

2000-01-01

The ruffe, Gymnocephalus cernuus, is a nonindigenous percid in the Great Lakes. Ruffe are aggressive benthivores and forage over soft substrates. Laboratory studies in pools (100 cm in diameter, 15 cm water depth) were conducted to determine whether fish density (low = 2, medium = 4, high = 6 ruffe per pool) changed foraging and aggressive behaviors with a limited food supply of chironomid larvae. All fish densities demonstrated a hierarchy based on aggressive interactions, but ruffe were most aggressive at low and high fish densities. Time spent in foraging was lowest at the low fish density. The best forager at the low fish density was the most aggressive individual, but the second most aggressive fish at the medium and high fish density was the best forager and also the one chased most frequently. A medium fish density offered the best energetic benefits to ruffe by providing the lowest ratio of time spent in aggression to that spent foraging. Based on our results, ruffe should grow best at an intermediate density. With high ruffe densities, we would also expect disparity in size as the more aggressive fish are able to garner a disproportionate amount of the resources. Alternatively, as the Great Lakes are a fairly open system, ruffe could migrate out of one area to colonize another as populations exceed optimal densities.

SNP-RFLPing 2: an updated and integrated PCR-RFLP tool for SNP genotyping.

PubMed

Chang, Hsueh-Wei; Cheng, Yu-Huei; Chuang, Li-Yeh; Yang, Cheng-Hong

2010-04-08

PCR-restriction fragment length polymorphism (RFLP) assay is a cost-effective method for SNP genotyping and mutation detection, but the manual mining for restriction enzyme sites is challenging and cumbersome. Three years after we constructed SNP-RFLPing, a freely accessible database and analysis tool for restriction enzyme mining of SNPs, significant improvements over the 2006 version have been made and incorporated into the latest version, SNP-RFLPing 2. The primary aim of SNP-RFLPing 2 is to provide comprehensive PCR-RFLP information with multiple functionality about SNPs, such as SNP retrieval to multiple species, different polymorphism types (bi-allelic, tri-allelic, tetra-allelic or indels), gene-centric searching, HapMap tagSNPs, gene ontology-based searching, miRNAs, and SNP500Cancer. The RFLP restriction enzymes and the corresponding PCR primers for the natural and mutagenic types of each SNP are simultaneously analyzed. All the RFLP restriction enzyme prices are also provided to aid selection. Furthermore, the previously encountered updating problems for most SNP related databases are resolved by an on-line retrieval system. The user interfaces for functional SNP analyses have been substantially improved and integrated. SNP-RFLPing 2 offers a new and user-friendly interface for RFLP genotyping that can be used in association studies and is freely available at http://bio.kuas.edu.tw/snp-rflping2.

Colonisation of soilless growing media for tomato by Trichoderma harzianum.

PubMed

De Schutter, B; Aerts, R; Rombouts, L

2001-01-01

An experiment was conducted to evaluate the distribution of T. harzianum in soilless media used in greenhouse growing systems for tomatoes. Growing media based on rockwool and based on coconut fibre were included. The fungus was applied to the roots of the plant by means of a conidial suspension. The upper plant parts were removed from the coconut fibre an the rockwool slab after 10 and 15 weeks respectively. Both the coconut fibre and the rockwool slab were divided into fragments with a width of 10 cm. The coconut fibre medium fragments were again divided in an upper and a lower part. For every fragment the CFU/g was determined by two different methods. In the first method a known volume of growing medium was brought into suspension using a blender and diluted. Appropriate dilutions were plated on a selective medium. In the second method a known volume of growing medium was spread directly upon a selective medium in petri dishes. All dishes were incubated at room temperature and colonies were counted. Results showed that in the case of the coconut fibre growing medium T. harzianum was isolated in every fragment of the substrate. Highest densities were measured at the site of inoculation. In the lower part of the fragments less CFU/g were counted than in the upper part. In the case of the rockwool growing medium, there were several fragments in which no T. harzianum was isolated. The dilution technique demonstrated to be most useful in cases of high density. The direct spreading-method is best applied when low densities are expected. These observations demonstrate that the growing medium based upon coconut fibre is more appropriate for colonisation by T. harzianum. However, densities are higher at the site of inoculation in both tested growing media.

A cost effective cultivation medium for biocalcification of Bacillus pasteurii KCTC 3558 and its effect on cement cubes properties.

PubMed

Yoosathaporn, S; Tiangburanatham, P; Bovonsombut, S; Chaipanich, A; Pathom-Aree, W

2016-01-01

Application of carbonate precipitation induced by Bacillus pasteurii for improving some properties of cement has been reported. However, it is not yet successful in commercial scale due to the high cost of cultivation medium. This is the first report on the application of effluent from chicken manure bio-gas plant, a high protein content agricultural waste, as an alternative growth medium for carbonate precipitation by B. pasteurii KCTC3558. Urease activity of B. pasteurii KCTC3558 cultured in chicken manure effluent medium and other three standard media were examined using phenate method. The highest urease production was achieved in chicken manure effluent medium (16.756Umg(-1) protein). Cost per liter of chicken manure effluent medium is up to 88.2% lower than other standard media. The most effective cultivation media was selected for carbonate precipitation study in cement cubes. Water absorption, voids, apparent density and compressive strength of cement cubes were measured according to the ASTM standard. The correlation between the increasing density and compressive strength of bacterial added cement cube was evident. The density of bacterial cement cube is 5.1% higher than control while the compressive strength of cement mixed with bacterial cells in chicken manure effluent medium increases up to 30.2% compared with control. SEM and XRD analysis also found the crystalline phase of calcium carbonate within bacterial cement which confirmed that the increasing density and compressive strength were resulted from bacterial carbonate precipitation. This study indicated that the effluent from chicken manure bio-gas plant could be used as an alternative cost effective culture medium for cultivation and biocalcification of B. pasteurii KCTC3558 in cement. Copyright © 2016. Published by Elsevier GmbH.

Adiponectin and resistin gene polymorphisms in association with their respective adipokine levels.

PubMed

Lau, Cia-Hin; Muniandy, Sekaran

2011-05-01

Single nucleotide polymorphisms (SNPs) at the adiponectin and resistin loci are strongly associated with hypoadiponectinemia and hyperresistinemia, which may eventually increase risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease. Real-time PCR was used to genotype SNPs of the adiponectin (SNP+45T>G, SNP+276G>T, SNP+639T>C, and SNP+1212A>G) and resistin (SNP-420C>G and SNP+299G>A) genes in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40 and 70 years old. The genotyping results for each SNP marker was verified by sequencing. The anthropometric clinical and metabolic parameters of subjects were recorded. None of these SNPs at the adiponectin and resistin loci were associated with T2DM and MS susceptibility in Malaysian men. SNP+45T>G, SNP+276G>T, and SNP+639T>C of the adiponectin gene did not influence circulating levels of adiponectin. However, the G-allele of SNP+1212A>G at the adiponectin locus was marginally associated (P= 0.0227) with reduced circulating adiponectin levels. SNP-420C>G (df = 2; F= 16.026; P= 1.50×10(-7) ) and SNP+299G>A (df = 2; F= 22.944; P= 2.04×10(-10) ) of the resistin gene were strongly associated with serum resistin levels. Thus, SNP-420C>G and SNP+299G>A of the resistin gene are strongly associated with the risk of hyperresistinemia in Malaysian men. © 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.

Identification of QTL and Qualitative Trait Loci for Agronomic Traits Using SNP Markers in the Adzuki Bean.

PubMed

Li, Yuan; Yang, Kai; Yang, Wei; Chu, Liwei; Chen, Chunhai; Zhao, Bo; Li, Yisong; Jian, Jianbo; Yin, Zhichao; Wang, Tianqi; Wan, Ping

2017-01-01

The adzuki bean ( Vigna angularis ) is an important grain legume. Fine mapping of quantitative trait loci (QTL) and qualitative trait genes plays an important role in gene cloning, molecular-marker-assisted selection (MAS), and trait improvement. However, the genetic control of agronomic traits in the adzuki bean remains poorly understood. Single-nucleotide polymorphisms (SNPs) are invaluable in the construction of high-density genetic maps. We mapped 26 agronomic QTLs and five qualitative trait genes related to pigmentation using 1,571 polymorphic SNP markers from the adzuki bean genome via restriction-site-associated DNA sequencing of 150 members of an F 2 population derived from a cross between cultivated and wild adzuki beans. We mapped 11 QTLs for flowering time and pod maturity on chromosomes 4, 7, and 10. Six 100-seed weight (SD100WT) QTLs were detected. Two major flowering time QTLs were located on chromosome 4, firstly VaFld4.1 (PEVs 71.3%), co-segregating with SNP marker s690-144110, and VaFld4.2 (PEVs 67.6%) at a 0.974 cM genetic distance from the SNP marker s165-116310. Three QTLs for seed number per pod ( Snp3.1, Snp3.2 , and Snp4.1 ) were mapped on chromosomes 3 and 4. One QTL VaSdt4.1 of seed thickness (SDT) and three QTLs for branch number on the main stem were detected on chromosome 4. QTLs for maximum leaf width (LFMW) and stem internode length were mapped to chromosomes 2 and 9, respectively. Trait genes controlling the color of the seed coat, pod, stem and flower were mapped to chromosomes 3 and 1. Three candidate genes, VaAGL, VaPhyE , and VaAP2 , were identified for flowering time and pod maturity. VaAGL encodes an agamous-like MADS-box protein of 379 amino acids. VaPhyE encodes a phytochrome E protein of 1,121 amino acids. Four phytochrome genes ( VaPhyA1, VaPhyA2, VaPhyB , and VaPhyE ) were identified in the adzuki bean genome. We found candidate genes VaAP2/ERF.81 and VaAP2/ERF.82 of SD100WT, VaAP2-s4 of SDT, and VaAP2/ERF.86 of LFMW. A candidate gene VaUGT related to black seed coat color was identified. These mapped QTL and qualitative trait genes provide information helpful for future adzuki bean candidate gene cloning and MAS breeding to improve cultivars with desirable growth periods, yields, and seed coat color types.

Genomic prediction using imputed whole-genome sequence data in Holstein Friesian cattle.

PubMed

van Binsbergen, Rianne; Calus, Mario P L; Bink, Marco C A M; van Eeuwijk, Fred A; Schrooten, Chris; Veerkamp, Roel F

2015-09-17

In contrast to currently used single nucleotide polymorphism (SNP) panels, the use of whole-genome sequence data is expected to enable the direct estimation of the effects of causal mutations on a given trait. This could lead to higher reliabilities of genomic predictions compared to those based on SNP genotypes. Also, at each generation of selection, recombination events between a SNP and a mutation can cause decay in reliability of genomic predictions based on markers rather than on the causal variants. Our objective was to investigate the use of imputed whole-genome sequence genotypes versus high-density SNP genotypes on (the persistency of) the reliability of genomic predictions using real cattle data. Highly accurate phenotypes based on daughter performance and Illumina BovineHD Beadchip genotypes were available for 5503 Holstein Friesian bulls. The BovineHD genotypes (631,428 SNPs) of each bull were used to impute whole-genome sequence genotypes (12,590,056 SNPs) using the Beagle software. Imputation was done using a multi-breed reference panel of 429 sequenced individuals. Genomic estimated breeding values for three traits were predicted using a Bayesian stochastic search variable selection (BSSVS) model and a genome-enabled best linear unbiased prediction model (GBLUP). Reliabilities of predictions were based on 2087 validation bulls, while the other 3416 bulls were used for training. Prediction reliabilities ranged from 0.37 to 0.52. BSSVS performed better than GBLUP in all cases. Reliabilities of genomic predictions were slightly lower with imputed sequence data than with BovineHD chip data. Also, the reliabilities tended to be lower for both sequence data and BovineHD chip data when relationships between training animals were low. No increase in persistency of prediction reliability using imputed sequence data was observed. Compared to BovineHD genotype data, using imputed sequence data for genomic prediction produced no advantage. To investigate the putative advantage of genomic prediction using (imputed) sequence data, a training set with a larger number of individuals that are distantly related to each other and genomic prediction models that incorporate biological information on the SNPs or that apply stricter SNP pre-selection should be considered.

Common PCSK1 haplotypes are associated with obesity in the Chinese population.

PubMed

Chang, Yi-Cheng; Chiu, Yen-Feng; Shih, Kuang-Chung; Lin, Ming-Wei; Sheu, Wayne Huey-Herng; Donlon, Timothy; Curb, Jess David; Jou, Yuh-Shan; Chang, Tien-Jyun; Li, Hung-Yuan; Chuang, Lee-Ming

2010-07-01

Prohormone convertase subtilisin/kexin type 1 (PCSK1) genetic polymorphisms have recently been associated with obesity in European populations. This study aimed to examine whether common PCSK1 genetic variation is associated with obesity and related metabolic phenotypes in the Chinese population. We genotyped nine common tag single-nucleotide polymorphisms (tagSNP) of the PCSK1 gene in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. One SNP in the PCSK1 gene (rs155971) were nominally associated with risk of obesity in the SAPPHIRe cohort (P = 0.01). A common protective haplotype was associated with reduced risk of obesity (23.79% vs. 32.89%, P = 0.01) and smaller waist circumference (81.71 +/- 10.22 vs. 84.75 +/- 10.48 cm, P = 0.02). Another common haplotype was significantly associated with increased risk of obesity (37.07% vs. 23.84%, P = 0.005). The global P value for haplotype association with obesity was 0.02. We also identified a suggestive association of another PCSK1 SNP (rs3811951) with fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA(IR)), triglycerides, and high-density lipoprotein cholesterol (P = 0.05, 0.003, 0.001, 0.04, and 0.04, respectively). These data indicate common PCSK1 genetic variants are associated with obesity in the Chinese population.

Genome-Wide Linkage and Association Analysis Identifies Major Gene Loci for Guttural Pouch Tympany in Arabian and German Warmblood Horses

PubMed Central

Metzger, Julia; Ohnesorge, Bernhard; Distl, Ottmar

2012-01-01

Equine guttural pouch tympany (GPT) is a hereditary condition affecting foals in their first months of life. Complex segregation analyses in Arabian and German warmblood horses showed the involvement of a major gene as very likely. Genome-wide linkage and association analyses including a high density marker set of single nucleotide polymorphisms (SNPs) were performed to map the genomic region harbouring the potential major gene for GPT. A total of 85 Arabian and 373 German warmblood horses were genotyped on the Illumina equine SNP50 beadchip. Non-parametric multipoint linkage analyses showed genome-wide significance on horse chromosomes (ECA) 3 for German warmblood at 16–26 Mb and 34–55 Mb and for Arabian on ECA15 at 64–65 Mb. Genome-wide association analyses confirmed the linked regions for both breeds. In Arabian, genome-wide association was detected at 64 Mb within the region with the highest linkage peak on ECA15. For German warmblood, signals for genome-wide association were close to the peak region of linkage at 52 Mb on ECA3. The odds ratio for the SNP with the highest genome-wide association was 0.12 for the Arabian. In conclusion, the refinement of the regions with the Illumina equine SNP50 beadchip is an important step to unravel the responsible mutations for GPT. PMID:22848553

Estimation of genetic parameters and detection of quantitative trait loci for metabolites in Danish Holstein milk.

PubMed

Buitenhuis, A J; Sundekilde, U K; Poulsen, N A; Bertram, H C; Larsen, L B; Sørensen, P

2013-05-01

Small components and metabolites in milk are significant for the utilization of milk, not only in dairy food production but also as disease predictors in dairy cattle. This study focused on estimation of genetic parameters and detection of quantitative trait loci for metabolites in bovine milk. For this purpose, milk samples were collected in mid lactation from 371 Danish Holstein cows in first to third parity. A total of 31 metabolites were detected and identified in bovine milk by using (1)H nuclear magnetic resonance (NMR) spectroscopy. Cows were genotyped using a bovine high-density single nucleotide polymorphism (SNP) chip. Based on the SNP data, a genomic relationship matrix was calculated and used as a random factor in a model together with 2 fixed factors (herd and lactation stage) to estimate the heritability and breeding value for individual metabolites in the milk. Heritability was in the range of 0 for lactic acid to >0.8 for orotic acid and β-hydroxybutyrate. A single SNP association analysis revealed 7 genome-wide significant quantitative trait loci [malonate: Bos taurus autosome (BTA)2 and BTA7; galactose-1-phosphate: BTA2; cis-aconitate: BTA11; urea: BTA12; carnitine: BTA25; and glycerophosphocholine: BTA25]. These results demonstrate that selection for metabolites in bovine milk may be possible. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genomewide single nucleotide polymorphism discovery in Atlantic salmon (Salmo salar): validation in wild and farmed American and European populations.

PubMed

Yáñez, J M; Naswa, S; López, M E; Bassini, L; Correa, K; Gilbey, J; Bernatchez, L; Norris, A; Neira, R; Lhorente, J P; Schnable, P S; Newman, S; Mileham, A; Deeb, N; Di Genova, A; Maass, A

2016-07-01

A considerable number of single nucleotide polymorphisms (SNPs) are required to elucidate genotype-phenotype associations and determine the molecular basis of important traits. In this work, we carried out de novo SNP discovery accounting for both genome duplication and genetic variation from American and European salmon populations. A total of 9 736 473 nonredundant SNPs were identified across a set of 20 fish by whole-genome sequencing. After applying six bioinformatic filtering steps, 200 K SNPs were selected to develop an Affymetrix Axiom(®) myDesign Custom Array. This array was used to genotype 480 fish representing wild and farmed salmon from Europe, North America and Chile. A total of 159 099 (79.6%) SNPs were validated as high quality based on clustering properties. A total of 151 509 validated SNPs showed a unique position in the genome. When comparing these SNPs against 238 572 markers currently available in two other Atlantic salmon arrays, only 4.6% of the SNP overlapped with the panel developed in this study. This novel high-density SNP panel will be very useful for the dissection of economically and ecologically relevant traits, enhancing breeding programmes through genomic selection as well as supporting genetic studies in both wild and farmed populations of Atlantic salmon using high-resolution genomewide information. © 2016 John Wiley & Sons Ltd.

Metabolic active-high density VERO cell cultures on microcarriers following apoptosis prevention by galactose/glutamine feeding.

PubMed

Mendonça, Ronaldo Z; Arrózio, Sara J; Antoniazzi, Marta M; Ferreira, Jorge M C; Pereira, Carlos A

2002-07-17

The control of cell death occurring in high density cultures performed in bioreactors is an important factor in production processes. In this work, medium nutrient removal or feeding was used to determine at which extension apoptosis could be, respectively, involved or prevented in VERO cell cultures on microcarriers. Glutamine and galactose present in the VERO cell culture medium was consumed after, respectively, 6 and 12 days of culture. Kinetics studies showed that fresh medium replacement and, to some extent, galactose or glutamine depleted-fresh medium replacement provided a nutritional environment, allowing the VERO cell cultures to attain high densities. Galactose was shown to be a more critical nutrient when cultures reached a high density. In agreement with that, VERO cell cultures supplemented with galactose and/or glutamine were shown to confirm previous findings and, again at high densities, galactose was shown to be a critical nutrient for VERO cell growth. These observations also indicated that in VERO cell cultures, for feeding purposes, the glutamine could be replaced by galactose. The inverse was not true and led, at high densities, to a decrease of cell viability. In the absence of glutamine and galactose, apoptosis was observed in VERO cell cultures by cytofluorometry, Acridine orange staining or light and electron microscopy, reaching high levels when compared to cultures performed with complete medium. VERO cells apoptosis process could be prevented by the galactose and/or glutamine feeding and, at high densities, galactose was more efficient in protecting the cultures. These cultures, prevented from apoptosis, were shown to synthesize high levels of measles virus following infection. Our data show that apoptosis prevention by glutamine/galactose feeding, led to high productive and metabolic active VERO cell cultures, as indicated by the high cell density obtained and the virus multiplication leading to higher virus titers.

Utilization of Chinese tallow tree and bagasse for medium density fiberboard

Treesearch

Sangyeob Lee; Todd F. Shupe; Chung Y. Hse

2004-01-01

The objective of this research was to investigate various adhesive systems and determine the best composite formulation for selected mechanical and physical properties of medium density fiberboard (MDF) made from wood and bagasse fibers. This study investigated opportunities ofbiomass utilization for natural fiber-based composites from agricultural (bagasse) and...

Aldehyde emissions from particleboard and medium density fiberboard products

Treesearch

Melissa G. D. Baumann; Linda F. Lorenz; Stuart A. Batterman; Guo-Zheng Zhang

2000-01-01

Indoor air quality problems resulting from the emission of volatile organic compounds (VOCs) have become an issue of increasing concern. Emissions from building and furnishing materials, which are frequently constructed from particleboard and medium density fiberboard (MDF), are a potentially important contributor of indoor VOCs. In this research, VOC emissions from...

Difference in distribution of membrane proteins between low- and high-density secretory granules in parotid acinar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita-Yoshigaki, Junko; Katsumata, Osamu; Matsuki, Miwako

Secretory granules (SGs) are considered to be generated as immature granules and to mature by condensation of their contents. In this study, SGs of parotid gland were separated into low-, medium-, and high-density granule fractions by Percoll-density gradient centrifugation, since it was proposed that the density corresponds to the degree of maturation. The observation with electron microscopy showed that granules in the three fractions were very similar. The average diameter of high-density granules was a little but significantly larger than that of low-density granules. Although the three fractions contained amylase, suggesting that they are all SGs, distribution of membrane proteinsmore » was markedly different. Syntaxin6 and VAMP4 were localized in the low-density granule fraction, while VAMP2 was concentrated in the high-density granule fraction. Immunoprecipitation with anti-syntaxin6 antibody caused coprecipitation of VAMP2 from the medium-density granule fraction without solubilization, but not from Triton X-100-solubilized fraction, while VAMP4 was coprecipitated from both fractions. Therefore, VAMP2 is present on the same granules, but is separated from syntaxin6 and VAMP4, which are expected to be removed from immature granules. These results suggest that the medium-density granules are intermediates from low- to high-density granules, and that the membrane components of SGs dynamically change by budding and fusion during maturation.« less

[The relationship of the saturation density of multilayer cell cultures to their mass exchange with the medium].

PubMed

Akatov, V S; Lavrovskaia, V P

1991-01-01

Chinese hamster fibroblasts (CHF) and NIH 3T3 cells were cultured on a glass substrate at different distances from the porous membrane separating the cells from the perfusing medium. It is shown that with perfusion of medium above the membrane there is no movement of the medium near the cells. In both the types of culture, the cells grow in multilayers, however the multilayer character of growth in CHF is more pronounced than in NIH 3T3 cells. The saturation density of the cultures depends on the cell-membrane separation, and at separations of no more than 0.2 mm exceeds the saturation density in the monolayer by 8-10 fold. The dependences of the saturation density on separation are different for CHE and NIH 3T3 cells, indicating qualitative differences in the inhibition of cell growth in monolayers between these cultures. The results obtained indicate that the inhibition of cell growth in monolayer is due to mass exchange limitations, rather than to intercellular contact interactions.

Response learning stimulates dendritic spine growth on dorsal striatal medium spiny neurons.

PubMed

Briones, Brandy A; Tang, Vincent D; Haye, Amanda E; Gould, Elizabeth

2018-06-23

Increases in the number and/or the size of dendritic spines, sites of excitatory synapses, have been linked to different types of learning as well as synaptic plasticity in several brain regions, including the hippocampus, sensory cortex, motor cortex, and cerebellum. By contrast, a previous study reported that training on a maze task requiring the dorsal striatum has no effect on medium spiny neuron dendritic spines in this area. These findings might suggest brain region-specific differences in levels of plasticity as well as different cellular processes underlying different types of learning. No previous studies have investigated whether dendritic spine density changes may be localized to specific subpopulations of medium spiny neurons, nor have they examined dendritic spines in rats trained on a dorsolateral striatum-dependent maze task in comparison to rats exposed to the same type of maze in the absence of training. To address these questions further, we labeled medium spiny neurons with the lipophilic dye DiI and stained for the protein product of immediate early gene zif 268, an indirect marker of neuronal activation, in both trained and untrained groups. We found a small but significant increase in dendritic spine density on medium spiny neurons of the dorsolateral striatum after short-term intensive training, along with robust increases in the density of spines with mushroom morphology coincident with reductions in the density of spines with thin morphology. However, these results were not associated with zif 268 expression. Our findings suggest that short-term intensive training on a dorsolateral striatum-dependent maze task induces rapid increases in dendritic spine density and maturation on medium spiny neurons of the dorsolateral striatum, an effect which may contribute to early acquisition of the learned response in maze training. Copyright © 2018. Published by Elsevier Inc.

Long-term culture of rat hippocampal neurons at low density in serum-free medium: combination of the sandwich culture technique with the three-dimensional nanofibrous hydrogel PuraMatrix.

PubMed

Kaneko, Ai; Sankai, Yoshiyuki

2014-01-01

The primary culture of neuronal cells plays an important role in neuroscience. There has long been a need for methods enabling the long-term culture of primary neurons at low density, in defined serum-free medium. However, the lower the cell density, the more difficult it is to maintain the cells in culture. Therefore, we aimed to develop a method for long-term culture of neurons at low density, in serum-free medium, without the need for a glial feeder layer. Here, we describe the work leading to our determination of a protocol for long-term (>2 months) primary culture of rat hippocampal neurons in serum-free medium at the low density of 3×10(4) cells/mL (8.9×10(3) cells/cm2) without a glial feeder layer. Neurons were cultured on a three-dimensional nanofibrous hydrogel, PuraMatrix, and sandwiched under a coverslip to reproduce the in vivo environment, including the three-dimensional extracellular matrix, low-oxygen conditions, and exposure to concentrated paracrine factors. We examined the effects of varying PuraMatrix concentrations, the timing and presence or absence of a coverslip, the timing of neuronal isolation from embryos, cell density at plating, medium components, and changing the medium or not on parameters such as developmental pattern, cell viability, neuronal ratio, and neurite length. Using our method of combining the sandwich culture technique with PuraMatrix in Neurobasal medium/B27/L-glutamine for primary neuron culture, we achieved longer neurites (≥3,000 µm), greater cell viability (≥30%) for 2 months, and uniform culture across the wells. We also achieved an average neuronal ratio of 97%, showing a nearly pure culture of neurons without astrocytes. Our method is considerably better than techniques for the primary culture of neurons, and eliminates the need for a glial feeder layer. It also exhibits continued support for axonal elongation and synaptic activity for long periods (>6 weeks).

Does the prediction of breast cancer improve using a combination of mammographic density measures compared to individual measures alone?

NASA Astrophysics Data System (ADS)

Wong Sik Hee, Joseph Ryan; Harkness, Elaine F.; Gadde, Soujanya; Lim, Yit Y.; Maxwell, Anthony J.; Evans, D. Gareth; Howell, Anthony; Astley, Susan M.

2017-03-01

High mammographic density is associated with an increased risk of breast cancer, however whether the association is stronger when there is agreement across measures is unclear. This study investigates whether a combination of density measures is a better predictor of breast cancer risk than individual methods alone. Women recruited to the Predicting Risk of Cancer At Screening (PROCAS) study and with mammographic density assessed using three different methods were included (n=33,304). Density was assessed visually using Visual Analogue Scales (VAS) and by two fully automated methods, Quantra and Volpara. Percentage breast density was divided into (high, medium and low) and combinations of measures were used to further categorise individuals (e.g. `all high'). A total of 667 breast cancers were identified and logistic regression was used to determine the relationship between breast density and breast cancer risk. In total, 44% of individuals were in the same tertile for all three measures, 8.6% were in non-adjacent (high and low) or mixed categories (high, medium and low). For individual methods the strongest association with breast cancer risk was for medium and high tertiles of VAS with odds ratios (OR) adjusted for age and BMI of 1.63 (95% CI 1.31-2.03) and 2.33 (1.87-2.90) respectively. For the combination of density methods the strongest association was for `all high' (OR 2.42, 1.77-3.31) followed by "two high" (OR 1.90, 1.35-3.31) and "two medium" (OR 1.88, 1.40-2.52). Combining density measures did not affect the magnitude of risk compared to using individual methods.

Genetic polymorphism directs IL-6 expression in fibroblasts but not selected other cell types

PubMed Central

Noss, Erika H.; Nguyen, Hung N.; Chang, Sook Kyung; Watts, Gerald F. M.; Brenner, Michael B.

2015-01-01

Interleukin (IL)-6 blockade is an effective treatment for rheumatoid arthritis (RA), and synovial fibroblasts are a major IL-6 producer in the inflamed joint. We found that human RA and osteoarthritis (OA) synovial fibroblasts derived from independent donors reproducibly segregated into low, medium, and high IL-6 producers, independent of stimulus, cell passage, or disease state. IL-6 expression pattern correlated strongly with total mRNA expression, not mRNA stability, suggesting transcriptional rather than posttranscriptional regulation. High-fibroblast IL-6 expression was significantly associated with the IL-6 proximal promoter single nucleotide polymorphism (SNP) rs1800795 minor allele (CC) genotype. In contrast, no association between this SNP and IL-6 production was detected in CD14+ monocytes, another major producer of synovial IL-6. Luciferase expression assays confirmed that this SNP was associated with differential IL-6 expression in fibroblasts. To date, several association studies examining rs1800795 allele frequency and disease risk have reported seemingly conflicting results ranging from no association to association with either the major or minor allele across a spectrum of conditions, including cancer and autoimmune, cardiovascular, infectious, and metabolic diseases. This study points to a prominent contribution from promoter genetic variation in fibroblast IL-6 regulation, but not in other IL-6–producing cell types. We propose that some of the heterogeneity in these clinical studies likely reflects the cellular source of IL-6 in specific diseases, much of which may be produced by nonhematopoietic cells. These results highlight that functional analysis of disease-associated SNPs on gene expression and pathologic processes must consider variation in diverse cell types. PMID:26578807

Screening of a Brassica napus bacterial artificial chromosome library using highly parallel single nucleotide polymorphism assays

PubMed Central

2013-01-01

Background Efficient screening of bacterial artificial chromosome (BAC) libraries with polymerase chain reaction (PCR)-based markers is feasible provided that a multidimensional pooling strategy is implemented. Single nucleotide polymorphisms (SNPs) can be screened in multiplexed format, therefore this marker type lends itself particularly well for medium- to high-throughput applications. Combining the power of multiplex-PCR assays with a multidimensional pooling system may prove to be especially challenging in a polyploid genome. In polyploid genomes two classes of SNPs need to be distinguished, polymorphisms between accessions (intragenomic SNPs) and those differentiating between homoeologous genomes (intergenomic SNPs). We have assessed whether the highly parallel Illumina GoldenGate® Genotyping Assay is suitable for the screening of a BAC library of the polyploid Brassica napus genome. Results A multidimensional screening platform was developed for a Brassica napus BAC library which is composed of almost 83,000 clones. Intragenomic and intergenomic SNPs were included in Illumina’s GoldenGate® Genotyping Assay and both SNP classes were used successfully for screening of the multidimensional BAC pools of the Brassica napus library. An optimized scoring method is proposed which is especially valuable for SNP calling of intergenomic SNPs. Validation of the genotyping results by independent methods revealed a success of approximately 80% for the multiplex PCR-based screening regardless of whether intra- or intergenomic SNPs were evaluated. Conclusions Illumina’s GoldenGate® Genotyping Assay can be efficiently used for screening of multidimensional Brassica napus BAC pools. SNP calling was specifically tailored for the evaluation of BAC pool screening data. The developed scoring method can be implemented independently of plant reference samples. It is demonstrated that intergenomic SNPs represent a powerful tool for BAC library screening of a polyploid genome. PMID:24010766

Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels[S

PubMed Central

Wu, Ying; Marvelle, Amanda F.; Li, Jin; Croteau-Chonka, Damien C.; Feranil, Alan B.; Kuzawa, Christopher W.; Li, Yun; Adair, Linda S.; Mohlke, Karen L.

2013-01-01

Blood levels of lipoprotein cholesterol and triglycerides (TGs) are highly heritable and are major risk factors for cardiovascular disease (CVD). Approximately 100 lipid-associated loci have been identified in populations of European ancestry. We performed a genome-wide association study of lipid traits in 1,782 Filipino women from the Cebu Longitudinal Health and Nutrition Survey, and tested for evidence of interactions with waist circumference. We conducted additional association and interaction analyses in 1,719 of their young adult offspring. Genome-wide significant associations (P < 5 × 10−8) were detected at APOE for low density lipoprotein cholesterol and total cholesterol, and at APOA5 for TGs. Suggestive associations (P < 10−6) were detected at GCKR for TGs, and at CETP and TOM1 for high density lipoprotein cholesterol. Our data also supported the existence of allelic heterogeneity at APOA5, CETP, LIPC, and APOE. The secondary signal (Gly185Cys) at APOA5 exhibited a single nucleotide polymorphism (SNP)-by-waist circumference interaction affecting TGs (Pinteraction = 1.6 × 10−4), manifested by stronger SNP effects as waist circumference increased. These findings provide the first evidence that central obesity may accentuate the effect of the TG-increasing allele of the APOA5 signal, emphasizing that CVD risk could be reduced by central obesity control. PMID:24023260

Genetic association with lipids in Filipinos: waist circumference modifies an APOA5 effect on triglyceride levels.

PubMed

Wu, Ying; Marvelle, Amanda F; Li, Jin; Croteau-Chonka, Damien C; Feranil, Alan B; Kuzawa, Christopher W; Li, Yun; Adair, Linda S; Mohlke, Karen L

2013-11-01

Blood levels of lipoprotein cholesterol and triglycerides (TGs) are highly heritable and are major risk factors for cardiovascular disease (CVD). Approximately 100 lipid-associated loci have been identified in populations of European ancestry. We performed a genome-wide association study of lipid traits in 1,782 Filipino women from the Cebu Longitudinal Health and Nutrition Survey, and tested for evidence of interactions with waist circumference. We conducted additional association and interaction analyses in 1,719 of their young adult offspring. Genome-wide significant associations (P < 5 × 10⁻⁸) were detected at APOE for low density lipoprotein cholesterol and total cholesterol, and at APOA5 for TGs. Suggestive associations (P < 10⁻⁶) were detected at GCKR for TGs, and at CETP and TOM1 for high density lipoprotein cholesterol. Our data also supported the existence of allelic heterogeneity at APOA5, CETP, LIPC, and APOE. The secondary signal (Gly185Cys) at APOA5 exhibited a single nucleotide polymorphism (SNP)-by-waist circumference interaction affecting TGs (Pinteraction = 1.6 × 10⁻⁴), manifested by stronger SNP effects as waist circumference increased. These findings provide the first evidence that central obesity may accentuate the effect of the TG-increasing allele of the APOA5 signal, emphasizing that CVD risk could be reduced by central obesity control.

High-Resolution Detection of Identity by Descent in Unrelated Individuals

PubMed Central

Browning, Sharon R.; Browning, Brian L.

2010-01-01

Detection of recent identity by descent (IBD) in population samples is important for population-based linkage mapping and for highly accurate genotype imputation and haplotype-phase inference. We present a method for detection of recent IBD in population samples. Our method accounts for linkage disequilibrium between SNPs to enable full use of high-density SNP data. We find that our method can detect segments of a length of 2 cM with moderate power and negligible false discovery rate in Illumina 550K data in Northwestern Europeans. We compare our method with GERMLINE and PLINK, and we show that our method has a level of resolution that is significantly better than these existing methods, thus extending the usefulness of recent IBD in analysis of high-density SNP data. We survey four genomic regions in a sample of UK individuals of European descent and find that on average, at a given location, our method detects IBD in 2.7 per 10,000 pairs of individuals in Illumina 550K data. We also present methodology and results for detection of homozygosity by descent (HBD) and survey the whole genome in a sample of 1373 UK individuals of European descent. We detect HBD in 4.7 individuals per 10,000 on average at a given location. Our methodology is implemented in the freely available BEAGLE software package. PMID:20303063

Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection

PubMed Central

Kijas, James W.; Lenstra, Johannes A.; Hayes, Ben; Boitard, Simon; Porto Neto, Laercio R.; San Cristobal, Magali; Servin, Bertrand; McCulloch, Russell; Whan, Vicki; Gietzen, Kimberly; Paiva, Samuel; Barendse, William; Ciani, Elena; Raadsma, Herman; McEwan, John; Dalrymple, Brian

2012-01-01

Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species. PMID:22346734

SNPServer: a real-time SNP discovery tool.

PubMed

Savage, David; Batley, Jacqueline; Erwin, Tim; Logan, Erica; Love, Christopher G; Lim, Geraldine A C; Mongin, Emmanuel; Barker, Gary; Spangenberg, German C; Edwards, David

2005-07-01

SNPServer is a real-time flexible tool for the discovery of SNPs (single nucleotide polymorphisms) within DNA sequence data. The program uses BLAST, to identify related sequences, and CAP3, to cluster and align these sequences. The alignments are parsed to the SNP discovery software autoSNP, a program that detects SNPs and insertion/deletion polymorphisms (indels). Alternatively, lists of related sequences or pre-assembled sequences may be entered for SNP discovery. SNPServer and autoSNP use redundancy to differentiate between candidate SNPs and sequence errors. For each candidate SNP, two measures of confidence are calculated, the redundancy of the polymorphism at a SNP locus and the co-segregation of the candidate SNP with other SNPs in the alignment. SNPServer is available at http://hornbill.cspp.latrobe.edu.au/snpdiscovery.html.

Polymorphisms and haplotypes in the bovine neuropeptide Y, growth hormone receptor, ghrelin, insulin-like growth factor 2, and uncoupling proteins 2 and 3 genes and their associations with measures of growth, performance, feed efficiency, and carcass merit in beef cattle.

PubMed

Sherman, E L; Nkrumah, J D; Murdoch, B M; Li, C; Wang, Z; Fu, A; Moore, S S

2008-01-01

Genes that regulate metabolism and energy partitioning have the potential to influence economically important traits in farm animals, as do polymorphisms within these genes. In the current study, SNP in the bovine neuropeptide Y (NPY), growth hormone receptor (GHR), ghrelin (GHRL), uncoupling proteins 2 and 3 (UCP2 and UCP3), IGF2, corticotrophin-releasing hormone (CRH), cocaine and amphetamine regulated transcript (CART), melanocortin-4 receptor (MC4R), proopiomelanocortin (POMC), and GH genes were evaluated for associations with growth, feed efficiency, and carcass merit in beef steers. In total, 24 SNP were evaluated for associations with these traits and haplotypes were constructed within each gene when 2 or more SNP showed significant associations. An A/G SNP located in intron 4 of the GHR gene had the largest effects on BW of the animals (dominance effect P < 0.01) and feed efficiency (allele substitution effect P < 0.05). Another A/G SNP located in the promoter region of GHR had similar effects but the haplotypes of these 2 SNP reduced the effects of the SNP located in intron 4. Three SNP in the NPY gene showed associations to marbling (P < 0.001) as well as with ADG, BW, and feed conversion ratio (FCR; P < 0.05). The combination of these 3 SNP into haplotypes generally improved the association or had a similar scale of association as each single SNP. Only 1 SNP in UCP3, an A/G SNP in intron 3, was associated with ADG (P = 0.025), partial efficiency of growth, and FCR (P < 0.01). Three SNP in UCP2 gene were in almost complete linkage disequilibrium and showed associations with lean meat yield, yield grade, DMI, and BW (P < 0.05). Haplo-types between the SNP in UCP3 and UCP2 generally reduced the associations seen individually in each SNP. An A/G SNP in the GHRL gene tended to show effects on residual feed intake, FCR, and partial efficiency of growth (P < 0.10). The IGF2 SNP most strongly affected LM area (P < 0.01), back fat, ADG, and FCR (P < 0.05). The SNP in the CART, MC4R, POMC, GH, and CRH genes did not show associations at P < 0.05 with any of the traits. Although most of the SNP that showed associations do not cause amino acid changes, these SNP could be linked to other yet to be detected causative mutations or nearby QTL. It will be very important to verify these results in other cattle populations.

Photodynamic synchrotron x-ray therapy in Glioma cell using superparamagnetic iron nanoparticle

NASA Astrophysics Data System (ADS)

Kim, Hong-Tae; Kim, Ki-Hong; Choi, Gi-Hwan; Jheon, Sanghoon; Park, Sung-Hwan; Kim, Bong-Il; Hyodo, Kazuyuki; Ando, Masami; Kim, Jong-Ki

2009-06-01

In order to evaluate cytotoxic effects of secondary Auger electron emission(Photon Activation Therapy:PAT) from alginate-coated iron nanoparticles(Alg-SNP), Alg-SNP-uptaken C6 glioma cell lines were irradiated with 6.89/7.2 Kev synchrotron X-ray. 0-125 Gy were irradiated on three experimental groups including No-SNP group incubating without SNP as control group, 6hr-SNP group incubating with SNP for 6hr and ON-SNP group incubating with SNP overnight. Irradiated cells were stained with Acridine Orange(AO) and Edithium Bromide(EB) to count their viability with fluorescent microscopy in comparison with control groups. AO stained in damaged DNA, giving FL color change in X-ray plus SNP group. EB did not or less enter inside the cell nucleus of control group. In contrast, EB entered inside the cell nucleus of Alg-SNP group which means more damage compared with Control groups. The results of MTT assay demonstrated a X-ray dose-dependent reduction generally in cell viability in the experimental groups. 3 or 9 times increase in cell survival loss rate was observed at 6hr-SNP and ON-SNP groups, respectively compared to No-SNP control group in first experiment that was done to test cell survival rate at relatively lower dose, from 0 to 50 Gy. In second experiment X-ray dose was increased to 125 Gy. Survival loss was sharply decreased in a relatively lower dose from 5 to 25 Gy, and then demonstrated an exponentially decreasing behavior with a convergence until 125 Gy for each group. This observation suggests PAT effects on the cell directly by X-ray in the presence of Alg-SNP occurs within lower X-ray dose, and conventional X-ray radiation effect becomes dominant in higher X-ray dose. The cell viability loss of ON-SNP group was three times higher compared with that of 6hr-SNP group. In conclusion, it is possible to design photodynamic X-ray therapy study using a monochromatic x-ray energy and metal nanoparticle as x-ray sensitizer, which may enable new X-ray PDT to disseminated tumors without side effects to normal surrounding tissue.

Decay and termite resistance of medium density fiberboard (MDF) made from different wood species

Treesearch

S. Nami Kartal; Frederick Green

2003-01-01

Medium density fiberboard (MDF) production worldwide is increasing due to the development of new manufacturing technologies. As a result, MDF products are increasingly utilized in traditional wood applications that require fungal and insect resistance. This study evaluated the ability of white and brown rot fungi and termites to decompose MDF consisting of different...

Medium density fiberboard from mixed southern hardwoods

Treesearch

George E. Woodson

1977-01-01

Medium-density fiberboards of acceptable quality were made from a mixture of barky chips from 14 southern hardwoods. Boards made from fiber refined at three different plate clearances did not vary significantly in bending, internal bond (IB), or linear expansion. but, lack of replications and the fact that the refiner was not loaded to capacity caused these results to...

Dry chips versus green chips as furnish for medium-density fiberboard

Treesearch

Paul H. Short; George E. Woodson; Duane E. Lyon

1978-01-01

The fiber characteristics and the physical and mechanical properties of medium-density fiberboard (MDF), manufactured with pressure-refined fiber from green and partially dried raw material, were analyzed to determine if dry wood chips made a better furnish than green wood chips. Pressure-refining dry material produced coarser fiber than those obtained from green...

Dry chips versus green chips as furnish for medium-density fiberboard

Treesearch

P.H. Short; G.E. Woodson; D.E. Lyon

1978-01-01

The fiber characteristics and the physical and mechanical properties of medium-density fiberboard (MDF), manufactured with pressure-refined fiber from green and partially dried raw material, were analyzed to determine if dry wood chips made a better furnish than green wood chips. Pressure-refined dry material produced coarser fiber than those obtained from green...

Detection of genetic association and functional polymorphisms of UGDH affecting milk production trait in Chinese Holstein cattle.

PubMed

Xu, Qing; Mei, Gui; Sun, Dongxiao; Zhang, Qin; Zhang, Yuan; Yin, Cengceng; Chen, Huiyong; Ding, Xiangdong; Liu, Jianfeng

2012-11-02

We previously localized a quantitative trait locus (QTL) on bovine chromosome 6 affecting milk production traits to a 1.5-Mb region between BMS483 and MNB-209 via genome scanning followed by fine mapping. Totally 15 genes were mapped within such linkage region through bioinformatic analysis of the cattle-human comparative map and bovine genome assembly. Of them, the UDP-glucose dehydrogenase (UGDH) was suggested as a potential positional candidate gene for milk production traits based on its corresponding physiological and biochemical functions and genetic effects. By sequencing all the coding exons and the untranslated regions in UGDH with pooled DNA of 8 sires represented the separated families detected in our previous studies, a total of ten SNPs were identified and genotyped in 1417 Holstein cows of 8 separation families. Individual SNP-based association analysis revealed 4 significant associations of SNP Ex1-1, SNP Int3-1, SNP Int5-1, and SNP Ex12-3 with milk yield (P < 0.05), and 2 significant associations of SNP Ex1-1 and SNP Ex12-3 with protein yield (P < 0.05). Furthermore, our haplotype-based association analyses indicated that haplotypes G-C-C, formed by SNP Ex12-2-SNP Int11-1-SNP Ex11-1, T-G, formed by SNP Int9-3-SNP Int9-2, and C-C, formed by SNP Int5-1-SNP Int3-1, are significantly associated with protein percentage (F=4.15; P=0.0418) and fat percentage (F=5.18~7.25; P=0.0072~0.0231). Finally, by using an in vitro expression assay, we demonstrated that the A allele of SNP Ex1-1 and T allele of SNP Ex11-1of UGDH significantly decreases the expression of UGDH by 68.0% at the RNA, and 50.1% at the protein level, suggesting that SNP Ex1-1 and Ex11-1 represent two functional polymorphisms affecting expression of UGDH and may partly contributed to the observed association of the gene with milk production traits in our samples. Taken together, our findings strongly indicate that UGDH gene could be involved in genetic variation underlying the QTL for milk production traits.

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

PubMed

Guo, Liyuan; Wang, Jing

2018-01-04

Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks

PubMed Central

2018-01-01

Abstract Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element–target gene pairs (E–G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. PMID:29140525

High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.).

PubMed

Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong; Yu, Shuxun

2017-01-01

Due to China's rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding.

High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.)

PubMed Central

Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong

2017-01-01

Due to China’s rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding. PMID:28809947

Evaluation of microvascular endothelial function and capillary density in patients with infective endocarditis using laser speckle contrast imaging and video-capillaroscopy.

PubMed

Barcelos, Amanda; Tibirica, Eduardo; Lamas, Cristiane

2018-07-01

To evaluate the systemic microcirculation of patients with infective endocarditis (IE). This is a comparative study of patients with definite IE by the modified Duke criteria admitted to our center for treatment. A reference group of sex- and age-matched healthy volunteers was included. Microvascular flow was evaluated in the forearm using a laser speckle contrast imaging system, for noninvasive measurement of cutaneous microvascular perfusion, in combination with skin iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to test microvascular reactivity. Microvascular density was evaluated using skin video-capillaroscopy. We studied 22 patients with IE; 15 were male and seven female. The mean age and standard deviation (SD) were 45.5 ± 17.3 years. Basal skin microvascular conductance was significantly increased in patients with IE, compared with healthy individuals (0.36 ± 0.13 versus 0.21 ± 0.08 APU/mmHg; P < 0.0001). The increase in microvascular conductance induced by ACh in patients was 0.21 ± 0.17 and in the reference group, it was 0.37 ± 0.14 APU/mmHg (P = 0.0012). The increase in microvascular conductance induced by SNP in patients was 0.18 ± 0.14 and it was 0.29 ± 0.15 APU/mmHg (P = 0.0140) in the reference group. The basal mean skin capillary density of patients (135 ± 24 capillaries/mm 2 ) was significantly higher, compared with controls (97 ± 21 capillaries/mm 2 ; P < 0.0001). The main findings in the microcirculation of patients with IE were greater basal vasodilation and a reduction of the endothelium-dependent and -independent microvascular reactivity, as well as greater functional skin capillary density compared to healthy individuals. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of high-order SNP barcodes in mitochondrial D-loop for chronic dialysis susceptibility.

PubMed

Yang, Cheng-Hong; Lin, Yu-Da; Chuang, Li-Yeh; Chang, Hsueh-Wei

2016-10-01

Positively identifying disease-associated single nucleotide polymorphism (SNP) markers in genome-wide studies entails the complex association analysis of a huge number of SNPs. Such large numbers of SNP barcode (SNP/genotype combinations) continue to pose serious computational challenges, especially for high-dimensional data. We propose a novel exploiting SNP barcode method based on differential evolution, termed IDE (improved differential evolution). IDE uses a "top combination strategy" to improve the ability of differential evolution to explore high-order SNP barcodes in high-dimensional data. We simulate disease data and use real chronic dialysis data to test four global optimization algorithms. In 48 simulated disease models, we show that IDE outperforms existing global optimization algorithms in terms of exploring ability and power to detect the specific SNP/genotype combinations with a maximum difference between cases and controls. In real data, we show that IDE can be used to evaluate the relative effects of each individual SNP on disease susceptibility. IDE generated significant SNP barcode with less computational complexity than the other algorithms, making IDE ideally suited for analysis of high-order SNP barcodes. Copyright © 2016 Elsevier Inc. All rights reserved.

The extent of linkage disequilibrium in beef cattle breeds using high-density SNP genotypes.

PubMed

Porto-Neto, Laercio R; Kijas, James W; Reverter, Antonio

2014-03-24

The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome. In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (<10 kb), taurine breeds showed higher LD (r2=0.45) than their indicine (r2=0.25) and composite (r2=0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes. The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb.

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

PubMed

Oesterreich, Steffi; Henry, N Lynn; Kidwell, Kelley M; Van Poznak, Catherine H; Skaar, Todd C; Dantzer, Jessica; Li, Lang; Hangartner, Thomas N; Peacock, Munro; Nguyen, Anne T; Rae, James M; Desta, Zeruesenay; Philips, Santosh; Storniolo, Anna M; Stearns, Vered; Hayes, Daniel F; Flockhart, David A

2015-11-01

Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.

Construction of a High-Density American Cranberry (Vaccinium macrocarpon Ait.) Composite Map Using Genotyping-by-Sequencing for Multi-pedigree Linkage Mapping.

PubMed

Schlautman, Brandon; Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Iorizzo, Massimo; Polashock, James; Grygleski, Edward; Vorsa, Nicholi; Zalapa, Juan

2017-04-03

The American cranberry ( Vaccinium macrocarpon Ait.) is a recently domesticated, economically important, fruit crop with limited molecular resources. New genetic resources could accelerate genetic gain in cranberry through characterization of its genomic structure and by enabling molecular-assisted breeding strategies. To increase the availability of cranberry genomic resources, genotyping-by-sequencing (GBS) was used to discover and genotype thousands of single nucleotide polymorphisms (SNPs) within three interrelated cranberry full-sib populations. Additional simple sequence repeat (SSR) loci were added to the SNP datasets and used to construct bin maps for the parents of the populations, which were then merged to create the first high-density cranberry composite map containing 6073 markers (5437 SNPs and 636 SSRs) on 12 linkage groups (LGs) spanning 1124 cM. Interestingly, higher rates of recombination were observed in maternal than paternal gametes. The large number of markers in common (mean of 57.3) and the high degree of observed collinearity (mean Pair-wise Spearman rank correlations >0.99) between the LGs of the parental maps demonstrates the utility of GBS in cranberry for identifying polymorphic SNP loci that are transferable between pedigrees and populations in future trait-association studies. Furthermore, the high-density of markers anchored within the component maps allowed identification of segregation distortion regions, placement of centromeres on each of the 12 LGs, and anchoring of genomic scaffolds. Collectively, the results represent an important contribution to the current understanding of cranberry genomic structure and to the availability of molecular tools for future genetic research and breeding efforts in cranberry. Copyright © 2017 Schlautman et al.

Unlocking Diversity in Germplasm Collections via Genomic Selection: A Case Study Based on Quantitative Adult Plant Resistance to Stripe Rust in Spring Wheat.

PubMed

Muleta, Kebede T; Bulli, Peter; Zhang, Zhiwu; Chen, Xianming; Pumphrey, Michael

2017-11-01

Harnessing diversity from germplasm collections is more feasible today because of the development of lower-cost and higher-throughput genotyping methods. However, the cost of phenotyping is still generally high, so efficient methods of sampling and exploiting useful diversity are needed. Genomic selection (GS) has the potential to enhance the use of desirable genetic variation in germplasm collections through predicting the genomic estimated breeding values (GEBVs) for all traits that have been measured. Here, we evaluated the effects of various scenarios of population genetic properties and marker density on the accuracy of GEBVs in the context of applying GS for wheat ( L.) germplasm use. Empirical data for adult plant resistance to stripe rust ( f. sp. ) collected on 1163 spring wheat accessions and genotypic data based on the wheat 9K single nucleotide polymorphism (SNP) iSelect assay were used for various genomic prediction tests. Unsurprisingly, the results of the cross-validation tests demonstrated that prediction accuracy increased with an increase in training population size and marker density. It was evident that using all the available markers (5619) was unnecessary for capturing the trait variation in the germplasm collection, with no further gain in prediction accuracy beyond 1 SNP per 3.2 cM (∼1850 markers), which is close to the linkage disequilibrium decay rate in this population. Collectively, our results suggest that larger germplasm collections may be efficiently sampled via lower-density genotyping methods, whereas genetic relationships between the training and validation populations remain critical when exploiting GS to select from germplasm collections. Copyright © 2017 Crop Science Society of America.

Dissection of Genetic Factors underlying Wheat Kernel Shape and Size in an Elite × Nonadapted Cross using a High Density SNP Linkage Map.

PubMed

Kumar, Ajay; Mantovani, E E; Seetan, R; Soltani, A; Echeverry-Solarte, M; Jain, S; Simsek, S; Doehlert, D; Alamri, M S; Elias, E M; Kianian, S F; Mergoum, M

2016-03-01

Wheat kernel shape and size has been under selection since early domestication. Kernel morphology is a major consideration in wheat breeding, as it impacts grain yield and quality. A population of 160 recombinant inbred lines (RIL), developed using an elite (ND 705) and a nonadapted genotype (PI 414566), was extensively phenotyped in replicated field trials and genotyped using Infinium iSelect 90K assay to gain insight into the genetic architecture of kernel shape and size. A high density genetic map consisting of 10,172 single nucleotide polymorphism (SNP) markers, with an average marker density of 0.39 cM/marker, identified a total of 29 genomic regions associated with six grain shape and size traits; ∼80% of these regions were associated with multiple traits. The analyses showed that kernel length (KL) and width (KW) are genetically independent, while a large number (∼59%) of the quantitative trait loci (QTL) for kernel shape traits were in common with genomic regions associated with kernel size traits. The most significant QTL was identified on chromosome 4B, and could be an ortholog of major rice grain size and shape gene or . Major and stable loci also were identified on the homeologous regions of Group 5 chromosomes, and in the regions of (6A) and (7A) genes. Both parental genotypes contributed equivalent positive QTL alleles, suggesting that the nonadapted germplasm has a great potential for enhancing the gene pool for grain shape and size. This study provides new knowledge on the genetic dissection of kernel morphology, with a much higher resolution, which may aid further improvement in wheat yield and quality using genomic tools. Copyright © 2016 Crop Science Society of America.

Haplotype-based approach to known MS-associated regions increases the amount of explained risk

PubMed Central

Khankhanian, Pouya; Gourraud, Pierre-Antoine; Lizee, Antoine; Goodin, Douglas S

2015-01-01

Genome-wide association studies (GWAS), using single nucleotide polymorphisms (SNPs), have yielded 110 non-human leucocyte antigen genomic regions that are associated with multiple sclerosis (MS). Despite this large number of associations, however, only 28% of MS-heritability can currently be explained. Here we compare the use of multi-SNP-haplotypes to the use of single-SNPs as alternative methods to describe MS genetic risk. SNP-haplotypes (of various lengths from 1 up to 15 contiguous SNPs) were constructed at each of the 110 previously identified, MS-associated, genomic regions. Even after correcting for the larger number of statistical comparisons made when using the haplotype-method, in 32 of the regions, the SNP-haplotype based model was markedly more significant than the single-SNP based model. By contrast, in no region was the single-SNP based model similarly more significant than the SNP-haplotype based model. Moreover, when we included the 932 MS-associated SNP-haplotypes (that we identified from 102 regions) as independent variables into a logistic linear model, the amount of MS-heritability, as assessed by Nagelkerke's R-squared, was 38%, which was considerably better than 29%, which was obtained by using only single-SNPs. This study demonstrates that SNP-haplotypes can be used to fine-map the genetic associations within regions of interest previously identified by single-SNP GWAS. Moreover, the amount of the MS genetic risk explained by the SNP-haplotype associations in the 110 MS-associated genomic regions was considerably greater when using SNP-haplotypes than when using single-SNPs. Also, the use of SNP-haplotypes can lead to the discovery of new regions of interest, which have not been identified by a single-SNP GWAS. PMID:26185143

X-ray emission from SN 2012ca: A Type Ia-CSM supernova explosion in a dense surrounding medium

NASA Astrophysics Data System (ADS)

Bochenek, Christopher D.; Dwarkadas, Vikram V.; Silverman, Jeffrey M.; Fox, Ori D.; Chevalier, Roger A.; Smith, Nathan; Filippenko, Alexei V.

2018-01-01

X-ray emission is one of the signposts of circumstellar interaction in supernovae (SNe), but until now, it has been observed only in core-collapse SNe. The level of thermal X-ray emission is a direct measure of the density of the circumstellar medium (CSM), and the absence of X-ray emission from Type Ia SNe has been interpreted as a sign of a very low density CSM. In this paper, we report late-time (500-800 d after discovery) X-ray detections of SN 2012ca in Chandra data. The presence of hydrogen in the initial spectrum led to a classification of Type Ia-CSM, ostensibly making it the first SN Ia detected with X-rays. Our analysis of the X-ray data favours an asymmetric medium, with a high-density component which supplies the X-ray emission. The data suggest a number density >108 cm-3 in the higher density medium, which is consistent with the large observed Balmer decrement if it arises from collisional excitation. This is high compared to most core-collapse SNe, but it may be consistent with densities suggested for some Type IIn or superluminous SNe. If SN 2012ca is a thermonuclear SN, the large CSM density could imply clumps in the wind, or a dense torus or disc, consistent with the single-degenerate channel. A remote possibility for a core-degenerate channel involves a white dwarf merging with the degenerate core of an asymptotic giant branch star shortly before the explosion, leading to a common envelope around the SN.

VCS: Tool for Visualizing Copy Number Variation and Single Nucleotide Polymorphism.

PubMed

Kim, HyoYoung; Sung, Samsun; Cho, Seoae; Kim, Tae-Hun; Seo, Kangseok; Kim, Heebal

2014-12-01

Copy number variation (CNV) or single nucleotide phlyorphism (SNP) is useful genetic resource to aid in understanding complex phenotypes or deseases susceptibility. Although thousands of CNVs and SNPs are currently avaliable in the public databases, they are somewhat difficult to use for analyses without visualization tools. We developed a web-based tool called the VCS (visualization of CNV or SNP) to visualize the CNV or SNP detected. The VCS tool can assist to easily interpret a biological meaning from the numerical value of CNV and SNP. The VCS provides six visualization tools: i) the enrichment of genome contents in CNV; ii) the physical distribution of CNV or SNP on chromosomes; iii) the distribution of log2 ratio of CNVs with criteria of interested; iv) the number of CNV or SNP per binning unit; v) the distribution of homozygosity of SNP genotype; and vi) cytomap of genes within CNV or SNP region.

Measurement of OH, O, and NO densities and their correlations with mouse melanoma cell death rate treated by a nanosecond pulsed streamer discharge

NASA Astrophysics Data System (ADS)

Yagi, Ippei; Shirakawa, Yuki; Hirakata, Kenta; Akiyama, Taketoshi; Yonemori, Seiya; Mizuno, Kazue; Ono, Ryo; Oda, Tetsuji

2015-10-01

Mouse melanoma cells in a culture medium are treated using a nanosecond pulsed streamer discharge plasma and the correlations between the rate of cell death and the densities of reactive species (OH, O, and NO) in the plasma are measured. The plasma is irradiated onto the culture medium surface with a vertical gas flow of an O2/N2 mixture from a glass tube at various gas flow rates and O2 concentrations. The densities of the reactive species are measured very close to the culture medium surface, where the reactive species interact with the culture medium, using laser-induced fluorescence. In the case of the N2 discharge (O2 = 0%), an increase in gas flow rate decreases OH density because it lowers the water vapor concentration by diluting the vapor, which is required for OH production. The increase in gas flow rate also leads to a decreased cell death rate. In the case of the O2/N2 discharge, on the other hand, an increase in O2 concentration at a fixed flow rate does not affect the rate of cell death, although it considerably changes the O and NO densities. These findings indicate that some reactive species derived from water vapor such as OH are responsible for the melanoma cell death, whereas those from O2, such as O and NO, are less likely responsible. They also indicate the importance of water evaporation from the culture medium surface in cell treatment.

Aircraft requirements for low/medium density markets

NASA Technical Reports Server (NTRS)

Ausrotas, R.; Dodge, S.; Faulkner, H.; Glendinning, I.; Hays, A.; Simpson, R.; Swan, W.; Taneja, N.; Vittek, J.

1973-01-01

A study was conducted to determine the demand for and the economic factors involved in air transportation in a low and medium density market. The subjects investigated are as follows: (1) industry and market structure, (2) aircraft analysis, (3) economic analysis, (4) field surveys, and (5) computer network analysis. Graphs are included to show the economic requirements and the aircraft performance characteristics.

Effects of post heat-treatment on surface characteristics and adhesive bonding performance of medium density fiberboard

Treesearch

Nadir Ayrilimis; Jerrold E. Winandy

2009-01-01

A series of commercially manufactured medium density fiberboard (MDF) panels were exposed to a post-manufacture heat-treatment at various temperatures and durations using a hot press and just enough pressure to ensure firm contact between the panel and the press platens. Post-manufacture heat-treatment improved surface roughness of the exterior MDF panels. Panels...

SNPConvert: SNP Array Standardization and Integration in Livestock Species.

PubMed

Nicolazzi, Ezequiel Luis; Marras, Gabriele; Stella, Alessandra

2016-06-09

One of the main advantages of single nucleotide polymorphism (SNP) array technology is providing genotype calls for a specific number of SNP markers at a relatively low cost. Since its first application in animal genetics, the number of available SNP arrays for each species has been constantly increasing. However, conversely to that observed in whole genome sequence data analysis, SNP array data does not have a common set of file formats or coding conventions for allele calling. Therefore, the standardization and integration of SNP array data from multiple sources have become an obstacle, especially for users with basic or no programming skills. Here, we describe the difficulties related to handling SNP array data, focusing on file formats, SNP allele coding, and mapping. We also present SNPConvert suite, a multi-platform, open-source, and user-friendly set of tools to overcome these issues. This tool, which can be integrated with open-source and open-access tools already available, is a first step towards an integrated system to standardize and integrate any type of raw SNP array data. The tool is available at: https://github. com/nicolazzie/SNPConvert.git.

Antimicrobial Properties of Biofunctionalized Silver Nanoparticles on Clinical Isolates of Streptococcus mutans and Its Serotypes

PubMed Central

Martínez-Robles, Ángel Manuel; Loyola-Rodríguez, Juan Pablo; Zavala-Alonso, Norma Verónica; Martinez-Martinez, Rita Elizabeth; Ruiz, Facundo; Lara-Castro, René Homero; Donohué-Cornejo, Alejandro; Reyes-López, Simón Yobanny; Espinosa-Cristóbal, León Francisco

2016-01-01

(1) Background: Streptococcus mutans (S. mutans) is the principal pathogen involved in the formation of dental caries. Other systemic diseases have also been associated with specific S. mutans serotypes (c, e, f, and k). Silver nanoparticles (SNP) have been demonstrated to have good antibacterial effects against S. mutans; therefore, limited studies have evaluated the antimicrobial activity of biofunctionalized SNP on S. mutans serotypes. The purpose of this work was to prepare and characterize coated SNP using two different organic components and to evaluate the antimicrobial activity of SNP in clinical isolates of S. mutans strains and serotypes; (2) Methods: SNP with bovine serum albumin (BSA) or chitosan (CS) coatings were prepared and the physical, chemical and microbiological properties of SNP were evaluated; (3) Results: Both types of coated SNP showed antimicrobial activity against S. mutans bacteria and serotypes. Better inhibition was associated with smaller particles and BSA coatings; however, no significant differences were found between the different serotypes, indicating a similar sensitivity to the coated SNP; (4) Conclusion: This study concludes that BSA and CS coated SNP had good antimicrobial activity against S. mutans strains and the four serotypes, and this study suggest the widespread use of SNP as an antimicrobial agent for the inhibition of S. mutans bacteria. PMID:28335264

Antimicrobial Properties of Biofunctionalized Silver Nanoparticles on Clinical Isolates of Streptococcus mutans and Its Serotypes.

PubMed

Martínez-Robles, Ángel Manuel; Loyola-Rodríguez, Juan Pablo; Zavala-Alonso, Norma Verónica; Martinez-Martinez, Rita Elizabeth; Ruiz, Facundo; Lara-Castro, René Homero; Donohué-Cornejo, Alejandro; Reyes-López, Simón Yobanny; Espinosa-Cristóbal, León Francisco

2016-07-22

(1) Background: Streptococcus mutans ( S. mutans ) is the principal pathogen involved in the formation of dental caries. Other systemic diseases have also been associated with specific S. mutans serotypes ( c , e , f , and k ). Silver nanoparticles (SNP) have been demonstrated to have good antibacterial effects against S. mutans ; therefore, limited studies have evaluated the antimicrobial activity of biofunctionalized SNP on S. mutans serotypes. The purpose of this work was to prepare and characterize coated SNP using two different organic components and to evaluate the antimicrobial activity of SNP in clinical isolates of S. mutans strains and serotypes; (2) Methods: SNP with bovine serum albumin (BSA) or chitosan (CS) coatings were prepared and the physical, chemical and microbiological properties of SNP were evaluated; (3) Results: Both types of coated SNP showed antimicrobial activity against S. mutans bacteria and serotypes. Better inhibition was associated with smaller particles and BSA coatings; however, no significant differences were found between the different serotypes, indicating a similar sensitivity to the coated SNP; (4) Conclusion: This study concludes that BSA and CS coated SNP had good antimicrobial activity against S. mutans strains and the four serotypes, and this study suggest the widespread use of SNP as an antimicrobial agent for the inhibition of S. mutans bacteria.

LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

PubMed Central

Chang, Hsueh-Wei; Chuang, Li-Yeh; Chang, Yan-Jhu; Cheng, Yu-Huei; Hung, Yu-Chen; Chen, Hsiang-Chi; Yang, Cheng-Hong

2009-01-01

Background Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP) enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at . PMID:19500380

Synthesis of different-sized silver nanoparticles by simply varying reaction conditions with leaf extracts of Bauhinia variegata L.

PubMed

Kumar, V; Yadav, S K

2012-03-01

Green synthesis of nanoparticles is one of the crucial requirements in today's climate change scenario all over the world. In view of this, leaf extract (LE) of Bauhinia variegata L. possessing strong antidiabetic and antibacterial properties has been used to synthesise silver nanoparticles (SNP) in a controlled manner. Various-sized SNP (20-120 nm) were synthesised by varying incubation temperature, silver nitrate and LE concentrations. The rate of SNP synthesis and their size increased with increase in AgNO(3) concentration up to 4 mM. With increase in LE concentration, size and aggregation of SNP was increased. The size and aggregation of SNP were also increased at temperatures above and below 40°C. This has suggested that size and dispersion of SNP can be controlled by varying reaction components and conditions. Polarity-based fractionation of B. variegata LE has suggested that only water-soluble fraction is responsible for SNP synthesis. Fourier transform infrared spectroscopy analysis revealed the attachment of polyphenolic and carbohydrate moieties to SNP. The synthesised SNPs were found stable in double distilled water, BSA and phosphate buffer (pH 7.4). On the contrary, incubation of SNP with NaCl induced aggregation. This suggests the safe use of SNP for various in vivo applications.

Sorting process of nanoparticles and applications of same

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyler, Timothy P.; Henry, Anne-Isabelle; Van Duyne, Richard P.

In one aspect of the present invention, a method for sorting nanoparticles includes preparing a high-viscosity density gradient medium filled in a container, dispersing nanoparticles into an aqueous solution to form a suspension of the nanoparticles, each nanoparticle having one or more cores and a shell encapsulating the one or more cores, layering the suspension of the nanoparticles on the top of the high-viscosity density gradient medium in the container, and centrifugating the layered suspension of the nanoparticles on the top of the high-viscosity density gradient medium in the container at a predetermined speed for a predetermined period of timemore » to form a gradient of fractions of the nanoparticles along the container, where each fraction comprises nanoparticles in a respective one of aggregation states of the nanoparticles.« less

Dynamics and Afterglow Light Curves of Gamma-Ray Burst Blast Waves Encountering a Density Bump or Void

NASA Astrophysics Data System (ADS)

Uhm, Z. Lucas; Zhang, Bing

2014-07-01

We investigate the dynamics and afterglow light curves of gamma-ray burst blast waves that encounter various density structures (such as bumps, voids, or steps) in the surrounding ambient medium. We present and explain the characteristic response features that each type of density structure in the medium leaves on the forward shock (FS) and reverse shock (RS) dynamics for blast waves with either a long-lived or short-lived RS. We show that when the ambient medium density drops, the blast waves exhibit in some cases a period of an actual acceleration (even during their deceleration stage) due to adiabatic cooling of blast waves. Comparing numerical examples that have different shapes of bumps or voids, we propose a number of consistency tests that must be satisfied by correct modeling of blast waves. Our model results successfully pass these tests. Employing a Lagrangian description of blast waves, we perform a sophisticated calculation of afterglow emission. We show that as a response to density structures in the ambient medium, the RS light curves produce more significant variations than the FS light curves. Some observed features (such as rebrightenings, dips, or slow wiggles) can be more easily explained within the RS model. We also discuss the origin of these different features imprinted on the FS and RS light curves.

Dynamics and afterglow light curves of gamma-ray burst blast waves encountering a density bump or void

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uhm, Z. Lucas; Zhang, Bing, E-mail: uhm@pku.edu.cn, E-mail: zhang@physics.unlv.edu

2014-07-01

We investigate the dynamics and afterglow light curves of gamma-ray burst blast waves that encounter various density structures (such as bumps, voids, or steps) in the surrounding ambient medium. We present and explain the characteristic response features that each type of density structure in the medium leaves on the forward shock (FS) and reverse shock (RS) dynamics for blast waves with either a long-lived or short-lived RS. We show that when the ambient medium density drops, the blast waves exhibit in some cases a period of an actual acceleration (even during their deceleration stage) due to adiabatic cooling of blastmore » waves. Comparing numerical examples that have different shapes of bumps or voids, we propose a number of consistency tests that must be satisfied by correct modeling of blast waves. Our model results successfully pass these tests. Employing a Lagrangian description of blast waves, we perform a sophisticated calculation of afterglow emission. We show that as a response to density structures in the ambient medium, the RS light curves produce more significant variations than the FS light curves. Some observed features (such as rebrightenings, dips, or slow wiggles) can be more easily explained within the RS model. We also discuss the origin of these different features imprinted on the FS and RS light curves.« less

Effectiveness of a confinement strategy for reducing campsite impacts in Shenandoah National Park

USGS Publications Warehouse

Reid, S.E.; Marion, J.L.

2004-01-01

The expansion and proliferation of backcountry campsites is a persistent problem in many parks and protected areas. Shenandoah National Park (SNP) has one of the highest backcountry overnight use densities in the USA national parks system. SNP managers implemented a multi-option backcountry camping policy in 2000 that included camping containment with established campsites. These actions were intended to reduce the number of campsites and the area of camping disturbance at each site. This paper describes a longitudinal adaptive management assessment of the new campsite policies, applying quantitative measures of campsite conditions to evaluate the efficacy of management interventions. Physical campsite measurements combined with qualitative visitor interviews indicated SNP had successfully reduced the number of campsites and aggregate measures of camping-related disturbance in the Park, while minimizing the use of regulations, site facilities and staff resources. Implications for managers of other protected areas are that an established site camping policy can minimize camping disturbance, including the number and size of campsites, provided managers can sustain rehabilitation efforts to close and restore unneeded campsites. Experiential attributes, such as the potential for solitude, can also be manipulated through control over the selection of established campsites. Integrating resource and social science methods also provided a more holistic perspective on management policy assessments. Adaptive management research provided a timely evaluation of management success while facilitating effective modifications in response to unforeseen challenges. Conclusions regarding the effectiveness of a visitor impact containment strategy involving an established site camping option are offered.

Glutamate decarboxylase genes and alcoholism in Han Taiwanese men.

PubMed

Loh, El-Wui; Lane, Hsien-Yuan; Chen, Chien-Hsiun; Chang, Pi-Shan; Ku, Li-Wen; Wang, Kathy H T; Cheng, Andrew T A

2006-11-01

Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.

qpure: A Tool to Estimate Tumor Cellularity from Genome-Wide Single-Nucleotide Polymorphism Profiles

PubMed Central

Song, Sarah; Nones, Katia; Miller, David; Harliwong, Ivon; Kassahn, Karin S.; Pinese, Mark; Pajic, Marina; Gill, Anthony J.; Johns, Amber L.; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Newell, Felicity; Cowley, Mark J.; Wu, Jianmin; Wilson, Peter; Fink, Lynn; Biankin, Andrew V.; Waddell, Nic; Grimmond, Sean M.; Pearson, John V.

2012-01-01

Tumour cellularity, the relative proportion of tumour and normal cells in a sample, affects the sensitivity of mutation detection, copy number analysis, cancer gene expression and methylation profiling. Tumour cellularity is traditionally estimated by pathological review of sectioned specimens; however this method is both subjective and prone to error due to heterogeneity within lesions and cellularity differences between the sample viewed during pathological review and tissue used for research purposes. In this paper we describe a statistical model to estimate tumour cellularity from SNP array profiles of paired tumour and normal samples using shifts in SNP allele frequency at regions of loss of heterozygosity (LOH) in the tumour. We also provide qpure, a software implementation of the method. Our experiments showed that there is a medium correlation 0.42 (-value = 0.0001) between tumor cellularity estimated by qpure and pathology review. Interestingly there is a high correlation 0.87 (-value 2.2e-16) between cellularity estimates by qpure and deep Ion Torrent sequencing of known somatic KRAS mutations; and a weaker correlation 0.32 (-value = 0.004) between IonTorrent sequencing and pathology review. This suggests that qpure may be a more accurate predictor of tumour cellularity than pathology review. qpure can be downloaded from https://sourceforge.net/projects/qpure/. PMID:23049875

Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study.

PubMed

Kocarnik, Jonathan M; Pendergrass, Sarah A; Carty, Cara L; Pankow, James S; Schumacher, Fredrick R; Cheng, Iona; Durda, Peter; Ambite, José Luis; Deelman, Ewa; Cook, Nancy R; Liu, Simin; Wactawski-Wende, Jean; Hutter, Carolyn; Brown-Gentry, Kristin; Wilson, Sarah; Best, Lyle G; Pankratz, Nathan; Hong, Ching-Ping; Cole, Shelley A; Voruganti, V Saroja; Bůžkova, Petra; Jorgensen, Neal W; Jenny, Nancy S; Wilkens, Lynne R; Haiman, Christopher A; Kolonel, Laurence N; Lacroix, Andrea; North, Kari; Jackson, Rebecca; Le Marchand, Loic; Hindorff, Lucia A; Crawford, Dana C; Gross, Myron; Peters, Ulrike

2014-04-01

C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes mellitus, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP. We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40 473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected P<3.1×10(-3) for replication, P<2.0×10(-4) for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (P=2.0×10(-6)) and rs646776 (P=3.1×10(-5)). We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and/or low-density lipoprotein-cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups and looking for pleiotropic relationships among SNPs previously associated with related phenotypes.

Accuracy of various human NAT2 SNP genotyping panels to infer rapid, intermediate and slow acetylator phenotypes

PubMed Central

Hein, David W; Doll, Mark A

2012-01-01

Aim Humans exhibit genetic polymorphism in NAT2 resulting in rapid, intermediate and slow acetylator phenotypes. Over 65 NAT2 variants possessing one or more SNPs in the 870-bp NAT2 coding region have been reported. The seven most frequent SNPs are rs1801279 (191G>A), rs1041983 (282C>T), rs1801280 (341T>C), rs1799929 (481C>T), rs1799930 (590G>A), rs1208 (803A>G) and rs1799931 (857G>A). The majority of studies investigate the NAT2 genotype assay for three SNPs: 481C>T, 590G>A and 857G>A. A tag-SNP (rs1495741) recently identified in a genome-wide association study has also been proposed as a biomarker for the NAT2 phenotype. Materials & methods Sulfamethazine N-acetyltransferase catalytic activities were measured in cryopreserved human hepatocytes from a convenience sample of individuals in the USA with an ethnic frequency similar to the 2010 US population census. These activities were segregated by the tag-SNP rs1495741 and each of the seven SNPs described above. We assessed the accuracy of the tag-SNP and various two-, three-, four- and seven-SNP genotyping panels for their ability to accurately infer NAT2 phenotype. Results The accuracy of the various NAT2 SNP genotype panels to infer NAT2 phenotype were as follows: seven-SNP: 98.4%; tag-SNP: 77.7%; two-SNP: 96.1%; three-SNP: 92.2%; and four-SNP: 98.4%. Conclusion A NAT2 four-SNP genotype panel of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high accuracy, and is recommended over the tag-, two-, three- and (for economy of scale) the seven-SNP genotyping panels, particularly in populations of non-European ancestry. PMID:22092036

Variability of dental cone beam CT grey values for density estimations

PubMed Central

Pauwels, R; Nackaerts, O; Bellaiche, N; Stamatakis, H; Tsiklakis, K; Walker, A; Bosmans, H; Bogaerts, R; Jacobs, R; Horner, K

2013-01-01

Objective The aim of this study was to investigate the use of dental cone beam CT (CBCT) grey values for density estimations by calculating the correlation with multislice CT (MSCT) values and the grey value error after recalibration. Methods A polymethyl methacrylate (PMMA) phantom was developed containing inserts of different density: air, PMMA, hydroxyapatite (HA) 50 mg cm−3, HA 100, HA 200 and aluminium. The phantom was scanned on 13 CBCT devices and 1 MSCT device. Correlation between CBCT grey values and CT numbers was calculated, and the average error of the CBCT values was estimated in the medium-density range after recalibration. Results Pearson correlation coefficients ranged between 0.7014 and 0.9996 in the full-density range and between 0.5620 and 0.9991 in the medium-density range. The average error of CBCT voxel values in the medium-density range was between 35 and 1562. Conclusion Even though most CBCT devices showed a good overall correlation with CT numbers, large errors can be seen when using the grey values in a quantitative way. Although it could be possible to obtain pseudo-Hounsfield units from certain CBCTs, alternative methods of assessing bone tissue should be further investigated. Advances in knowledge The suitability of dental CBCT for density estimations was assessed, involving a large number of devices and protocols. The possibility for grey value calibration was thoroughly investigated. PMID:23255537

TIA: algorithms for development of identity-linked SNP islands for analysis by massively parallel DNA sequencing.

PubMed

Farris, M Heath; Scott, Andrew R; Texter, Pamela A; Bartlett, Marta; Coleman, Patricia; Masters, David

2018-04-11

Single nucleotide polymorphisms (SNPs) located within the human genome have been shown to have utility as markers of identity in the differentiation of DNA from individual contributors. Massively parallel DNA sequencing (MPS) technologies and human genome SNP databases allow for the design of suites of identity-linked target regions, amenable to sequencing in a multiplexed and massively parallel manner. Therefore, tools are needed for leveraging the genotypic information found within SNP databases for the discovery of genomic targets that can be evaluated on MPS platforms. The SNP island target identification algorithm (TIA) was developed as a user-tunable system to leverage SNP information within databases. Using data within the 1000 Genomes Project SNP database, human genome regions were identified that contain globally ubiquitous identity-linked SNPs and that were responsive to targeted resequencing on MPS platforms. Algorithmic filters were used to exclude target regions that did not conform to user-tunable SNP island target characteristics. To validate the accuracy of TIA for discovering these identity-linked SNP islands within the human genome, SNP island target regions were amplified from 70 contributor genomic DNA samples using the polymerase chain reaction. Multiplexed amplicons were sequenced using the Illumina MiSeq platform, and the resulting sequences were analyzed for SNP variations. 166 putative identity-linked SNPs were targeted in the identified genomic regions. Of the 309 SNPs that provided discerning power across individual SNP profiles, 74 previously undefined SNPs were identified during evaluation of targets from individual genomes. Overall, DNA samples of 70 individuals were uniquely identified using a subset of the suite of identity-linked SNP islands. TIA offers a tunable genome search tool for the discovery of targeted genomic regions that are scalable in the population frequency and numbers of SNPs contained within the SNP island regions. It also allows the definition of sequence length and sequence variability of the target region as well as the less variable flanking regions for tailoring to MPS platforms. As shown in this study, TIA can be used to discover identity-linked SNP islands within the human genome, useful for differentiating individuals by targeted resequencing on MPS technologies.

Identification of an interaction between VWF rs7965413 and platelet count as a novel risk marker for metabolic syndrome: an extensive search of candidate polymorphisms in a case-control study.

PubMed

Nakatochi, Masahiro; Ushida, Yasunori; Yasuda, Yoshinari; Yoshida, Yasuko; Kawai, Shun; Kato, Ryuji; Nakashima, Toru; Iwata, Masamitsu; Kuwatsuka, Yachiyo; Ando, Masahiko; Hamajima, Nobuyuki; Kondo, Takaaki; Oda, Hiroaki; Hayashi, Mutsuharu; Kato, Sawako; Yamaguchi, Makoto; Maruyama, Shoichi; Matsuo, Seiichi; Honda, Hiroyuki

2015-01-01

Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP-SNP interaction, SNP-environment interaction, and SNP-clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS.

Effect of oxalic acid pretreatment of wood chips on manufacturing medium-density fiberboard

Treesearch

Xianjun Li; Zhiyong Cai; Eric Horn; Jerrold E. Winandy

2011-01-01

The main objective of this study was to evaluate the effect of oxalic acid (OA) wood chips pretreatment prior to refining, which is done to reduce energy used during the refining process. Selected mechanical and physical performances of medium-density fiberboard (MDF) – internal bonding (IB), modulus of elasticity (MOE), modulus of rupture (MOR), water absorption (WA)...

Comparative in vivo assessment of the subacute toxicity of gold and silver nanoparticles

NASA Astrophysics Data System (ADS)

Rathore, Mansee; Mohanty, Ipseeta Ray; Maheswari, Ujjwala; Dayal, Navami; Suman, Rajesh; Joshi, D. S.

2014-04-01

In spite of the projected therapeutic potentials of gold nanoparticles (GNP) and silver nanoparticles (SNP), very limited data are available on the interaction of nanoparticles with the biological systems. The present investigation was designed to evaluate as well as compare the subacute toxicity of GNP and SNP. Stable suspensions of GNP and SNP with mean particle diameter 10 and 25 nm, respectively, were prepared. Wistar rats were orally fed SNP (3 mg/kg) or GNP (20 μg/kg), once a day for 21 days. Biochemical indices (creatinine phosphokinase-MB, urea, blood urea nitrogen, aspartate transaminase, alkaline alanine transferase) and histopathological features of the liver, heart, brain, lungs, and kidney were evaluated for signs of toxicity. A significant decline in hepatic and renal function in the GNP treated group was observed as compared to SNP. GNP was found to be relatively more toxic on the lungs and SNP on the myocardial tissue as compared to SNP and GNP treatments, respectively. Interestingly, neither SNP nor GNP adversely affected the basal architecture of the brain as compared to sham. The present study demonstrated that GNP was significantly more noxious on the liver and kidney as compared with SNP.

SNPMeta: SNP annotation and SNP metadata collection without a reference genome

USDA-ARS?s Scientific Manuscript database

The increase in availability of resequencing data is greatly accelerating SNP discovery and has facilitated the development of SNP genotyping assays. This, in turn, is increasing interest in annotation of individual SNPs. Currently, these data are only available through curation, or comparison to a ...

Hydrostatic factors affect the gravity responses of algae and roots

NASA Technical Reports Server (NTRS)

Staves, Mark P.; Wayne, Randy; Leopold, A. C.

1991-01-01

The hypothesis of Wayne et al. (1990) that plant cells perceive gravity by sensing a pressure differential between the top and the bottom of the cell was tested by subjecting rice roots and cells of Caracean algae to external solutions of various densities. It was found that increasing the density of the external medium had a profound effect on the polar ratio (PR, the ratio between velocities of the downwardly and upwardly streaming cytoplasm) of the Caracean algae cells. When these cells were placed in solutions of denser compound, the PR decreased to less than 1, as the density of the external medium became higher than that of the cell; thus, the normal gravity-induced polarity was reversed, indicating that the osmotic pressure of the medium affects the cell's ability to respond to gravity. In rice roots, an increase of the density of the solution inhibited the rate of gravitropism. These results agree with predictions of a hydrostatic model for graviperception.

Scattering of an electromagnetic light wave from a quasi-homogeneous medium with semisoft boundary

NASA Astrophysics Data System (ADS)

Zhou, Jianyang; Zhao, Daomu

2016-08-01

Based on the first-order Born approximation, the scattering of an electromagnetic plane wave from a relatively more realistic random medium, a quasi-homogeneous medium with semisoft boundary, has been investigated. The analytic expressions for the spectral density, the spectral degree of coherence and the spectral degree of polarization have been derived, and the effects of the characteristics of the medium and the polarization of the incident light wave on the far-zone scattered field are determined. The numerical simulations indicate that, with the increasing of the edge softness M of the medium, the spectral density presents a pattern with interference fringes, and the number, position and width of interference fringes can be modified by the parameter. It is also found that there is an obvious value saltation in the coherence profile. Besides, unlike the intensity and the coherence are significantly affected by the properties of the medium, the polarization of the scattered field is irrelevant to them due to the quasi-homogeneity and isotropy of the medium, and it is only connected with the polarization of the incident light.

Inferring responses to climate dynamics from historical demography in neotropical forest lizards

PubMed Central

Xue, Alexander T.; Brown, Jason L.; Alvarado-Serrano, Diego F.; Rodrigues, Miguel T.; Hickerson, Michael J.; Carnaval, Ana C.

2016-01-01

We apply a comparative framework to test for concerted demographic changes in response to climate shifts in the neotropical lowland forests, learning from the past to inform projections of the future. Using reduced genomic (SNP) data from three lizard species codistributed in Amazonia and the Atlantic Forest (Anolis punctatus, Anolis ortonii, and Polychrus marmoratus), we first reconstruct former population history and test for assemblage-level responses to cycles of moisture transport recently implicated in changes of forest distribution during the Late Quaternary. We find support for population shifts within the time frame of inferred precipitation fluctuations (the last 250,000 y) but detect idiosyncratic responses across species and uniformity of within-species responses across forest regions. These results are incongruent with expectations of concerted population expansion in response to increased rainfall and fail to detect out-of-phase demographic syndromes (expansions vs. contractions) across forest regions. Using reduced genomic data to infer species-specific demographical parameters, we then model the plausible spatial distribution of genetic diversity in the Atlantic Forest into future climates (2080) under a medium carbon emission trajectory. The models forecast very distinct trajectories for the lizard species, reflecting unique estimated population densities and dispersal abilities. Ecological and demographic constraints seemingly lead to distinct and asynchronous responses to climatic regimes in the tropics, even among similarly distributed taxa. Incorporating such constraints is key to improve modeling of the distribution of biodiversity in the past and future. PMID:27432951

Inferring responses to climate dynamics from historical demography in neotropical forest lizards.

PubMed

Prates, Ivan; Xue, Alexander T; Brown, Jason L; Alvarado-Serrano, Diego F; Rodrigues, Miguel T; Hickerson, Michael J; Carnaval, Ana C

2016-07-19

We apply a comparative framework to test for concerted demographic changes in response to climate shifts in the neotropical lowland forests, learning from the past to inform projections of the future. Using reduced genomic (SNP) data from three lizard species codistributed in Amazonia and the Atlantic Forest (Anolis punctatus, Anolis ortonii, and Polychrus marmoratus), we first reconstruct former population history and test for assemblage-level responses to cycles of moisture transport recently implicated in changes of forest distribution during the Late Quaternary. We find support for population shifts within the time frame of inferred precipitation fluctuations (the last 250,000 y) but detect idiosyncratic responses across species and uniformity of within-species responses across forest regions. These results are incongruent with expectations of concerted population expansion in response to increased rainfall and fail to detect out-of-phase demographic syndromes (expansions vs. contractions) across forest regions. Using reduced genomic data to infer species-specific demographical parameters, we then model the plausible spatial distribution of genetic diversity in the Atlantic Forest into future climates (2080) under a medium carbon emission trajectory. The models forecast very distinct trajectories for the lizard species, reflecting unique estimated population densities and dispersal abilities. Ecological and demographic constraints seemingly lead to distinct and asynchronous responses to climatic regimes in the tropics, even among similarly distributed taxa. Incorporating such constraints is key to improve modeling of the distribution of biodiversity in the past and future.

In-depth genome characterization of a Brazilian common bean core collection using DArTseq high-density SNP genotyping.

PubMed

Valdisser, Paula A M R; Pereira, Wendell J; Almeida Filho, Jâneo E; Müller, Bárbara S F; Coelho, Gesimária R C; de Menezes, Ivandilson P P; Vianna, João P G; Zucchi, Maria I; Lanna, Anna C; Coelho, Alexandre S G; de Oliveira, Jaison P; Moraes, Alessandra da Cunha; Brondani, Claudio; Vianello, Rosana P

2017-05-30

Common bean is a legume of social and nutritional importance as a food crop, cultivated worldwide especially in developing countries, accounting for an important source of income for small farmers. The availability of the complete sequences of the two common bean genomes has dramatically accelerated and has enabled new experimental strategies to be applied for genetic research. DArTseq has been widely used as a method of SNP genotyping allowing comprehensive genome coverage with genetic applications in common bean breeding programs. Using this technology, 6286 SNPs (1 SNP/86.5 Kbp) were genotyped in genic (43.3%) and non-genic regions (56.7%). Genetic subdivision associated to the common bean gene pools (K = 2) and related to grain types (K = 3 and K = 5) were reported. A total of 83% and 91% of all SNPs were polymorphic within the Andean and Mesoamerican gene pools, respectively, and 26% were able to differentiate the gene pools. Genetic diversity analysis revealed an average H E of 0.442 for the whole collection, 0.102 for Andean and 0.168 for Mesoamerican gene pools (F ST  = 0.747 between gene pools), 0.440 for the group of cultivars and lines, and 0.448 for the group of landrace accessions (F ST  = 0.002 between cultivar/line and landrace groups). The SNP effects were predicted with predominance of impact on non-coding regions (77.8%). SNPs under selection were identified within gene pools comparing landrace and cultivar/line germplasm groups (Andean: 18; Mesoamerican: 69) and between the gene pools (59 SNPs), predominantly on chromosomes 1 and 9. The LD extension estimate corrected for population structure and relatedness (r 2 SV ) was ~ 88 kbp, while for the Andean gene pool was ~ 395 kbp, and for the Mesoamerican was ~ 130 kbp. For common bean, DArTseq provides an efficient and cost-effective strategy of generating SNPs for large-scale genome-wide studies. The DArTseq resulted in an operational panel of 560 polymorphic SNPs in linkage equilibrium, providing high genome coverage. This SNP set could be used in genotyping platforms with many applications, such as population genetics, phylogeny relation between common bean varieties and support to molecular breeding approaches.

A combinatorial approach of comprehensive QTL-based comparative genome mapping and transcript profiling identified a seed weight-regulating candidate gene in chickpea

PubMed Central

Bajaj, Deepak; Upadhyaya, Hari D.; Khan, Yusuf; Das, Shouvik; Badoni, Saurabh; Shree, Tanima; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Singh, Sube; Sharma, Shivali; Tyagi, Akhilesh K.; Chattopdhyay, Debasis; Parida, Swarup K.

2015-01-01

High experimental validation/genotyping success rate (94–96%) and intra-specific polymorphic potential (82–96%) of 1536 SNP and 472 SSR markers showing in silico polymorphism between desi ICC 4958 and kabuli ICC 12968 chickpea was obtained in a 190 mapping population (ICC 4958 × ICC 12968) and 92 diverse desi and kabuli genotypes. A high-density 2001 marker-based intra-specific genetic linkage map comprising of eight LGs constructed is comparatively much saturated (mean map-density: 0.94 cM) in contrast to existing intra-specific genetic maps in chickpea. Fifteen robust QTLs (PVE: 8.8–25.8% with LOD: 7.0–13.8) associated with pod and seed number/plant (PN and SN) and 100 seed weight (SW) were identified and mapped on 10 major genomic regions of eight LGs. One of 126.8 kb major genomic region harbouring a strong SW-associated robust QTL (Caq'SW1.1: 169.1–171.3 cM) has been delineated by integrating high-resolution QTL mapping with comprehensive marker-based comparative genome mapping and differential expression profiling. This identified one potential regulatory SNP (G/A) in the cis-acting element of candidate ERF (ethylene responsive factor) TF (transcription factor) gene governing seed weight in chickpea. The functionally relevant molecular tags identified have potential to be utilized for marker-assisted genetic improvement of chickpea. PMID:25786576

Coupling of light into the fundamental diffusion mode of a scattering medium (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ojambati, Oluwafemi S.; Yılmaz, Hasan; Lagendijk, Ad; Mosk, Allard P.; Vos, Willem L.

2016-03-01

Diffusion equation describes the energy density inside a scattering medium such as biological tissues and paint [1]. The solution of the diffusion equation is a sum over a complete set of eigensolutions that shows a characteristic linear decrease with depth in the medium. It is of particular interest if one could launch energy in the fundamental eigensolution, as this opens the opportunity to achieve a much greater internal energy density. For applications in optics, an enhanced energy density is vital for solid-state lighting, light harvesting in solar cells, low-threshold random lasers, and biomedical optics. Here we demonstrate the first ever selective coupling of optical energy into a diffusion eigensolution of a scattering medium of zinc oxide (ZnO) paint. To this end, we exploit wavefront shaping to selectively couple energy into the fundamental diffusion mode, employing fluorescence of nanoparticles randomly positioned inside the medium as a probe of the energy density. We observe an enhanced fluorescence in case of optimized incident wavefronts, and the enhancement increases with sample thickness, a typical mesoscopic control parameter. We interpret successfully our result by invoking the fundamental eigensolution of the diffusion equation, and we obtain excellent agreement with our observations, even in absence of adjustable parameters [2]. References [1] R. Pierrat, P. Ambichl, S. Gigan, A. Haber, R. Carminati, and R. Rotter, Proc. Natl. Acad. Sci. U.S.A. 111, 17765 (2014). [2] O. S. Ojambati, H. Yilmaz, A. Lagendijk, A. P. Mosk, and W. L. Vos, arXiv:1505.08103.

Devices, systems, and methods for conducting assays with improved sensitivity using sedimentation

DOEpatents

Schaff, Ulrich Y.; Koh, Chung-Yan; Sommer, Gregory J.

2016-04-05

Embodiments of the present invention are directed toward devices, systems, and method for conducting assays using sedimentation. In one example, a method includes layering a mixture on a density medium, subjecting sedimentation particles in the mixture to sedimentation forces to cause the sedimentation particles to move to a detection area through a density medium, and detecting a target analyte in a detection region of the sedimentation channel. In some examples, the sedimentation particles and labeling agent may have like charges to reduce non-specific binding of labeling agent and sedimentation particles. In some examples, the density medium is provided with a separation layer for stabilizing the assay during storage and operation. In some examples, the sedimentation channel may be provided with a generally flat sedimentation chamber for dispersing the particle pellet over a larger surface area.

Devices, systems, and methods for conducting assays with improved sensitivity using sedimentation

DOEpatents

Schaff, Ulrich Y; Koh, Chung-Yan; Sommer, Gregory J

2015-02-24

Embodiments of the present invention are directed toward devices, systems, and method for conducting assays using sedimentation. In one example, a method includes layering a mixture on a density medium, subjecting sedimentation particles in the mixture to sedimentation forces to cause the sedimentation particles to move to a detection area through a density medium, and detecting a target analyte in a detection region of the sedimentation channel. In some examples, the sedimentation particles and labeling agent may have like charges to reduce non-specific binding of labeling agent and sedimentation particles. In some examples, the density medium is provided with a separation layer for stabilizing the assay during storage and operation. In some examples, the sedimentation channel may be provided with a generally flat sedimentation chamber for dispersing the particle pellet over a larger surface area.

The common -55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population.

PubMed

Hamada, Taku; Kotani, Kazuhiko; Fujiwara, Shinji; Sano, Yoshiko; Domichi, Masayuki; Tsuzaki, Kokoro; Sakane, Naoki

2008-03-01

Uncoupling protein 3 (UCP3) is considered to be associated with obesity, given its function in the regulation of energy and lipid metabolism. An increased body mass index (BMI) and a decreased level of high-density lipoprotein cholesterol (HDL-C) are risk factors for cardiovascular disease. The purpose of this study was to investigate whether the UCP3 promoter -55 C/T single nucleotide polymorphism (UCP3 -55 C/T SNP) was associated with obesity according to the criteria for Japanese (BMI > or = 25 kg/m2), BMI, and serum HDL-C levels in the general Japanese population. The subjects, numbering 282 and aged 65 +/- 13 years (mean +/- SD), were recruited through an annual health checkup of residents of Mima city, Tokushima, in Japan. Body mass index, blood pressure, biochemical indexes including lipid, and lipoprotein profiles were measured. The UCP3 -55 C/T SNP was determined with a fluorescence-based allele-specific DNA primer assay system. The frequency of the -55 T allele was 30.0%. Subjects with the T/T genotype had significantly higher HDL-C levels than those with the C/C genotype or the C/T genotype. Furthermore, subjects with the T/T genotype had a significantly lower BMI than those with the C/C genotype. A multivariate analysis revealed that the -55 T allele was a significant independent variable contributing to the variance in HDL-C levels and BMI. The T/T genotype was associated with a lower prevalence of obesity than the C/C and C/T genotypes, with an odds ratio of 0.358 (95% confidence interval, 0.132-0.972; P = .037). In conclusion, the UCP3 -55 C/T SNP was associated with elevated HDL-C levels and a reduced BMI, independent of modifiable factors such as lifestyle. Furthermore, this polymorphism, when expressed in its homozygous form, reduced the prevalence of obesity in Japanese.

UGbS-Flex, a novel bioinformatics pipeline for imputation-free SNP discovery in polyploids without a reference genome: finger millet as a case study.

PubMed

Qi, Peng; Gimode, Davis; Saha, Dipnarayan; Schröder, Stephan; Chakraborty, Debkanta; Wang, Xuewen; Dida, Mathews M; Malmberg, Russell L; Devos, Katrien M

2018-06-15

Research on orphan crops is often hindered by a lack of genomic resources. With the advent of affordable sequencing technologies, genotyping an entire genome or, for large-genome species, a representative fraction of the genome has become feasible for any crop. Nevertheless, most genotyping-by-sequencing (GBS) methods are geared towards obtaining large numbers of markers at low sequence depth, which excludes their application in heterozygous individuals. Furthermore, bioinformatics pipelines often lack the flexibility to deal with paired-end reads or to be applied in polyploid species. UGbS-Flex combines publicly available software with in-house python and perl scripts to efficiently call SNPs from genotyping-by-sequencing reads irrespective of the species' ploidy level, breeding system and availability of a reference genome. Noteworthy features of the UGbS-Flex pipeline are an ability to use paired-end reads as input, an effective approach to cluster reads across samples with enhanced outputs, and maximization of SNP calling. We demonstrate use of the pipeline for the identification of several thousand high-confidence SNPs with high representation across samples in an F 3 -derived F 2 population in the allotetraploid finger millet. Robust high-density genetic maps were constructed using the time-tested mapping program MAPMAKER which we upgraded to run efficiently and in a semi-automated manner in a Windows Command Prompt Environment. We exploited comparative GBS with one of the diploid ancestors of finger millet to assign linkage groups to subgenomes and demonstrate the presence of chromosomal rearrangements. The paper combines GBS protocol modifications, a novel flexible GBS analysis pipeline, UGbS-Flex, recommendations to maximize SNP identification, updated genetic mapping software, and the first high-density maps of finger millet. The modules used in the UGbS-Flex pipeline and for genetic mapping were applied to finger millet, an allotetraploid selfing species without a reference genome, as a case study. The UGbS-Flex modules, which can be run independently, are easily transferable to species with other breeding systems or ploidy levels.

Impact of QTL minor allele frequency on genomic evaluation using real genotype data and simulated phenotypes in Japanese Black cattle.

PubMed

Uemoto, Yoshinobu; Sasaki, Shinji; Kojima, Takatoshi; Sugimoto, Yoshikazu; Watanabe, Toshio

2015-11-19

Genetic variance that is not captured by single nucleotide polymorphisms (SNPs) is due to imperfect linkage disequilibrium (LD) between SNPs and quantitative trait loci (QTLs), and the extent of LD between SNPs and QTLs depends on different minor allele frequencies (MAF) between them. To evaluate the impact of MAF of QTLs on genomic evaluation, we performed a simulation study using real cattle genotype data. In total, 1368 Japanese Black cattle and 592,034 SNPs (Illumina BovineHD BeadChip) were used. We simulated phenotypes using real genotypes under different scenarios, varying the MAF categories, QTL heritability, number of QTLs, and distribution of QTL effect. After generating true breeding values and phenotypes, QTL heritability was estimated and the prediction accuracy of genomic estimated breeding value (GEBV) was assessed under different SNP densities, prediction models, and population size by a reference-test validation design. The extent of LD between SNPs and QTLs in this population was higher in the QTLs with high MAF than in those with low MAF. The effect of MAF of QTLs depended on the genetic architecture, evaluation strategy, and population size in genomic evaluation. In genetic architecture, genomic evaluation was affected by the MAF of QTLs combined with the QTL heritability and the distribution of QTL effect. The number of QTL was not affected on genomic evaluation if the number of QTL was more than 50. In the evaluation strategy, we showed that different SNP densities and prediction models affect the heritability estimation and genomic prediction and that this depends on the MAF of QTLs. In addition, accurate QTL heritability and GEBV were obtained using denser SNP information and the prediction model accounted for the SNPs with low and high MAFs. In population size, a large sample size is needed to increase the accuracy of GEBV. The MAF of QTL had an impact on heritability estimation and prediction accuracy. Most genetic variance can be captured using denser SNPs and the prediction model accounted for MAF, but a large sample size is needed to increase the accuracy of GEBV under all QTL MAF categories.

LS-SNP/PDB: annotated non-synonymous SNPs mapped to Protein Data Bank structures.

PubMed

Ryan, Michael; Diekhans, Mark; Lien, Stephanie; Liu, Yun; Karchin, Rachel

2009-06-01

LS-SNP/PDB is a new WWW resource for genome-wide annotation of human non-synonymous (amino acid changing) SNPs. It serves high-quality protein graphics rendered with UCSF Chimera molecular visualization software. The system is kept up-to-date by an automated, high-throughput build pipeline that systematically maps human nsSNPs onto Protein Data Bank structures and annotates several biologically relevant features. LS-SNP/PDB is available at (http://ls-snp.icm.jhu.edu/ls-snp-pdb) and via links from protein data bank (PDB) biology and chemistry tabs, UCSC Genome Browser Gene Details and SNP Details pages and PharmGKB Gene Variants Downloads/Cross-References pages.

Two Novel SNPs of PPARγ Significantly Affect Weaning Growth Traits of Nanyang Cattle.

PubMed

Huang, Jieping; Chen, Ningbo; Li, Xin; An, Shanshan; Zhao, Minghui; Sun, Taihong; Hao, Ruijie; Ma, Yun

2018-01-02

Peroxisome-proliferator-activated receptor gamma (PPARγ) is a key transcription factor that controls adipocyte differentiation and energy in mammals. Therefore, PPARγ is a potential factor influencing animal growth traits. This study primarily evaluates PPARγ as candidate gene for growth traits of cattle and identifies potential molecular marker for cattle breeding. Per previous studies, PPARγ mRNA was mainly expressed at extremely high levels in adipose tissues as shown by quantitative real-time polymerase chain reaction analysis. Three novel SNPs of the bovine PPARγ gene were identified in 514 individuals from six Chinese cattle breeds: SNP1 (AC_000179.1 g.57386668 C > G) in intron 2 and SNP2 (AC_000179.1 g.57431964 C > T) and SNP3 (AC_000179.1 g.57431994 T > C) in exon 7. The present study also investigated genetic characteristics of these SNP loci in six populations. Association analysis showed that SNP1 and SNP3 loci significantly affect weaning growth traits, especially body weight of Nanyang cattle. These results revealed that SNP1 and SNP3 are potential molecular markers for cattle breeding.

A high-density genetic map of Arachis duranensis, a diploid ancestor of cultivated peanut

PubMed Central

2012-01-01

Background Cultivated peanut (Arachis hypogaea) is an allotetraploid species whose ancestral genomes are most likely derived from the A-genome species, A. duranensis, and the B-genome species, A. ipaensis. The very recent (several millennia) evolutionary origin of A. hypogaea has imposed a bottleneck for allelic and phenotypic diversity within the cultigen. However, wild diploid relatives are a rich source of alleles that could be used for crop improvement and their simpler genomes can be more easily analyzed while providing insight into the structure of the allotetraploid peanut genome. The objective of this research was to establish a high-density genetic map of the diploid species A. duranensis based on de novo generated EST databases. Arachis duranensis was chosen for mapping because it is the A-genome progenitor of cultivated peanut and also in order to circumvent the confounding effects of gene duplication associated with allopolyploidy in A. hypogaea. Results More than one million expressed sequence tag (EST) sequences generated from normalized cDNA libraries of A. duranensis were assembled into 81,116 unique transcripts. Mining this dataset, 1236 EST-SNP markers were developed between two A. duranensis accessions, PI 475887 and Grif 15036. An additional 300 SNP markers also were developed from genomic sequences representing conserved legume orthologs. Of the 1536 SNP markers, 1054 were placed on a genetic map. In addition, 598 EST-SSR markers identified in A. hypogaea assemblies were included in the map along with 37 disease resistance gene candidate (RGC) and 35 other previously published markers. In total, 1724 markers spanning 1081.3 cM over 10 linkage groups were mapped. Gene sequences that provided mapped markers were annotated using similarity searches in three different databases, and gene ontology descriptions were determined using the Medicago Gene Atlas and TAIR databases. Synteny analysis between A. duranensis, Medicago and Glycine revealed significant stretches of conserved gene clusters spread across the peanut genome. A higher level of colinearity was detected between A. duranensis and Glycine than with Medicago. Conclusions The first high-density, gene-based linkage map for A. duranensis was generated that can serve as a reference map for both wild and cultivated Arachis species. The markers developed here are valuable resources for the peanut, and more broadly, to the legume research community. The A-genome map will have utility for fine mapping in other peanut species and has already had application for mapping a nematode resistance gene that was introgressed into A. hypogaea from A. cardenasii. PMID:22967170

Acute and repeated exposure with the nitric oxide (NO) donor sodium nitroprusside (SNP) differentially modulate responses in a rat model of anxiety.

PubMed

Orfanidou, Martha A; Lafioniatis, Anastasios; Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

2017-09-30

The nitric oxide (NO) donor sodium nitroprusside (SNP) actually is under investigation for the treatment of schizophrenia. That anxiety disorders are noted to occur commonly in schizophrenia patients is known. Contradictory results were reported however, concerning the effects of SNP in animal models of anxiety disorders. The present study investigated the effects of acute and repeated administration of SNP on anxiety-like behaviour in rats assessed in the light/dark test. The effects of SNP on motility in a locomotor activity chamber were also investigated in rats. Acute administration of 1 mg/kg SNP 30 but not 60 min before testing induced anxiolytic-like behaviour which cannot be attributed to changes in locomotor activity. Conversely, a single injection of 3 mg/kg SNP at 30 min before testing depressed rats' general activity, while at 60 min this dose did not influence performance of animals either in the light/dark or in the motor activity test. Repeated application of SNP (1 and 3 mg/kg, for 5 consecutive days) did not alter rodents' performance in the above described behavioural paradigms. The present results suggest that the effects exerted by SNP in the light/dark test in rats are dose, time and treatment schedule-dependent. The current findings propose also a narrow therapeutic window for SNP in this animal model of anxiety. Copyright © 2017 Elsevier Inc. All rights reserved.

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

PubMed

De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

2002-06-01

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

Familial Analysis of Epistatic and Sex-Dependent Association of Genes of the Renin-Angiotensin-Aldosterone System and Blood Pressure.

PubMed

Scurrah, Katrina J; Lamantia, Angela; Ellis, Justine A; Harrap, Stephen B

2017-06-01

Renin-angiotensin-aldosterone system genes have been inconsistently associated with blood pressure, possibly because of unrecognized influences of sex-dependent genetic effects or gene-gene interactions (epistasis). We tested association of systolic blood pressure with single-nucleotide polymorphisms (SNPs) at renin ( REN ), angiotensinogen ( AGT ), angiotensin-converting enzyme ( ACE ), angiotensin II type 1 receptor ( AGTR1 ), and aldosterone synthase ( CYP11B2 ), including sex-SNP or SNP-SNP interactions. Eighty-eight tagSNPs were tested in 2872 white individuals in 809 pedigrees from the Victorian Family Heart Study using variance components models. Three SNPs (rs8075924 and rs4277404 at ACE and rs12721297 at AGTR1 ) were individually associated with lower systolic blood pressure with significant ( P <0.00076) effect sizes ≈1.7 to 2.5 mm Hg. Sex-specific associations were seen for 3 SNPs in men (rs2468523 and rs2478544 at AGT and rs11658531 at ACE ) and 1 SNP in women (rs12451328 at ACE ). SNP-SNP interaction was suggested ( P <0.005) for 14 SNP pairs, none of which had shown individual association with systolic blood pressure. Four SNP pairs were at the same gene (2 for REN , 1 for AGT , and 1 for AGTR1 ). The SNP rs3097 at CYP11B2 was represented in 5 separate pairs. SNPs at key renin-angiotensin-aldosterone system genes associate with systolic blood pressure individually in both sexes, individually in one sex only and only when combined with another SNP. Analyses that incorporate sex-dependent and epistatic effects could reconcile past inconsistencies and account for some of the missing heritability of blood pressure and are generally relevant to SNP association studies for any phenotype. © 2017 American Heart Association, Inc.

Single Nucleotide Polymorphism (SNP)-Strings: An Alternative Method for Assessing Genetic Associations

PubMed Central

Goodin, Douglas S.; Khankhanian, Pouya

2014-01-01

Background Genome-wide association studies (GWAS) identify disease-associations for single-nucleotide-polymorphisms (SNPs) from scattered genomic-locations. However, SNPs frequently reside on several different SNP-haplotypes, only some of which may be disease-associated. This circumstance lowers the observed odds-ratio for disease-association. Methodology/Principal Findings Here we develop a method to identify the two SNP-haplotypes, which combine to produce each person’s SNP-genotype over specified chromosomal segments. Two multiple sclerosis (MS)-associated genetic regions were modeled; DRB1 (a Class II molecule of the major histocompatibility complex) and MMEL1 (an endopeptidase that degrades both neuropeptides and β-amyloid). For each locus, we considered sets of eleven adjacent SNPs, surrounding the putative disease-associated gene and spanning ∼200 kb of DNA. The SNP-information was converted into an ordered-set of eleven-numbers (subject-vectors) based on whether a person had zero, one, or two copies of particular SNP-variant at each sequential SNP-location. SNP-strings were defined as those ordered-combinations of eleven-numbers (0 or 1), representing a haplotype, two of which combined to form the observed subject-vector. Subject-vectors were resolved using probabilistic methods. In both regions, only a small number of SNP-strings were present. We compared our method to the SHAPEIT-2 phasing-algorithm. When the SNP-information spanning 200 kb was used, SHAPEIT-2 was inaccurate. When the SHAPEIT-2 window was increased to 2,000 kb, the concordance between the two methods, in both of these eleven-SNP regions, was over 99%, suggesting that, in these regions, both methods were quite accurate. Nevertheless, correspondence was not uniformly high over the entire DNA-span but, rather, was characterized by alternating peaks and valleys of concordance. Moreover, in the valleys of poor-correspondence, SHAPEIT-2 was also inconsistent with itself, suggesting that the SNP-string method is more accurate across the entire region. Conclusions/Significance Accurate haplotype identification will enhance the detection of genetic-associations. The SNP-string method provides a simple means to accomplish this and can be extended to cover larger genomic regions, thereby improving a GWAS’s power, even for those published previously. PMID:24727690

Detection of quantitative trait loci in Bos indicus and Bos taurus cattle using genome-wide association studies

PubMed Central

2013-01-01

Background The apparent effect of a single nucleotide polymorphism (SNP) on phenotype depends on the linkage disequilibrium (LD) between the SNP and a quantitative trait locus (QTL). However, the phase of LD between a SNP and a QTL may differ between Bos indicus and Bos taurus because they diverged at least one hundred thousand years ago. Here, we test the hypothesis that the apparent effect of a SNP on a quantitative trait depends on whether the SNP allele is inherited from a Bos taurus or Bos indicus ancestor. Methods Phenotype data on one or more traits and SNP genotype data for 10 181 cattle from Bos taurus, Bos indicus and composite breeds were used. All animals had genotypes for 729 068 SNPs (real or imputed). Chromosome segments were classified as originating from B. indicus or B. taurus on the basis of the haplotype of SNP alleles they contained. Consequently, SNP alleles were classified according to their sub-species origin. Three models were used for the association study: (1) conventional GWAS (genome-wide association study), fitting a single SNP effect regardless of subspecies origin, (2) interaction GWAS, fitting an interaction between SNP and subspecies-origin, and (3) best variable GWAS, fitting the most significant combination of SNP and sub-species origin. Results Fitting an interaction between SNP and subspecies origin resulted in more significant SNPs (i.e. more power) than a conventional GWAS. Thus, the effect of a SNP depends on the subspecies that the allele originates from. Also, most QTL segregated in only one subspecies, suggesting that many mutations that affect the traits studied occurred after divergence of the subspecies or the mutation became fixed or was lost in one of the subspecies. Conclusions The results imply that GWAS and genomic selection could gain power by distinguishing SNP alleles based on their subspecies origin, and that only few QTL segregate in both B. indicus and B. taurus cattle. Thus, the QTL that segregate in current populations likely resulted from mutations that occurred in one of the subspecies and can have both positive and negative effects on the traits. There was no evidence that selection has increased the frequency of alleles that increase body weight. PMID:24168700

A variant reference data set for the Africanized honeybee, Apis mellifera

PubMed Central

Kadri, Samir M.; Harpur, Brock A.; Orsi, Ricardo O.; Zayed, Amro

2016-01-01

The Africanized honeybee (AHB) is a population of Apis mellifera found in the Americas. AHBs originated in 1956 in Rio Clara, Brazil where imported African A. m. scutellata escaped and hybridized with local populations of European A. mellifera. Africanized populations can now be found from Northern Argentina to the Southern United States. AHBs—often referred to as ‘Killer Bees’— are a major concern to the beekeeping industry as well as a model for the evolutionary genetics of colony defence. We performed high coverage pooled-resequencing of 360 diploid workers from 30 Brazilian AHB colonies using Illumina Hi-Seq (150 bp PE). This yielded a high density SNP data set with an average read depth at each site of 20.25 reads. With 3,606,720 SNPs and 155,336 SNPs within 11,365 genes, this data set is the largest genomic resource available for AHBs and will enable high-resolution studies of the population dynamics, evolution, and genetics of this successful biological invader, in addition to facilitating the development of SNP-based tools for identifying AHBs. PMID:27824336

Semi-nonparametric VaR forecasts for hedge funds during the recent crisis

NASA Astrophysics Data System (ADS)

Del Brio, Esther B.; Mora-Valencia, Andrés; Perote, Javier

2014-05-01

The need to provide accurate value-at-risk (VaR) forecasting measures has triggered an important literature in econophysics. Although these accurate VaR models and methodologies are particularly demanded for hedge fund managers, there exist few articles specifically devoted to implement new techniques in hedge fund returns VaR forecasting. This article advances in these issues by comparing the performance of risk measures based on parametric distributions (the normal, Student’s t and skewed-t), semi-nonparametric (SNP) methodologies based on Gram-Charlier (GC) series and the extreme value theory (EVT) approach. Our results show that normal-, Student’s t- and Skewed t- based methodologies fail to forecast hedge fund VaR, whilst SNP and EVT approaches accurately success on it. We extend these results to the multivariate framework by providing an explicit formula for the GC copula and its density that encompasses the Gaussian copula and accounts for non-linear dependences. We show that the VaR obtained by the meta GC accurately captures portfolio risk and outperforms regulatory VaR estimates obtained through the meta Gaussian and Student’s t distributions.

Genetic Mapping and Exome Sequencing Identify Variants Associated with Five Novel Diseases

PubMed Central

Puffenberger, Erik G.; Jinks, Robert N.; Sougnez, Carrie; Cibulskis, Kristian; Willert, Rebecca A.; Achilly, Nathan P.; Cassidy, Ryan P.; Fiorentini, Christopher J.; Heiken, Kory F.; Lawrence, Johnny J.; Mahoney, Molly H.; Miller, Christopher J.; Nair, Devika T.; Politi, Kristin A.; Worcester, Kimberly N.; Setton, Roni A.; DiPiazza, Rosa; Sherman, Eric A.; Eastman, James T.; Francklyn, Christopher; Robey-Bond, Susan; Rider, Nicholas L.; Gabriel, Stacey; Morton, D. Holmes; Strauss, Kevin A.

2012-01-01

The Clinic for Special Children (CSC) has integrated biochemical and molecular methods into a rural pediatric practice serving Old Order Amish and Mennonite (Plain) children. Among the Plain people, we have used single nucleotide polymorphism (SNP) microarrays to genetically map recessive disorders to large autozygous haplotype blocks (mean = 4.4 Mb) that contain many genes (mean = 79). For some, uninformative mapping or large gene lists preclude disease-gene identification by Sanger sequencing. Seven such conditions were selected for exome sequencing at the Broad Institute; all had been previously mapped at the CSC using low density SNP microarrays coupled with autozygosity and linkage analyses. Using between 1 and 5 patient samples per disorder, we identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. Our results reveal the power of coupling new genotyping technologies to population-specific genetic knowledge and robust clinical data. PMID:22279524

A variant reference data set for the Africanized honeybee, Apis mellifera.

PubMed

Kadri, Samir M; Harpur, Brock A; Orsi, Ricardo O; Zayed, Amro

2016-11-08

The Africanized honeybee (AHB) is a population of Apis mellifera found in the Americas. AHBs originated in 1956 in Rio Clara, Brazil where imported African A. m. scutellata escaped and hybridized with local populations of European A. mellifera. Africanized populations can now be found from Northern Argentina to the Southern United States. AHBs-often referred to as 'Killer Bees'- are a major concern to the beekeeping industry as well as a model for the evolutionary genetics of colony defence. We performed high coverage pooled-resequencing of 360 diploid workers from 30 Brazilian AHB colonies using Illumina Hi-Seq (150 bp PE). This yielded a high density SNP data set with an average read depth at each site of 20.25 reads. With 3,606,720 SNPs and 155,336 SNPs within 11,365 genes, this data set is the largest genomic resource available for AHBs and will enable high-resolution studies of the population dynamics, evolution, and genetics of this successful biological invader, in addition to facilitating the development of SNP-based tools for identifying AHBs.

NordicDB: a Nordic pool and portal for genome-wide control data.

PubMed

Leu, Monica; Humphreys, Keith; Surakka, Ida; Rehnberg, Emil; Muilu, Juha; Rosenström, Päivi; Almgren, Peter; Jääskeläinen, Juha; Lifton, Richard P; Kyvik, Kirsten Ohm; Kaprio, Jaakko; Pedersen, Nancy L; Palotie, Aarno; Hall, Per; Grönberg, Henrik; Groop, Leif; Peltonen, Leena; Palmgren, Juni; Ripatti, Samuli

2010-12-01

A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from ∼5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW-SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries.

Population Structure With Localized Haplotype Clusters

PubMed Central

Browning, Sharon R.; Weir, Bruce S.

2010-01-01

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. PMID:20457877

Maximum-likelihood estimation of recent shared ancestry (ERSA).

PubMed

Huff, Chad D; Witherspoon, David J; Simonson, Tatum S; Xing, Jinchuan; Watkins, W Scott; Zhang, Yuhua; Tuohy, Therese M; Neklason, Deborah W; Burt, Randall W; Guthery, Stephen L; Woodward, Scott R; Jorde, Lynn B

2011-05-01

Accurate estimation of recent shared ancestry is important for genetics, evolution, medicine, conservation biology, and forensics. Established methods estimate kinship accurately for first-degree through third-degree relatives. We demonstrate that chromosomal segments shared by two individuals due to identity by descent (IBD) provide much additional information about shared ancestry. We developed a maximum-likelihood method for the estimation of recent shared ancestry (ERSA) from the number and lengths of IBD segments derived from high-density SNP or whole-genome sequence data. We used ERSA to estimate relationships from SNP genotypes in 169 individuals from three large, well-defined human pedigrees. ERSA is accurate to within one degree of relationship for 97% of first-degree through fifth-degree relatives and 80% of sixth-degree and seventh-degree relatives. We demonstrate that ERSA's statistical power approaches the maximum theoretical limit imposed by the fact that distant relatives frequently share no DNA through a common ancestor. ERSA greatly expands the range of relationships that can be estimated from genetic data and is implemented in a freely available software package.

NordicDB: a Nordic pool and portal for genome-wide control data

PubMed Central

Leu, Monica; Humphreys, Keith; Surakka, Ida; Rehnberg, Emil; Muilu, Juha; Rosenström, Päivi; Almgren, Peter; Jääskeläinen, Juha; Lifton, Richard P; Kyvik, Kirsten Ohm; Kaprio, Jaakko; Pedersen, Nancy L; Palotie, Aarno; Hall, Per; Grönberg, Henrik; Groop, Leif; Peltonen, Leena; Palmgren, Juni; Ripatti, Samuli

2010-01-01

A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from ∼5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW–SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries. PMID:20664631

Development of a semidefined growth medium for Pedobacter cryoconitis BG5 using statistical experimental design.

PubMed

Ong, Magdalena; Ongkudon, Clarence M; Wong, Clemente Michael Vui Ling

2016-10-02

Pedobacter cryoconitis BG5 are psychrophiles isolated from the cold environment and capable of proliferating and growing well at low temperature regime. Their cellular products have found a broad spectrum of applications, including in food, medicine, and bioremediation. Therefore, it is imperative to develop a high-cell density cultivation strategy coupled with optimized growth medium for P. cryoconitis BG5. To date, there has been no published report on the design and optimization of growth medium for P. cryoconitis, hence the objective of this research project. A preliminary screening of four commercially available media, namely tryptic soy broth, R2A, Luria Bertani broth, and nutrient broth, was conducted to formulate the basal medium. Based on the preliminary screening, tryptone, glucose, NaCl, and K2HPO4 along with three additional nutrients (yeast extract, MgSO4, and NH4Cl) were identified to form the basal medium which was further analyzed by Plackett-Burman experimental design. Central composite experimental design using response surface methodology was adopted to optimize tryptone, yeast extract, and NH4Cl concentrations in the formulated growth medium. Statistical data analysis showed a high regression factor of 0.84 with a predicted optimum optical (600 nm) cell density of 7.5 using 23.7 g/L of tryptone, 8.8 g/L of yeast extract, and 0.7 g/L of NH4Cl. The optimized medium for P. cryoconitis BG5 was tested, and the observed optical density was 7.8. The cost-effectiveness of the optimized medium was determined as 6.25 unit prices per gram of cell produced in a 250-ml Erlenmeyer flask.

Random forest estimation of genomic breeding values for disease susceptibility over different disease incidences and genomic architectures in simulated cow calibration groups.

PubMed

Naderi, S; Yin, T; König, S

2016-09-01

A simulation study was conducted to investigate the performance of random forest (RF) and genomic BLUP (GBLUP) for genomic predictions of binary disease traits based on cow calibration groups. Training and testing sets were modified in different scenarios according to disease incidence, the quantitative-genetic background of the trait (h(2)=0.30 and h(2)=0.10), and the genomic architecture [725 quantitative trait loci (QTL) and 290 QTL, populations with high and low levels of linkage disequilibrium (LD)]. For all scenarios, 10,005 SNP (depicting a low-density 10K SNP chip) and 50,025 SNP (depicting a 50K SNP chip) were evenly spaced along 29 chromosomes. Training and testing sets included 20,000 cows (4,000 sick, 16,000 healthy, disease incidence 20%) from the last 2 generations. Initially, 4,000 sick cows were assigned to the testing set, and the remaining 16,000 healthy cows represented the training set. In the ongoing allocation schemes, the number of sick cows in the training set increased stepwise by moving 10% of the sick animals from the testing set to the training set, and vice versa. The size of the training and testing sets was kept constant. Evaluation criteria for both GBLUP and RF were the correlations between genomic breeding values and true breeding values (prediction accuracy), and the area under the receiving operating characteristic curve (AUROC). Prediction accuracy and AUROC increased for both methods and all scenarios as increasing percentages of sick cows were allocated to the training set. Highest prediction accuracies were observed for disease incidences in training sets that reflected the population disease incidence of 0.20. For this allocation scheme, the largest prediction accuracies of 0.53 for RF and of 0.51 for GBLUP, and the largest AUROC of 0.66 for RF and of 0.64 for GBLUP, were achieved using 50,025 SNP, a heritability of 0.30, and 725 QTL. Heritability decreases from 0.30 to 0.10 and QTL reduction from 725 to 290 were associated with decreasing prediction accuracy and decreasing AUROC for all scenarios. This decrease was more pronounced for RF. Also, the increase of LD had stronger effect on RF results than on GBLUP results. The highest prediction accuracy from the low LD scenario was 0.30 from RF and 0.36 from GBLUP, and increased to 0.39 for both methods in the high LD population. Random forest successfully identified important SNP in close map distance to QTL explaining a high proportion of the phenotypic trait variations. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

IUE study of the very local interstellar medium. [Copernicus spacecraft

NASA Technical Reports Server (NTRS)

Henry, R. C.; Murthy, J.; Moos, H. W.; Landsman, W. B.; Linsky, J. L.; Vidal-Madjar, A.; Gry, C.

1986-01-01

The IUE and Copernicus results for the very local interstellar medium are compared. Despite its lower resolution, IUE produces results of comparable quality, giving important confirmation of Copernicus results on the density, temperature, turbulence, and deuterium-to-hydrogen ratio in the region within 10 pc of the Sun. The stars observed are in a very low-density quarter of the galaxy: multicomponent structure seen in other directions may not be present in the direction of most of the observed stars. The exceedingly low densities observed in certain directions encourages the idea that EUV studies of certain normal stars may be possible.

Effect of medium components and culture conditions in Bacillus subtilis EA-CB0575 spore production.

PubMed

Posada-Uribe, Luisa F; Romero-Tabarez, Magally; Villegas-Escobar, Valeska

2015-10-01

Bacillus subtilis spores have important biotechnological applications; however, achieving both, high spore cell densities and sporulation efficiencies in fermentation, is poorly reported. In this study, medium components and culture conditions were optimized with different statistical methods to increase spore production of the plant growth promoting rhizobacteria B. subtilis EA-CB0575. Key medium components were determined with Plackett-Burman (PB) design, and the optimum concentration levels of two components (glucose, MgSO4·7H2O) were optimized with a full factorial and central composite design, achieving 1.37 × 10(9) CFU/mL of spore cell density and 93.5 % of sporulation efficiency in shake flask. The optimized medium was used to determine the effect of culture conditions on spore production at bioreactor level, finding that maintaining pH control did not affect significantly spore production, while the interaction of agitation and aeration rates had a significant effect on spore cell density. The overall optimization generated a 17.2-fold increase in spore cell density (8.78 × 10(9) CFU/mL) and 1.9-fold increase in sporulation efficiency (94.2 %) compared to that of PB design. These results indicate the potential of B. subtilis EA-CB0575 to produce both, high spore cell densities and sporulation efficiencies, with very low nutrient requirements and short incubation period which can represent savings of process production.

Nonequilibrium forces following quenches in active and thermal matter.

PubMed

Rohwer, Christian M; Solon, Alexandre; Kardar, Mehran; Krüger, Matthias

2018-03-01

Nonequilibrium systems with conserved quantities like density or momentum are known to exhibit long-ranged correlations. This, in turn, leads to long-ranged fluctuation-induced (Casimir) forces, predicted to arise in a variety of nonequilibrium settings. Here, we study such forces, which arise transiently between parallel plates or compact inclusions in a gas of particles, following a change ("quench") in temperature or activity of the medium. Analytical calculations, as well as numerical simulations of passive or active Brownian particles, indicate two distinct forces: (i) The immediate effect of the quench is adsorption or desorption of particles of the medium to the immersed objects, which in turn initiates a front of relaxing (mean) density. This leads to time-dependent density-induced forces. (ii) A long-term effect of the quench is that density fluctuations are modified, manifested as transient (long-ranged) (pair-)correlations that relax diffusively to their (short-ranged) steady-state limit. As a result, transient fluctuation-induced forces emerge. We discuss the properties of fluctuation-induced and density-induced forces as regards universality, relaxation as a function of time, and scaling with distance between objects. Their distinct signatures allow us to distinguish the two types of forces in simulation data. Our simulations also show that a quench of the effective temperature of an active medium gives rise to qualitatively similar effects to a temperature quench in a passive medium. Based on this insight, we propose several scenarios for the experimental observation of the forces described here.

Nonequilibrium forces following quenches in active and thermal matter

NASA Astrophysics Data System (ADS)

Rohwer, Christian M.; Solon, Alexandre; Kardar, Mehran; Krüger, Matthias

2018-03-01

Nonequilibrium systems with conserved quantities like density or momentum are known to exhibit long-ranged correlations. This, in turn, leads to long-ranged fluctuation-induced (Casimir) forces, predicted to arise in a variety of nonequilibrium settings. Here, we study such forces, which arise transiently between parallel plates or compact inclusions in a gas of particles, following a change ("quench") in temperature or activity of the medium. Analytical calculations, as well as numerical simulations of passive or active Brownian particles, indicate two distinct forces: (i) The immediate effect of the quench is adsorption or desorption of particles of the medium to the immersed objects, which in turn initiates a front of relaxing (mean) density. This leads to time-dependent density-induced forces. (ii) A long-term effect of the quench is that density fluctuations are modified, manifested as transient (long-ranged) (pair-)correlations that relax diffusively to their (short-ranged) steady-state limit. As a result, transient fluctuation-induced forces emerge. We discuss the properties of fluctuation-induced and density-induced forces as regards universality, relaxation as a function of time, and scaling with distance between objects. Their distinct signatures allow us to distinguish the two types of forces in simulation data. Our simulations also show that a quench of the effective temperature of an active medium gives rise to qualitatively similar effects to a temperature quench in a passive medium. Based on this insight, we propose several scenarios for the experimental observation of the forces described here.

Spiral waves in driven dusty plasma medium: Generalized hydrodynamic fluid description

NASA Astrophysics Data System (ADS)

Kumar, Sandeep; Patel, Bhavesh; Das, Amita

2018-04-01

Spiral waves are observed in many natural phenomena. They have been extensively represented by the mathematical FitzHugh-Nagumo model [Barkley et al., Phys. Rev. A 42, 2489 (1990)] of excitable media. Also, in incompressible fluid simulations, the excitation of thermal spiral waves has been reported by Li et al. [Phys. of Fluids 22, 011701 (2010)]. In the present paper, the spatiotemporal development of spiral waves in the context of weak and strong coupling limits has been shown. While the weakly coupled medium has been represented by a simple fluid description, for strong coupling, a generalized visco-elastic fluid description has been employed. The medium has been driven by an external force in the form of a rotating electric field. It is shown that when the amplitude of force is small, the density perturbations in the medium are also small. In this case, the excitations do not develop as a spiral wave. Only when the amplitude of force is high so as to drive the density perturbations to nonlinear amplitudes does the spiral density wave formation occurs. The role of the forcing frequency and the effect of strong coupling and the sound velocity of medium in the formation and evolution of spiral waves have been investigated in detail.

Establishment of an efficient plant regeneration culture protocol and achievement of successful genetic transformation in Jatropha curcas L.

PubMed

Liu, Ying; Liu, Guoxuan; Yang, Yali; Niu, Sufang; Yang, Fuguang; Yang, Shaoxia; Tang, Jianian; Chen, Jianping

2017-12-01

An efficient and reproducible protocol is described for shoot-bud regeneration and Agrobacterium tumefaciens-mediated genetic transformation of J. curcas. Treating the explants with high concentrations (5-120 mg/L) of TDZ for short durations (5-80 min) before inoculation culture increased significantly the regeneration frequency and improved the quality of the regenerated buds. The highest shoot-buds induction rate (87.35%) was achieved when petiole explants were treated with 20 mg/L TDZ solution for 20 min and inoculated on hormone-free MS medium for 30 days. Regenerated shoots of 0.5 cm or a little longer were isolated and grafted to seedling stocks of the same species, and then the grafted plantlets were planted on half-strength MS medium containing 0.1 mg/L IBA and 2 mg/L sodium nitroprusside (SNP). This grafting strategy was found to be very effective, to obtain that healthy grafted plantlets ready for acclimatization within 20 days. By the above mentioned protocol and with general Agrobacterium - mediated genetic transformation methods only 65 days were needed to obtain intact transgenic plants.

Numerical simulation of rotating body movement in medium with various densities

NASA Astrophysics Data System (ADS)

Tenenev, Valentin A.; Korolev, Stanislav A.; Rusyak, Ivan G.

2016-10-01

The paper proposes an approach to calculate the motion of rotating bodies in resisting medium by solving the Kirchhoff equations of motion in a coordinate system moving with the body and in determination of aerodynamic characteristics of the body with a given geometry by solving the Navier-Stokes equations. We present the phase trajectories of the perturbed motion of a rotating projectile in media with different densities: gas and liquid.

Changes in the chemical composition and spectroscopy of loblolly pine medium density fiberboard furnish as a function of age and refining pressure

Treesearch

Stephen S. Kelley; Thomas Elder; Leslie H. Groom

2005-01-01

Loblolly pine wood between the ages of 5-35 was refined into medium density fiberboard furnish at steam pressures from 2 to 18 bar, The effect of age and processing conditions on the properties of the fibers was assessed by wet chemical analyses, Near Infared Spectroscopy (NIR) and powder X-ray diffraction (XRD).In general ,the percentages of extractives and glucose...

Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density

DTIC Science & Technology

2010-11-01

shear, such as 129J and AKR (reported previously), would also exhibit this same A G SNP at nucleotide 1075 of the Lepr. Our future work will address...no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control...CLASSIFICATION OF: “U” 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 362 19a. NAME OF RESPONSIBLE PERSON USAMRMC a . REPORT U b. ABSTRACT U c. THIS

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside.

PubMed

Hurtubise, Jessica L; Marks, Wendie N; Davies, Don A; Catton, Jillian K; Baker, Glen B; Howland, John G

2017-01-01

The cognitive symptoms observed in schizophrenia are not consistently alleviated by conventional antipsychotics. Following a recent pilot study, sodium nitroprusside (SNP) has been identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients. The present experiments were designed to explore the effects of SNP on the highly translatable trial-unique, delayed nonmatching-to-location (TUNL) task in rats with and without acute MK-801 treatment. SNP (0.5, 1.0, 2.0, 4.0, and 5.0 mg/kg) and MK-801 (0.05, 0.075, and 0.1 mg/kg) were acutely administered to rats trained on the TUNL task. Acute MK-801 treatment impaired TUNL task accuracy. Administration of SNP (2.0 mg/kg) with MK-801 (0.1 mg/kg) failed to rescue performance on TUNL. SNP (5.0 mg/kg) administration nearly 4 h prior to MK-801 (0.05 mg/kg) treatment had no preventative effect on performance impairments. SNP (2.0 mg/kg) improved performance on a subset of trials. These results suggest that SNP may possess intrinsic cognitive-enhancing properties but is unable to block the effects of acute MK-801 treatment on the TUNL task. These results are inconsistent with the effectiveness of SNP as an adjunct therapy for working memory impairments in schizophrenia patients. Future studies in rodents that assess SNP as an adjunct therapy will be valuable in understanding the mechanisms underlying the effectiveness of SNP as a treatment for schizophrenia.

Genome-wide Target Enrichment-aided Chip Design: a 66 K SNP Chip for Cashmere Goat.

PubMed

Qiao, Xian; Su, Rui; Wang, Yang; Wang, Ruijun; Yang, Ting; Li, Xiaokai; Chen, Wei; He, Shiyang; Jiang, Yu; Xu, Qiwu; Wan, Wenting; Zhang, Yaolei; Zhang, Wenguang; Chen, Jiang; Liu, Bin; Liu, Xin; Fan, Yixing; Chen, Duoyuan; Jiang, Huaizhi; Fang, Dongming; Liu, Zhihong; Wang, Xiaowen; Zhang, Yanjun; Mao, Danqing; Wang, Zhiying; Di, Ran; Zhao, Qianjun; Zhong, Tao; Yang, Huanming; Wang, Jian; Wang, Wen; Dong, Yang; Chen, Xiaoli; Xu, Xun; Li, Jinquan

2017-08-17

Compared with the commercially available single nucleotide polymorphism (SNP) chip based on the Bead Chip technology, the solution hybrid selection (SHS)-based target enrichment SNP chip is not only design-flexible, but also cost-effective for genotype sequencing. In this study, we propose to design an animal SNP chip using the SHS-based target enrichment strategy for the first time. As an update to the international collaboration on goat research, a 66 K SNP chip for cashmere goat was created from the whole-genome sequencing data of 73 individuals. Verification of this 66 K SNP chip with the whole-genome sequencing data of 436 cashmere goats showed that the SNP call rates was between 95.3% and 99.8%. The average sequencing depth for target SNPs were 40X. The capture regions were shown to be 200 bp that flank target SNPs. This chip was further tested in a genome-wide association analysis of cashmere fineness (fiber diameter). Several top hit loci were found marginally associated with signaling pathways involved in hair growth. These results demonstrate that the 66 K SNP chip is a useful tool in the genomic analyses of cashmere goats. The successful chip design shows that the SHS-based target enrichment strategy could be applied to SNP chip design in other species.

Rice SNP-seek database update: new SNPs, indels, and queries.

PubMed

Mansueto, Locedie; Fuentes, Roven Rommel; Borja, Frances Nikki; Detras, Jeffery; Abriol-Santos, Juan Miguel; Chebotarov, Dmytro; Sanciangco, Millicent; Palis, Kevin; Copetti, Dario; Poliakov, Alexandre; Dubchak, Inna; Solovyev, Victor; Wing, Rod A; Hamilton, Ruaraidh Sackville; Mauleon, Ramil; McNally, Kenneth L; Alexandrov, Nickolai

2017-01-04

We describe updates to the Rice SNP-Seek Database since its first release. We ran a new SNP-calling pipeline followed by filtering that resulted in complete, base, filtered and core SNP datasets. Besides the Nipponbare reference genome, the pipeline was run on genome assemblies of IR 64, 93-11, DJ 123 and Kasalath. New genotype query and display features are added for reference assemblies, SNP datasets and indels. JBrowse now displays BAM, VCF and other annotation tracks, the additional genome assemblies and an embedded VISTA genome comparison viewer. Middleware is redesigned for improved performance by using a hybrid of HDF5 and RDMS for genotype storage. Query modules for genotypes, varieties and genes are improved to handle various constraints. An integrated list manager allows the user to pass query parameters for further analysis. The SNP Annotator adds traits, ontology terms, effects and interactions to markers in a list. Web-service calls were implemented to access most data. These features enable seamless querying of SNP-Seek across various biological entities, a step toward semi-automated gene-trait association discovery. URL: http://snp-seek.irri.org. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

SNPHunter: a bioinformatic software for single nucleotide polymorphism data acquisition and management.

PubMed

Wang, Lin; Liu, Simin; Niu, Tianhua; Xu, Xin

2005-03-18

Single nucleotide polymorphisms (SNPs) provide an important tool in pinpointing susceptibility genes for complex diseases and in unveiling human molecular evolution. Selection and retrieval of an optimal SNP set from publicly available databases have emerged as the foremost bottlenecks in designing large-scale linkage disequilibrium studies, particularly in case-control settings. We describe the architectural structure and implementations of a novel software program, SNPHunter, which allows for both ad hoc-mode and batch-mode SNP search, automatic SNP filtering, and retrieval of SNP data, including physical position, function class, flanking sequences at user-defined lengths, and heterozygosity from NCBI dbSNP. The SNP data extracted from dbSNP via SNPHunter can be exported and saved in plain text format for further down-stream analyses. As an illustration, we applied SNPHunter for selecting SNPs for 10 major candidate genes for type 2 diabetes, including CAPN10, FABP4, IL6, NOS3, PPARG, TNF, UCP2, CRP, ESR1, and AR. SNPHunter constitutes an efficient and user-friendly tool for SNP screening, selection, and acquisition. The executable and user's manual are available at http://www.hsph.harvard.edu/ppg/software.htm

Acute blood pressure effects of YC-1-induced activation of soluble guanylyl cyclase in normotensive and hypertensive rats

PubMed Central

Rothermund, Lars; Friebe, Andreas; Paul, Martin; Koesling, Doris; Kreutz, Reinhold

2000-01-01

We used YC-1 as a pharmacological tool to investigate the short-term blood pressure effects of NO-independent activation of sGC in normotensive and hypertensive rats. Four groups of normotensive Wistar-Kyoto rats were treated by i.v. injection with vehicle (V), YC-1 (YC-1), sodium nitroprusside (SNP), or YC-1 and SNP (YC-1+SNP). Hypertension was induced in four additional groups of WKY rats by 3 weeks of oral treatment with L-NAME. These animals were investigated with the same protocol as the normotensive animals: L-NAME/V, L-NAME/YC-1, L-NAME/SNP, L-NAME/YC-1+SNP. YC-1 lowered mean arterial blood pressure (MAP) in normotensive and hypertensive animals similarly to SNP alone (P<0.05, respectively). The combination of YC-1 with SNP caused a strong decrease of MAP in both the hypertensive and normotensive animals (P<0.05, respectively). SNP with YC-1 also induced a pronounced cyclic GMP increase in the aorta. This study shows for the first time the blood pressure lowering potential of bimodal targeting of the NO-sGC-system. PMID:10807655

Measurement of Fe2+ ion by coulometry method at incubation of Thiobacillus ferrooxidans.

PubMed

Tsuda, I; Kato, K; Nozaki, K

1996-12-01

Thiobacillus ferrooxidans is a chemoautotrophic bacterium that is capable of using Fe2+ oxidation by O2 as the sole source of energy for growth and CO2 fixation. The idea of the solar bacterial biomass farm by using of this bacterium is proposed. The incubation experiment of these bacteria was carried out, and the 9K culture medium as the standard medium for T. ferrooxidans was used. The measurement of Fe2+ in the growth stage was carried out as the first step of the experiments to clarify the possibility of this system. The items of measurement were Fe2+ ion density, pH of the medium, bacterium density and quantity of total organic carbon (TOC). The density of Fe2+ ion in the medium was measured by coulometry method. This method has the following advantage, high accuracy (<1%), easy operation, short measurement time (a few minutes) and small sample quantity (about 0.1 ml). The experimental results show that the Fe 2+ ion density is measured as same as the accuracy of pH measurement. At the final stage of the growth, the pH decreased due to the generation of the iron hydroxide (Fe(OH)3). The bacterium density and TOC slightly increased after that Fe2+ runs short. This result shows that the CO2 fixation speed is slower than Fe2+ oxidation speed. It is shown by the experiment that the growth limit of T. ferrooxidans is caused by the disappearance of the Fe2+ ion. It may be possible that the bacterium density increases by the continuous supply of Fe2+ ion.

Prevalence and distribution of Aeromonas hydrophila in the United States.

PubMed

Hazen, T C; Fliermans, C B; Hirsch, R P; Esch, G W

1978-11-01

The abundance of Aeromonas hydrophila was measured in 147 natural aquatic habitats in 30 states and Puerto Rico. Viable cell counts were used to estimate density at all sites by using Rimler-Shotts medium, a differential presumptive medium for A. hydrophila. Temperature, pH, conductivity, salinity, and turbidity were measured simultaneously with water sample collection. The density of A. hydrophila was higher in lotic than in lentic systems. Saline systems had higher densities of A. hydrophila than did freshwater systems. A. hydrophila could not be isolated from extremely saline, thermal, or polluted waters, even though it was found over wide ranges of salinity, conductivity, temperature, pH, and turbidity. Of the water quality parameters measured, only conductivity was significantly regressed with density of A. hydrophila.

Correlation between polymorphism of FTO gene and type 2 diabetes mellitus in Uygur people from northwest China.

PubMed

Xiao, Shan; Zeng, Xiaoyun; Quan, Li; Zhu, Jun

2015-01-01

To explore the correlation between FTO (fat mass and obesity associated) gene, which is associated with 3 single nucleotide polymorphisms (SNP) of fat mass and obesity, type 2 diabetes and body mass index (BMI) in the Uygur population in northwest China. A total of 849 Uygur patients with type 2 diabetes mellitus were selected from the hospitalized patients in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Kashi and the hospitals in the Turpan areas. At the same time, 873 cases of healthy persons who conducted a medical checkup in the physical examination centre of the above hospitals were enrolled as controls. The present investigation used the case-control research method, and physical examination and biochemical index determination were carried out. The Sequenom MassARRAY technology was employed in the detection of 3 SNP loci of the FTO gene. The representative population of each SNP in the control group was analyzed by Hardy-Weinberg law. The differences of each clinical parameter in the two groups were analyzed by t-test analysis. The differences of genotype and allele of each SNP in the two groups were analyzed by χ(2) test. BMI, waistline (WL), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the type 2 diabetes group were higher than those in the control group, while the high density lipoprotein (HDL) and low density lipoprotein (LDL) were lower than those of the control group; 2. The allele frequency of A of rs8050136 and rs9939609 in the type 2 diabetes mellitus group was higher than that of the control group. The BMI of the whole population and type 2 diabetes group with genotype C/A+A/A of rs8050136 was higher than that in C/C group, and the BMI with genotype T/A+A/A of rs9939609 was higher than that in group T/T. Stratification was conducted on BMI according to the normal, overweight and obesity criteria. There were significant differences in the distribution of genotype frequency of rs9939609 in the type 2 diabetes group and the control group of the normal BMI group. Single nucleotide mutation of rs7195539 in FTO gene may be a protective factor against the Uygur type 2 diabetes. Single nucleotide mutations of rs8050136 and rs9939609 may be associated with the Uygur type 2 diabetes and obesity, with A as a potential risk allele. The gene polymorphism of rs8050136 may correlate with type 2 diabetes mellitus through the function of BMI, while the correlation between rs9939609 gene polymorphism and type 2 diabetes is not depending from BMI.

The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

PubMed Central

Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder; Sabourin, David; Collas, Philippe; Bruus, Henrik; Dufva, Martin

2013-01-01

Introduction High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. Methods and results Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. Conclusions Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process. PMID:23723991

Genome-wide SNP scan in a porcine Large White×Minzhu intercross population reveals a locus influencing muscle mass on chromosome 2.

PubMed

Liu, Xin; Wang, Li Gang; Luo, Wei Zhen; Li, Yong; Liang, Jing; Yan, Hua; Zhao, Ke Bin; Wang, Li Xian; Zhang, Long Chao

2014-12-01

A high-density single nucleotide polymorphism (SNP) array containing 62 163 markers was employed for a genome-wide association study (GWAS) to identify variants associated with lean meat in ham (LMH, %) and lean meat percentage (LMP, %) within a porcine Large White×Minzhu intercross population. For each individual, LMH and LMP were measured after slaughter at the age of 240±7 days. A total of 557 F2 animals were genotyped. The GWAS revealed that 21 SNPs showed significant genome-wide or chromosome-wide associations with LMH and LMP by the Genome-wide Rapid Association using Mixed Model and Regression-Genomic Control approach. Nineteen significant genome-wide SNPs were mapped to the distal end of Sus Scrofa Chromosome (SSC) 2, where a major known gene responsible for muscle mass, IGF2 is located. A conditioned analysis, in which the genotype of the strongest associated SNP is included as a fixed effect in the model, showed that those significant SNPs on SSC2 were derived from a single quantitative trait locus. The two chromosome-wide association SNPs on SSC1 disappeared after conditioned analysis suggested the association signal is a false association derived from using a F2 population. The present result is expected to lead to novel insights into muscle mass in different pig breeds and lays a preliminary foundation for follow-up studies for identification of causal mutations for subsequent application in marker-assisted selection programs for improving muscle mass in pigs. © 2014 Japanese Society of Animal Science.

Kernel machine SNP set analysis provides new insight into the association between obesity and polymorphisms located on the chromosomal 16q.12.2 region: Tehran Lipid and Glucose Study.

PubMed

Javanrouh, Niloufar; Daneshpour, Maryam S; Soltanian, Ali Reza; Tapak, Leili

2018-06-05

Obesity is a serious health problem that leads to low quality of life and early mortality. To the purpose of prevention and gene therapy for such a worldwide disease, genome wide association study is a powerful tool for finding SNPs associated with increased risk of obesity. To conduct an association analysis, kernel machine regression is a generalized regression method, has an advantage of considering the epistasis effects as well as the correlation between individuals due to unknown factors. In this study, information of the people who participated in Tehran cardio-metabolic genetic study was used. They were genotyped for the chromosomal region, evaluation 986 variations located at 16q12.2; build 38hg. Kernel machine regression and single SNP analysis were used to assess the association between obesity and SNPs genotyped data. We found that associated SNP sets with obesity, were almost in the FTO (P = 0.01), AIKTIP (P = 0.02) and MMP2 (P = 0.02) genes. Moreover, two SNPs, i.e., rs10521296 and rs11647470, showed significant association with obesity using kernel regression (P = 0.02). In conclusion, significant sets were randomly distributed throughout the region with more density around the FTO, AIKTIP and MMP2 genes. Furthermore, two intergenic SNPs showed significant association after using kernel machine regression. Therefore, more studies have to be conducted to assess their functionality or precise mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of the external medium on the gravitropic curvature of rice (Oryza sativa, Poaceae) roots

NASA Technical Reports Server (NTRS)

Staves, M. P.; Wayne, R.; Leopold, A. C.

1997-01-01

The roots of rice seedlings, growing in artificial pond water, exhibit robust gravitropic curvature when placed perpendicular to the vector of gravity. To determine whether the statolith theory (in which intracellular sedimenting particles are responsible for gravity sensing) or the gravitational pressure theory (in which the entire protoplast acts as the gravity sensor) best accounts for gravity sensing in rice roots, we changed the physical properties of the external medium with impermeant solutes and examined the effect on gravitropism. As the density of the external medium is increased, the rate of gravitropic curvature decreases. The decrease in the rate of gravicurvature cannot be attributed to an inhibition of growth, since rice roots grown in 100 Osm/m3 (0.248 MPa) solutions of different densities all support the same root growth rate but inhibit gravicurvature increasingly with increasing density. By contrast, the sedimentation rate of amyloplasts in the columella cells is unaffected by the external density. These results are consistent with the gravitational pressure theory of gravity sensing, but cannot be explained by the statolith theory.

Short communication: relationship of call rate and accuracy of single nucleotide polymorphism genotypes in dairy cattle.

PubMed

Cooper, T A; Wiggans, G R; VanRaden, P M

2013-05-01

Call rates on both a single nucleotide polymorphism (SNP) basis and an animal basis are used as measures of data quality and as screening tools for genomic studies and evaluations of dairy cattle. To investigate the relationship of SNP call rate and genotype accuracy for individual SNP, the correlation between percentages of missing genotypes and parent-progeny conflicts for each SNP was calculated for 103,313 Holsteins. Correlations ranged from 0.14 to 0.38 for the BovineSNP50 and BovineLD (Illumina Inc., San Diego, CA) and GeneSeek Genomic Profiler (Neogen Corp., Lincoln, NE) chips, with lower correlations for newer chips. For US genomic evaluations, genotypes are excluded for animals with a call rate of <90% across autosomal SNP or <80% across X-specific SNP. Mean call rate for 220,175 Holstein, Jersey, and Brown Swiss genotypes was 99.6%. Animal genotypes with a call rate of ≤99% were examined from the US Department of Agriculture genotype database to determine how genotype call rate is related to accuracy of calls on an animal basis. Animal call rate was determined from SNP used in genomic evaluation and is the number of called autosomal and X-specific SNP genotypes divided by the number of SNP from that type of chip. To investigate the relationship of animal call rate and parentage validation, conflicts between a genotyped animal and its sire or dam were determined through a duo test (opposite homozygous SNP genotypes between sire and progeny; 1,374 animal genotypes) and a trio test (also including conflicts with dam and heterozygous SNP genotype for the animal when both parents are the same homozygote; 482 animal genotypes). When animal call rate was ≤ 80%, parentage validation was no longer reliable with the duo test. With the trio test, parentage validation was no longer reliable when animal call rate was ≤ 90%. To investigate how animal call rate was related to genotyping accuracy for animals with multiple genotypes, concordance between genotypes for 1,216 animals that had a genotype with a call rate of ≤ 99% (low call rate) as well as a genotype with a call rate of >99% (high call rate) were calculated by dividing the number of identical SNP genotype calls by the number of SNP that were called for both genotypes. Mean concordance between low- and high-call genotypes was >99% for a low call rate of >90% but decreased to 97% for a call rate of 86 to 90% and to 58% for a call rate of <60%. Edits on call rate reduce the use of incorrect SNP genotypes to calculate genomic evaluations. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effect of dissipative inhomogeneous medium on the statistics of the wave intensity

NASA Technical Reports Server (NTRS)

Saatchi, Sasan S.

1993-01-01

One of the main theoretical points in the theory of wave propagation in random medium is the derivation of closed form equations to describe the statistics of the propagating waves. In particular, in one dimensional problems, the closed form representation of the multiple scattering effects is important since it contributes in understanding such problems like wave localization, backscattering enhancement, and intensity fluctuations. In this the propagation of plane waves in a layer of one-dimensional dissipative random medium is considered. The medium is modeled by a complex permittivity whose real part is a constant representing the absorption. The one dimensional problem is mathematically equivalent to the analysis of a transmission line with randomly perturbed distributed parameters and a single mode lossy waveguide and the results can be used to study the propagation of radio waves through atmosphere and the remote sensing of geophysical media. It is assumed the scattering medium consists of an ensemble of one-dimensional point scatterers randomly positioned in a layer of thickness L with diffuse boundaries. A Poisson impulse process with density lambda is used to model the position of scatterers in the medium. By employing the Markov properties of this process an exact closed form equation of Kolmogorov-Feller type was obtained for the probability density of the reflection coefficient. This equation was solved by combining two limiting cases: (1) when the density of scatterers is small; and (2) when the medium is weakly dissipative. A two variable perturbation method for small lambda was used to obtain solutions valid for thick layers. These solutions are then asymptotically evaluated for small dissipation. To show the effect of dissipation, the mean and fluctuations of the reflected power are obtained. The results were compared with a lossy homogeneous medium and with a lossless inhomogeneous medium and the regions where the effect of absorption is not essential were discussed.

When Whole-Genome Alignments Just Won't Work: kSNP v2 Software for Alignment-Free SNP Discovery and Phylogenetics of Hundreds of Microbial Genomes

PubMed Central

Gardner, Shea N.; Hall, Barry G.

2013-01-01

Effective use of rapid and inexpensive whole genome sequencing for microbes requires fast, memory efficient bioinformatics tools for sequence comparison. The kSNP v2 software finds single nucleotide polymorphisms (SNPs) in whole genome data. kSNP v2 has numerous improvements over kSNP v1 including SNP gene annotation; better scaling for draft genomes available as assembled contigs or raw, unassembled reads; a tool to identify the optimal value of k; distribution of packages of executables for Linux and Mac OS X for ease of installation and user-friendly use; and a detailed User Guide. SNP discovery is based on k-mer analysis, and requires no multiple sequence alignment or the selection of a single reference genome. Most target sets with hundreds of genomes complete in minutes to hours. SNP phylogenies are built by maximum likelihood, parsimony, and distance, based on all SNPs, only core SNPs, or SNPs present in some intermediate user-specified fraction of targets. The SNP-based trees that result are consistent with known taxonomy. kSNP v2 can handle many gigabases of sequence in a single run, and if one or more annotated genomes are included in the target set, SNPs are annotated with protein coding and other information (UTRs, etc.) from Genbank file(s). We demonstrate application of kSNP v2 on sets of viral and bacterial genomes, and discuss in detail analysis of a set of 68 finished E. coli and Shigella genomes and a set of the same genomes to which have been added 47 assemblies and four “raw read” genomes of H104:H4 strains from the recent European E. coli outbreak that resulted in both bloody diarrhea and hemolytic uremic syndrome (HUS), and caused at least 50 deaths. PMID:24349125

When whole-genome alignments just won't work: kSNP v2 software for alignment-free SNP discovery and phylogenetics of hundreds of microbial genomes.

PubMed

Gardner, Shea N; Hall, Barry G

2013-01-01

Effective use of rapid and inexpensive whole genome sequencing for microbes requires fast, memory efficient bioinformatics tools for sequence comparison. The kSNP v2 software finds single nucleotide polymorphisms (SNPs) in whole genome data. kSNP v2 has numerous improvements over kSNP v1 including SNP gene annotation; better scaling for draft genomes available as assembled contigs or raw, unassembled reads; a tool to identify the optimal value of k; distribution of packages of executables for Linux and Mac OS X for ease of installation and user-friendly use; and a detailed User Guide. SNP discovery is based on k-mer analysis, and requires no multiple sequence alignment or the selection of a single reference genome. Most target sets with hundreds of genomes complete in minutes to hours. SNP phylogenies are built by maximum likelihood, parsimony, and distance, based on all SNPs, only core SNPs, or SNPs present in some intermediate user-specified fraction of targets. The SNP-based trees that result are consistent with known taxonomy. kSNP v2 can handle many gigabases of sequence in a single run, and if one or more annotated genomes are included in the target set, SNPs are annotated with protein coding and other information (UTRs, etc.) from Genbank file(s). We demonstrate application of kSNP v2 on sets of viral and bacterial genomes, and discuss in detail analysis of a set of 68 finished E. coli and Shigella genomes and a set of the same genomes to which have been added 47 assemblies and four "raw read" genomes of H104:H4 strains from the recent European E. coli outbreak that resulted in both bloody diarrhea and hemolytic uremic syndrome (HUS), and caused at least 50 deaths.

Drift effect and "negative" mass transport in an inhomogeneous medium: limiting case of a two-component lattice gas.

PubMed

Lukyanets, Sergei P; Kliushnychenko, Oleksandr V

2010-11-01

The mass transport in an inhomogeneous medium is modeled as the limiting case of a two-component lattice gas with excluded volume constraint and one of the components fixed. In the long-wavelength approximation, the density relaxation of mobile particles is governed by diffusion and interaction with a medium inhomogeneity represented by the static component distribution. It is shown that the density relaxation can be locally accompanied by density distribution compression, i.e., the local mass transport directed from low-to high-density regions. The origin of such a "negative" mass transport is shown to be associated with the presence of a stationary drift flow defined by the medium inhomogeneity. In the quasi-one-dimensional case, the compression dynamics manifests itself in the hoppinglike motion of packet front position of diffusing substance due to staged passing through inhomogeneity barriers, and it leads to fragmentation of the packet and retardation of its spreading. The root-mean-square displacement reflects only the averaged packet front dynamics and becomes inappropriate as the transport characteristic in this regime. In the stationary case, the mass transport throughout the whole system may be directed from the boundary with lower concentration towards the boundary with higher concentration. Implications of the excluded volume constraint and particle distinguishability for these effects are discussed.

Association of methionine synthase gene polymorphisms with wool production and quality traits in Chinese Merino population.

PubMed

Rong, E G; Yang, H; Zhang, Z W; Wang, Z P; Yan, X H; Li, H; Wang, N

2015-10-01

Methionine synthase (MTR) plays a crucial role in maintaining homeostasis of intracellular methionine, folate, and homocysteine, and its activity correlates with DNA methylation in many mammalian tissues. Our previous genomewide association study identified that 1 SNP located in the gene was associated with several wool production and quality traits in Chinese Merino. To confirm the potential involvement of the gene in sheep wool production and quality traits, we performed sheep tissue expression profiling, SNP detection, and association analysis with sheep wool production and quality traits. The semiquantitative reverse transcription PCR analysis showed that the gene was differentially expressed in skin from Merino and Kazak sheep. The sequencing analysis identified a total of 13 SNP in the gene from Chinese Merino sheep. Comparison of the allele frequencies revealed that these 13 identified SNP were significantly different among the 6 tested Chinese Merino strains ( < 0.001). Linkage disequilibrium analysis showed that SNP 3 to 11 were strongly linked in a single haplotype block in the tested population. Association analysis showed that SNP 2 to 11 were significantly associated with the average wool fiber diameter and the fineness SD and that SNP 4 to 11 were significantly associated with the CV of fiber diameter trait ( < 0.05). Single nucleotide polymorphism 2 and SNP 5 to 12 were weakly associated with wool crimp. Similarly, the haplotypes derived from these 13 identified SNP were also significantly associated with the average wool fiber diameter, fineness SD, and the CV of fiber diameter ( < 0.05). Our results suggest that is a candidate gene for sheep wool production and quality traits, and the identified SNP might be used in sheep breeding.

Whole-genome single-nucleotide polymorphism (SNP) marker discovery and association analysis with the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in Larimichthys crocea

PubMed Central

Xiao, Shijun; Wang, Panpan; Dong, Linsong; Zhang, Yaguang; Han, Zhaofang; Wang, Qiurong

2016-01-01

Whole-genome single-nucleotide polymorphism (SNP) markers are valuable genetic resources for the association and conservation studies. Genome-wide SNP development in many teleost species are still challenging because of the genome complexity and the cost of re-sequencing. Genotyping-By-Sequencing (GBS) provided an efficient reduced representative method to squeeze cost for SNP detection; however, most of recent GBS applications were reported on plant organisms. In this work, we used an EcoRI-NlaIII based GBS protocol to teleost large yellow croaker, an important commercial fish in China and East-Asia, and reported the first whole-genome SNP development for the species. 69,845 high quality SNP markers that evenly distributed along genome were detected in at least 80% of 500 individuals. Nearly 95% randomly selected genotypes were successfully validated by Sequenom MassARRAY assay. The association studies with the muscle eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content discovered 39 significant SNP markers, contributing as high up to ∼63% genetic variance that explained by all markers. Functional genes that involved in fat digestion and absorption pathway were identified, such as APOB, CRAT and OSBPL10. Notably, PPT2 Gene, previously identified in the association study of the plasma n-3 and n-6 polyunsaturated fatty acid level in human, was re-discovered in large yellow croaker. Our study verified that EcoRI-NlaIII based GBS could produce quality SNP markers in a cost-efficient manner in teleost genome. The developed SNP markers and the EPA and DHA associated SNP loci provided invaluable resources for the population structure, conservation genetics and genomic selection of large yellow croaker and other fish organisms. PMID:28028455

Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.

PubMed

Diniz, Mariana C; Olivon, Vania C; Tavares, Lívia D; Simplicio, Janaina A; Gonzaga, Natália A; de Souza, Daniele G; Bendhack, Lusiane M; Tirapelli, Carlos R; Bonaventura, Daniella

2017-05-01

To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O 2 - ) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF 2 α receptor antagonist) or SQ29584 [PGH 2 /thromboxane TXA 2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O 2 - and hydrogen peroxide (H 2 O 2 ) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. Copyright © 2017 Elsevier Inc. All rights reserved.

Germline Mutation of the CCK Receptor: A Novel Biomarker for Pancreas Cancer.

PubMed

Alsubai, Jelal; Matters, Gail L; McGovern, Christopher O; Liao, Jiangang; Gilius, Evan L; Smith, Jill P

2016-01-07

Today, genetic biomarkers have been demonstrated to play an important role in identifying at-risk subjects for familial or inherited cancers. We have identified a single-nucleotide polymorphism (SNP) that results in missplicing of the cholecystokinin (CCK) receptor gene and expressing a larger mutated receptor in pancreatic cancer. The purpose of this study was to evaluate the significance and specificity of this SNP as a potential biomarker in patients with pancreatic cancer compared with other gastrointestinal (GI) cancers that also have CCK receptors. DNA was isolated and genotyped for the CCK receptor SNP from frozen tumor tissue from banked specimens of patients with pancreas, gastric, or colon cancer and from human cancer cell lines. Genotype and allelic frequencies were compared between the cancer cohort and two normal control databases using Fisher's exact test and odds ratio (OR). The Kaplan-Meier method was used to estimate the survival for patients with the CCK-B receptor SNP compared with those with the wild-type genotype. Immunohistochemical staining of cancer cells was done to detect the mutated receptor. Colon and gastric cancer patients had similar genotype frequencies for the CCK receptor SNP as that reported in the normal population. In contrast, the prevalence of the SNP in subjects with pancreatic cancer was twice that of controls and other GI cancers. Survival was adversely affected by the presence of the SNP only in those with pancreatic cancer. Immunoreactivity for the mutated receptor was positive in pancreatic cancer tissues with the SNP but absent in other GI cancers. A SNP of the CCK receptor is significantly increased in patients with pancreatic cancer but not in those with other GI malignancies. Therefore, this SNP may be a potential biomarker for pancreatic cancer.

AA9int: SNP Interaction Pattern Search Using Non-Hierarchical Additive Model Set.

PubMed

Lin, Hui-Yi; Huang, Po-Yu; Chen, Dung-Tsa; Tung, Heng-Yuan; Sellers, Thomas A; Pow-Sang, Julio; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Hamdy, Freddie; Neal, David E; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen N; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lu, Yong-Jie; Park, Jong Y

2018-06-07

The use of single nucleotide polymorphism (SNP) interactions to predict complex diseases is getting more attention during the past decade, but related statistical methods are still immature. We previously proposed the SNP Interaction Pattern Identifier (SIPI) approach to evaluate 45 SNP interaction patterns/patterns. SIPI is statistically powerful but suffers from a large computation burden. For large-scale studies, it is necessary to use a powerful and computation-efficient method. The objective of this study is to develop an evidence-based mini-version of SIPI as the screening tool or solitary use and to evaluate the impact of inheritance mode and model structure on detecting SNP-SNP interactions. We tested two candidate approaches: the 'Five-Full' and 'AA9int' method. The Five-Full approach is composed of the five full interaction models considering three inheritance modes (additive, dominant and recessive). The AA9int approach is composed of nine interaction models by considering non-hierarchical model structure and the additive mode. Our simulation results show that AA9int has similar statistical power compared to SIPI and is superior to the Five-Full approach, and the impact of the non-hierarchical model structure is greater than that of the inheritance mode in detecting SNP-SNP interactions. In summary, it is recommended that AA9int is a powerful tool to be used either alone or as the screening stage of a two-stage approach (AA9int+SIPI) for detecting SNP-SNP interactions in large-scale studies. The 'AA9int' and 'parAA9int' functions (standard and parallel computing version) are added in the SIPI R package, which is freely available at https://linhuiyi.github.io/LinHY_Software/. hlin1@lsuhsc.edu. Supplementary data are available at Bioinformatics online.

SNP-Based Typing: A Useful Tool to Study Bordetella pertussis Populations

PubMed Central

van der Heide, Han G. J.; Heuvelman, Kees J.; Kallonen, Teemu; He, Qiushui; Mertsola, Jussi; Advani, Abdolreza; Hallander, Hans O.; Janssens, Koen; Hermans, Peter W.; Mooi, Frits R.

2011-01-01

To monitor changes in Bordetella pertussis populations, mainly two typing methods are used; Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable-Number Tandem Repeat Analysis (MLVA). In this study, a single nucleotide polymorphism (SNP) typing method, based on 87 SNPs, was developed and compared with PFGE and MLVA. The discriminatory indices of SNP typing, PFGE and MLVA were found to be 0.85, 0.95 and 0.83, respectively. Phylogenetic analysis, using SNP typing as Gold Standard, revealed false homoplasies in the PFGE and MLVA trees. Further, in contrast to the SNP-based tree, the PFGE- and MLVA-based trees did not reveal a positive correlation between root-to-tip distance and the isolation year of strains. Thus PFGE and MLVA do not allow an estimation of the relative age of the selected strains. In conclusion, SNP typing was found to be phylogenetically more informative than PFGE and more discriminative than MLVA. Further, in contrast to PFGE, it is readily standardized allowing interlaboratory comparisons. We applied SNP typing to study strains with a novel allele for the pertussis toxin promoter, ptxP3, which have a worldwide distribution and which have replaced the resident ptxP1 strains in the last 20 years. Previously, we showed that ptxP3 strains showed increased pertussis toxin expression and that their emergence was associated with increased notification in the Netherlands. SNP typing showed that the ptxP3 strains isolated in the Americas, Asia, Australia and Europe formed a monophyletic branch which recently diverged from ptxP1 strains. Two predominant ptxP3 SNP types were identified which spread worldwide. The widespread use of SNP typing will enhance our understanding of the evolution and global epidemiology of B. pertussis. PMID:21647370

Resolving the interactions between population density and air pollution emissions controls in the San Joaquin Valley, USA.

PubMed

Hixson, Mark; Mahmud, Abdullah; Hu, Jianlin; Kleeman, Michael J

2012-05-01

The effectiveness of emissions control programs designed to reduce concentrations of airborne particulate matter with an aerodynamic diameter < 2.5 microm (PM2.5) in California's San Joaquin Valley was studied in the year 2030 under three growth scenarios: low, medium, and high population density. Base-case inventories for each choice of population density were created using a coupled emissions modeling system that simultaneously considered interactions between land use and transportation, area source, and point source emissions. The ambient PM2.5 response to each combination of population density and emissions control was evaluated using a regional chemical transport model over a 3-week winter stagnation episode. Comparisons between scenarios were based on regional average and population-weighted PM2.5 concentrations. In the absence of any emissions control program, population-weighted concentrations of PM2.5 in the future San Joaquin Valley are lowest undergrowth scenarios that emphasize low population density. A complete ban on wood burning and a 90% reduction in emissions from food cooking operations and diesel engines must occur before medium- to high-density growth scenarios result in lower population-weighted concentrations of PM2.5. These trends partly reflect the fact that existing downtown urban cores that naturally act as anchor points for new high-density growth in the San Joaquin Valley are located close to major transportation corridors for goods movement. Adding growth buffers around transportation corridors had little impact in the current analysis, since the 8-km resolution of the chemical transport model already provided an artificial buffer around major emissions sources. Assuming that future emissions controls will greatly reduce or eliminate emissions from residential wood burning, food cooking, and diesel engines, the 2030 growth scenario using "as-planned" (medium) population density achieves the lowest population-weighted average PM2.5 concentration in the future San Joaquin Valley during a severe winter stagnation event. The San Joaquin Valley is one of the most heavily polluted air basins in the United States that are projected to experience strong population growth in the coming decades. The best plan to improve air quality in the region combines medium- or high-density population growth with rigorous emissions controls. In the absences of controls, high-density growth leads to increased population exposure to PM2.5 compared with low-density growth scenarios (urban sprawl).

IRF4 rs12203592 functional variant and melanoma survival.

PubMed

Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

2017-04-15

Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour. © 2017 UICC.

A set of 14 DIP-SNP markers to detect unbalanced DNA mixtures.

PubMed

Liu, Zhizhen; Liu, Jinding; Wang, Jiaqi; Chen, Deqing; Liu, Zidong; Shi, Jie; Li, Zeqin; Li, Wenyan; Zhang, Gengqian; Du, Bing

2018-03-04

Unbalanced DNA mixture is still a difficult problem for forensic practice. DIP-STRs are useful markers for detection of minor DNA but they are not widespread in the human genome and having long amplicons. In this study, we proposed a novel type of genetic marker, termed DIP-SNP. DIP-SNP refers to the combination of INDEL and SNP in less than 300bp length of human genome. The multiplex PCR and SNaPshot assay were established for 14 DIP-SNP markers in a Chinese Han population from Shanxi, China. This novel compound marker allows detection of the minor DNA contributor with sensitivity from 1:50 to 1:1000 in a DNA mixture of any gender with 1 ng-10 ng DNA template. Most of the DIP-SNP markers had a relatively high probability of informative alleles with an average I value of 0.33. In all, we proposed DIP-SNP as a novel kind of genetic marker for detection of minor contributor from unbalanced DNA mixture and established the detection method by associating the multiplex PCR and SNaPshot assay. DIP-SNP polymorphisms are promising markers for forensic or clinical mixture examination because they are shorter, widespread and higher sensitive. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of SNP rs16754 of WT1 gene in a series of de novo acute myeloid leukemia patients.

PubMed

Luna, Irene; Such, Esperanza; Cervera, Jose; Barragán, Eva; Jiménez-Velasco, Antonio; Dolz, Sandra; Ibáñez, Mariam; Gómez-Seguí, Inés; López-Pavía, María; Llop, Marta; Fuster, Óscar; Oltra, Silvestre; Moscardó, Federico; Martínez-Cuadrón, David; Senent, M Leonor; Gascón, Adriana; Montesinos, Pau; Martín, Guillermo; Bolufer, Pascual; Sanz, Miguel A

2012-12-01

The single nucleotide polymorphism (SNP) rs16754 of the WT1 gene has been previously described as a possible prognostic marker in normal karyotype acute myeloid leukemia (AML) patients. Nevertheless, the findings in this field are not always reproducible in different series. One hundred and seventy-five adult de novo AML patients were screened with two different methods for the detection of SNP rs16754: high-resolution melting (HRM) and FRET hybridization probes. Direct sequencing was used to validate both techniques. The SNP was detected in 52 out of 175 patients (30 %), both by HRM and hybridization probes. Direct sequencing confirmed that every positive sample in the screening methods had a variation in the DNA sequence. Patients with the wild-type genotype (WT1(AA)) for the SNP rs16754 were significantly younger than those with the heterozygous WT1(AG) genotype. No other difference was observed for baseline characteristic or outcome between patients with or without the SNP. Both techniques are equally reliable and reproducible as screening methods for the detection of the SNP rs16754, allowing for the selection of those samples that will need to be sequenced. We were unable to confirm the suggested favorable outcome of SNP rs16754 in de novo AML.

Activity study of biogenic spherical silver nanoparticles towards microbes and oxidants

NASA Astrophysics Data System (ADS)

Hoskote Anand, Kiran Kumar; Mandal, Badal Kumar

2015-01-01

The eco-friendly approach for the green synthesis of silver nanoparticles (SNP) using Terminalia bellirica (T. bellirica) fruit extract is reported herein. Initially formation of SNP was noticed through visual color change from yellow to reddish brown and further analyzed by surface plasmonic resonance (SPR) band at 429 nm using UV-Vis spectroscopy. Identification of different polyphenols present in T. bellirica extract was done using High Pressure Liquid Chromatography (HPLC). Aqueous T. bellirica extract contains high amount of gallic acid which is major secondary metabolite responsible for the reduction and stabilization process. It was established by analyses of extracts before and after reduction using HPLC. Formation of spherical SNP was characterized by Transmission Electron Microscopy (TEM) analysis. X-ray Diffraction (XRD) study revealed crystalline nature of SNP. Presence of different functional groups on the surface of SNP was evidenced by Fourier Transform Infrared Spectroscopy (FTIR) study. A plausible mechanism of reduction and stabilization processes involved in the synthesis of stable SNP was also explained based on HPLC and FTIR data. In addition, the synthesized SNP was tested for antibacterial and antioxidant activities. SNP showed good antimicrobial activity against both gram positive (S. aureus) and gram negative (E. coli) bacteria. It also showed good antioxidant activity compared to ascorbic acid as standard antioxidant by using standard DPPH method.

Effects of pressing schedule on formation of vertical density profile for MDF panels

Treesearch

Zhiyong Cai; James H. Muehl; Jerrold E. Winandy

2006-01-01

A fundamental understanding of mat consolidation during hot pressing will help to optimize the medium-density fiberboard (MDF) manufacturing process by increasing productivity, improving product quality, and enhancing durability. Effects of panel density, fiber moisture content (MC), and pressing schedule on formation of vertical density profile (VDP) during hot...

Construction of a versatile SNP array for pyramiding useful genes of rice.

PubMed

Kurokawa, Yusuke; Noda, Tomonori; Yamagata, Yoshiyuki; Angeles-Shim, Rosalyn; Sunohara, Hidehiko; Uehara, Kanako; Furuta, Tomoyuki; Nagai, Keisuke; Jena, Kshirod Kumar; Yasui, Hideshi; Yoshimura, Atsushi; Ashikari, Motoyuki; Doi, Kazuyuki

2016-01-01

DNA marker-assisted selection (MAS) has become an indispensable component of breeding. Single nucleotide polymorphisms (SNP) are the most frequent polymorphism in the rice genome. However, SNP markers are not readily employed in MAS because of limitations in genotyping platforms. Here the authors report a Golden Gate SNP array that targets specific genes controlling yield-related traits and biotic stress resistance in rice. As a first step, the SNP genotypes were surveyed in 31 parental varieties using the Affymetrix Rice 44K SNP microarray. The haplotype information for 16 target genes was then converted to the Golden Gate platform with 143-plex markers. Haplotypes for the 14 useful allele are unique and can discriminate among all other varieties. The genotyping consistency between the Affymetrix microarray and the Golden Gate array was 92.8%, and the accuracy of the Golden Gate array was confirmed in 3 F2 segregating populations. The concept of the haplotype-based selection by using the constructed SNP array was proofed. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study

PubMed Central

Rupérez, Azahara I.; Gil-Campos, Mercedes; Leis, Rosaura; Cañete, Ramón; Tojo, Rafael

2017-01-01

Leptin is an endocrine hormone that has a critical role in body weight homoeostasis and mediates its effects via the leptin receptor (LEPR). Common polymorphisms in the genes coding leptin receptors have been associated with metabolic abnormalities. We assessed the association of 28 LEPR polymorphisms with body mass index (BMI) and their relationship with obesity-related phenotypes, inflammation and cardiovascular disease risk biomarkers. A multicentre case-control study was conducted in 522 children (286 with obesity and 236 with normal-BMI). All anthropometric, metabolic factors and biomarkers were higher in children with obesity except apolipoprotein (Apo)-AI, cholesterol, high-density lipoprotein cholesterol (HDL-c), and adiponectin, which were lower in the obesity group; and glucose, low-density lipoprotein cholesterol (LDL-c), and matrix metalloproteinase-9 that did not differ between groups. We identified the associations between rs11208659, rs11804091, rs10157275, rs9436303 and rs1627238, and BMI in the whole population, as well as the association of rs11804091, rs10157275, and rs1327118 with BMI in the female group, although only the rs11804091 remained associated after Bonferroni correction (p = 0.038). This single nucleotide polymorphisms (SNP) was also associated with insulin (p = 0.004), homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.006), quantitative insulin sensitivity check index (QUICKI) (p = 0.005) and adiponectin (p = 0.046) after adjusting for age, Tanner stage and BMI. Our results show a sex-specific association between the rs11804091 and obesity suggesting an influence of this SNP on insulin resistance. PMID:28771179

Polymorphisms in the Estrogen Receptor β (ESR2) Gene Are Associated with Bone Mineral Density in Caucasian Men and Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L.; Peacock, Munro; Johnson, Michelle L.; Lai, Dongbing; Hui, Siu L.; Johnston, C. Conrad; Foroud, Tatiana M.; Econs, Michael J.

2007-01-01

Context A major determinant of osteoporotic fractures is peak bone mineral density (BMD), which is a highly heritable trait. Recently, we identified significant linkage for hip BMD in premenopausal sister pairs at chromosome 14q (LOD score = 3.5), where the estrogen receptor β gene (ESR2) is located. Objective The objective of the study was to determine whether ESR2 polymorphisms are associated with normal BMD variation. Design This was a population‐based genetic association study, using 11 single nucleotide polymorphisms (SNPs) distributed across the ESR2 gene. Setting The study was conducted at an academic research laboratory and medical center. Patients and Other Participants A total of 411 healthy men (aged 18–61 yr) and 1291 healthy premenopausal women (aged 20–50 yr) living in Indiana participated in the study. Intervention(s) There were no interventions. Main Outcome Measure(s) The main outcome measures were SNP genotype distributions and their association with BMD at the femoral neck and lumbar spine. Results Significant association of spine BMD was found with three SNPs in men and one SNP in women (P ≤ 0.05). The conditional linkage analysis using the ESR2 haplotypes showed that the ESR2 gene accounts for, at most, 18% of the original linkage. Conclusions ESR2 polymorphisms are significantly associated with bone mass in both men and women. However, the ESR2 gene is not entirely responsible for our original linkage, and an additional gene(s) in chromosome 14q contributes to the determination of BMD. PMID:16118344

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map.

PubMed

N'Diaye, Amidou; Haile, Jemanesh K; Cory, Aron T; Clarke, Fran R; Clarke, John M; Knox, Ron E; Pozniak, Curtis J

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat.

Dose specification for radiation therapy: dose to water or dose to medium?

NASA Astrophysics Data System (ADS)

Ma, C.-M.; Li, Jinsheng

2011-05-01

The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

Energetics and Birth Rates of Supernova Remnants in the Large Magellanic Cloud

NASA Astrophysics Data System (ADS)

Leahy, D. A.

2017-03-01

Published X-ray emission properties for a sample of 50 supernova remnants (SNRs) in the Large Magellanic Cloud (LMC) are used as input for SNR evolution modeling calculations. The forward shock emission is modeled to obtain the initial explosion energy, age, and circumstellar medium density for each SNR in the sample. The resulting age distribution yields a SNR birthrate of 1/(500 yr) for the LMC. The explosion energy distribution is well fit by a log-normal distribution, with a most-probable explosion energy of 0.5× {10}51 erg, with a 1σ dispersion by a factor of 3 in energy. The circumstellar medium density distribution is broader than the explosion energy distribution, with a most-probable density of ˜0.1 cm-3. The shape of the density distribution can be fit with a log-normal distribution, with incompleteness at high density caused by the shorter evolution times of SNRs.

Review of NASA short-haul studies

NASA Technical Reports Server (NTRS)

Kenyon, G. C.

1975-01-01

The paper summarizes the results of NASA-conducted technological and economic studies of low, medium, and high density short-haul transportation systems. Aircraft concepts considered included CTOL, RTOL, STOL, and general aviation aircraft. For low density systems, it was found that viable air service becomes possible if city pairs are at least 100 km apart and a two-way total travel demand of at least 200 daily passengers exists. Currently available aircraft were found suitable. The medium-density study showed that a 60-passenger twin engine turbofan was the best suited aircraft. For high density systems, STOL appears to be an economically viable means of reducing noise and congestion at major hub airports. Adequate runways 914 m in length or greater either already exist or could be added to most existing major hub airports.

Surface-peaked medium effects in the interaction of nucleons with finite nuclei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguayo, F. J.; Arellano, H. F.

We investigate the asymptotic separation of the optical model potential for nucleon-nucleus scattering in momentum space, where the potential is split into a medium-independent term and another depending exclusively on the gradient of the density-dependent g matrix. This decomposition confines the medium sensitivity of the nucleon-nucleus coupling to the surface of the nucleus. We examine this feature in the context of proton-nucleus scattering at beam energies between 30 and 100 MeV and find that the pn coupling accounts for most of this sensitivity. Additionally, based on this general structure of the optical potential we are able to treat both, themore » medium dependence of the effective interaction and the full mixed density as described by single-particle shell models. The calculated scattering observables agree within 10% with those obtained by Arellano, Brieva, and Love in their momentum-space g-folding approach.« less

Fine coal cleaning via the micro-mag process

DOEpatents

Klima, Mark S.; Maronde, Carl P.; Killmeyer, Richard P.

1991-01-01

A method of cleaning particulate coal which is fed with a dense medium slurry as an inlet feed to a cyclone separator. The coal particle size distribution is in the range of from about 37 microns to about 600 microns. The dense medium comprises water and ferromagnetic particles that have a relative density in the range of from about 4.0 to about 7.0. The ferromagnetic particles of the dense medium have particle sizes of less than about 15 microns and at least a majority of the particle sizes are less than about 5 microns. In the cyclone, the particulate coal and dense-medium slurry is separated into a low gravity product stream and a high gravity produce stream wherein the differential in relative density between the two streams is not greater than about 0.2. The low gravity and high gravity streams are treated to recover the ferromagnetic particles therefrom.

Forensic SNP Genotyping with SNaPshot: Development of a Novel In-house SBE Multiplex SNP Assay.

PubMed

Zar, Mian Sahib; Shahid, Ahmad Ali; Shahzad, Muhammad Saqib; Shin, Kyoung-Jin; Lee, Hwan Young; Lee, Sang-Seob; Israr, Muhammad; Wiegand, Peter; Kulstein, Galina

2018-04-10

This study introduces a newly developed in-house SNaPshot single-base extension (SBE) multiplex assay for forensic single nucleotide polymorphism (SNP) genotyping of fresh and degraded samples. The assay was validated with fresh blood samples from four different populations. In addition, altogether 24 samples from skeletal remains were analyzed with the multiplex. Full SNP profiles could be obtained from 14 specimens, while ten remains showed partial SNP profiles. Minor allele frequencies (MAF) of bone samples and different populations were compared and used for association of skeletal remains with a certain population. The results reveal that the SNPs of the bone samples are genetically close to the Pathan population. The findings show that the new multiplex system can be utilized for SNP genotyping of degraded and forensic relevant skeletal material, enabling to provide additional investigative leads in criminal cases. © 2018 American Academy of Forensic Sciences.

Analysis of operational requirements for medium density air transportation, volume 2

NASA Technical Reports Server (NTRS)

1975-01-01

The medium density air travel market is examined and defined in terms of numbers of people transported per route per day and frequency of service. The operational characteristics for aircraft to serve this market are determined and a basepoint aircraft is designed from which tradeoff studies and parametric variations can be conducted. The impact of the operational characteristics on the air travel system is evaluated along with the economic viability of the study aircraft. Research and technology programs for future study consideration are identified.

What does the fox say? Monitoring antimicrobial resistance in the environment using wild red foxes as an indicator.

PubMed

Mo, Solveig Sølverød; Urdahl, Anne Margrete; Madslien, Knut; Sunde, Marianne; Nesse, Live L; Slettemeås, Jannice Schau; Norström, Madelaine

2018-01-01

The objective of this study was to estimate and compare the occurrence of AMR in wild red foxes in relation to human population densities. Samples from wild red foxes (n = 528) included in the Norwegian monitoring programme on antimicrobial resistance in bacteria from food, feed and animals were included. All samples were divided into three different groups based on population density in the municipality where the foxes were hunted. Of the 528 samples included, 108 (20.5%), 328 (62.1%) and 92 (17.4%) originated from areas with low, medium and high population density, respectively. A single faecal swab was collected from each fox. All samples were plated out on a selective medium for Enterobacteriaceae for culturing followed by inclusion and susceptibility testing of one randomly selected Escherichia coli to assess the overall occurrence of AMR in the Gram-negative bacterial population. Furthermore, the samples were subjected to selective screening for detection of E. coli displaying resistance towards extended-spectrum cephalosporins and fluoroquinolones. In addition, a subset of samples (n = 387) were subjected to selective culturing to detect E. coli resistant to carbapenems and colistin, and enterococci resistant to vancomycin. Of these, 98 (25.3%), 200 (51.7%) and 89 (23.0%) originated from areas with low, medium and high population density, respectively. Overall, the occurrence of AMR in indicator E. coli from wild red foxes originating from areas with different human population densities in Norway was low to moderate (8.8%). The total occurrence of AMR was significantly higher; χ2 (1,N = 336) = 6.53, p = 0.01 in areas with high population density compared to areas with medium population density. Similarly, the occurrence of fluoroquinolone resistant E. coli isolated using selective detection methods was low in areas with low population density and more common in areas with medium or high population density. In conclusion, we found indications that occurrence of AMR in wild red foxes in Norway is associated with human population density. Foxes living in urban areas are more likely to be exposed to AMR bacteria and resistance drivers from food waste, garbage, sewage, waste water and consumption of contaminated prey compared to foxes living in remote areas. The homerange of red fox has been shown to be limited thereby the red fox constitutes a good sentinel for monitoring antimicrobial resistance in the environment. Continuous monitoring on the occurrence of AMR in different wild species, ecological niches and geographical areas can facilitate an increased understanding of the environmental burden of AMR in the environment. Such information is needed to further assess the impact for humans, and enables implementation of possible control measures for AMR in humans, animals and the environment in a true "One Health" approach.

Strategies for repair of white matter: influence of osmolarity and microglia on proliferation and apoptosis of oligodendrocyte precursor cells in different basal culture media.

PubMed

Kleinsimlinghaus, Karolina; Marx, Romy; Serdar, Meray; Bendix, Ivo; Dietzel, Irmgard D

2013-01-01

The aim of the present study has been to obtain high yields of oligodendrocyte precursor cells (OPCs) in culture. This is a first step in facilitation of myelin repair. We show that, in addition to factors, known to promote proliferation, such as basic fibroblast growth factor (FGF-2) and platelet derived growth factor (PDGF) the choice of the basal medium exerts a significant influence on the yield of OPCs in cultures from newborn rats. During a culture period of up to 9 days we observed larger numbers of surviving cells in Dulbecco's Modified Eagle Medium (DMEM), and Roswell Park Memorial Institute Medium (RPMI) compared with Neurobasal Medium (NB). A larger number of A2B5-positive OPCs was found after 6 days in RPMI based media compared with NB. The percentage of bromodeoxyuridine (BrdU)-positive cells was largest in cultures maintained in DMEM and RPMI. The percentage of caspase-3 positive cells was largest in NB, suggesting that this medium inhibits OPC proliferation and favors apoptosis. A difference between NB and DMEM as well as RPMI is the reduced Na(+)-content. The addition of equiosmolar supplements of mannitol or NaCl to NB medium rescued the BrdU-incorporation rate. This suggested that the osmolarity influences the proliferation of OPCs. Plating density as well as residual microglia influence OPC survival, BrdU incorporation, and caspase-3 expression. We found, that high density cultures secrete factors that inhibit BrdU incorporation whereas the presence of additional microglia induces an increase in caspase-3 positive cells, indicative of enhanced apoptosis. An enhanced number of microglia could thus also explain the stronger inhibition of OPC differentiation observed in high density cultures in response to treatment with the cytokines TNF-α and IFN-γ. We conclude that a maximal yield of OPCs is obtained in a medium of an osmolarity higher than 280 mOsm plated at a relatively low density in the presence of as little microglia as technically achievable.

[Isolation and purification of BMScs of GFP transgenic mouse using the method of adhering to cuture plastic in different time].

PubMed

Li, Fu-Qiang; Zhou, Hong-Ying; Yang, Hui-Lun; Xiang, Tao; Mei, Yan; Hu, Huo-Zhen; Wang, Ting-Hua

2006-03-01

To adopt the method of adhering to culture plastic in different time for cultivating and purifying BMSCs of green fluorescent protein (GFP) transgenic mice. Bone marrow cells isolated from GFP transgenic mice are directly planted in culture flask and an exchange of the total volume medium is made at different time. Then the cells adhering to culture plastic are differently counted according to the cell types and are examined by immunohistochemistry using the antibodies of CD44, CD45 and CD54 in three days. Moreover, the cells after the exchange of the total volume medium in 4 hours, 8 hours and 24 hours are selected and successively subcultured down to the fifth passage. Then the result of amplification is calculated and the cells are examined by immunohistochemistry using the antibodies of CD44, CD45 and CD54. With the extending of the time for the first exchange of medium, the density of cells adhering to culture plastic increased accordingly, but the BMSCs proportion decreased. The cells after first exchange of medium in 4 hours had high BMSCs proportion but low BMSCs density, and the cells in 24 hours had high BMSCs density and low BMSCs proportion. However, the cells in 8-10 hours had high BMSCs density and also high BMSCs proportion. The subcultured BMSCs could stably express GFP. The method of adhering to culture plastic in different time for cultivating and purifying BMSCs of GFP transgenic mice is effective. It is suitable to make the first exchange of total volume medium in 8-10 hours. The subcultured cell has the capacity for amplification and will probably be a seed cell for the research of tissue engineering and gene therapy.

Fission fragment excited laser system

DOEpatents

McArthur, David A.; Tollefsrud, Philip B.

1976-01-01

A laser system and method for exciting lasing action in a molecular gas lasing medium which includes cooling the lasing medium to a temperature below about 150 K and injecting fission fragments through the lasing medium so as to preferentially excite low lying vibrational levels of the medium and to cause population inversions therein. The cooled gas lasing medium should have a mass areal density of about 5 .times. 10.sup.-.sup.3 grams/square centimeter, relaxation times of greater than 50 microseconds, and a broad range of excitable vibrational levels which are excitable by molecular collisions.

Fine Mapping of a Clubroot Resistance Gene in Chinese Cabbage Using SNP Markers Identified from Bulked Segregant RNA Sequencing

PubMed Central

Huang, Zhen; Peng, Gary; Liu, Xunjia; Deora, Abhinandan; Falk, Kevin C.; Gossen, Bruce D.; McDonald, Mary R.; Yu, Fengqun

2017-01-01

Clubroot, caused by Plasmodiophora brassicae, is an important disease of canola (Brassica napus) in western Canada and worldwide. In this study, a clubroot resistance gene (Rcr2) was identified and fine mapped in Chinese cabbage cv. “Jazz” using single-nucleotide polymorphisms (SNP) markers identified from bulked segregant RNA sequencing (BSR-Seq) and molecular markers were developed for use in marker assisted selection. In total, 203.9 million raw reads were generated from one pooled resistant (R) and one pooled susceptible (S) sample, and >173,000 polymorphic SNP sites were identified between the R and S samples. One significant peak was observed between 22 and 26 Mb of chromosome A03, which had been predicted by BSR-Seq to contain the causal gene Rcr2. There were 490 polymorphic SNP sites identified in the region. A segregating population consisting of 675 plants was analyzed with 15 SNP sites in the region using the Kompetitive Allele Specific PCR method, and Rcr2 was fine mapped between two SNP markers, SNP_A03_32 and SNP_A03_67 with 0.1 and 0.3 cM from Rcr2, respectively. Five SNP markers co-segregated with Rcr2 in this region. Variants were identified in 14 of 36 genes annotated in the Rcr2 target region. The numbers of poly variants differed among the genes. Four genes encode TIR-NBS-LRR proteins and two of them Bra019410 and Bra019413, had high numbers of polymorphic variants and so are the most likely candidates of Rcr2. PMID:28894454

Novel single nucleotide polymorphisms of the bovine methyltransferase 3b gene and their association with meat quality traits in beef cattle.

PubMed

Liu, X; Guo, X Y; Xu, X Z; Wu, M; Zhang, X; Li, Q; Ma, P P; Zhang, Y; Wang, C Y; Geng, F J; Qin, C H; Liu, L; Shi, W H; Wang, Y C; Yu, Y

2012-08-16

DNA methylation is essential for adipose deposition in mammals. We screened SNPs of the bovine DNA methyltransferase 3b (DNMT3b) gene in Snow Dragon beef, a commercial beef cattle population in China. Nine SNPs were found in the population and three of six novel SNPs were chosen for genotyping and analyzing a possible association with 16 meat quality traits. The frequencies of the alleles and genotypes of the three SNPs in Snow Dragon beef were similar to those in their terminal-paternal breed, Wagyu. Association analysis disclosed that SNP1 was not associated with any of the traits; SNP2 was significantly associated with lean meat color score and chuck short rib score, and SNP3 had a significant effect on dressing percentage and back-fat thickness in the beef population. The individuals with genotype GG for SNP2 had a 25.7% increase in lean meat color score and a 146% increase in chuck short rib score, compared with genotype AA. The cattle with genotype AG for SNP3 had 35.7 and 24% increases in dressing percentage and 28.8 and 29.2% increases in back-fat thickness, compared with genotypes GG and AA, respectively. Genotypic combination analysis revealed significant interactions between SNP1 and SNP2 and between SNP2 and SNP3 for the traits rib-eye area and live weight. We conclude that there is considerable evidence that DNMT3b is a determiner of beef quality traits.

Variable selection models for genomic selection using whole-genome sequence data and singular value decomposition.

PubMed

Meuwissen, Theo H E; Indahl, Ulf G; Ødegård, Jørgen

2017-12-27

Non-linear Bayesian genomic prediction models such as BayesA/B/C/R involve iteration and mostly Markov chain Monte Carlo (MCMC) algorithms, which are computationally expensive, especially when whole-genome sequence (WGS) data are analyzed. Singular value decomposition (SVD) of the genotype matrix can facilitate genomic prediction in large datasets, and can be used to estimate marker effects and their prediction error variances (PEV) in a computationally efficient manner. Here, we developed, implemented, and evaluated a direct, non-iterative method for the estimation of marker effects for the BayesC genomic prediction model. The BayesC model assumes a priori that markers have normally distributed effects with probability [Formula: see text] and no effect with probability (1 - [Formula: see text]). Marker effects and their PEV are estimated by using SVD and the posterior probability of the marker having a non-zero effect is calculated. These posterior probabilities are used to obtain marker-specific effect variances, which are subsequently used to approximate BayesC estimates of marker effects in a linear model. A computer simulation study was conducted to compare alternative genomic prediction methods, where a single reference generation was used to estimate marker effects, which were subsequently used for 10 generations of forward prediction, for which accuracies were evaluated. SVD-based posterior probabilities of markers having non-zero effects were generally lower than MCMC-based posterior probabilities, but for some regions the opposite occurred, resulting in clear signals for QTL-rich regions. The accuracies of breeding values estimated using SVD- and MCMC-based BayesC analyses were similar across the 10 generations of forward prediction. For an intermediate number of generations (2 to 5) of forward prediction, accuracies obtained with the BayesC model tended to be slightly higher than accuracies obtained using the best linear unbiased prediction of SNP effects (SNP-BLUP model). When reducing marker density from WGS data to 30 K, SNP-BLUP tended to yield the highest accuracies, at least in the short term. Based on SVD of the genotype matrix, we developed a direct method for the calculation of BayesC estimates of marker effects. Although SVD- and MCMC-based marker effects differed slightly, their prediction accuracies were similar. Assuming that the SVD of the marker genotype matrix is already performed for other reasons (e.g. for SNP-BLUP), computation times for the BayesC predictions were comparable to those of SNP-BLUP.

A Larger Chocolate Chip-Development of a 15K Theobroma cacao L. SNP Array to Create High-Density Linkage Maps.

PubMed

Livingstone, Donald; Stack, Conrad; Mustiga, Guiliana M; Rodezno, Dayana C; Suarez, Carmen; Amores, Freddy; Feltus, Frank A; Mockaitis, Keithanne; Cornejo, Omar E; Motamayor, Juan C

2017-01-01

Cacao ( Theobroma cacao L.) is an important cash crop in tropical regions around the world and has a rich agronomic history in South America. As a key component in the cosmetic and confectionary industries, millions of people worldwide use products made from cacao, ranging from shampoo to chocolate. An Illumina Infinity II array was created using 13,530 SNPs identified within a small diversity panel of cacao. Of these SNPs, 12,643 derive from variation within annotated cacao genes. The genotypes of 3,072 trees were obtained, including two mapping populations from Ecuador. High-density linkage maps for these two populations were generated and compared to the cacao genome assembly. Phenotypic data from these populations were combined with the linkage maps to identify the QTLs for yield and disease resistance.

POLYMORPHISMS NEAR SOCS3 ARE ASSOCIATED WITH OBESITY AND GLUCOSE HOMEOSTASIS TRAITS IN HISPANIC AMERICANS FROM THE INSULIN RESISTANCE ATHEROSCLEROSIS FAMILY STUDY

PubMed Central

Talbert, Matthew E; Langefeld, Carl D; Ziegler, Julie; Mychaleckyj, Josyf C; Haffner, Steven M; Norris, Jill M; Bowden, Donald W

2009-01-01

The SOCS3 gene product participates in the feedback inhibition of a range of cytokine signals. Most notably, SOCS3 inhibits the functioning of leptin and downstream steps in insulin signaling after being expressed by terminal transcription factors, such as STAT3 and c-fos. The SOCS3 gene is located in the chromosome region 17q24–17q25, previously linked to body mass index (BMI), visceral adipose tissue (VAT), and waist circumference (WAIST) in Hispanic families in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A high density map of 1536 single nucleotide polymorphisms (SNPs) was constructed to cover a portion of the 17q linkage interval in DNA samples from 1425 Hispanic subjects from 90 extended families in IRASFS. Analysis of this dense SNP map data revealed evidence of association of rs9914220 (located 10 kb 5’ of the SOCS3 gene) with BMI, VAT, and WAIST (P-value ranging from 0 003 to 0.017). Using a tagging SNP approach, rs9914220 and 22 additional SOCS3 SNPs were genotyped for genetic association analysis with measures of adiposity and glucose homeostasis. The adiposity phenotypes utilized in association analyses included BMI, WAIST, waist to hip ratio (WHR), subcutaneous adipose tissue (SAT), VAT, and visceral to subcutaneous ratio (VSR). Linkage disequilibrium (LD) calculations revealed three haplotype blocks near SOCS3. Haplotype Block 1 (5’ of SOCS3) contained SNPs consistently associated with BMI, WAIST, WHR, and VAT (P-values ranging from 2.00x10−4 to .036). Haplotype Block 3 contained single-SNPs that were associated with most adiposity traits except for VSR (P-values ranging from 0.002 to 0.047). When trait associated SNPs were included in linkage analyses as covariates, a reduction of VAT LOD score from 1.26 to .76 above the SOCS3 locus (110 cM) was observed. Multi-SNP haplotype testing using the quantitative pedigree disequilibrium test (QPDT) was broadly consistent with the single-SNP associations. In conclusion, these results support a role for SOCS3 genetic variants in human obesity. PMID:19083014

Association, effects and validation of polymorphisms within the NCAPG - LCORL locus located on BTA6 with feed intake, gain, meat and carcass traits in beef cattle

PubMed Central

2011-01-01

Background In a previously reported genome-wide association study based on a high-density bovine SNP genotyping array, 8 SNP were nominally associated (P ≤ 0.003) with average daily gain (ADG) and 3 of these were also associated (P ≤ 0.002) with average daily feed intake (ADFI) in a population of crossbred beef cattle. The SNP were clustered in a 570 kb region around 38 Mb on the draft sequence of bovine chromosome 6 (BTA6), an interval containing several positional and functional candidate genes including the bovine LAP3, NCAPG, and LCORL genes. The goal of the present study was to develop and examine additional markers in this region to optimize the ability to distinguish favorable alleles, with potential to identify functional variation. Results Animals from the original study were genotyped for 47 SNP within or near the gene boundaries of the three candidate genes. Sixteen markers in the NCAPG-LCORL locus displayed significant association with both ADFI and ADG even after stringent correction for multiple testing (P ≤ 005). These markers were evaluated for their effects on meat and carcass traits. The alleles associated with higher ADFI and ADG were also associated with higher hot carcass weight (HCW) and ribeye area (REA), and lower adjusted fat thickness (AFT). A reduced set of markers was genotyped on a separate, crossbred population including genetic contributions from 14 beef cattle breeds. Two of the markers located within the LCORL gene locus remained significant for ADG (P ≤ 0.04). Conclusions Several markers within the NCAPG-LCORL locus were significantly associated with feed intake and body weight gain phenotypes. These markers were also associated with HCW, REA and AFT suggesting that they are involved with lean growth and reduced fat deposition. Additionally, the two markers significant for ADG in the validation population of animals may be more robust for the prediction of ADG and possibly the correlated trait ADFI, across multiple breeds and populations of cattle. PMID:22168586

Novel Genetic Loci Identified for the Pathophysiology of Childhood Obesity in the Hispanic Population

PubMed Central

Comuzzie, Anthony G.; Cole, Shelley A.; Laston, Sandra L.; Voruganti, V. Saroja; Haack, Karin; Gibbs, Richard A.; Butte, Nancy F.

2012-01-01

Genetic variants responsible for susceptibility to obesity and its comorbidities among Hispanic children have not been identified. The VIVA LA FAMILIA Study was designed to genetically map childhood obesity and associated biological processes in the Hispanic population. A genome-wide association study (GWAS) entailed genotyping 1.1 million single nucleotide polymorphisms (SNPs) using the Illumina Infinium technology in 815 children. Measured genotype analysis was performed between genetic markers and obesity-related traits i.e., anthropometry, body composition, growth, metabolites, hormones, inflammation, diet, energy expenditure, substrate utilization and physical activity. Identified genome-wide significant loci: 1) corroborated genes implicated in other studies (MTNR1B, ZNF259/APOA5, XPA/FOXE1 (TTF-2), DARC, CCR3, ABO); 2) localized novel genes in plausible biological pathways (PCSK2, ARHGAP11A, CHRNA3); and 3) revealed novel genes with unknown function in obesity pathogenesis (MATK, COL4A1). Salient findings include a nonsynonymous SNP (rs1056513) in INADL (p = 1.2E-07) for weight; an intronic variant in MTNR1B associated with fasting glucose (p = 3.7E-08); variants in the APOA5-ZNF259 region associated with triglycerides (p = 2.5-4.8E-08); an intronic variant in PCSK2 associated with total antioxidants (p = 7.6E-08); a block of 23 SNPs in XPA/FOXE1 (TTF-2) associated with serum TSH (p = 5.5E-08 to 1.0E-09); a nonsynonymous SNP (p = 1.3E-21), an intronic SNP (p = 3.6E-13) in DARC identified for MCP-1; an intronic variant in ARHGAP11A associated with sleep duration (p = 5.0E-08); and, after adjusting for body weight, variants in MATK for total energy expenditure (p = 2.7E-08) and in CHRNA3 for sleeping energy expenditure (p = 6.0E-08). Unprecedented phenotyping and high-density SNP genotyping enabled localization of novel genetic loci associated with the pathophysiology of childhood obesity. PMID:23251661

Linkage maps of the Atlantic salmon (Salmo salar) genome derived from RAD sequencing

PubMed Central

2014-01-01

Background Genetic linkage maps are useful tools for mapping quantitative trait loci (QTL) influencing variation in traits of interest in a population. Genotyping-by-sequencing approaches such as Restriction-site Associated DNA sequencing (RAD-Seq) now enable the rapid discovery and genotyping of genome-wide SNP markers suitable for the development of dense SNP linkage maps, including in non-model organisms such as Atlantic salmon (Salmo salar). This paper describes the development and characterisation of a high density SNP linkage map based on SbfI RAD-Seq SNP markers from two Atlantic salmon reference families. Results Approximately 6,000 SNPs were assigned to 29 linkage groups, utilising markers from known genomic locations as anchors. Linkage maps were then constructed for the four mapping parents separately. Overall map lengths were comparable between male and female parents, but the distribution of the SNPs showed sex-specific patterns with a greater degree of clustering of sire-segregating SNPs to single chromosome regions. The maps were integrated with the Atlantic salmon draft reference genome contigs, allowing the unique assignment of ~4,000 contigs to a linkage group. 112 genome contigs mapped to two or more linkage groups, highlighting regions of putative homeology within the salmon genome. A comparative genomics analysis with the stickleback reference genome identified putative genes closely linked to approximately half of the ordered SNPs and demonstrated blocks of orthology between the Atlantic salmon and stickleback genomes. A subset of 47 RAD-Seq SNPs were successfully validated using a high-throughput genotyping assay, with a correspondence of 97% between the two assays. Conclusions This Atlantic salmon RAD-Seq linkage map is a resource for salmonid genomics research as genotyping-by-sequencing becomes increasingly common. This is aided by the integration of the SbfI RAD-Seq SNPs with existing reference maps and the draft reference genome, as well as the identification of putative genes proximal to the SNPs. Differences in the distribution of recombination events between the sexes is evident, and regions of homeology have been identified which are reflective of the recent salmonid whole genome duplication. PMID:24571138

Molecular and genealogical analysis of grain dormancy in Japanese wheat varieties, with specific focus on MOTHER OF FT AND TFL1 on chromosome 3A.

PubMed

Chono, Makiko; Matsunaka, Hitoshi; Seki, Masako; Fujita, Masaya; Kiribuchi-Otobe, Chikako; Oda, Shunsuke; Kojima, Hisayo; Nakamura, Shingo

2015-03-01

In the wheat (Triticum aestivum L.) cultivar 'Zenkoujikomugi', a single nucleotide polymorphism (SNP) in the promoter of MOTHER OF FT AND TFL1 on chromosome 3A (MFT-3A) causes an increase in the level of gene expression, resulting in strong grain dormancy. We used a DNA marker to detect the 'Zenkoujikomugi'-type (Zen-type) SNP and examined the genotype of MFT-3A in Japanese wheat varieties, and we found that 169 of 324 varieties carry the Zen-type SNP. In Japanese commercial varieties, the frequency of the Zen-type SNP was remarkably high in the southern part of Japan, but low in the northern part. To examine the relationship between MFT-3A genotype and grain dormancy, we performed a germination assay in three wheat-growing seasons. On average, the varieties carrying the Zen-type SNP showed stronger grain dormancy than the varieties carrying the non-Zen-type SNP. Among commercial cultivars, 'Iwainodaichi' (Kyushu), 'Junreikomugi' (Kinki-Chugoku-Shikoku), 'Kinuhime' (Kanto-Tokai), 'Nebarigoshi' (Tohoku-Hokuriku), and 'Kitamoe' (Hokkaido) showed the strongest grain dormancy in each geographical group, and all these varieties, except for 'Kitamoe', were found to carry the Zen-type SNP. In recent years, the number of varieties carrying the Zen-type SNP has increased in the Tohoku-Hokuriku region, but not in the Hokkaido region.

Two combinatorial optimization problems for SNP discovery using base-specific cleavage and mass spectrometry.

PubMed

Chen, Xin; Wu, Qiong; Sun, Ruimin; Zhang, Louxin

2012-01-01

The discovery of single-nucleotide polymorphisms (SNPs) has important implications in a variety of genetic studies on human diseases and biological functions. One valuable approach proposed for SNP discovery is based on base-specific cleavage and mass spectrometry. However, it is still very challenging to achieve the full potential of this SNP discovery approach. In this study, we formulate two new combinatorial optimization problems. While both problems are aimed at reconstructing the sample sequence that would attain the minimum number of SNPs, they search over different candidate sequence spaces. The first problem, denoted as SNP - MSP, limits its search to sequences whose in silico predicted mass spectra have all their signals contained in the measured mass spectra. In contrast, the second problem, denoted as SNP - MSQ, limits its search to sequences whose in silico predicted mass spectra instead contain all the signals of the measured mass spectra. We present an exact dynamic programming algorithm for solving the SNP - MSP problem and also show that the SNP - MSQ problem is NP-hard by a reduction from a restricted variation of the 3-partition problem. We believe that an efficient solution to either problem above could offer a seamless integration of information in four complementary base-specific cleavage reactions, thereby improving the capability of the underlying biotechnology for sensitive and accurate SNP discovery.

Isolation, characterization, and radiation protection of Sipunculus nudus L. polysaccharide.

PubMed

Li, Na; Shen, Xianrong; Liu, Yuming; Zhang, Junling; He, Ying; Liu, Qiong; Jiang, Dingwen; Zong, Jie; Li, Jiamei; Hou, Dengyong; Chen, Wei; Wang, Qingrong; Luo, Qun; Li, Kexian

2016-02-01

Sipunculus nudus Linnaeus polysaccharide (SNP) was purified from S. nudus L. via NaOH extraction, trichloroacetic acid deproteination, DEAE-cellulose 52 and Sephacryl S-300 chromatography. The monosaccharide analysis and molecular weight was detected with HPLC. FT-IR, 1H spectrum and 13C NMR spectrum were performed to detect the chemical characteristics. The antioxidant activity was assayed in vitro. The radiation protection effects were detected on mice. The results showed that SNP was composed of mannose, rhamnose, galacturonic acid, glucose, arabinose and fucose, and the average molecular weight was 680 kDa. Above the concentration of 10 mg/mL, SNP showed powerful scavenging activity on hydroxyl radical. In the animals irradiated with a 7.5 Gy γ-rays, the 90 mg/kg and the 270 mg/kg SNP groups survived significantly longer than the radiation control group. In the animals irradiated with a 4.0 Gy γ-rays, SNP showed significant protection effect. The contents of DNA in bone marrow cells were significantly increased by SNP treatment, and the micronucleus rates of 30 mg/kg and 270 mg/kg SNP groups were decrease significantly compared to the radiation control group. These findings suggest that SNP possesses marked antioxidant and bone marrow damage protection capacity which play important roles in the prevention of radiation damage. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical Utility of a Coronary Heart Disease Risk Prediction Gene Score in UK Healthy Middle Aged Men and in the Pakistani Population

PubMed Central

Beaney, Katherine E.; Cooper, Jackie A.; Ullah Shahid, Saleem; Ahmed, Waqas; Qamar, Raheel; Drenos, Fotios; Crockard, Martin A.; Humphries, Steve E.

2015-01-01

Background Numerous risk prediction algorithms based on conventional risk factors for Coronary Heart Disease (CHD) are available but provide only modest discrimination. The inclusion of genetic information may improve clinical utility. Methods We tested the use of two gene scores (GS) in the prospective second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases), and Pakistani case-control studies from Islamabad/Rawalpindi (321 cases/228 controls) and Lahore (414 cases/219 controls). The 19-SNP GS included SNPs in loci identified by GWAS and candidate gene studies, while the 13-SNP GS only included SNPs in loci identified by the CARDIoGRAMplusC4D consortium. Results In NPHSII, the mean of both gene scores was higher in those who went on to develop CHD over 13.5 years of follow-up (19-SNP p=0.01, 13-SNP p=7x10-3). In combination with the Framingham algorithm the GSs appeared to show improvement in discrimination (increase in area under the ROC curve, 19-SNP p=0.48, 13-SNP p=0.82) and risk classification (net reclassification improvement (NRI), 19-SNP p=0.28, 13-SNP p=0.42) compared to the Framingham algorithm alone, but these were not statistically significant. When considering only individuals who moved up a risk category with inclusion of the GS, the improvement in risk classification was statistically significant (19-SNP p=0.01, 13-SNP p=0.04). In the Pakistani samples, risk allele frequencies were significantly lower compared to NPHSII for 13/19 SNPs. In the Islamabad study, the mean gene score was higher in cases than controls only for the 13-SNP GS (2.24 v 2.34, p=0.04). There was no association with CHD and either score in the Lahore study. Conclusion The performance of both GSs showed potential clinical utility in European men but much less utility in subjects from Pakistan, suggesting that a different set of risk loci or SNPs may be required for risk prediction in the South Asian population. PMID:26133560

Identification of an Interaction between VWF rs7965413 and Platelet Count as a Novel Risk Marker for Metabolic Syndrome: An Extensive Search of Candidate Polymorphisms in a Case-Control Study

PubMed Central

Nakatochi, Masahiro; Ushida, Yasunori; Yasuda, Yoshinari; Yoshida, Yasuko; Kawai, Shun; Kato, Ryuji; Nakashima, Toru; Iwata, Masamitsu; Kuwatsuka, Yachiyo; Ando, Masahiko; Hamajima, Nobuyuki; Kondo, Takaaki; Oda, Hiroaki; Hayashi, Mutsuharu; Kato, Sawako; Yamaguchi, Makoto; Maruyama, Shoichi; Matsuo, Seiichi; Honda, Hiroyuki

2015-01-01

Although many single nucleotide polymorphisms (SNPs) have been identified to be associated with metabolic syndrome (MetS), there was only a slight improvement in the ability to predict future MetS by the simply addition of SNPs to clinical risk markers. To improve the ability to predict future MetS, combinational effects, such as SNP—SNP interaction, SNP—environment interaction, and SNP—clinical parameter (SNP × CP) interaction should be also considered. We performed a case-control study to explore novel SNP × CP interactions as risk markers for MetS based on health check-up data of Japanese male employees. We selected 99 SNPs that were previously reported to be associated with MetS and components of MetS; subsequently, we genotyped these SNPs from 360 cases and 1983 control subjects. First, we performed logistic regression analyses to assess the association of each SNP with MetS. Of these SNPs, five SNPs were significantly associated with MetS (P < 0.05): LRP2 rs2544390, rs1800592 between UCP1 and TBC1D9, APOA5 rs662799, VWF rs7965413, and rs1411766 between MYO16 and IRS2. Furthermore, we performed multiple logistic regression analyses, including an SNP term, a CP term, and an SNP × CP interaction term for each CP and SNP that was significantly associated with MetS. We identified a novel SNP × CP interaction between rs7965413 and platelet count that was significantly associated with MetS [SNP term: odds ratio (OR) = 0.78, P = 0.004; SNP × CP interaction term: OR = 1.33, P = 0.001]. This association of the SNP × CP interaction with MetS remained nominally significant in multiple logistic regression analysis after adjustment for either the number of MetS components or MetS components excluding obesity. Our results reveal new insight into platelet count as a risk marker for MetS. PMID:25646961

Density profile and fiber alignment in fiberboard from three southern hardwoods

Treesearch

George E. Woodson

1977-01-01

Density profile and fiber orientation were evaluated for their effects on selected mechanical properties of medium density fiberboard. Bending MOE and modulus of rigidity were predicted from density profiles established by x-ray radiography. Orthotropic ratios ranged from 1.19 to 2.32 for electrically aligned fiberboards from three southern hardwoods. Off-axis tensile...

Chapman Enskog-maximum entropy method on time-dependent neutron transport equation

NASA Astrophysics Data System (ADS)

Abdou, M. A.

2006-09-01

The time-dependent neutron transport equation in semi and infinite medium with linear anisotropic and Rayleigh scattering is proposed. The problem is solved by means of the flux-limited, Chapman Enskog-maximum entropy for obtaining the solution of the time-dependent neutron transport. The solution gives the neutron distribution density function which is used to compute numerically the radiant energy density E(x,t), net flux F(x,t) and reflectivity Rf. The behaviour of the approximate flux-limited maximum entropy neutron density function are compared with those found by other theories. Numerical calculations for the radiant energy, net flux and reflectivity of the proposed medium are calculated at different time and space.

Effects of test media on reproduction in Potamopyrgus antipodarum and of pre-exposure population densities on sensitivity to cadmium in a reproduction test.

PubMed

Sieratowicz, Agnes; Schulte-Oehlmann, Ulrike; Wigh, Adriana; Oehlmann, Jörg

2013-01-01

Molluscan species can be affected by various anthropogenic substances. Yet, these effects are disregarded in chemical risk assessment as molluscs are unrepresented in standard OECD guidelines. The project "validation of a mollusc reproduction test" (Federal Environment Agency, code 371165417) deals with the development of a test method with the mudsnail Potamopyrgus antipodarum for OECD purposes. In this context, the influence on reproduction of both, different media and varying snail density, has been observed in independent experiments. Further, the impact of density on the outcome of subsequent cadmium (Cd) toxicity in a test has been investigated to refine the existing methodology. First, adult snails were kept in different test media for 12 weeks. Second, snail density was increased for 4 weeks to induce stress. Snails from each density scenario were used for another 4 weeks in a reproduction test at an equal density with 12 μg Cd/L, respectively. Significant differences in reproduction between medium groups were noted after 4 and 8, but not 12, weeks. Further, reproduction was significantly altered by snail density in the beakers but after subsequent 4 weeks at a constant density, no differences were observed between control groups. Cd reduced reproduction and this effect increased with snail density in the pre-exposure period, demonstrating that a previous stress factor may result in increased sensitivity to chemicals and underlines the need for more standardized breeding conditions to minimize effect variations. Based on the outcome of this study, an acclimatization period of 12 weeks must be guaranteed for specimens transferred to another medium. Further, 4 weeks of acclimatization are necessary after density stress. An additional 12 weeks density experiment showed that medium volume in each replicate can be decreased by half to save on chemicals, water and space during tests.

Conservation of a domestic metapopulation structured into related and partly admixed strains.

PubMed

Ramljak, Jelena; Bunevski, Gjoko; Bytyqi, Hysen; Marković, Božidarka; Brka, Muhamed; Ivanković, Ante; Kume, Kristaq; Stojanović, Srđan; Nikolov, Vasil; Simčič, Mojca; Sölkner, Johann; Kunz, Elisabeth; Rothammer, Sophie; Seichter, Doris; Grünenfelder, Hans-Peter; Broxham, Elli T; Kugler, Waltraud; Medugorac, Ivica

2018-04-01

Preservation of genetic diversity is one of the most pressing challenges in the planetary boundaries concept. Within this context, we focused on genetic diversity in a native, unselected and highly admixed domesticated metapopulation. A set of 1,828 individuals from 60 different cattle breeds was analysed using a medium density SNP chip. Among these breeds, 14 Buša strains formed a metapopulation represented by 350 individuals, while the remaining 46 breeds represented the global cattle population. Genetic analyses showed that the scarcely selected and less differentiated Buša metapopulation contributed a substantial proportion (52.6%) of the neutral allelic diversity to this global taurine population. Consequently, there is an urgent need for synchronized maintenance of this highly fragmented domestic metapopulation, which is distributed over several countries without sophisticated infrastructure and highly endangered by continuous replacement crossing as part of the global genetic homogenization process. This study collected and evaluated samples, data and genomewide information and developed genome-assisted cross-border conservation concepts. To detect and maintain genetic integrity of the metapopulation strains, we designed and applied a composite test that combines six metrics based on additive genetic relationships, a nearest neighbour graph and the distribution of semiprivate alleles. Each metric provides distinct information components about past admixture events and offers an objective and powerful tool for the detection of admixed outliers. The here developed conservation methods and presented experiences could easily be adapted to comparable conservation programmes of domesticated or other metapopulations bred and kept in captivity or under some other sort of human control. © 2018 John Wiley & Sons Ltd.

Development of a rapid SNP-typing assay to differentiate Bifidobacterium animalis ssp. lactis strains used in probiotic-supplemented dairy products.

PubMed

Lomonaco, Sara; Furumoto, Emily J; Loquasto, Joseph R; Morra, Patrizia; Grassi, Ausilia; Roberts, Robert F

2015-02-01

Identification at the genus, species, and strain levels is desirable when a probiotic microorganism is added to foods. Strains of Bifidobacterium animalis ssp. lactis (BAL) are commonly used worldwide in dairy products supplemented with probiotic strains. However, strain discrimination is difficult because of the high degree of genome identity (99.975%) between different genomes of this subspecies. Typing of monomorphic species can be carried out efficiently by targeting informative single nucleotide polymorphisms (SNP). Findings from a previous study analyzing both reference and commercial strains of BAL identified SNP that could be used to discriminate common strains into 8 groups. This paper describes development of a minisequencing assay based on the primer extension reaction (PER) targeting multiple SNP that can allow strain differentiation of BAL. Based on previous data, 6 informative SNP were selected for further testing, and a multiplex preliminary PCR was optimized to amplify the DNA regions containing the selected SNP. Extension primers (EP) annealing immediately adjacent to the selected SNP were developed and tested in simplex and multiplex PER to evaluate their performance. Twenty-five strains belonging to 9 distinct genomic clusters of B. animalis ssp. lactis were selected and analyzed using the developed minisequencing assay, simultaneously targeting the 6 selected SNP. Fragment analysis was subsequently carried out in duplicate and demonstrated that the assay yielded 8 specific profiles separating the most commonly used commercial strains. This novel multiplex PER approach provides a simple, rapid, flexible SNP-based subtyping method for proper characterization and identification of commercial probiotic strains of BAL from fermented dairy products. To assess the usefulness of this method, DNA was extracted from yogurt manufactured with and without the addition of B. animalis ssp. lactis BB-12. Extracted DNA was then subjected to the minisequencing protocol, resulting in a SNP profile matching the profile for the strain BB-12. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction.

PubMed

Buzinari, Tereza Cristina; Oishi, Jorge Camargo; De Moraes, Thiago Francisco; Vatanabe, Izabela Pereira; Selistre-de-Araújo, Heloisa Sobreiro; Pestana, Cezar Rangel; Rodrigues, Gerson Jhonatan

2017-07-15

Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1μM. The detection of intracellular superoxide radical (O 2 •- ) was obtained by using DHE probe. Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O 2 •- in HUVEC cells. The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction. Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Copyright © 2017 Elsevier B.V. All rights reserved.

Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes

PubMed Central

Gong, Bin-Sheng; Zhang, Qing-Pu; Zhang, Guang-Mei; Zhang, Shao-Jun; Zhang, Wei; Lv, Hong-Chao; Zhang, Fan; Lv, Sa-Li; Li, Chuan-Xing; Rao, Shao-Qi; Li, Xia

2007-01-01

Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges. PMID:18466544

SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity.

PubMed

Kumar, Sunil; Ambrosini, Giovanna; Bucher, Philipp

2017-01-04

SNP2TFBS is a computational resource intended to support researchers investigating the molecular mechanisms underlying regulatory variation in the human genome. The database essentially consists of a collection of text files providing specific annotations for human single nucleotide polymorphisms (SNPs), namely whether they are predicted to abolish, create or change the affinity of one or several transcription factor (TF) binding sites. A SNP's effect on TF binding is estimated based on a position weight matrix (PWM) model for the binding specificity of the corresponding factor. These data files are regenerated at regular intervals by an automatic procedure that takes as input a reference genome, a comprehensive SNP catalogue and a collection of PWMs. SNP2TFBS is also accessible over a web interface, enabling users to view the information provided for an individual SNP, to extract SNPs based on various search criteria, to annotate uploaded sets of SNPs or to display statistics about the frequencies of binding sites affected by selected SNPs. Homepage: http://ccg.vital-it.ch/snp2tfbs/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Linkage disequilibrium between STRPs and SNPs across the human genome.

PubMed

Payseur, Bret A; Place, Michael; Weber, James L

2008-05-01

Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this idea, we measured associations between short-tandem-repeat polymorphisms (STRPs), which can mutate rapidly and recurrently, and SNPs in 721 regions across the human genome. We directly compared STRP-SNP LD with SNP-SNP LD from the same genomic regions in the human HapMap populations. The intensity of STRP-SNP LD, measured by the average of D', was reduced, consistent with the action of recurrent mutation. Nevertheless, a higher fraction of STRP-SNP pairs than SNP-SNP pairs showed significant LD, on both short (up to 50 kb) and long (cM) scales. These results reveal the substantial effects of mutational processes on LD at STRPs and provide important measures of the potential of STRPs for association mapping of disease genes.

Modulation of chondrogenic differentiation of human mesenchymal stem cells in jellyfish collagen scaffolds by cell density and culture medium.

PubMed

Pustlauk, W; Paul, B; Brueggemeier, S; Gelinsky, M; Bernhardt, A

2017-06-01

Studies on tissue-engineering approaches for the regeneration of traumatized cartilage focus increasingly on multipotent human mesenchymal stem cells (hMSCs) as an alternative to autologous chondrocytes. The present study applied porous scaffolds made of collagen from the jellyfish Rhopilema esculentum for the in vitro chondrogenic differentiation of hMSCs. Culture conditions in those scaffolds differ from conditions in high-density pellet cultures, making a re-examination of these data necessary. We systematically investigated the influence of seeding density, basic culture media [Dulbecco's modified Eagle's medium (DMEM), α-minimum essential medium (α-MEM)] with varying glucose content and supplementation with fetal calf serum (FCS) or bovine serum albumin (BSA) on the chondrogenic differentiation of hMSCs. Gene expression analyses of selected markers for chondrogenic differentiation and hypertrophic development were conducted. Furthermore, the production of cartilage extracellular matrix (ECM) was analysed by quantification of sulphated glycosaminoglycan and collagen type II contents. The strongest upregulation of chondrogenic markers, along with the highest ECM deposition was observed in scaffolds seeded with 2.4 × 10 6 cells/cm 3 after cultivation in high-glucose DMEM and 0.125% BSA. Lower seeding densities compared to high-density pellet cultures were sufficient to induce in vitro chondrogenic differentiation of hMSCs in collagen scaffolds, which reduces the amount of cells required for the seeding of scaffolds and thus the monolayer expansion period. Furthermore, examination of the impact of FCS and α-MEM on chondrogenic MSC differentiation is an important prerequisite for the development of an osteochondral medium for simultaneous osteogenic and chondrogenic differentiation in biphasic scaffolds for osteochondral tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Variability in sublingual microvessel density and flow measurements in healthy volunteers.

PubMed

Hubble, Sheena M A; Kyte, Hayley L; Gooding, Kim; Shore, Angela C

2009-02-01

As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. Measurements of sublingual capillary density and flow were obtained by recording three 15-second images in 20 healthy volunteers over three days. Two independent observers quantified capillary density by using two methods: total vessel length (mm/mm2) and counting (number/mm). Both intraoral and temporal variabilities within subject and observer reproducibilities were determined by using coefficients of variability and reproducibility indices. For small (1-10 microm), medium (11-20 microm), and large (21-50 microm) diameter, mean vessel density with standard deviations (SDs) in volunteers was 21.3(+/- 4.9), 5.2 (+/- 1.2), and 2.7 (+/- 0.9) mm/mm2, respectively. Also, 94.0 +/- 1.4% of small vessels, 94.5 +/- 1.4% of medium vessels, and 94.5+/- 4.0% of large vessels had continuous perfusion. Within subjects, the means of all measurements over three days varied less than 13, 22, and 35% in small, medium, and large vessels, respectively. Interobserver reproducibility was good, especially for capillary (1-10 microm) density and flow measurements. Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.

Selection of transformation-efficient barley genotypes based on TFA (transformation amenability) haplotype and higher resolution mapping of the TFA loci.

PubMed

Hisano, Hiroshi; Meints, Brigid; Moscou, Matthew J; Cistue, Luis; Echávarri, Begoña; Sato, Kazuhiro; Hayes, Patrick M

2017-04-01

The genetic substitution of transformation amenability alleles from 'Golden Promise' can facilitate the development of transformation-efficient lines from recalcitrant barley cultivars. Barley (Hordeum vulgare) cv. 'Golden Promise' is one of the most useful and well-studied cultivars for genetic manipulation. In a previous report, we identified several transformation amenability (TFA) loci responsible for Agrobacterium-mediated transformation using the F 2 generation of immature embryos, derived from 'Haruna Nijo' × 'Golden Promise,' as explants. In this report, we describe higher density mapping of these TFA regions with additional SNP markers using the same transgenic plants. To demonstrate the robustness of transformability alleles at the TFA loci, we genotyped 202 doubled haploid progeny from the cross 'Golden Promise' × 'Full Pint.' Based on SNP genotype, we selected lines having 'Golden Promise' alleles at TFA loci and used them for transformation. Of the successfully transformed lines, DH120366 came the closest to achieving a level of transformation efficiency comparable to 'Golden Promise.' The results validate that the genetic substitution of TFA alleles from 'Golden Promise' can facilitate the development of transformation-efficient lines from recalcitrant barley cultivars.

Diagnosis of Familial Wolf-Hirschhorn Syndrome due to a Paternal Cryptic Chromosomal Rearrangement by Conventional and Molecular Cytogenetic Techniques

PubMed Central

Venegas-Vega, Carlos A.; Zepeda, Luis M.; Garduño-Zarazúa, Luz M.; Berumen, Jaime; Kofman, Susana; Cervantes, Alicia

2013-01-01

The use of conventional cytogenetic techniques in combination with fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarrays is necessary for the identification of cryptic rearrangements in the diagnosis of chromosomal syndromes. We report two siblings, a boy of 9 years and 9 months of age and his 7-years- and 5-month-old sister, with the classic Wolf-Hirschhorn syndrome (WHS) phenotype. Using high-resolution GTG- and NOR-banding karyotypes, as well as FISH analysis, we characterized a pure 4p deletion in both sibs and a balanced rearrangement in their father, consisting in an insertion of 4p material within a nucleolar organizing region of chromosome 15. Copy number variant (CNV) analysis using SNP arrays showed that both siblings have a similar size of 4p deletion (~6.5 Mb). Our results strongly support the need for conventional cytogenetic and FISH analysis, as well as high-density microarray mapping for the optimal characterization of the genetic imbalance in patients with WHS; parents must always be studied for recognizing cryptic balanced chromosomal rearrangements for an adequate genetic counseling. PMID:23484094

Detecting selection signatures between Duroc and Duroc synthetic pig populations using high-density SNP chip.

PubMed

Edea, Z; Hong, J-K; Jung, J-H; Kim, D-W; Kim, Y-M; Kim, E-S; Shin, S S; Jung, Y C; Kim, K-S

2017-08-01

The development of high throughput genotyping techniques has facilitated the identification of selection signatures of pigs. The detection of genomic selection signals in a population subjected to differential selection pressures may provide insights into the genes associated with economically and biologically important traits. To identify genomic regions under selection, we genotyped 488 Duroc (D) pigs and 155 D × Korean native pigs (DKNPs) using the Porcine SNP70K BeadChip. By applying the F ST and extended haplotype homozygosity (EHH-Rsb) methods, we detected genes under directional selection associated with growth/stature (DOCK7, PLCB4, HS2ST1, FBP2 and TG), carcass and meat quality (TG, COL14A1, FBXO5, NR3C1, SNX7, ARHGAP26 and DPYD), number of teats (LOC100153159 and LRRC1), pigmentation (MME) and ear morphology (SOX5), which are all mostly near or at fixation. These results could be a basis for investigating the underlying mutations associated with observed phenotypic variation. Validation using genome-wide association analysis would also facilitate the inclusion of some of these markers in genetic evaluation programs. © 2017 Stichting International Foundation for Animal Genetics.

Enhanced superconductivity in SnSb under pressure: a first principles study

NASA Astrophysics Data System (ADS)

Sreenivasa Reddy, P. V.; Kanchana, V.

2017-10-01

First principles electronic structure calculations reveal both SnP and SnSb to be stable in the NaCl structure. In SnSb, a first order phase transition from NaCl to CsCl type structure is observed at around 13 GPa, which is also confirmed from enthalpy calculations and agrees well with experimental and other theoretical reports. Calculations of the phonon spectra, and hence the electron-phonon coupling λep and superconducting transition temperature T c, were performed at zero pressure for both the compounds, and at high pressure for SnSb. These calculations report Tc of 0.614 K and 3.083 K for SnP and SnSb respectively, in the NaCl structure—in good agreement with experiment—whilst at the transition pressure, in the CsCl structure, a drastically increased value of T c around 9.18 K (9.74 K at 20 GPa) is found for SnSb, together with a dramatic increase in the electronic density of states at this pressure. The lowest energy acoustic phonon branches in each structure also demonstrate some softening effects, which are well addressed in this work.

A periodic pattern of SNPs in the human genome

PubMed Central

Madsen, Bo Eskerod; Villesen, Palle; Wiuf, Carsten

2007-01-01

By surveying a filtered, high-quality set of SNPs in the human genome, we have found that SNPs positioned 1, 2, 4, 6, or 8 bp apart are more frequent than SNPs positioned 3, 5, 7, or 9 bp apart. The observed pattern is not restricted to genomic regions that are known to cause sequencing or alignment errors, for example, transposable elements (SINE, LINE, and LTR), tandem repeats, and large duplicated regions. However, we found that the pattern is almost entirely confined to what we define as “periodic DNA.” Periodic DNA is a genomic region with a high degree of periodicity in nucleotide usage. It turned out that periodic DNA is mainly small regions (average length 16.9 bp), widely distributed in the genome. Furthermore, periodic DNA has a 1.8 times higher SNP density than the rest of the genome and SNPs inside periodic DNA have a significantly higher genotyping error rate than SNPs outside periodic DNA. Our results suggest that not all SNPs in the human genome are created by independent single nucleotide mutations, and that care should be taken in analysis of SNPs from periodic DNA. The latter may have important consequences for SNP and association studies. PMID:17673700

Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum

PubMed Central

Miles, Alistair; Iqbal, Zamin; Vauterin, Paul; Pearson, Richard; Campino, Susana; Theron, Michel; Gould, Kelda; Mead, Daniel; Drury, Eleanor; O'Brien, John; Ruano Rubio, Valentin; MacInnis, Bronwyn; Mwangi, Jonathan; Samarakoon, Upeka; Ranford-Cartwright, Lisa; Ferdig, Michael; Hayton, Karen; Su, Xin-zhuan; Wellems, Thomas; Rayner, Julian; McVean, Gil; Kwiatkowski, Dominic

2016-01-01

The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of parasite evolution is impeded by the fact that a large fraction of the genome is either highly repetitive or highly variable and thus difficult to analyze using short-read sequencing technologies. Here, we describe a resource of deep sequencing data on parents and progeny from genetic crosses, which has enabled us to perform the first genome-wide, integrated analysis of SNP, indel and complex polymorphisms, using Mendelian error rates as an indicator of genotypic accuracy. These data reveal that indels are exceptionally abundant, being more common than SNPs and thus the dominant mode of polymorphism within the core genome. We use the high density of SNP and indel markers to analyze patterns of meiotic recombination, confirming a high rate of crossover events and providing the first estimates for the rate of non-crossover events and the length of conversion tracts. We observe several instances of meiotic recombination within copy number variants associated with drug resistance, demonstrating a mechanism whereby fitness costs associated with resistance mutations could be compensated and greater phenotypic plasticity could be acquired. PMID:27531718

A phasing and imputation method for pedigreed populations that results in a single-stage genomic evaluation

PubMed Central

2012-01-01

Background Efficient, robust, and accurate genotype imputation algorithms make large-scale application of genomic selection cost effective. An algorithm that imputes alleles or allele probabilities for all animals in the pedigree and for all genotyped single nucleotide polymorphisms (SNP) provides a framework to combine all pedigree, genomic, and phenotypic information into a single-stage genomic evaluation. Methods An algorithm was developed for imputation of genotypes in pedigreed populations that allows imputation for completely ungenotyped animals and for low-density genotyped animals, accommodates a wide variety of pedigree structures for genotyped animals, imputes unmapped SNP, and works for large datasets. The method involves simple phasing rules, long-range phasing and haplotype library imputation and segregation analysis. Results Imputation accuracy was high and computational cost was feasible for datasets with pedigrees of up to 25 000 animals. The resulting single-stage genomic evaluation increased the accuracy of estimated genomic breeding values compared to a scenario in which phenotypes on relatives that were not genotyped were ignored. Conclusions The developed imputation algorithm and software and the resulting single-stage genomic evaluation method provide powerful new ways to exploit imputation and to obtain more accurate genetic evaluations. PMID:22462519

Plasma diagnostics from intensities of resonance line series of He-like ions

NASA Astrophysics Data System (ADS)

Ryazantsev, S. N.; Skobelev, I. Yu.; Faenov, A. Ya.; Grum-Grzhimailo, A. N.; Pikuz, T. A.; Pikuz, S. A.

2017-04-01

The possibility of using the relative intensities of the 1 snp 1P1-1 s 2 1S0 transitions with n = 3-6 in He-like multicharged ions to diagnose plasma in a nonstationary ionization state is considered. The calculations performed for F VIII ions show that, at electron temperatures of T e = 10-100 eV, the intensity ratios are sensitive to the plasma electron density in the range of N e = 1016-1020 cm-3. The universal calculated dependences can be used to diagnose various kinds of recombining or ionizing plasmas containing such ions.

Schlieren System and method for moving objects

NASA Technical Reports Server (NTRS)

Weinstein, Leonard M. (Inventor)

1995-01-01

A system and method are provided for recording density changes in a flow field surrounding a moving object. A mask having an aperture for regulating the passage of images is placed in front of an image recording medium. An optical system is placed in front of the mask. A transition having a light field-of-view and a dark field-of-view is located beyond the test object. The optical system focuses an image of the transition at the mask such that the aperture causes a band of light to be defined on the image recording medium. The optical system further focuses an image of the object through the aperture of the mask so that the image of the object appears on the image recording medium. Relative motion is minimized between the mask and the transition. Relative motion is also minimized between the image recording medium and the image of the object. In this way, the image of the object and density changes in a flow field surrounding the object are recorded on the image recording medium when the object crosses the transition in front of the optical system.

Systematic development and optimization of chemically defined medium supporting high cell density growth of Bacillus coagulans.

PubMed

Chen, Yu; Dong, Fengqing; Wang, Yonghong

2016-09-01

With determined components and experimental reducibility, the chemically defined medium (CDM) and the minimal chemically defined medium (MCDM) are used in many metabolism and regulation studies. This research aimed to develop the chemically defined medium supporting high cell density growth of Bacillus coagulans, which is a promising producer of lactic acid and other bio-chemicals. In this study, a systematic methodology combining the experimental technique with flux balance analysis (FBA) was proposed to design and simplify a CDM. The single omission technique and single addition technique were employed to determine the essential and stimulatory compounds, before the optimization of their concentrations by the statistical method. In addition, to improve the growth rationally, in silico omission and addition were performed by FBA based on the construction of a medium-size metabolic model of B. coagulans 36D1. Thus, CDMs were developed to obtain considerable biomass production of at least five B. coagulans strains, in which two model strains B. coagulans 36D1 and ATCC 7050 were involved.

Coupled granular/continuous medium for thermally stable perpendicular magnetic recording

NASA Astrophysics Data System (ADS)

Sonobe, Y.; Weller, D.; Ikeda, Y.; Takano, K.; Schabes, M. E.; Zeltzer, G.; Do, H.; Yen, B. K.; Best, M. E.

2001-10-01

We studied coupled granular/continuous (CGC) perpendicular media consisting of a continuous multilayer structure and a granular layer. The addition of Co/Pt multilayers decreased the nucleation field from 200 to -1800 Oe and increased the squareness from 0.9 to 1.0. The moment decay at room temperature was significantly reduced from -4.8% to -0.05% per decade. At elevated temperatures, strong exchange coupling between a granular layer and a continuous layer is needed for thermal stability. The exchange-coupled continuous layer reduces thermal demagnetization as it effectively increases the grain size, tightens the grain distribution, and prevents the reversal of individual grains. Magnetic Force Microscope image showed a larger magnetic cluster size for the CGC structure. Compared to the CoCr 18Pt 12 medium, the CGC medium had 2.3 dB higher output. However, the noise for the CGC medium increased with the recording density, while the noise for the CoCr 18Pt 12 medium remained constant from 4 to 15 kfc/mm. Further optimization and noise reduction are still required for future high density recording.

Excitation of Molecular Hydrogen in the Orion Bar Photodissociation Region from a Deep Near-infrared IGRINS Spectrum

NASA Astrophysics Data System (ADS)

Kaplan, Kyle F.; Dinerstein, Harriet L.; Oh, Heeyoung; Mace, Gregory N.; Kim, Hwihyun; Sokal, Kimberly R.; Pavel, Michael D.; Lee, Sungho; Pak, Soojong; Park, Chan; Sok Oh, Jae; Jaffe, Daniel T.

2017-04-01

We present a deep near-infrared spectrum of the Orion Bar Photodissociation Region (PDR) taken with the Immersion Grating INfrared Spectrometer (IGRINS) on the 2.7 m telescope at the McDonald Observatory. IGRINS has high spectral resolution (R˜ {{45,000}}) and instantaneous broad wavelength coverage (1.45-2.45 μm), enabling us to detect 87 emission lines from rovibrationally excited molecular hydrogen (H2) that arise from transitions out of 69 upper rovibration levels of the electronic ground state. These levels cover a large range of rotational and vibrational quantum numbers and excitation energies, making them excellent probes of the excitation mechanisms of H2 and physical conditions within the PDR. The Orion Bar PDR is thought to consist of cooler high density clumps or filaments (T=50{--}250 K, {n}H={10}5{--}{10}7 cm-3) embedded in a warmer lower density medium (T=250{--}1000 K, {n}H={10}4{--}{10}5 cm-3). We fit a grid of constant temperature and density Cloudy models, which recreate the observed H2 level populations well, to constrain the temperature to a range of 600-650 K and the density to {n}H=2.5× {10}3{--}{10}4 cm-3. The best-fit model gives T = 625 K and {n}H=5× {10}3 cm-3. This well-constrained warm temperature is consistent with kinetic temperatures found by other studies for the Orion Bar’s lower density medium. However, the range of densities well fit by the model grid is marginally lower than those reported by other studies. We could be observing lower density gas than the surrounding medium, or perhaps a density-sensitive parameter in our models is not properly estimated.

Optimization of Methods for Articular Cartilage Surface Tissue Engineering: Cell Density and Transforming Growth Factor Beta Are Critical for Self-Assembly and Lubricin Secretion.

PubMed

Iwasa, Kenjiro; Reddi, A Hari

2017-07-01

Lubricin/superficial zone protein (SZP)/proteoglycan4 (PRG4) plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes and synoviocytes of the synovium. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and lubricin secretion as a functional assessment. Superficial zone chondrocytes were cultivated as a monolayer at low, medium, and high densities. Chondrocytes at the three different densities were treated with transforming growth factor beta (TGF-β)1 twice a week or daily, and the accumulated lubricin in the culture medium was analyzed by immunoblots and quantitated by enzyme-linked immunosorbent assay (ELISA). Cell numbers in low and medium densities were increased by TGF-β1; whereas cell numbers in high-density cell cultures were decreased by twice-a-week treatment of TGF-β1. On the other hand, the cell numbers were maintained by daily TGF-β treatment. Immunoblots and quantitation of lubricin by ELISA analysis indicated that TGF-β1 stimulated lubricin secretion by superficial zone chondrocytes at all densities with twice-a-week TGF-β treatment. It is noteworthy that the daily treatment of TGF-β1 increased lubricin much higher compared with twice-a-week treatment. These data demonstrate that daily treatment is optimal for the TGF-β1 response in a higher density of monolayer cultures. These findings have implications for self-assembly of surface zone chondrocytes of articular cartilage for application in tissue engineering of articular cartilage surface.

Electromagnetic energy flux vector for a dispersive linear medium.

PubMed

Crenshaw, Michael E; Akozbek, Neset

2006-05-01

The electromagnetic energy flux vector in a dispersive linear medium is derived from energy conservation and microscopic quantum electrodynamics and is found to be of the Umov form as the product of an electromagnetic energy density and a velocity vector.

Genetic analysis and chromosome mapping of resistance to Fusarium oxysporum f. sp. niveum (FON) race 1 and race 2 in watermelon (Citrullus lanatus L.).

PubMed

Ren, Yi; Di Jiao; Gong, Guoyi; Zhang, Haiying; Guo, Shaogui; Zhang, Jie; Xu, Yong

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp . niveum (FON) is the major soilborne disease of watermelon ( Citrullus lanatus L.). The development and deployment of resistant cultivars is generally considered to be an effective approach to control FW. In this study, an F8 population consisting of 103 recombinant inbred lines derived from a cross between the cultivar 97103 and a wild accession PI 296341-FR was used for FON race 1 and race 2 fungal inoculations. One major QTL on chromosome 1 for FON race 1 resistance was detected with a logarithm of odds of 13.2 and explained phenotypic variation R 2  = 48.1 %; two QTLs of FON race 2 resistance on chromosomes 9 and 10 were discovered based on the high-density integrated genetic map we constructed. The nearest molecular marker should be useful for marker-assisted selection of FON race 1 and race 2 resistance. One receptor kinase, one glucan endo-1,3-β-glucosidase precursors and three acidic chitinase located in the FON-1 QTL genomic region. In Qfon2.1 QTL region, one lipoxygenase gene, five receptor-like kinases and four glutathione S-transferase genes are discovered. One arginine biosynthesis bifunctional protein, two receptor kinase proteins and one lipid-transfer protein located in Qfon2.2 QTL region. Based on SNP analysis by using 20 re-sequenced accessions of watermelon and 231-plant F 2 population generated from Black Diamond × Calhoun Grey, we developed a SNP marker Chr1SNP_502124 for FON-1 detection.

Analysis of the influence of the T393C polymorphism of the GNAS gene on the clinical expression of primary hyperparathyroidism.

PubMed

Piedra, María; Berja, Ana; Ramos, Laura; García-Unzueta, María Teresa; Morán, Jesús Manuel; Ruiz, David; Amado, José Antonio

2017-12-01

The receptor of parathyroid hormone and parathyroid hormone-related-protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney and osteoblasts. It is a G protein-coupled-receptor whose G s α subunit is encoded by the GNAS gene. Our aim was to study whether the single nucleotide polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism (PHPT). An analysis was made of clinical and biochemical parameters and densitometric values in three areas and their relationship with the T393C SNP of the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy controls. Genotyping was performed using the Custom Taqman ® SNP Genotyping assay. The genotype frequencies of GNAS T/C 393 were similar in the control and PHPT groups. No association was found between genotypes and clinical expression of PHPT (renal stones and bone fractures). A nonstatistically significant trend was seen to lower BMD in the lumbar spine, femoral neck, and total hip in both PHPT and control C homozygote subjects. Genetic susceptibility to PHPT related to the GNAS T393C polymorphism or a major influence in its development and clinical expression were found. A C allele-related susceptibility to lower BMD in trabecular bone in both PHPT and control subjects is not sufficient to suggest a more severe clinical expression of PHPT. This trend may be considered as a basis for further studies with larger sample sizes and complementary functional evaluation. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

UPD detection using homozygosity profiling with a SNP genotyping microarray.

PubMed

Papenhausen, Peter; Schwartz, Stuart; Risheg, Hiba; Keitges, Elisabeth; Gadi, Inder; Burnside, Rachel D; Jaswaney, Vikram; Pappas, John; Pasion, Romela; Friedman, Kenneth; Tepperberg, James

2011-04-01

Single nucleotide polymorphism (SNP) based chromosome microarrays provide both a high-density whole genome analysis of copy number and genotype. In the past 21 months we have analyzed over 13,000 samples primarily referred for developmental delay using the Affymetrix SNP/CN 6.0 version array platform. In addition to copy number, we have focused on the relative distribution of allele homozygosity (HZ) throughout the genome to confirm a strong association of uniparental disomy (UPD) with regions of isoallelism found in most confirmed cases of UPD. We sought to determine whether a long contiguous stretch of HZ (LCSH) greater than a threshold value found only in a single chromosome would correlate with UPD of that chromosome. Nine confirmed UPD cases were retrospectively analyzed with the array in the study, each showing the anticipated LCSH with the smallest 13.5 Mb in length. This length is well above the average longest run of HZ in a set of control patients and was then set as the prospective threshold for reporting possible UPD correlation. Ninety-two cases qualified at that threshold, 46 of those had molecular UPD testing and 29 were positive. Including retrospective cases, 16 showed complete HZ across the chromosome, consistent with total isoUPD. The average size LCSH in the 19 cases that were not completely HZ was 46.3 Mb with a range of 13.5-127.8 Mb. Three patients showed only segmental UPD. Both the size and location of the LCSH are relevant to correlation with UPD. Further studies will continue to delineate an optimal threshold for LCSH/UPD correlation. Copyright © 2011 Wiley-Liss, Inc.

Genome–wide association study of carcass weight in commercial Hanwoo cattle

PubMed Central

Edea, Zewdu; Jeoung, Yeong Ho; Shin, Sung-Sub; Ku, Jaeul; Seo, Sungbo; Kim, Il-Hoi; Kim, Sang-Wook

2018-01-01

Objective The objective of the present study was to validate genes and genomic regions associated with carcass weight using a low-density single nucleotide polymorphism (SNP) Chip in Hanwoo cattle breed. Methods Commercial Hanwoo steers (n = 220) were genotyped with 20K GeneSeek genomic profiler BeadChip. After applying the quality control of criteria of a call rate ≥90% and minor allele frequency (MAF) ≥0.01, a total of 15,235 autosomal SNPs were left for genome-wide association (GWA) analysis. The GWA tests were performed using single-locus mixed linear model. Age at slaughter was fitted as fixed effect and sire included as a covariate. The level of genome-wide significance was set at 3.28×10−6 (0.05/15,235), corresponding to Bonferroni correction for 15,235 multiple independent tests. Results By employing EMMAX approach which is based on a mixed linear model and accounts for population stratification and relatedness, we identified 17 and 16 loci significantly (p<0.001) associated with carcass weight for the additive and dominant models, respectively. The second most significant (p = 0.000049) SNP (ARS-BFGL-NGS-28234) on bovine chromosome 4 (BTA4) at 21 Mb had an allele substitution effect of 43.45 kg. Some of the identified regions on BTA2, 6, 14, 22, and 24 were previously reported to be associated with quantitative trait loci for carcass weight in several beef cattle breeds. Conclusion This is the first genome-wide association study using SNP chips on commercial Hanwoo steers, and some of the loci newly identified in this study may help to better DNA markers that determine increased beef production in commercial Hanwoo cattle. Further studies using a larger sample size will allow confirmation of the candidates identified in this study. PMID:29103288