A quantitative method for determining spatial discriminative capacity.

PubMed

Zhang, Zheng; Tannan, Vinay; Holden, Jameson K; Dennis, Robert G; Tommerdahl, Mark

2008-03-10

between two vibrotactile stimulations was degraded as the inter-stimulus distance approached the limit of their two-point spatial discriminative capacity. This degradation of spatial discriminative capacity lessened when an adapting stimulus was used. Performance of the task, as well as improvement on the task with adaptation, would most likely be impaired if the cortical information processing capacity of a subject or subject population were systemically altered, and thus, the methods described could be effective measures for use in clinical or clinical research applications.

Target discrimination method for SAR images based on semisupervised co-training

NASA Astrophysics Data System (ADS)

Wang, Yan; Du, Lan; Dai, Hui

2018-01-01

Synthetic aperture radar (SAR) target discrimination is usually performed in a supervised manner. However, supervised methods for SAR target discrimination may need lots of labeled training samples, whose acquirement is costly, time consuming, and sometimes impossible. This paper proposes an SAR target discrimination method based on semisupervised co-training, which utilizes a limited number of labeled samples and an abundant number of unlabeled samples. First, Lincoln features, widely used in SAR target discrimination, are extracted from the training samples and partitioned into two sets according to their physical meanings. Second, two support vector machine classifiers are iteratively co-trained with the extracted two feature sets based on the co-training algorithm. Finally, the trained classifiers are exploited to classify the test data. The experimental results on real SAR images data not only validate the effectiveness of the proposed method compared with the traditional supervised methods, but also demonstrate the superiority of co-training over self-training, which only uses one feature set.

A rapid, highly accurate method for quantifying CALR mutant allele burden in persons with myeloproliferative neoplasms.

PubMed

Yao, Qiu-Mei; Zhou, Jiao; Gale, Robert Peter; Li, Jin-Lan; Li, Ling-Di; Li, Ning; Chen, Shan-Shan; Ruan, Guo-Rui

2015-10-01

Calreticulin (CALR) mutations were recently identified in a substantial proportion of persons with essential thrombocythemia (ET) and with primary myelofibrosis (PMF) without JAK2(V617F). Consequently rapid, sensitive, and specific methods to detect and quantify these mutations are needed. We studied samples from 1088 persons with myeloproliferative neoplasms (MPNs) including 421 JAK2(V617F) negative subjects with ET, PMF, polycythemia vera (PV), chronic myeloid leukemia (CML) and hyper-eosinophilic syndrome (HES). Detection of CALR exon 9 mutations was done by PCR amplification followed by fragment length analysis and direct sequencing. Dilution assays were used to determine CALR mutant allele burden. We detected CALR mutations in blood and bone marrow samples from 152 subjects with ET and with PMF but not in samples from normal or persons with PV, CML, or HES. CALR mutant peaks were distinct from wild-type peaks and dilution experiments indicated a sensitivity level of 0.5-5% for a CALR mutant allele in a wild-type background. Diverse types of mutations were detected including deletions, insertions, and complex indels. All mutations were confirmed by direct sequencing. We also used dilution experiments to quantify mutant allele burden. We were able to reproducibly detect mutant allele levels as low 5% (0.5-5%) in a wild-type background. PCR amplification followed by fragment length analysis is a rapid, sensitive, and specific method for screening persons with MPNs for CALR mutations, especially those with ET and PMF and for estimating mutant allele burden.

A Wavelet Packet Transform Inspired Method of Neutron-Gamma Discrimination

NASA Astrophysics Data System (ADS)

Shippen, David I.; Joyce, Malcolm J.; Aspinall, Michael D.

2010-10-01

A Simplified Digital Charge Collection (SDCC) method of discrimination between neutron and gamma pulses in an organic scintillator is presented and compared to the Pulse Gradient Analysis (PGA) discrimination method. Data used in this research were gathered from events arising from the 7Li(p,n)7Be reaction detected by an EJ-301 organic liquid scintillator recorded with a fast digital oscilloscope. Time-of-Flight (TOF) data were also recorded and used as a second means of identification. The SDCC method is found to improve on the figure of merit (FOM) given by PGA method at the equivalent sampling rate.

FREQ-Seq: A Rapid, Cost-Effective, Sequencing-Based Method to Determine Allele Frequencies Directly from Mixed Populations

PubMed Central

Delaney, Nigel F.; Marx, Christopher J.

2012-01-01

Understanding evolutionary dynamics within microbial populations requires the ability to accurately follow allele frequencies through time. Here we present a rapid, cost-effective method (FREQ-Seq) that leverages Illumina next-generation sequencing for localized, quantitative allele frequency detection. Analogous to RNA-Seq, FREQ-Seq relies upon counts from the >105 reads generated per locus per time-point to determine allele frequencies. Loci of interest are directly amplified from a mixed population via two rounds of PCR using inexpensive, user-designed oligonucleotides and a bar-coded bridging primer system that can be regenerated in-house. The resulting bar-coded PCR products contain the adapters needed for Illumina sequencing, eliminating further library preparation. We demonstrate the utility of FREQ-Seq by determining the order and dynamics of beneficial alleles that arose as a microbial population, founded with an engineered strain of Methylobacterium, evolved to grow on methanol. Quantifying allele frequencies with minimal bias down to 1% abundance allowed effective analysis of SNPs, small in-dels and insertions of transposable elements. Our data reveal large-scale clonal interference during the early stages of adaptation and illustrate the utility of FREQ-Seq as a cost-effective tool for tracking allele frequencies in populations. PMID:23118913

Assessing Auditory Discrimination Skill of Malay Children Using Computer-based Method.

PubMed

Ting, H; Yunus, J; Mohd Nordin, M Z

2005-01-01

The purpose of this paper is to investigate the auditory discrimination skill of Malay children using computer-based method. Currently, most of the auditory discrimination assessments are conducted manually by Speech-Language Pathologist. These conventional tests are actually general tests of sound discrimination, which do not reflect the client's specific speech sound errors. Thus, we propose computer-based Malay auditory discrimination test to automate the whole process of assessment as well as to customize the test according to the specific speech error sounds of the client. The ability in discriminating voiced and unvoiced Malay speech sounds was studied for the Malay children aged between 7 and 10 years old. The study showed no major difficulty for the children in discriminating the Malay speech sounds except differentiating /g/-/k/ sounds. Averagely the children of 7 years old failed to discriminate /g/-/k/ sounds.

Assessment of imprinting- and genetic variation-dependent monoallelic expression using reciprocal allele descendants between human family trios.

PubMed

Chuang, Trees-Juen; Tseng, Yu-Hsiang; Chen, Chia-Ying; Wang, Yi-Da

2017-08-01

Genomic imprinting is an important epigenetic process that silences one of the parentally-inherited alleles of a gene and thereby exhibits allelic-specific expression (ASE). Detection of human imprinting events is hampered by the infeasibility of the reciprocal mating system in humans and the removal of ASE events arising from non-imprinting factors. Here, we describe a pipeline with the pattern of reciprocal allele descendants (RADs) through genotyping and transcriptome sequencing data across independent parent-offspring trios to discriminate between varied types of ASE (e.g., imprinting, genetic variation-dependent ASE, and random monoallelic expression (RME)). We show that the vast majority of ASE events are due to sequence-dependent genetic variant, which are evolutionarily conserved and may themselves play a cis-regulatory role. Particularly, 74% of non-RAD ASE events, even though they exhibit ASE biases toward the same parentally-inherited allele across different individuals, are derived from genetic variation but not imprinting. We further show that the RME effect may affect the effectiveness of the population-based method for detecting imprinting events and our pipeline can help to distinguish between these two ASE types. Taken together, this study provides a good indicator for categorization of different types of ASE, opening up this widespread and complex mechanism for comprehensive characterization.

A small test of a sequence-based typing method: definition of the B*1520 allele.

PubMed

Domena, J D; Little, A M; Arnett, K L; Adams, E J; Marsh, S G; Parham, P

1994-10-01

Santamaria et al. (Human Immunology 1993 37: 39-50) describe a method of sequence-based typing (SBT) for HLA-A, B and C alleles said to give "unambiguous typing of any sample, heterozygous or homozygous, without requiring additional typing information". From SBT analysis, which involves determination of partial sequences of mixed alleles, these investigators reported that cell lines KT17 (HLA-B35,62) and OLGA (HLA-B62) from the reference panel of the 10th International Histocompatibility Workshop express novel variants of HLA-B15 (B1501-MN6) and HLA-B35 (B3501-MN7) respectively. To study further the novel alleles, we cloned and sequenced full-length HLA-B cDNA clones isolated from the KT17 and OLGA cell lines. We find that KT17 expresses B*3501, as assigned by SBT, and B*1501, the common allele encoding the B62 antigen. We were unable to confirm that KT17 expresses the novel B1501-MN6 variant identified by SBT. For OLGA our analysis confirms the partial sequences obtained by SBT. Thus OLGA expresses B*1501 and a novel HLA-B allele. The complete sequence of the latter shows it is a hybrid having exons 1 and 2 in common with B*1501 and other B15 subtypes and exons 3-7 in common with B*3501 and related molecules including B*5301 and B*5801. The novel allele has been designated B*1520 because of its sequence similarity with the B15 group; furthermore, serological analysis shows that the B*1520 product does not express epitopes in common with either B35, B53 or B58. The B*1520 heavy chain has a similar isoelectric point to A*3101; B*1520 was undetected by previous applications of isoelectric focusing because B*1520 and A31 are both expressed by OLGA. In conclusion, HLA-B typing of two cell lines by cDNA cloning and sequencing gives concordant results with SBT for three of the four alleles. The cause of the discrepancy for the fourth allele is unknown, however, this finding indicates that the novel HLA-A, B and C sequences emerging from SBT studies need independent

Molecular strain typing of Brucella abortus isolates from Italy by two VNTR allele sizing technologies.

PubMed

De Santis, Riccardo; Ancora, Massimo; De Massis, Fabrizio; Ciammaruconi, Andrea; Zilli, Katiuscia; Di Giannatale, Elisabetta; Pittiglio, Valentina; Fillo, Silvia; Lista, Florigio

2013-10-01

Brucellosis, one of the most important re-emerging zoonoses in many countries, is caused by bacteria belonging to the genus Brucella. Furthermore these bacteria represent potential biological warfare agents and the identification of species and biovars of field strains may be crucial for tracing back source of infection, allowing to discriminate naturally occurring outbreaks instead of bioterrorist events. In the last years, multiple-locus variable-number tandem repeat analysis (MLVA) has been proposed as complement of the classical biotyping methods and it has been applied for genotyping large collections of Brucella spp. At present, the MLVA band profiles may be resolved by automated or manual procedures. The Lab on a chip technology represents a valid alternative to standard genotyping techniques (as agarose gel electrophoresis) and it has been previously used for Brucella genotyping. Recently, a new high-throughput genotyping analysis system based on capillary gel electrophoresis, the QIAxcel, has been described. The aim of the study was to evaluate the ability of two DNA sizing equipments, the QIAxcel System and the Lab chip GX, to correctly call alleles at the sixteen loci including one frequently used MLVA assay for Brucella genotyping. The results confirmed that these technologies represent a meaningful advancement in high-throughput Brucella genotyping. Considering the accuracy required to confidently resolve loci discrimination, QIAxcel shows a better ability to measure VNTR allele sizes compared to LabChip GX.

Evaluation of Allele-Specific Somatic Changes of Genome-Wide Association Study Susceptibility Alleles in Human Colorectal Cancers

PubMed Central

Gerber, Madelyn M.; Hampel, Heather; Schulz, Nathan P.; Fernandez, Soledad; Wei, Lai; Zhou, Xiao-Ping; de la Chapelle, Albert; Toland, Amanda Ewart

2012-01-01

Background Tumors frequently exhibit loss of tumor suppressor genes or allelic gains of activated oncogenes. A significant proportion of cancer susceptibility loci in the mouse show somatic losses or gains consistent with the presence of a tumor susceptibility or resistance allele. Thus, allele-specific somatic gains or losses at loci may demarcate the presence of resistance or susceptibility alleles. The goal of this study was to determine if previously mapped susceptibility loci for colorectal cancer show evidence of allele-specific somatic events in colon tumors. Methods We performed quantitative genotyping of 16 single nucleotide polymorphisms (SNPs) showing statistically significant association with colorectal cancer in published genome-wide association studies (GWAS). We genotyped 194 paired normal and colorectal tumor DNA samples and 296 paired validation samples to investigate these SNPs for allele-specific somatic gains and losses. We combined analysis of our data with published data for seven of these SNPs. Results No statistically significant evidence for allele-specific somatic selection was observed for the tested polymorphisms in the discovery set. The rs6983267 variant, which has shown preferential loss of the non-risk T allele and relative gain of the risk G allele in previous studies, favored relative gain of the G allele in the combined discovery and validation samples (corrected p-value = 0.03). When we combined our data with published allele-specific imbalance data for this SNP, the G allele of rs6983267 showed statistically significant evidence of relative retention (p-value = 2.06×10−4). Conclusions Our results suggest that the majority of variants identified as colon cancer susceptibility alleles through GWAS do not exhibit somatic allele-specific imbalance in colon tumors. Our data confirm previously published results showing allele-specific imbalance for rs6983267. These results indicate that allele-specific imbalance of cancer

Allele-specific siRNA knockdown as a personalized treatment strategy for vascular Ehlers-Danlos syndrome in human fibroblasts.

PubMed

Müller, Gerd A; Hansen, Uwe; Xu, Zhi; Griswold, Benjamin; Talan, Mark I; McDonnell, Nazli B; Briest, Wilfried

2012-02-01

The vascular type of the Ehlers-Danlos syndrome (vEDS) is caused by dominant-negative mutations in the procollagen type III (COL3A1) gene. Patients with this autosomal dominant disorder have a shortened life expectancy due to complications from ruptured vessels or hollow organs. We tested the effectiveness of allele-specific RNA interference (RNAi) to reduce the mutated phenotype in fibroblasts. Small-interfering RNAs (siRNAs) discriminating between wild-type and mutant COL3A1 allele were identified by a luciferase reporter gene assay and in primary fibroblasts from a normal donor and a patient with vEDS. The best discriminative siRNA with the mutation at position 10 resulted in >90% silencing of the mutant allele without affecting the wild-type allele. Transmission and immunogold electron microscopy of extracted extracellular matrices from untreated fibroblasts of the patient with vEDS revealed structurally abnormal fibrils. After siRNA treatment, collagen fibrils became similar to fibrils from fibroblasts of normal and COL3A1 haploinsufficient donors. In addition, it was shown that expression of mutated COL3A1 activates the unfolded protein response and that reduction of the amount of mutated protein by siRNA reduces cellular stress. Taken together, the results provide evidence that allele-specific siRNAs are able to reduce negative effects of mutated COL3A1 proteins. Thus, the application of allele-specific RNAi may be a promising direction for future personalized therapies to reduce the severity of vEDS.

Graphical methods for the sensitivity analysis in discriminant analysis

DOE PAGES

Kim, Youngil; Anderson-Cook, Christine M.; Dae-Heung, Jang

2015-09-30

Similar to regression, many measures to detect influential data points in discriminant analysis have been developed. Many follow similar principles as the diagnostic measures used in linear regression in the context of discriminant analysis. Here we focus on the impact on the predicted classification posterior probability when a data point is omitted. The new method is intuitive and easily interpretative compared to existing methods. We also propose a graphical display to show the individual movement of the posterior probability of other data points when a specific data point is omitted. This enables the summaries to capture the overall pattern ofmore » the change.« less

Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder.

PubMed

Le Hellard, Stephanie; Lee, Andrew J; Underwood, Sarah; Thomson, Pippa A; Morris, Stewart W; Torrance, Helen S; Anderson, Susan M; Adams, Richard R; Navarro, Pau; Christoforou, Andrea; Houlihan, Lorna M; Detera-Wadleigh, Sevilla; Owen, Michael J; Asherson, Philip; Muir, Walter J; Blackwood, Douglas H R; Wray, Naomi R; Porteous, David J; Evans, Kathryn L

2007-03-15

Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies.

Allele frequencies of 15 STR loci in Bosnian and Herzegovinian population

PubMed Central

Pilav, Amela; Pojskić, Naris; Ahatović, Anesa; Džehverović, Mirela; Čakar, Jasmina; Marjanović, Damir

2017-01-01

Aim To determine newest the most accurate allele frequencies for 15 short tandem repeat (STR) loci in the Bosnian and Herzegovinian population, calculate statistical parameters, and compare them with the relevant data for seven neighboring populations. Methods Genomic DNA was obtained from buccal swabs of 1000 unrelated individuals from all regions of Bosnia and Herzegovina. Genotyping was performed using PowerPlex® 16 System to obtain allele frequencies for 15 polymorphic STR loci including D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX, and FGA. The calculated allele frequencies were also compared with the data from neighboring populations. Results The highest detected value of polymorphism information content (PIC) was detected at the PentaE locus, whereas the lowest value was detected at the TPOX locus. The power of discrimination (PD) values had similar distribution, with Penta E showing the highest PD of 0.9788. While D18S51 had the highest value of power of exclusion (PE), the lowest PE value was detected at the TPOX locus. Conclusion Upon comparison of Bosnian and Herzegovinian population data with those of seven neighboring populations, the highest allele frequency differentiation was noticed between Bosnian and Herzegovinian and Turkish population at 5 loci, the most informative of which was Penta E. The neighbor-joining dendrogram constructed on the basis of genetic distance showed grouping of Slovenian, Austrian, Hungarian, and Croatian populations. Bosnian and Herzegovinian population was between the mentioned cluster and Serbian population. To determine more accurate distribution of allelic frequencies and forensic parameters, our study included 1000 unrelated individuals from all regions of Bosnia and Herzegovina, and our findings demonstrated the applicability of these markers in both forensics and future population genetic studies. PMID:28613042

Interactive influences of ethnicity, endothelin-1 gene, and everyday discrimination upon nocturnal ambulatory blood pressure.

PubMed

Gregoski, Mathew J; Buxbaum, Sarah G; Kapuku, Gaston; Dong, Yanbin; Zhu, Haidong; Davis, Mary; Gonto, Kelsey; Treiber, Frank A

2013-06-01

Everyday discrimination scale scores are associated with increased ambulatory blood pressure (BP) and reduced nocturnal dipping, and the endothelin-1 (ET-1)/Lys198Asn polymorphism is associated with increased resting BP and exaggerated BP reactivity among African Americans compared to European Americans. Combined influences of these factors on BP control are unknown. This study tested the hypothesis of a three-way interaction between ethnicity, ET-1 carrier status, and everyday discrimination upon ambulatory BP and nocturnal dipping. Baseline laboratory anthropometrics and the everyday discrimination scale were completed by 352 (175 African American) young adult normotensives, followed by 24-h ambulatory BP monitoring. For nocturnal dipping, multiple regression models controlling for age, sex, ethnicity, and body mass index revealed significant three-way ET-1 × everyday discrimination × ethnicity interactions. Specifically, among African American ET-1 T-allele carriers, increases in everyday discrimination led to reduced nocturnal dipping. African Americans that carry the ET-1/Lys198Asn T-allele and report higher everyday discrimination scores may be at particular risk for reduced nocturnal dipping.

Robust Identification of Local Adaptation from Allele Frequencies

PubMed Central

Günther, Torsten; Coop, Graham

2013-01-01

Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of “standardized allele frequencies” that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools—a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org. PMID:23821598

Serologic ambiguity and allelic frequency of the HLA-B40 family in the Korean population.

PubMed

Lee, K W; Kim, Y S

1997-04-01

The most frequently identified HLA-B type in Koreans is HLA-B40 (13.4%). Due to the lack of mono-specific alloantisera and cross reactivity of sera used as typing reagents, discrimination between the serologic splits of B40, B60 and B61, has been a problem in tissue typing laboratories. In this study, an efficient PCR-SSP typing system was established to distinguish B60 and B61 and to assess the difficulty in serologic assignment for these types. The SSP system was also used to elucidate the frequency of B40 alleles (B*4001-B*4008) encoding B40 molecules in the Korean population. Eighty eight unrelated individuals identified serologically as B40 positive were selected from 358 consecutive volunteers from the unrelated bone marrow registry. Seven sets of PCR that amplify exons 2 and 3 of the HLA-B gene using 10 sequence specific primers (SSP) were used for discrimination between B60 and B61, and for B40 allelic typing. A clear discrimination of B60 and B61 was possible in all samples including 48 serologically ambiguous samples (B60-14/48; B61-34/48) and 5 potentially B40 homozygous samples (B60/ B61 heterozygotes-4/5; B60 homozygote-1/5). Therefore, the use of a focused SSP approach enhances serologic definition of HLA types in routine clinical testing. In allelic typing, all B60 samples (26) appeared to be B*4001, but B61 samples revealed more heterogeneity (B*4002-36/58, B*4003-4/ 58, B*4006-18/58). In addition, B*4003 seemed to be closely associated with the A24-Cw3-DRB1*02 haplotype (3/4). The characterization of allele frequency as well as haplotypic association will be helpful in determination of the optimal size of the volunteer marrow donor pool in the Korean population.

Discriminant forest classification method and system

DOEpatents

Chen, Barry Y.; Hanley, William G.; Lemmond, Tracy D.; Hiller, Lawrence J.; Knapp, David A.; Mugge, Marshall J.

2012-11-06

A hybrid machine learning methodology and system for classification that combines classical random forest (RF) methodology with discriminant analysis (DA) techniques to provide enhanced classification capability. A DA technique which uses feature measurements of an object to predict its class membership, such as linear discriminant analysis (LDA) or Andersen-Bahadur linear discriminant technique (AB), is used to split the data at each node in each of its classification trees to train and grow the trees and the forest. When training is finished, a set of n DA-based decision trees of a discriminant forest is produced for use in predicting the classification of new samples of unknown class.

Allele Frequencies for 15 Short Tandem Repeat Loci in Representative Sample of Croatian Population

PubMed Central

Projić, Petar; Škaro, Vedrana; Šamija, Ivana; Pojskić, Naris; Durmić-Pašić, Adaleta; Kovačević, Lejla; Bakal, Narcisa; Primorac, Dragan; Marjanović, Damir

2007-01-01

Aim To study the distribution of allele frequencies of 15 short tandem repeat (STR) loci in a representative sample of the Croatian population. Methods A total of 195 unrelated Caucasian individuals born in Croatia, from 14 counties and the City of Zagreb, were sampled for the analysis. All the tested individuals were voluntary donors. Buccal swab was used as the DNA source. AmpFlSTR® Identifiler® was applied to simultaneously amplify 15 STR loci. Total reaction volume was 12.5 μL. The polymerase chain reaction (PCR) amplification was carried out in PE Gene Amp PCR System Thermal Cycler. Electrophoresis of the amplification products was preformed on an ABI PRISM 3130 Genetic Analyzer. After PCR amplification and separation by electrophoresis, raw data were compiled, analyzed, and numerical allele designations of the profiles were obtained. Deviation from Hardy-Weinberg equilibrium, observed and expected heterozygosity, power of discrimination, and power of exclusion were calculated. Bonferroni’s correction was used before each comparative analysis. Results We compared Croatian data with those obtained from geographically neighboring European populations. The significant difference (at P<0.01) in allele frequencies was recorded only between the Croatian and Slovenian populations for vWA locus. There was no significant deviation from Hardy-Weinberg equilibrium for all the observed loci. Conclusion Obtained population data concurred with the expected “STR data frame” for this part of Europe. PMID:17696301

Frequency of Cry1F resistance alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae) in Brazil.

PubMed

Farias, Juliano R; Andow, David A; Horikoshi, Renato J; Bernardi, Daniel; Ribeiro, Rebeca da S; Nascimento, Antonio Rb do; Santos, Antonio C Dos; Omoto, Celso

2016-12-01

The frequency of resistance alleles is a major factor influencing the rate of resistance evolution. Here, we adapted the F 2 screen procedure for Spodoptera frugiperda (J. E. Smith) with a discriminating concentration assay, and extended associated statistical methods to estimate the frequency of resistance to Cry1F protein in S. frugiperda in Brazil when resistance was not rare. We show that F 2 screen is efficient even when the resistance frequency is 0.250. It was possible to screen 517 isoparental lines from 12 populations sampled in five states of Brazil during the first half of 2012. Western Bahia had the highest allele frequency of Cry1F resistance, 0.192, with a 95% confidence interval (CI) between 0.163 and 0.220. All other states had a similar and lower frequency varying from 0.042 in Paraná to 0.080 in Mato Grosso do Sul. The high frequency in western Bahia may be related to year-round availability of maize, the high population density of S. frugiperda, the lack of refuges and the high adoption rate of Cry1F maize. Cry1F resistance alleles were not rare and occurred at frequencies that have already compromised the useful life of TC1507 maize in western Bahia. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Comparison of discriminant analysis methods: Application to occupational exposure to particulate matter

NASA Astrophysics Data System (ADS)

Ramos, M. Rosário; Carolino, E.; Viegas, Carla; Viegas, Sandra

2016-06-01

Health effects associated with occupational exposure to particulate matter have been studied by several authors. In this study were selected six industries of five different areas: Cork company 1, Cork company 2, poultry, slaughterhouse for cattle, riding arena and production of animal feed. The measurements tool was a portable device for direct reading. This tool provides information on the particle number concentration for six different diameters, namely 0.3 µm, 0.5 µm, 1 µm, 2.5 µm, 5 µm and 10 µm. The focus on these features is because they might be more closely related with adverse health effects. The aim is to identify the particles that better discriminate the industries, with the ultimate goal of classifying industries regarding potential negative effects on workers' health. Several methods of discriminant analysis were applied to data of occupational exposure to particulate matter and compared with respect to classification accuracy. The selected methods were linear discriminant analyses (LDA); linear quadratic discriminant analysis (QDA), robust linear discriminant analysis with selected estimators (MLE (Maximum Likelihood Estimators), MVE (Minimum Volume Elipsoid), "t", MCD (Minimum Covariance Determinant), MCD-A, MCD-B), multinomial logistic regression and artificial neural networks (ANN). The predictive accuracy of the methods was accessed through a simulation study. ANN yielded the highest rate of classification accuracy in the data set under study. Results indicate that the particle number concentration of diameter size 0.5 µm is the parameter that better discriminates industries.

Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems.

PubMed

Brody, Gene H; Beach, Steven R H; Chen, Yi-Fu; Obasi, Ezemenari; Philibert, Robert A; Kogan, Steven M; Simons, Ronald L

2011-05-01

This study examined the prospective relations of adolescents' perceptions of discrimination and their genetic status with increases in conduct problems. Participants were 461 African American youths residing in rural Georgia (Wave 1 mean age = 15.5 years) who provided three waves of data and a saliva sample from which a polymorphism in the SCL6A4 (serotonin transporter [5-HTT]) gene polymorphism known as the 5-HTT linked promoter region (5-HTTLPR) was genotyped. Data analyses using growth curve modeling indicated that perceived discrimination was significantly related to the slope of conduct problems. As hypothesized, interactions between perceived discrimination and genetic status emerged for male but not female youths. Compared with those carrying two copies of the long allele variant of 5-HTTLPR, male youths carrying one or two copies of its short allele variant evinced higher rates of conduct problems over time when they perceived high levels of racial discrimination. These findings are consistent with resilience and differential susceptibility propositions stating that genes can both foster sensitivity to adverse events and confer protection from those events.

Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for LDLR and Myocardial Infarction

PubMed Central

Schuberth, Christian; Won, Hong-Hee; Blattmann, Peter; Joggerst-Thomalla, Brigitte; Theiss, Susanne; Asselta, Rosanna; Duga, Stefano; Merlini, Pier Angelica; Ardissino, Diego; Lander, Eric S.; Gabriel, Stacey; Rader, Daniel J.; Peloso, Gina M.; Kathiresan, Sekar; Runz, Heiko

2015-01-01

A fundamental challenge to contemporary genetics is to distinguish rare missense alleles that disrupt protein functions from the majority of alleles neutral on protein activities. High-throughput experimental tools to securely discriminate between disruptive and non-disruptive missense alleles are currently missing. Here we establish a scalable cell-based strategy to profile the biological effects and likely disease relevance of rare missense variants in vitro. We apply this strategy to systematically characterize missense alleles in the low-density lipoprotein receptor (LDLR) gene identified through exome sequencing of 3,235 individuals and exome-chip profiling of 39,186 individuals. Our strategy reliably identifies disruptive missense alleles, and disruptive-allele carriers have higher plasma LDL-cholesterol (LDL-C). Importantly, considering experimental data refined the risk of rare LDLR allele carriers from 4.5- to 25.3-fold for high LDL-C, and from 2.1- to 20-fold for early-onset myocardial infarction. Our study generates proof-of-concept that systematic functional variant profiling may empower rare variant-association studies by orders of magnitude. PMID:25647241

Automated Discrimination Method of Muscular and Subcutaneous Fat Layers Based on Tissue Elasticity

NASA Astrophysics Data System (ADS)

Inoue, Masahiro; Fukuda, Osamu; Tsubai, Masayoshi; Muraki, Satoshi; Okumura, Hiroshi; Arai, Kohei

Balance between human body composition, e.g. bones, muscles, and fat, is a major and basic indicator of personal health. Body composition analysis using ultrasound has been developed rapidly. However, interpretation of echo signal is conducted manually, and accuracy and confidence in interpretation requires experience. This paper proposes an automated discrimination method of tissue boundaries for measuring the thickness of subcutaneous fat and muscular layers. A portable one-dimensional ultrasound device was used in this study. The proposed method discriminated tissue boundaries based on tissue elasticity. Validity of the proposed method was evaluated in twenty-one subjects (twelve women, nine men; aged 20-70 yr) at three anatomical sites. Experimental results show that the proposed method can achieve considerably high discrimination performance.

Comparison of allelic discrimination by dHPLC, HRM, and TaqMan in the detection of BRAF mutation V600E.

PubMed

Carbonell, Pablo; Turpin, María C; Torres-Moreno, Daniel; Molina-Martínez, Irene; García-Solano, José; Perez-Guillermo, Miguel; Conesa-Zamora, Pablo

2011-09-01

The V600E mutation in the BRAF oncogene is associated with colorectal carcinomas, with mismatch-repair deficiency and, recently, with nonresponse to epidermal growth factor receptor inhibitor therapy. The use of reliable techniques for its detection is important. The aim of our study was to compare the performance characteristics in V600E detection of denaturing high-performance liquid chromatography (dHPLC) and high-resolution melting (HRM) with TaqMan allelic discrimination as well as direct-sequencing methods in a series of 195 colorectal paraffin-embedded specimens up to the age of 15 years. The effectiveness for obtaining results on mutation status was best using TaqMan (96.9%), followed by dHPLC (93.3%), HRM (88.7%), and sequencing (88.2%). In general, TaqMan was best for analyzing older tissues, whereas sequencing was the least efficient. Heterozygotic V600E was detected in 11.6%, 9.9%, 11.6%, and 9.9% of tissues using TaqMan, dHPLC, HRM, and sequencing, respectively. Result concordances between dHPLC and TaqMan or sequencing were excellent (κ = 0.9411 and κ = 0.8988, respectively); for HRM, the concordances were good (κ = 0.7973 and κ = 0.7488, respectively). By using DNA dilutions from tumor tissue, a minimum of 10% of V600E harboring cancer content was required for the analysis by dHPLC and HRM. dHPLC could detect four non-V600E mutations, whereas HRM detected one. Our results indicate that dHPLC and HRM are techniques that can be reliably used for the detection of the BRAFV600E mutation in archival paraffin-embedded tissues. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Indonesian palm civet coffee discrimination using UV-visible spectroscopy and several chemometrics methods

NASA Astrophysics Data System (ADS)

Yulia, M.; Suhandy, D.

2017-05-01

Indonesian palm civet coffee or kopi luwak (Indonesian words for coffee and palm civet) is well known as the world’s priciest and rarest coffee. To protect the authenticity of luwak coffee and protect consumer from luwak coffee adulteration, it is very important to develop a simple and inexpensive method to discriminate between civet and non-civet coffee. The discrimination between civet and non-civet coffee in ground roasted (powder) samples is very challenging since it is very difficult to distinguish between the two by using conventional method. In this research, the use of UV-Visible spectra combined with two chemometric methods, SIMCA and PLS-DA, was evaluated to discriminate civet and non-civet ground coffee samples. The spectral data of civet and non-civet coffee were acquired using UV-Vis spectrometer (Genesys™ 10S UV-Vis, Thermo Scientific, USA). The result shows that using both supervised discrimination methods: SIMCA and PLS-DA, all samples were correctly classified into their corresponding classes with 100% rate for accuracy, sensitivity and specificity, respectively.

Fast discrimination of hydroxypropyl methyl cellulose using portable Raman spectrometer and multivariate methods

NASA Astrophysics Data System (ADS)

Song, Biao; Lu, Dan; Peng, Ming; Li, Xia; Zou, Ye; Huang, Meizhen; Lu, Feng

2017-02-01

Raman spectroscopy is developed as a fast and non-destructive method for the discrimination and classification of hydroxypropyl methyl cellulose (HPMC) samples. 44 E series and 41 K series of HPMC samples are measured by a self-developed portable Raman spectrometer (Hx-Raman) which is excited by a 785 nm diode laser and the spectrum range is 200-2700 cm-1 with a resolution (FWHM) of 6 cm-1. Multivariate analysis is applied for discrimination of E series from K series. By methods of principal components analysis (PCA) and Fisher discriminant analysis (FDA), a discrimination result with sensitivity of 90.91% and specificity of 95.12% is achieved. The corresponding receiver operating characteristic (ROC) is 0.99, indicting the accuracy of the predictive model. This result demonstrates the prospect of portable Raman spectrometer for rapid, non-destructive classification and discrimination of E series and K series samples of HPMC.

Allelic-based gene-gene interaction associated with quantitative traits.

PubMed

Jung, Jeesun; Sun, Bin; Kwon, Deukwoo; Koller, Daniel L; Foroud, Tatiana M

2009-05-01

Recent studies have shown that quantitative phenotypes may be influenced not only by multiple single nucleotide polymorphisms (SNPs) within a gene but also by the interaction between SNPs at unlinked genes. We propose a new statistical approach that can detect gene-gene interactions at the allelic level which contribute to the phenotypic variation in a quantitative trait. By testing for the association of allelic combinations at multiple unlinked loci with a quantitative trait, we can detect the SNP allelic interaction whether or not it can be detected as a main effect. Our proposed method assigns a score to unrelated subjects according to their allelic combination inferred from observed genotypes at two or more unlinked SNPs, and then tests for the association of the allelic score with a quantitative trait. To investigate the statistical properties of the proposed method, we performed a simulation study to estimate type I error rates and power and demonstrated that this allelic approach achieves greater power than the more commonly used genotypic approach to test for gene-gene interaction. As an example, the proposed method was applied to data obtained as part of a candidate gene study of sodium retention by the kidney. We found that this method detects an interaction between the calcium-sensing receptor gene (CaSR), the chloride channel gene (CLCNKB) and the Na, K, 2Cl cotransporter gene (CLC12A1) that contributes to variation in diastolic blood pressure.

Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

PubMed

Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

2015-07-01

Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population

Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts.

PubMed

Bouwman, Aniek C; Hayes, Ben J; Calus, Mario P L

2017-10-30

Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of allele counts results in less shrinkage towards the mean for low minor allele frequency (MAF) variants. Scaling may become relevant for estimating ASE as more low MAF variants will be used in genomic evaluations. We show the impact of scaling on estimates of ASE using real data and a theoretical framework, and in terms of power, model fit and predictive performance. In a dairy cattle dataset with 630 K SNP genotypes, the correlation between DGV for stature from a random regression model using centered allele counts (RRc) and centered and scaled allele counts (RRcs) was 0.9988, whereas the overall correlation between ASE using RRc and RRcs was 0.27. The main difference in ASE between both methods was found for SNPs with a MAF lower than 0.01. Both the ratio (ASE from RRcs/ASE from RRc) and the regression coefficient (regression of ASE from RRcs on ASE from RRc) were much higher than 1 for low MAF SNPs. Derived equations showed that scenarios with a high heritability, a large number of individuals and a small number of variants have lower ratios between ASE from RRc and RRcs. We also investigated the optimal scaling parameter [from - 1 (RRcs) to 0 (RRc) in steps of 0.1] in the bovine stature dataset. We found that the log-likelihood was maximized with a scaling parameter of - 0.8, while the mean squared error of prediction was minimized with a scaling parameter of - 1, i.e., RRcs. Large differences in estimated ASE were observed for low MAF SNPs when allele counts were scaled or not scaled because there is less shrinkage towards the mean for scaled allele counts. We derived a theoretical framework that shows that the difference in ASE due to shrinkage is heavily influenced by the

ALEA: a toolbox for allele-specific epigenomics analysis.

PubMed

Younesy, Hamid; Möller, Torsten; Heravi-Moussavi, Alireza; Cheng, Jeffrey B; Costello, Joseph F; Lorincz, Matthew C; Karimi, Mohammad M; Jones, Steven J M

2014-04-15

The assessment of expression and epigenomic status using sequencing based methods provides an unprecedented opportunity to identify and correlate allelic differences with epigenomic status. We present ALEA, a computational toolbox for allele-specific epigenomics analysis, which incorporates allelic variation data within existing resources, allowing for the identification of significant associations between epigenetic modifications and specific allelic variants in human and mouse cells. ALEA provides a customizable pipeline of command line tools for allele-specific analysis of next-generation sequencing data (ChIP-seq, RNA-seq, etc.) that takes the raw sequencing data and produces separate allelic tracks ready to be viewed on genome browsers. The pipeline has been validated using human and hybrid mouse ChIP-seq and RNA-seq data. The package, test data and usage instructions are available online at http://www.bcgsc.ca/platform/bioinfo/software/alea CONTACT: : mkarimi1@interchange.ubc.ca or sjones@bcgsc.ca Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Discriminative power of Campylobacter phenotypic and genotypic typing methods.

PubMed

Duarte, Alexandra; Seliwiorstow, Tomasz; Miller, William G; De Zutter, Lieven; Uyttendaele, Mieke; Dierick, Katelijne; Botteldoorn, Nadine

2016-06-01

The aim of this study was to compare different typing methods, individually and combined, for use in the monitoring of Campylobacter in food. Campylobacter jejuni (n=94) and Campylobacter coli (n=52) isolated from different broiler meat carcasses were characterized using multilocus sequence typing (MLST), flagellin gene A restriction fragment length polymorphism typing (flaA-RFLP), antimicrobial resistance profiling (AMRp), the presence/absence of 5 putative virulence genes; and, exclusively for C. jejuni, the determination of lipooligosaccharide (LOS) class. Discriminatory power was calculated by the Simpson's index of diversity (SID) and the congruence was measured by the adjusted Rand index and adjusted Wallace coefficient. MLST was individually the most discriminative typing method for both C. jejuni (SID=0.981) and C. coli (SID=0.957). The most discriminative combination with a SID of 0.992 for both C. jejuni and C. coli was obtained by combining MLST with flaA-RFLP. The combination of MLST with flaA-RFLP is an easy and feasible typing method for short-term monitoring of Campylobacter in broiler meat carcass. Copyright © 2016 Elsevier B.V. All rights reserved.

Implementation and validation of an improved allele specific stutter filtering method for electropherogram interpretation.

PubMed

Kalafut, Tim; Schuerman, Curt; Sutton, Joel; Faris, Tom; Armogida, Luigi; Bright, Jo-Anne; Buckleton, John; Taylor, Duncan

2018-03-31

Modern probabilistic genotyping (PG) software is capable of modeling stutter as part of the profile weighting statistic. This allows for peaks in stutter positions to be considered as allelic or stutter or both. However, prior to running any sample through a PG calculator, the examiner must first interpret the sample, considering such things as artifacts and number of contributors (NOC or N). Stutter can play a major role both during the assignment of the number of contributors, and the assessment of inclusion and exclusion. If stutter peaks are not filtered when they should be, it can lead to the assignment of an additional contributor, causing N contributors to be assigned as N + 1. If peaks in the stutter position of a major contributor are filtered using a threshold that is too high, true alleles of minor contributors can be lost. Until now, the software used to view the electropherogram stutter filters are based on a locus specific model. Combined stutter peaks occur when a peak could be the result of both back stutter (stutter one repeat shorter than the allele) and forward stutter (stutter one repeat unit larger than the allele). This can challenge existing filters. We present here a novel stutter filter model in the ArmedXpert™ software package that uses a linear model based on allele for back stutter and applies an additive filter for combined stutter. We term this the allele specific stutter model (AM). We compared AM with a traditional model based on locus specific stutter filters (termed LM). This improved stutter model has the benefit of: Instances of over filtering were reduced 78% from 101 for a traditional model (LM) to 22 for the allele specific model (AM) when scored against each other. Instances of under filtering were reduced 80% from 85 (LM) to 17 (AM) when scored against ground truth mixtures. Published by Elsevier B.V.

Automated fine structure image analysis method for discrimination of diabetic retinopathy stage using conjunctival microvasculature images

PubMed Central

Khansari, Maziyar M; O’Neill, William; Penn, Richard; Chau, Felix; Blair, Norman P; Shahidi, Mahnaz

2016-01-01

The conjunctiva is a densely vascularized mucus membrane covering the sclera of the eye with a unique advantage of accessibility for direct visualization and non-invasive imaging. The purpose of this study is to apply an automated quantitative method for discrimination of different stages of diabetic retinopathy (DR) using conjunctival microvasculature images. Fine structural analysis of conjunctival microvasculature images was performed by ordinary least square regression and Fisher linear discriminant analysis. Conjunctival images between groups of non-diabetic and diabetic subjects at different stages of DR were discriminated. The automated method’s discriminate rates were higher than those determined by human observers. The method allowed sensitive and rapid discrimination by assessment of conjunctival microvasculature images and can be potentially useful for DR screening and monitoring. PMID:27446692

Kennard-Stone combined with least square support vector machine method for noncontact discriminating human blood species

NASA Astrophysics Data System (ADS)

Zhang, Linna; Li, Gang; Sun, Meixiu; Li, Hongxiao; Wang, Zhennan; Li, Yingxin; Lin, Ling

2017-11-01

Identifying whole bloods to be either human or nonhuman is an important responsibility for import-export ports and inspection and quarantine departments. Analytical methods and DNA testing methods are usually destructive. Previous studies demonstrated that visible diffuse reflectance spectroscopy method can realize noncontact human and nonhuman blood discrimination. An appropriate method for calibration set selection was very important for a robust quantitative model. In this paper, Random Selection (RS) method and Kennard-Stone (KS) method was applied in selecting samples for calibration set. Moreover, proper stoichiometry method can be greatly beneficial for improving the performance of classification model or quantification model. Partial Least Square Discrimination Analysis (PLSDA) method was commonly used in identification of blood species with spectroscopy methods. Least Square Support Vector Machine (LSSVM) was proved to be perfect for discrimination analysis. In this research, PLSDA method and LSSVM method was used for human blood discrimination. Compared with the results of PLSDA method, this method could enhance the performance of identified models. The overall results convinced that LSSVM method was more feasible for identifying human and animal blood species, and sufficiently demonstrated LSSVM method was a reliable and robust method for human blood identification, and can be more effective and accurate.

A Discriminant Distance Based Composite Vector Selection Method for Odor Classification

PubMed Central

Choi, Sang-Il; Jeong, Gu-Min

2014-01-01

We present a composite vector selection method for an effective electronic nose system that performs well even in noisy environments. Each composite vector generated from a electronic nose data sample is evaluated by computing the discriminant distance. By quantitatively measuring the amount of discriminative information in each composite vector, composite vectors containing informative variables can be distinguished and the final composite features for odor classification are extracted using the selected composite vectors. Using the only informative composite vectors can be also helpful to extract better composite features instead of using all the generated composite vectors. Experimental results with different volatile organic compound data show that the proposed system has good classification performance even in a noisy environment compared to other methods. PMID:24747735

Use of allele scores as instrumental variables for Mendelian randomization

PubMed Central

Burgess, Stephen; Thompson, Simon G

2013-01-01

Background An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Methods Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate ‘weak instrument’ bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Results Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Conclusions Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score. PMID:24062299

QuASAR: quantitative allele-specific analysis of reads.

PubMed

Harvey, Chris T; Moyerbrailean, Gregory A; Davis, Gordon O; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

2015-04-15

Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. http://github.com/piquelab/QuASAR. fluca@wayne.edu or rpique@wayne.edu Supplementary Material is available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

QuASAR: quantitative allele-specific analysis of reads

PubMed Central

Harvey, Chris T.; Moyerbrailean, Gregory A.; Davis, Gordon O.; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

2015-01-01

Motivation: Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. Results: We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. Availability and implementation: http://github.com/piquelab/QuASAR. Contact: fluca@wayne.edu or rpique@wayne.edu Supplementary information: Supplementary Material is available at Bioinformatics online. PMID:25480375

Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.

PubMed

Picanço, Juliane Bentes; Raimann, Paulo Eduardo; Motta, Carlos Henrique Ares Silveira da; Rodenbusch, Rodrigo; Gusmão, Leonor; Alho, Clarice Sampaio

2015-05-01

Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation of 16 SNPs allele-specific to quantify post hSCT chimerism by SYBR green-based qRT-PCR.

PubMed

Almeida, Carlos Arthur Cardoso; Dreyfuss, Juliana Luporini; Azevedo-Shimmoto, Marily Maria; Figueiredo, Maria Stela; de Oliveira, José Salvador Rodrigues

2013-03-01

The importance of monitoring post haematopoietic stem cell transplantation (hSCT) chimerism has been defined in numerous publications. Single-nucleotide polymorphisms (SNPs) are molecular markers that vary significantly among different populations. Allied to a very sensible technique, SNP assays seem to be very sensitive (0.001%) when post hSCT chimerism is measured. However, well known SNP frequencies are limited to certain populations, mainly in countries where there is a high level of diversity in its population, therefore restricting their use worldwide. Amplification by SYBR green based quantitative real time PCR of eight pairs of allele-specific SNPs (MLH-1, PECAM-1, ICAM-1, SUR-1, HA-1, rs715405, rs713503, rs2296600) was conducted in 88 patient/donor pairs, who underwent allogeneic myeloablative or non-myeloablative hSCT. One informative allele was detected in at least 42% (n=37) of the samples; 20% (n=18) had at least two informative alleles; 10% (n=9) had at least three informative alleles; 9% (n=8) had more than three informative alleles and 18% (n=16) showed no informative allele at all. Overall, the frequency of informative alleles for these SNPs in the Brazilian population was very low. Consequently, the amount of information attained reached 9% of those expected, being able to discriminate only eight pairs of donor/recipient samples with more than three informative alleles, making them useless for the quantification of chimerism in our routine.

L-RCA (ligation-rolling circle amplification): a general method for genotyping of single nucleotide polymorphisms (SNPs)

PubMed Central

Qi, Xiaoquan; Bakht, Saleha; Devos, Katrien M.; Gale, Mike D.; Osbourn, Anne

2001-01-01

A flexible, non-gel-based single nucleotide polymorphism (SNP) detection method is described. The method adopts thermostable ligation for allele discrimination and rolling circle amplification (RCA) for signal enhancement. Clear allelic discrimination was achieved after staining of the final reaction mixtures with Cybr-Gold and visualisation by UV illumination. The use of a compatible buffer system for all enzymes allows the reaction to be initiated and detected in the same tube or microplate well, so that the experiment can be scaled up easily for high-throughput detection. Only a small amount of DNA (i.e. 50 ng) is required per assay, and use of carefully designed short padlock probes coupled with generic primers and probes make the SNP detection cost effective. Biallelic assay by hybridisation of the RCA products with fluorescence dye-labelled probes is demonstrated, indicating that ligation-RCA (L-RCA) has potential for multiplexed assays. PMID:11713336

Development and Validation of New Discriminative Dissolution Method for Carvedilol Tablets

PubMed Central

Raju, V.; Murthy, K. V. R.

2011-01-01

The objective of the present study was to develop and validate a discriminative dissolution method for evaluation of carvedilol tablets. Different conditions such as type of dissolution medium, volume of dissolution medium and rotation speed of paddle were evaluated. The best in vitro dissolution profile was obtained using Apparatus II (paddle), 50 rpm, 900 ml of pH 6.8 phosphate buffer as dissolution medium. The drug release was evaluated by high-performance liquid chromatographic method. The dissolution method was validated according to current ICH and FDA guidelines using parameters such as the specificity, accuracy, precision and stability were evaluated and obtained results were within the acceptable range. The comparison of the obtained dissolution profiles of three different products were investigated using ANOVA-based, model-dependent and model-independent methods, results showed that there is significant difference between the products. The dissolution test developed and validated was adequate for its higher discriminative capacity in differentiating the release characteristics of the products tested and could be applied for development and quality control of carvedilol tablets. PMID:22923865

Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual

DOEpatents

Apel, William A.; Thompson, Vicki S; Lacey, Jeffrey A.; Gentillon, Cynthia A.

2016-08-09

A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.

Identification of discriminant proteins through antibody profiling, methods and apparatus for identifying an individual

DOEpatents

Thompson, Vicki S; Lacey, Jeffrey A; Gentillon, Cynthia A; Apel, William A

2015-03-03

A method for determining a plurality of proteins for discriminating and positively identifying an individual based from a biological sample. The method may include profiling a biological sample from a plurality of individuals against a protein array including a plurality of proteins. The protein array may include proteins attached to a support in a preselected pattern such that locations of the proteins are known. The biological sample may be contacted with the protein array such that a portion of antibodies in the biological sample reacts with and binds to the proteins forming immune complexes. A statistical analysis method, such as discriminant analysis, may be performed to determine discriminating proteins for distinguishing individuals. Proteins of interest may be used to form a protein array. Such a protein array may be used, for example, to compare a forensic sample from an unknown source with a sample from a known source.

A Method Of Evaluating A Subsurface Region Using Gather Sensitive Data Discrimination

DOEpatents

Lazaratos, Spyridon K.

2000-01-11

A method of evaluating a subsurface region by separating/enhancing a certain type of seismic event data of interest from an overall set of seismic event data which includes other, different types of seismic event data is disclosed herein. In accordance with one feature, a particular type of gather is generated from the seismic event data such that the gather includes at least a portion of the data which is of interest and at least a portion of the other data. A series of data discrimination lines are incorporated into the gather at positions and directions which are established in the gather in a predetermined way. Using the data discrimination lines, the data of interest which is present in the gather is separated/enhanced with respect to the other data within the gather. The separated data may be used for example in producing a map of the particular subterranean region. In accordance with another feature, the gather is selected such that the incorporated discrimination lines approach a near parallel relationship with one another. Thereby, the data is transformed in a way which causes the discrimination lines to be parallel with one another, resulting in reduced frequency distortion accompanied by improved accuracy in the separation/enhancement of data. In accordance with still another feature, the disclosed data separation/enhancement method is compatible with an iterative approach.

Allelic variation in key peptide-binding pockets discriminates between closely related diabetes-protective and diabetes-susceptible HLA-DQB1*06 alleles.

PubMed

Ettinger, Ruth A; Papadopoulos, George K; Moustakas, Antonis K; Nepom, Gerald T; Kwok, William W

2006-02-01

HLA-DQA1*0102-DQB1*0602 is associated with protection against type 1 diabetes (T1D). A similar allele, HLA-DQA1*0102-DQB1*0604, contributes to T1D susceptibility in certain populations but differs only at seven amino acids from HLA-DQA1*0102-DQB1*0602. Five of these polymorphisms are found within the peptide-binding groove, suggesting that differences in peptide binding contribute to the mechanism of their association with T1D. In this study, we determine the peptide-binding motif for HLA-DQA1*0102-DQB1*0604 allelic protein (DQ0604) in comparison to the established HLA-DQA1*0102-DQB1*0602 (DQ0602) motif using binding assays with model peptides from T1D autoantigens and homology modeling using the coordinates of the DQ0602-hypocretin 1-13 crystal structure. The peptide binding preferences were deduced with a peptide from insulin that bound both with a 2- to 3-fold difference in avidity using the same amino acids in the peptide as anchors. Peptide binding differences directly influenced by the polymorphisms in or nearby pockets 1, 6, and 9 were observed. In pocket 1, DQ0604 was better able to accommodate aromatic residues due to the beta86 and beta87 polymorphisms. A negatively charged amino acid was preferred by DQ0604 in pocket 6 due to the positively charged beta30His. In pocket 9, DQ0604 preferred aromatic amino acids due to the beta9 and beta30 polymorphisms and had low tolerance of acidic residues. beta57Val in DQ0604 functions differently than beta57Ala, in that it pushes alpha76Arg outside of the pocket, preventing the formation of a salt bridge with an acidic amino acid in the peptide. This study furthers our understanding of the structure-function relationships of MHC class II polymorphisms.

Discrimination of inflammatory bowel disease using Raman spectroscopy and linear discriminant analysis methods

NASA Astrophysics Data System (ADS)

Ding, Hao; Cao, Ming; DuPont, Andrew W.; Scott, Larry D.; Guha, Sushovan; Singhal, Shashideep; Younes, Mamoun; Pence, Isaac; Herline, Alan; Schwartz, David; Xu, Hua; Mahadevan-Jansen, Anita; Bi, Xiaohong

2016-03-01

Inflammatory bowel disease (IBD) is an idiopathic disease that is typically characterized by chronic inflammation of the gastrointestinal tract. Recently much effort has been devoted to the development of novel diagnostic tools that can assist physicians for fast, accurate, and automated diagnosis of the disease. Previous research based on Raman spectroscopy has shown promising results in differentiating IBD patients from normal screening cases. In the current study, we examined IBD patients in vivo through a colonoscope-coupled Raman system. Optical diagnosis for IBD discrimination was conducted based on full-range spectra using multivariate statistical methods. Further, we incorporated several feature selection methods in machine learning into the classification model. The diagnostic performance for disease differentiation was significantly improved after feature selection. Our results showed that improved IBD diagnosis can be achieved using Raman spectroscopy in combination with multivariate analysis and feature selection.

Forensic Loci Allele Database (FLAD): Automatically generated, permanent identifiers for sequenced forensic alleles.

PubMed

Van Neste, Christophe; Van Criekinge, Wim; Deforce, Dieter; Van Nieuwerburgh, Filip

2016-01-01

It is difficult to predict if and when massively parallel sequencing of forensic STR loci will replace capillary electrophoresis as the new standard technology in forensic genetics. The main benefits of sequencing are increased multiplexing scales and SNP detection. There is not yet a consensus on how sequenced profiles should be reported. We present the Forensic Loci Allele Database (FLAD) service, made freely available on http://forensic.ugent.be/FLAD/. It offers permanent identifiers for sequenced forensic alleles (STR or SNP) and their microvariants for use in forensic allele nomenclature. Analogous to Genbank, its aim is to provide permanent identifiers for forensically relevant allele sequences. Researchers that are developing forensic sequencing kits or are performing population studies, can register on http://forensic.ugent.be/FLAD/ and add loci and allele sequences with a short and simple application interface (API). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population.

PubMed

Lee, K W; Oh, D H; Lee, C; Yang, S Y

2005-05-01

High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns of HLA allele and haplotype frequencies in each population. In this study, HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402, A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303) were found in more than 10% of the population. In each serologic group, a maximum of three alleles were found with several exceptions (A2, B62, DR4, DR14, and DQ6). In each serologic group exhibiting multiple alleles, two major alleles were present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles). Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51 A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and 30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of their high polymorphism in B and DRB1, identification of relatively small numbers of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of those two loci, respectively. Five-locus haplotypes defined by high-resolution DNA typing correlated well with previously identified serology-based haplotypes in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403-DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%), A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101-DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several sets of allele level haplotypes that could not be discriminated by routine HLA-A, -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61, DR4, and DR8 serologic groups. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology.

Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing technology.

PubMed

Koontz, Deborah A; Huckins, Jacqueline J; Spencer, Antonina; Gallagher, Margaret L

2009-08-24

Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1-2 are derived from CYP2A7, and exons 3-9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology. A single set of PCR primers was designed to specifically amplify both the CYP2A6*1 wild-type allele and the CYP2A6*12 hybrid allele. An internal Pyrosequencing primer was used to generate allele-specific sequence information, which detected homozygous wild-type, heterozygous hybrid, and homozygous hybrid alleles. We first validated the assay on 104 DNA samples that were also genotyped by conventional two-step PCR and by cycle sequencing. CYP2A6*12 allele frequencies were then determined using the Pyrosequencing assay on 181 multi-ethnic DNA samples from subjects of African American, European Caucasian, Pacific Rim, and Hispanic descent. Finally, we streamlined the Pyrosequencing assay by integrating liquid handling robotics into the workflow. Pyrosequencing results demonstrated 100% concordance with conventional two-step PCR and cycle sequencing methods. Allele frequency data showed slightly higher prevalence of the CYP2A6*12 allele in European Caucasians and Hispanics. This Pyrosequencing assay proved to be a simple, rapid, and accurate alternative to conventional methods, which can be easily adapted to the needs of higher-throughput studies.

Development and validation of a SYBR Green I-based real-time polymerase chain reaction method for detection of haptoglobin gene deletion in clinical materials.

PubMed

Soejima, Mikiko; Tsuchiya, Yuji; Egashira, Kouichi; Kawano, Hiroyuki; Sagawa, Kimitaka; Koda, Yoshiro

2010-06-01

Anhaptoglobinemic patients run the risk of severe anaphylactic transfusion reaction because they produce serum haptoglobin (Hp) antibodies. Being homozygous for the Hp gene deletion (HP(del)) is the only known cause of congenital anhaptoglobinemia, and clinical diagnosis of HP(del) before transfusion is important to prevent anaphylactic shock. We recently developed a 5'-nuclease (TaqMan) real-time polymerase chain reaction (PCR) method. A SYBR Green I-based duplex real-time PCR assay using two forward primers and a common reverse primer followed by melting curve analysis was developed to determine HP(del) zygosity in a single tube. In addition, to obviate initial DNA extraction, we examined serially diluted blood samples as PCR templates. Allelic discrimination of HP(del) yielded optimal results at blood sample dilutions of 1:64 to 1:1024. The results from 2231 blood samples were fully concordant with those obtained by the TaqMan-based real-time PCR method. The detection rate of the HP(del) allele by the SYBR Green I-based method is comparable with that using the TaqMan-based method. This method is readily applicable due to its low initial cost and analyzability using economical real-time PCR machines and is suitable for high-throughput analysis as an alternative method for allelic discrimination of HP(del).

A discrimination method for the detection of pneumonia using chest radiograph.

PubMed

Noor, Norliza Mohd; Rijal, Omar Mohd; Yunus, Ashari; Abu-Bakar, S A R

2010-03-01

This paper presents a statistical method for the detection of lobar pneumonia when using digitized chest X-ray films. Each region of interest was represented by a vector of wavelet texture measures which is then multiplied by the orthogonal matrix Q(2). The first two elements of the transformed vectors were shown to have a bivariate normal distribution. Misclassification probabilities were estimated using probability ellipsoids and discriminant functions. The result of this study recommends the detection of pneumonia by constructing probability ellipsoids or discriminant function using maximum energy and maximum column sum energy texture measures where misclassification probabilities were less than 0.15. 2009 Elsevier Ltd. All rights reserved.

Allele frequencies of 15 STR loci in Bosnian and Herzegovinian population.

PubMed

Pilav, Amela; Pojskić, Naris; Ahatović, Anesa; Džehverović, Mirela; Čakar, Jasmina; Marjanović, Damir

2017-06-14

To determine newest the most accurate allele frequencies for 15 short tandem repeat (STR) loci in the Bosnian and Herzegovinian population, calculate statistical parameters, and compare them with the relevant data for seven neighboring populations. Genomic DNA was obtained from buccal swabs of 1000 unrelated individuals from all regions of Bosnia and Herzegovina. Genotyping was performed using PowerPlex® 16 System to obtain allele frequencies for 15 polymorphic STR loci including D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX, and FGA. The calculated allele frequencies were also compared with the data from neighboring populations. The highest detected value of polymorphism information content (PIC) was detected at the PentaE locus, whereas the lowest value was detected at the TPOX locus. The power of discrimination (PD) values had similar distribution, with Penta E showing the highest PD of 0.9788. While D18S51 had the highest value of power of exclusion (PE), the lowest PE value was detected at the TPOX locus. Upon comparison of Bosnian and Herzegovinian population data with those of seven neighboring populations, the highest allele frequency differentiation was noticed between Bosnian and Herzegovinian and Turkish population at 5 loci, the most informative of which was Penta E. The neighbor-joining dendrogram constructed on the basis of genetic distance showed grouping of Slovenian, Austrian, Hungarian, and Croatian populations. Bosnian and Herzegovinian population was between the mentioned cluster and Serbian population. To determine more accurate distribution of allelic frequencies and forensic parameters, our study included 1000 unrelated individuals from all regions of Bosnia and Herzegovina, and our findings demonstrated the applicability of these markers in both forensics and future population genetic studies.

A comparison of stimulus presentation methods in temporal discrimination testing.

PubMed

Mc Govern, Eavan M; Butler, John S; Beiser, Ines; Williams, Laura; Quinlivan, Brendan; Narasiham, Shruti; Beck, Rebecca; O'Riordan, Sean; Reilly, Richard B; Hutchinson, Michael

2017-02-01

The temporal discrimination threshold (TDT) is the shortest time interval at which an individual detects two stimuli to be asynchronous (normal  =  30-50 ms). It has been shown to be abnormal in patients with disorders affecting the basal ganglia including adult onset idiopathic focal dystonia (AOIFD). Up to 97% of patients have an abnormal TDT with age- and sex-related penetrance in unaffected relatives, demonstrating an autosomal dominant inheritance pattern. These findings support the use of the TDT as a pre-clinical biomarker for AOIFD. The usual stimulus presentation method involves the presentation of progressively asynchronous stimuli; when three sequential stimuli are reported asynchronous is taken as a participant's TDT. To investigate the robustness of the 'staircase' method of presentation, we introduced a method of randomised presentation order to explore any potential 'learning effect' that may be associated with this existing method. The aim of this study was to investigate differences in temporal discrimination using two methods of stimulus presentation. Thirty healthy volunteers were recruited to the study (mean age 33.73  ±  3.4 years). Visual and tactile TDT testing using a staircase and randomised method of presentation order was carried out in a single session. There was a strong relationship between the staircase and random method for TDT values. This observed consistency between testing methods suggests that the existing experimental approach is a robust method of recording an individual's TDT. In addition, our newly devised randomised paradigm is a reproducible and more efficient method for data acquisition in the clinic setting. However, the two presentation methods yield different absolute TDT results and either of the two methods should be used uniformly in all participants in any one particular study.

Two sympatric types of Plasmodium ovale and discrimination by molecular methods.

PubMed

Zaw, Myo Thura; Lin, Zaw

2017-10-01

Plasmodium ovale is widely distributed in tropical countries, whereas it has not been reported in the Americas. It is not a problem globally because it is rarely detected by microscopy owing to low parasite density, which is a feature of clinical ovale malaria. P.o. curtisi and P.o. wallikeri are widespread in both Africa and Asia, and were known to be sympatric in many African countries and in southeast Asian countries. Small subunit ribosomal RNA (SSUrRNA) gene, cytochrome b (cytb) gene, and merozoite surface protein-1 (msp-1) gene were initially studied for molecular discrimination of P.o. curtisi and P.o. wallikeri using polymerase chain reaction (PCR) and DNA sequencing. DNA sequences of other genes from P. ovale in Southeast Asia and the southwestern Pacific regions were also targeted to differentiate the two sympatric types. In terms of clinical manifestations, P.o. wallikeri tended to produce higher parasitemia levels and more severe symptoms. To date, there have been a few studies that used the quantitative PCR method for discrimination of the two distinct P. ovale types. Conventional PCR with consequent DNA sequencing is the common method used to differentiate these two types. It is necessary to identify these two types because relapse periodicity, drug susceptibility, and mosquito species preference need to be studied to reduce ovale malaria. In this article, an easier method of molecular-level discrimination of P.o. curtisi and P.o. wallikeri is proposed. Copyright © 2016. Published by Elsevier B.V.

Modification method to reduce the impact of blood vessel on noncontact discrimination of human blood based on ;M+N; theory

NASA Astrophysics Data System (ADS)

Zhang, Linna; Ding, Hongyan; Lin, Ling; Wang, Yimin; Guo, Xin

2018-01-01

Noncontact discriminating human blood is significantly crucial for import-export ports and inspection and quarantine departments. We had already demonstrated that visible diffuse reflectance spectroscopy combining PLS-DA method can successfully realize noncontact human blood discrimination. However, the circulated blood vessels may be produced with different materials. The use of various kinds of blood tubes may have a negative effect on the discrimination, based on ;M+N; theory (Li et al., 2016). In this research, we explored the impact of different material of blood vessels, such as glass tube and plastic tube, on the prediction ability of the discrimination model. Furthermore, we searched for the modification method to reduce the influence from the blood tubes. Our work indicated that generalized diffuse reflectance method can greatly improve the discrimination accuracy. This research can greatly facilitate the application of noncontact discrimination method based on visible and near-infrared diffuse reflectance spectroscopy.

Novel microsatellite markers for the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) and effects of null alleles on population genetics analyses.

PubMed

Song, W; Cao, L-J; Wang, Y-Z; Li, B-Y; Wei, S-J

2017-06-01

The oriental fruit moth (OFM) Grapholita molesta (Lepidoptera: Tortricidae) is an important economic pest of stone and pome fruits worldwide. We sequenced the OFM genome using next-generation sequencing and characterized the microsatellite distribution. In total, 56,674 microsatellites were identified, with 11,584 loci suitable for primer design. Twenty-seven polymorphic microsatellites, including 24 loci with trinucleotide repeat and three with pentanucleotide repeat, were validated in 95 individuals from four natural populations. The allele numbers ranged from 4 to 40, with an average value of 13.7 per locus. A high frequency of null alleles was observed in most loci developed for the OFM. Three marker panels, all of the loci, nine loci with the lowest null allele frequencies, and nine loci with the highest null allele frequencies, were established for population genetics analyses. The null allele influenced estimations of genetic diversity parameters but not the OFM's genetic structure. Both a STRUCTURE analysis and a discriminant analysis of principal components, using the three marker panels, divided the four natural populations into three groups. However, more individuals were incorrectly assigned by the STRUCTURE analysis when the marker panel with the highest null allele frequency was used compared with the other two panels. Our study provides empirical research on the effects of null alleles on population genetics analyses. The microsatellites developed will be valuable markers for genetic studies of the OFM.

A Discriminative Sentence Compression Method as Combinatorial Optimization Problem

NASA Astrophysics Data System (ADS)

Hirao, Tsutomu; Suzuki, Jun; Isozaki, Hideki

In the study of automatic summarization, the main research topic was `important sentence extraction' but nowadays `sentence compression' is a hot research topic. Conventional sentence compression methods usually transform a given sentence into a parse tree or a dependency tree, and modify them to get a shorter sentence. However, this method is sometimes too rigid. In this paper, we regard sentence compression as an combinatorial optimization problem that extracts an optimal subsequence of words. Hori et al. also proposed a similar method, but they used only a small number of features and their weights were tuned by hand. We introduce a large number of features such as part-of-speech bigrams and word position in the sentence. Furthermore, we train the system by discriminative learning. According to our experiments, our method obtained better score than other methods with statistical significance.

Forensic genetic informativeness of an SNP panel consisting of 19 multi-allelic SNPs.

PubMed

Gao, Zehua; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Zhang, Shu; Yang, Yiwen; Wang, Yufang; Zhang, Ji

2018-05-01

Current research focusing on forensic personal identification, phenotype inference and ancestry information on single-nucleotide polymorphisms (SNPs) has been widely reported. In the present study, we focused on tetra-allelic SNPs in the Chinese Han population. A total of 48 tetra-allelic SNPs were screened out from the Chinese Han population of the 1000 Genomes Database, including Chinese Han in Beijing (CHB) and Chinese Han South (CHS). Considering the forensic genetic requirement for the polymorphisms, only 11 tetra-allelic SNPs with a heterozygosity >0.06 were selected for further multiplex panel construction. In order to meet the demands of personal identification and parentage identification, an additional 8 tri-allelic SNPs were combined into the final multiplex panel. To ensure application in the degraded DNA analysis, all the PCR products were designed to be 87-188 bp. Employing multiple PCR reactions and SNaPshot minisequencing, 511 unrelated Chinese Han individuals from Sichuan were genotyped. The combined match probability (CMP), combined discrimination power (CDP), and cumulative probability of exclusion (CPE) of the panel were 6.07 × 10 -11 , 0.9999999999393 and 0.996764, respectively. Based on the population data retrieved from the 1000 Genomes Project, Fst values between Chinese Han in Sichuan (SCH) and all the populations included in the 1000 Genomes Project were calculated. The results indicated that two SNPs in this panel may contain ancestry information and may be used as markers of forensic biogeographical ancestry inference. Copyright © 2018 Elsevier B.V. All rights reserved.

Global distribution of malaria-resistant MHC-HLA alleles: the number and frequencies of alleles and malaria risk.

PubMed

Garamszegi, László Zsolt

2014-09-03

The major histocompatibility complex (MHC) is the most polymorphic genetic region in vertebrates, but the origin of such genetic diversity remains unresolved. Several studies have demonstrated at the within-population level that individuals harbouring particular alleles can be less or more susceptible to malaria, but these do not allow strong generalization. Here worldwide data on the frequencies of several hundred MHC alleles of the human leucocyte antigen (HLA) system in relation to malaria risk at the between-population level were analysed in a phylogenetic framework, and results for different alleles were quantitatively summarized in a meta-analysis. There was an overall positive relationship between malaria pressure and the frequency of several HLA alleles indicating that allele frequencies increase in countries with strong malaria pressure. Nevertheless, considerable heterogeneity was observed across alleles, and some alleles showed a remarkable negative relationship with malaria risk. When heterogeneities were partitioned into different organization groups of the MHC, the strongest positive relationships were detected for alleles of the HLA-A and HLA-B loci, but there were also differences between MHC supertypes that constitute functionally distinct nucleotide sequences. Finally, the number of MHC alleles that are maintained within countries was also related to malaria risk. Therefore, malaria represents a key selection pressure for the human MHC and has left clear evolutionary footprints on both the frequencies and the number of alleles observed in different countries.

Machine vision methods for use in grain variety discrimination and quality analysis

NASA Astrophysics Data System (ADS)

Winter, Philip W.; Sokhansanj, Shahab; Wood, Hugh C.

1996-12-01

Decreasing cost of computer technology has made it feasible to incorporate machine vision technology into the agriculture industry. The biggest attraction to using a machine vision system is the computer's ability to be completely consistent and objective. One use is in the variety discrimination and quality inspection of grains. Algorithms have been developed using Fourier descriptors and neural networks for use in variety discrimination of barley seeds. RGB and morphology features have been used in the quality analysis of lentils, and probability distribution functions and L,a,b color values for borage dockage testing. These methods have been shown to be very accurate and have a high potential for agriculture. This paper presents the techniques used and results obtained from projects including: a lentil quality discriminator, a barley variety classifier, a borage dockage tester, a popcorn quality analyzer, and a pistachio nut grading system.

A real-time neutron-gamma discriminator based on the support vector machine method for the time-of-flight neutron spectrometer

NASA Astrophysics Data System (ADS)

Wei, ZHANG; Tongyu, WU; Bowen, ZHENG; Shiping, LI; Yipo, ZHANG; Zejie, YIN

2018-04-01

A new neutron-gamma discriminator based on the support vector machine (SVM) method is proposed to improve the performance of the time-of-flight neutron spectrometer. The neutron detector is an EJ-299-33 plastic scintillator with pulse-shape discrimination (PSD) property. The SVM algorithm is implemented in field programmable gate array (FPGA) to carry out the real-time sifting of neutrons in neutron-gamma mixed radiation fields. This study compares the ability of the pulse gradient analysis method and the SVM method. The results show that this SVM discriminator can provide a better discrimination accuracy of 99.1%. The accuracy and performance of the SVM discriminator based on FPGA have been evaluated in the experiments. It can get a figure of merit of 1.30.

ABO, Rhesus, and Kell Antigens, Alleles, and Haplotypes in West Bengal, India

PubMed Central

Basu, Debapriya; Datta, Suvro Sankha; Montemayor, Celina; Bhattacharya, Prasun; Mukherjee, Krishnendu; Flegel, Willy A.

2018-01-01

Background Few studies have documented the blood group antigens in the population of eastern India. Frequencies of some common alleles and haplotypes were unknown. We describe phenotype, allele, and haplotype frequencies in the state of West Bengal, India. Methods We tested 1,528 blood donors at the Medical College Hospital, Kolkata. The common antigens of the ABO, Rhesus, and Kell blood group systems were determined by standard serologic methods in tubes. Allele and haplotype frequencies were calculated with an iterative method that yielded maximum-likelihood estimates under the assumption of a Hardy-Weinberg equilibrium. Results The prevalence of ABO antigens were B (34%), O (32%), A (25%), and AB (9%) with ABO allele frequencies for O = 0.567, A = 0.189, and B = 0.244. The D antigen (RH1) was observed in 96.6% of the blood donors with RH haplotype frequencies, such as for CDe = 0.688809, cde = 0.16983 and CdE = 0.000654. The K antigen (K1) was observed in 12 donors (0.79%) with KEL allele frequencies for K = 0.004 and k = 0.996. Conclusions: For the Bengali population living in the south of West Bengal, we established the frequencies of the major clinically relevant antigens in the ABO, Rhesus, and Kell blood group systems and derived estimates for the underlying ABO and KEL alleles and RH haplotypes. Such blood donor screening will improve the availability of compatible red cell units for transfusion. Our approach using widely available routine methods can readily be applied in other regions, where the sufficient supply of blood typed for the Rh and K antigens is lacking. PMID:29593462

Direct Fluorescence Detection of Allele-Specific PCR Products Using Novel Energy-Transfer Labeled Primers.

PubMed

Winn-Deen

1998-12-01

Background: Currently analysis of point mutations can be done by allele-specific polymerase chain reaction (PCR) followed by gel analysis or by gene-specific PCR followed by hybridization with an allele-specific probe. Both of these mutation detection methods require post-PCR laboratory time and run the risk of contaminating subsequent experiments with the PCR product liberated during the detection step. The author has combined the PCR amplification and detection steps into a single procedure suitable for closed-tube analysis. Methods and Results: Allele-specific PCR primers were designed as Sunrise energy-transfer primers and contained a 3' terminal mismatch to distinguish between normal and mutant DNA. Cloned normal (W64) and mutant (R64) templates of the beta3-adrenergic receptor gene were tested to verify amplification specificity and yield. A no-target negative control was also run with each reaction. After PCR, each reaction was tested for fluorescence yield by measuring fluorescence on a spectrofluorimeter or fluorescent microtitreplate reader. The cloned controls and 24 patient samples were tested for the W64R mutation by two methods. The direct fluorescence results with the Sunrise allele-specific PCR method gave comparable genotypes to those obtained with the PCR/ restriction digest/gel electrophoresis control method. No PCR artifacts were observed in the negative controls or in the PCR reactions run with the mismatched target. Conclusions: The results of this pilot study indicate good PCR product and fluorescence yield from allele-specific energy-transfer labeled primers, and the capability of distinguishing between normal and mutant alleles based on fluorescence alone, without the need for restriction digestion, gel electrophoresis, or hybridization with an allele-specific probe.

Study of n- γ discrimination by zero-crossing method with SiPM based scintillation detectors

NASA Astrophysics Data System (ADS)

Grodzicka-Kobylka, M.; Szczesniak, T.; Moszyński, M.; Swiderski, L.; Wolski, D.; Baszak, J.; Korolczuk, S.; Schotanus, P.

2018-03-01

The paper presents a study of n / γ discrimination with 4x4 ch and 8x8 ch Multi Pixel Photon Counter (MPPC) arrays in neutron detectors based on Stilbene and EJ299-33 plastic scintillators. The n / γ discrimination showed an excellent capability of the MPPC arrays, comparable to that observed earlier with the classical PMTs. Particularly, an application of a zero-crossing method of n - γ discrimination prevented deterioration of the discrimination by the slow response of the Silicon Photomultiplier (SiPM, or MPPC interchangeably) array related to its large capacitance. It was confirmed by a good agreement of the Figure of Merit normalized to the number of photoelectrons determined for the MPPC arrays and XP5500 PMT.

The impact of stress on the life history strategies of African American adolescents: cognitions, genetic moderation, and the role of discrimination.

PubMed

Gibbons, Frederick X; Roberts, Megan E; Gerrard, Meg; Li, Zhigang; Beach, Steven R H; Simons, Ronald L; Weng, Chih-Yuan; Philibert, Robert A

2012-05-01

The impact of 3 different sources of stress--environmental, familial (e.g., low parental investment), and interpersonal (i.e., racial discrimination)--on the life history strategies (LHS) and associated cognitions of African American adolescents were examined over an 11-year period (5 waves, from age 10.5 to 21.5). Analyses indicated that each one of the sources of stress was associated with faster LHS cognitions (e.g., tolerance of deviance, willingness to engage in risky sex), which, in turn, predicted faster LHS behaviors (e.g., frequent sexual behavior). LHS, then, negatively predicted outcome (resilience) at age 21.5 (i.e., faster LHS → less resilience). In addition, presence of the risk ("sensitivity") alleles of 2 monoamine-regulating genes, the serotonin transporter gene (5HTTLPR) and the dopamine D4 receptor gene (DRD4), moderated the impact of perceived racial discrimination on LHS cognitions: Participants with more risk alleles (higher "sensitivity") reported faster LHS cognitions at age 18 and less resilience at age 21 if they had experienced higher amounts of discrimination and slower LHS and more resilience if they had experienced smaller amounts of discrimination. Implications for LHS theories are discussed.

The Impact of Stress on the Life History Strategies of African American Adolescents: Cognitions, Genetic Moderation, and the Role of Discrimination

PubMed Central

Gibbons, Frederick X.; Roberts, Megan E.; Gerrard, Meg; Li, Zhigang; Beach, Steven R. H.; Simons, Ronald L.; Weng, Chih-Yuan; Philibert, Robert A.

2013-01-01

The impact of three different sources of stress—environmental, familial (e.g., low parental investment), and interpersonal (i.e., racial discrimination)—on the life history strategies (LHS) and associated cognitions of African American adolescents were examined over an 11-year period (five waves, from age 10.5 to 21.5). Analyses indicated that each one of the sources of stress was associated with faster LHS cognitions (e.g., tolerance of deviance, willingness to engage in risky sex), which, in turn, predicted faster LHS behaviors (e.g., frequent sexual behavior). LHS then negatively predicted outcome (resilience) at age 21.5; i.e., faster LHS → less resilience. In addition, presence of the risk (“sensitivity”) alleles of two monoamine-regulating genes, the serotonin transporter gene (5HTTLPR) and the dopamine D4 receptor gene (DRD4) moderated the impact of perceived racial discrimination on LHS cognitions: Participants with more risk alleles (higher “sensitivity”) reported: faster LHS cognitions at age 18 and less resilience at age 21, if they had experienced higher amounts of discrimination ; and slower LHS and more resilience if they had experienced smaller amounts of discrimination. Implications for LHS theories are discussed. PMID:22251000

HLA-A*02 allele frequencies and haplotypic associations in Koreans.

PubMed

Park, M H; Whang, D H; Kang, S J; Han, K S

2000-03-01

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.

Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

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

Sachse, C.; Brockmoeller, J.; Bauer, S.

Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015,more » respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.« less

S-genotype identification based on allele-specific PCR in Japanese pear

PubMed Central

Nashima, Kenji; Terakami, Shingo; Nishio, Sogo; Kunihisa, Miyuki; Nishitani, Chikako; Saito, Toshihiro; Yamamoto, Toshiya

2015-01-01

Gametophytic self-incompatibility in Japanese pear (Pyrus pyrifolia Nakai) is controlled by the single, multi-allelic S-locus. Information about the S-genotypes is important for breeding and the selection of pollen donors for fruit production. Rapid and reliable S-genotype identification system is necessary for efficient breeding of new cultivars in Japanese pear. We designed S allele-specific PCR primer pairs for ten previously reported S-RNase alleles (S1–S9 and Sk) as simple and reliable method. Specific nucleotide sequences were chosen to design the primers to amplify fragments of only the corresponding S alleles. The developed primer pairs were evaluated by using homozygous S-genotypes (S1/S1–S9/S9 and S4sm/S4sm) and 14 major Japanese pear cultivars, and found that S allele-specific primer pairs can identify S-genotypes effectively. The S allele-specific primer pairs developed in this study will be useful for efficient S-genotyping and for marker-assisted selection in Japanese pear breeding programs. PMID:26175617

Discrimination of particulate matter emission sources using stochastic methods

NASA Astrophysics Data System (ADS)

Szczurek, Andrzej; Maciejewska, Monika; Wyłomańska, Agnieszka; Sikora, Grzegorz; Balcerek, Michał; Teuerle, Marek

2016-12-01

Particulate matter (PM) is one of the criteria pollutants which has been determined as harmful to public health and the environment. For this reason the ability to recognize its emission sources is very important. There are a number of measurement methods which allow to characterize PM in terms of concentration, particles size distribution, and chemical composition. All these information are useful to establish a link between the dust found in the air, its emission sources and influence on human as well as the environment. However, the methods are typically quite sophisticated and not applicable outside laboratories. In this work, we considered PM emission source discrimination method which is based on continuous measurements of PM concentration with a relatively cheap instrument and stochastic analysis of the obtained data. The stochastic analysis is focused on the temporal variation of PM concentration and it involves two steps: (1) recognition of the category of distribution for the data i.e. stable or the domain of attraction of stable distribution and (2) finding best matching distribution out of Gaussian, stable and normal-inverse Gaussian (NIG). We examined six PM emission sources. They were associated with material processing in industrial environment, namely machining and welding aluminum, forged carbon steel and plastic with various tools. As shown by the obtained results, PM emission sources may be distinguished based on statistical distribution of PM concentration variations. Major factor responsible for the differences detectable with our method was the type of material processing and the tool applied. In case different materials were processed by the same tool the distinction of emission sources was difficult. For successful discrimination it was crucial to consider size-segregated mass fraction concentrations. In our opinion the presented approach is very promising. It deserves further study and development.

Physical activity classification with dynamic discriminative methods.

PubMed

Ray, Evan L; Sasaki, Jeffer E; Freedson, Patty S; Staudenmayer, John

2018-06-19

A person's physical activity has important health implications, so it is important to be able to measure aspects of physical activity objectively. One approach to doing that is to use data from an accelerometer to classify physical activity according to activity type (e.g., lying down, sitting, standing, or walking) or intensity (e.g., sedentary, light, moderate, or vigorous). This can be formulated as a labeled classification problem, where the model relates a feature vector summarizing the accelerometer signal in a window of time to the activity type or intensity in that window. These data exhibit two key characteristics: (1) the activity classes in different time windows are not independent, and (2) the accelerometer features have moderately high dimension and follow complex distributions. Through a simulation study and applications to three datasets, we demonstrate that a model's classification performance is related to how it addresses these aspects of the data. Dynamic methods that account for temporal dependence achieve better performance than static methods that do not. Generative methods that explicitly model the distribution of the accelerometer signal features do not perform as well as methods that take a discriminative approach to establishing the relationship between the accelerometer signal and the activity class. Specifically, Conditional Random Fields consistently have better performance than commonly employed methods that ignore temporal dependence or attempt to model the accelerometer features. © 2018, The International Biometric Society.

A platform-independent method to reduce CT truncation artifacts using discriminative dictionary representations.

PubMed

Chen, Yang; Budde, Adam; Li, Ke; Li, Yinsheng; Hsieh, Jiang; Chen, Guang-Hong

2017-01-01

When the scan field of view (SFOV) of a CT system is not large enough to enclose the entire cross-section of the patient, or the patient needs to be positioned partially outside the SFOV for certain clinical applications, truncation artifacts often appear in the reconstructed CT images. Many truncation artifact correction methods perform extrapolations of the truncated projection data based on certain a priori assumptions. The purpose of this work was to develop a novel CT truncation artifact reduction method that directly operates on DICOM images. The blooming of pixel values associated with truncation was modeled using exponential decay functions, and based on this model, a discriminative dictionary was constructed to represent truncation artifacts and nonartifact image information in a mutually exclusive way. The discriminative dictionary consists of a truncation artifact subdictionary and a nonartifact subdictionary. The truncation artifact subdictionary contains 1000 atoms with different decay parameters, while the nonartifact subdictionary contains 1000 independent realizations of Gaussian white noise that are exclusive with the artifact features. By sparsely representing an artifact-contaminated CT image with this discriminative dictionary, the image was separated into a truncation artifact-dominated image and a complementary image with reduced truncation artifacts. The artifact-dominated image was then subtracted from the original image with an appropriate weighting coefficient to generate the final image with reduced artifacts. This proposed method was validated via physical phantom studies and retrospective human subject studies. Quantitative image evaluation metrics including the relative root-mean-square error (rRMSE) and the universal image quality index (UQI) were used to quantify the performance of the algorithm. For both phantom and human subject studies, truncation artifacts at the peripheral region of the SFOV were effectively reduced, revealing

[Analysis of allele dropout at TH01 locus in paternity testing].

PubMed

Lai, Li; Shen, Xiao-li; Xue, Shi-jie; Hu, Jie

2013-10-01

To analyze allele dropout at TH01 locus in paternity testing in order to determine the accurate genotype. To use a two STR loci genotyping system to verify an abnormal genotype for the TH01 locus with PCR using specific primers, cloning and DNA sequencing. A rare allele at TH01 locus named 5.2, which was undetectable with PowerPlex 21 system, was detected with an Identifiler system. Genetic variations may result in rare alleles and loci loss. To avoid misjudgment, laboratories should have a variety of methods for detecting loci loss.

Allele-specific copy-number discovery from whole-genome and whole-exome sequencing

PubMed Central

Wang, WeiBo; Wang, Wei; Sun, Wei; Crowley, James J.; Szatkiewicz, Jin P.

2015-01-01

Copy-number variants (CNVs) are a major form of genetic variation and a risk factor for various human diseases, so it is crucial to accurately detect and characterize them. It is conceivable that allele-specific reads from high-throughput sequencing data could be leveraged to both enhance CNV detection and produce allele-specific copy number (ASCN) calls. Although statistical methods have been developed to detect CNVs using whole-genome sequence (WGS) and/or whole-exome sequence (WES) data, information from allele-specific read counts has not yet been adequately exploited. In this paper, we develop an integrated method, called AS-GENSENG, which incorporates allele-specific read counts in CNV detection and estimates ASCN using either WGS or WES data. To evaluate the performance of AS-GENSENG, we conducted extensive simulations, generated empirical data using existing WGS and WES data sets and validated predicted CNVs using an independent methodology. We conclude that AS-GENSENG not only predicts accurate ASCN calls but also improves the accuracy of total copy number calls, owing to its unique ability to exploit information from both total and allele-specific read counts while accounting for various experimental biases in sequence data. Our novel, user-friendly and computationally efficient method and a complete analytic protocol is freely available at https://sourceforge.net/projects/asgenseng/. PMID:25883151

The T-Allele of TCF7L2 rs7903146 Associates With a Reduced Compensation of Insulin Secretion for Insulin Resistance Induced by 9 Days of Bed Rest

PubMed Central

Alibegovic, Amra C.; Sonne, Mette P.; Højbjerre, Lise; Hansen, Torben; Pedersen, Oluf; van Hall, Gerrit; Holst, Jens J.; Stallknecht, Bente; Dela, Flemming; Vaag, Allan

2010-01-01

OBJECTIVE The aim of this study was to determine whether the type 2 diabetes–associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. RESEARCH DESIGN AND METHODS A total of 38 healthy young Caucasian men were studied before and after bed rest using the hyperinsulinemic-euglycemic clamp technique combined with indirect calorimetry preceded by an intravenous glucose tolerance test. The TCF7L2 rs7903146 was genotyped using allelic discrimination performed with an ABI 7900 system. The genetic analyses were done assuming a dominant model of inheritance. RESULTS The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P < 0.001). Fasting plasma glucagon levels were significantly lower in carriers of the T-allele before and after bed rest. While carriers of the CC genotype developed increased hepatic insulin resistance, the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. CONCLUSIONS Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of β-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes. PMID:20107109

Discrimination of several Indonesian specialty coffees using Fluorescence Spectroscopy combined with SIMCA method

NASA Astrophysics Data System (ADS)

Suhandy, D.; Yulia, M.

2018-03-01

Indonesia is one of the important producers of several specialty coffees, which have a particularly high economic value, including Civet coffee (‘kopi luwak’ in Indonesian language) and Peaberry coffee (‘kopi lanang’ in Indonesian language). The production of Civet and Peaberry coffee is very limited. In order to provide authentication of Civet and Peaberry coffee and protect consumers from adulteration, a robust and easy method for evaluating ground Civet and Peaberry coffee and detection of its adulteration is needed. In this study, we investigate the use of fluorescence spectroscopy combined with SIMCA (soft independent modelling of class analogies) method to discriminate three Indonesian specialty coffee: ground Peaberry, Civet and Pagar Alam coffee. Total 90 samples were used (30 samples for Civet, Peaberry and Pagar Alam coffee, respectively). All coffee samples were ground using a home-coffee-grinder. Since particle size in coffee powder has a significant influence on the spectra obtained, we sieved all coffee samples through a nest of U. S. standard sieves (mesh number of 40) on a Meinzer II sieve shaker for 10 minutes to obtain a particle size of 420 µm. The experiments were performed at room temperature (around 27-29°C). All samples were extracted with distilled water and then filtered. For each samples, 3 mL of extracted sample then was pipetted into 10 mm cuvettes for spectral data acquisition. The EEM (excitation-emission matrix) spectral data of coffee samples were acquired using JASCO FP-8300 Fluorescence Spectrometer. The principal component analysis (PCA) result shows that it is possible to discriminate types of coffee based on information from EEM (excitation-emission matrix) spectral data. Using SIMCA method, the discrimination model of Indonesian specialty coffee was successfully developed and resulted in high performance of discrimination with 100% of sensitivity and specificity for Peaberry, Civet and Pagar Alam coffee. This research

Multiplex PCR method to discriminate Artemisia iwayomogi from other Artemisia plants.

PubMed

Doh, Eui Jeong; Oh, Seung-Eun

2012-01-01

Some plants in the genus Artemisia have been used for medicinal purposes. Among them, Artemisia iwayomogi, commonly referred to as "Haninjin," is one of the major medicinal materials used in traditional Korean medicine. By contrast, Artemisia capillaris and both Artemisia argyi and Artemisia princeps, referred to as "Injinho" and "Aeyup," respectively, are used to treat diseases different from those for which "Haninjin" is prescribed. Therefore, the development of a reliable method to differentiate each Artemisia herb is necessary. We found that a random amplified polymorphic DNA (RAPD) method can be used to efficiently discriminate a few Artemisia plants from one another. To improve the reliability of RAPD amplification, we designed primer sets based on the nucleotide sequences of RAPD products to amplify a sequence-characterized amplified region (SCAR) marker of A. iwayomogi. In addition, we designed two other primer sets to amplify SCAR markers of "Aeyup" (A. argyi and A. princeps) along with "Injinho" (A. capillaris) and Artemisia japonica, which are also traded in Korean herbal markets. Using these three primer sets, we developed a multiplex PCR method concurrently not only to discriminate A. iwayomogi from other Artemisia plants, but also to identify Artemisia plants using a single PCR process.

Rapid and cost-effective method for the detection of the c.533G>A mutation in the HEXA gene.

PubMed

Ribeiro, Diogo; Duarte, Ana Joana; Amaral, Olga

2011-03-01

Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases. Additionally, this variant might also show a higher prevalence in populations of Portuguese and Spanish ancestry. A single mutation is invariably present in at least one of the alleles of B1 variant patients, HEXA mutation c.533G >A. To implement a method for c.533G >A testing in individuals and populations, we have optimized two distinct mutation analysis techniques, one based on restriction fragment length polymorphism analysis and the other based on allelic discrimination. We present the comparison of both methods and their advantages. Mutation screening by allelic discrimination proved to be particularly useful for the studying of large samples of individuals. It is time saving and highly reproducible, and under the conditions used, its cost is lower than the cost of polymerase chain reaction-based restriction fragment length polymorphism analysis.

Diversity of alleles encoding HLA-B40: relative frequencies in united states populations and description of five novel alleles.

PubMed

Pimtanothai, N; Rizzuto, G A; Slack, R; Steiner, N K; Kosman, C A; Jones, P F; Koester, R; Ng, J; Hartzman, R J; Katovich Hurley, C

2000-08-01

The frequency of each B*40 allele was determined by DNA sequencing in four major United States populations: Caucasians, African Americans, Asians/Pacific Islanders, and Hispanics. Thirty-two individuals from each ethnic group, who were previously described serologically as B40, B60, or B61, were randomly selected out of a pool of 82,979 unrelated individuals for allele characterization. Out of nine different B*40 alleles identified in this study, B*4001 and B*4002 were the two most frequent B*40 alleles in all the population groups. B*4001 was the primary B*40 allele seen in Caucasians (83%) and African Americans (76%), while B*4002 was found in the majority of Hispanics (62%). The distributions of both alleles were comparable in the Asian/Pacific Islander population. These two alleles were the only B*40 alleles detected in Caucasians while four to five additional B*40 alleles were seen in the other population groups. The other B*40 alleles detected in this study included: B*4003 and B*4010 in Asian/Pacific Islanders; B*4012 and B*4016 in African Americans; and B*4004, B*4006, and B*4027 in Hispanics. Analysis revealed significant differences between Hispanics and all other groups as well as between African Americans and Asian/Pacific Islanders. This report also describes five novel B*40 alleles: B*4019, B*4020, B*4024, B*4027, and B*4028.

A Feature Selection Method Based on Fisher's Discriminant Ratio for Text Sentiment Classification

NASA Astrophysics Data System (ADS)

Wang, Suge; Li, Deyu; Wei, Yingjie; Li, Hongxia

With the rapid growth of e-commerce, product reviews on the Web have become an important information source for customers' decision making when they intend to buy some product. As the reviews are often too many for customers to go through, how to automatically classify them into different sentiment orientation categories (i.e. positive/negative) has become a research problem. In this paper, based on Fisher's discriminant ratio, an effective feature selection method is proposed for product review text sentiment classification. In order to validate the validity of the proposed method, we compared it with other methods respectively based on information gain and mutual information while support vector machine is adopted as the classifier. In this paper, 6 subexperiments are conducted by combining different feature selection methods with 2 kinds of candidate feature sets. Under 1006 review documents of cars, the experimental results indicate that the Fisher's discriminant ratio based on word frequency estimation has the best performance with F value 83.3% while the candidate features are the words which appear in both positive and negative texts.

CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles

PubMed Central

Pretto, Dalyir I.; Mendoza-Morales, Guadalupe; Lo, Joyce; Cao, Ru; Hadd, Andrew; Latham, Gary J.; Durbin-Johnson, Blythe; Hagerman, Randi; Tassone, Flora

2014-01-01

Background Greater than 200 CGG repeats in the 5′UTR of the FMR1 gene leads to epigenetic silencing and lack of the FMR1 protein, causing Fragile X Syndrome. Individuals carriers of a premutation (PM) allele with 55–200 CGG repeats are typically unmethylated and can present with clinical features defined as FMR1 associated conditions. Methods Blood samples from 17 male PM carriers were assessed clinically and molecularly by Southern Blot, Western Blot, PCR and QRT-PCR. Blood and brain tissue from additional 18 PM males were also similarly examined. Continuous outcomes were modeled using linear regression and binary outcomes were modeled using logistic regression. Results Methylated alleles were detected in different fractions of blood cells in all PM cases (n= 17). CGG repeat numbers correlated with percent of methylation and mRNA levels and, especially in the upper PM range, with greater number of clinical involvements. Inter/intra- tissue somatic instability and differences in percent methylation were observed between blood and fibroblasts (n=4) and also observed between blood and different brain regions in three of the 18 premutation cases examined. CGG repeat lengths in lymphocytes remained unchanged over a period of time ranging from 2–6 years, three cases for whom multiple samples were available. Conclusion In addition to CGG size instability, individuals with a PM expanded alleles can exhibit methylation and display more clinical features likely due to RNA toxicity and/or FMR1 silencing. The observed association between CGG repeat length and percent of methylation with the severity of the clinical phenotypes underscores the potential value of methylation in affected PM to further understand penetrance, inform diagnosis and to expand treatment options. PMID:24591415

The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.

PubMed

Gai, Liping; Liu, Hui; Cui, Jing-Hui; Yu, Weijian; Ding, Xiao-Dong

2017-03-20

The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis. Copyright © 2016. Published by Elsevier B.V.

Multicolor-based discrimination of 21 short tandem repeats and amelogenin using four fluorescent universal primers.

PubMed

Asari, Masaru; Okuda, Katsuhiro; Hoshina, Chisato; Omura, Tomohiro; Tasaki, Yoshikazu; Shiono, Hiroshi; Matsubara, Kazuo; Shimizu, Keiko

2016-02-01

The aim of this study was to develop a cost-effective genotyping method using high-quality DNA for human identification. A total of 21 short tandem repeats (STRs) and amelogenin were selected, and fluorescent fragments at 22 loci were simultaneously amplified in a single-tube reaction using locus-specific primers with 24-base universal tails and four fluorescent universal primers. Several nucleotide substitutions in universal tails and fluorescent universal primers enabled the detection of specific fluorescent fragments from the 22 loci. Multiplex polymerase chain reaction (PCR) produced intense FAM-, VIC-, NED-, and PET-labeled fragments ranging from 90 to 400 bp, and these fragments were discriminated using standard capillary electrophoretic analysis. The selected 22 loci were also analyzed using two commercial kits (the AmpFLSTR Identifiler Kit and the PowerPlex ESX 17 System), and results for two loci (D19S433 and D16S539) were discordant between these kits due to mutations at the primer binding sites. All genotypes from the 100 samples were determined using 2.5 ng of DNA by our method, and the expected alleles were completely recovered. Multiplex 22-locus genotyping using four fluorescent universal primers effectively reduces the costs to less than 20% of genotyping using commercial kits, and our method would be useful to detect silent alleles from commercial kit analysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Neutron-gamma discrimination with UGAB scintillator using zero-crossing method.

PubMed

Divani-Vais, N; Bayat, E; Firoozabadi, M M; Ghal-Eh, N

2013-01-01

The new-type scintillator, Ultima Gold Alpha-Beta (UGAB), was studied for its neutron-gamma discrimination capability. The figure-of-merit and peak-to-valley values for the neutron-gamma discrimination spectra of UGAB scintillator when exposed to (241)Am-Be neutron source were presented. The results show that this new-type scintillator can efficiently be used in neutron-gamma discrimination experiments.

Allele-specific copy-number discovery from whole-genome and whole-exome sequencing.

PubMed

Wang, WeiBo; Wang, Wei; Sun, Wei; Crowley, James J; Szatkiewicz, Jin P

2015-08-18

Copy-number variants (CNVs) are a major form of genetic variation and a risk factor for various human diseases, so it is crucial to accurately detect and characterize them. It is conceivable that allele-specific reads from high-throughput sequencing data could be leveraged to both enhance CNV detection and produce allele-specific copy number (ASCN) calls. Although statistical methods have been developed to detect CNVs using whole-genome sequence (WGS) and/or whole-exome sequence (WES) data, information from allele-specific read counts has not yet been adequately exploited. In this paper, we develop an integrated method, called AS-GENSENG, which incorporates allele-specific read counts in CNV detection and estimates ASCN using either WGS or WES data. To evaluate the performance of AS-GENSENG, we conducted extensive simulations, generated empirical data using existing WGS and WES data sets and validated predicted CNVs using an independent methodology. We conclude that AS-GENSENG not only predicts accurate ASCN calls but also improves the accuracy of total copy number calls, owing to its unique ability to exploit information from both total and allele-specific read counts while accounting for various experimental biases in sequence data. Our novel, user-friendly and computationally efficient method and a complete analytic protocol is freely available at https://sourceforge.net/projects/asgenseng/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes

PubMed Central

Kofoed, Megan; Milbury, Karissa L.; Chiang, Jennifer H.; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C.

2015-01-01

Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. PMID:26175450

An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes.

PubMed

Kofoed, Megan; Milbury, Karissa L; Chiang, Jennifer H; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C

2015-07-14

Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. Copyright © 2015 Kofoed et al.

Precise Estimation of Allele Frequencies of Single-Nucleotide Polymorphisms by a Quantitative SSCP Analysis of Pooled DNA

PubMed Central

Sasaki, Tomonari; Tahira, Tomoko; Suzuki, Akari; Higasa, Koichiro; Kukita, Yoji; Baba, Shingo; Hayashi, Kenshi

2001-01-01

We show that single-nucleotide polymorphisms (SNPs) of moderate to high heterozygosity (minor allele frequencies >10%) can be efficiently detected, and their allele frequencies accurately estimated, by pooling the DNA samples and applying a capillary-based SSCP analysis. In this method, alleles are separated into peaks, and their frequencies can be reliably and accurately quantified from their peak heights (SD <1.8%). We found that as many as 40% of publicly available SNPs that were analyzed by this method have widely differing allele frequency distributions among groups of different ethnicity (parents of Centre d'Etude Polymorphisme Humaine families vs. Japanese individuals). These results demonstrate the effectiveness of the present pooling method in the reevaluation of candidate SNPs that have been collected by examination of limited numbers of individuals. The method should also serve as a robust quantitative technique for studies in which a precise estimate of SNP allele frequencies is essential—for example, in linkage disequilibrium analysis. PMID:11083945

Allelic frequencies and statistical data obtained from 48 AIM INDEL loci in an admixed population from the Brazilian Amazon.

PubMed

Francez, Pablo Abdon da Costa; Ribeiro-Rodrigues, Elzemar Martins; dos Santos, Sidney Emanuel Batista

2012-01-01

Allelic frequencies of 48 informative insert-delete (INDEL) loci were obtained from a sample set of 130 unrelated individuals living in Macapá, a city located in the northern Amazon region, in Brazil. The values of heterozygosity (H), polymorphic information content (PIC), power of discrimination (PD), power of exclusion (PE), matching probability (MP) and typical paternity index (TPI) were calculated and showed the forensic efficiency of these genetic markers. Based on the allele frequency obtained for the population of Macapá, we estimated an interethnic admixture for the three parental groups (European, Native American and African) of, respectively, 50%, 21% and 29%. Comparing these allele frequencies with those of other Brazilian populations and the parental populations, statistically significant distances were found. The interpopulation genetic distance (F(ST) coefficients) to the present database ranged from F(ST)=0.0431 (p<0.00001) between Macapá and Belém to F(ST)=0.266 (p<0.00001) between Macapá and the Native American group. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Allele frequencies of combined DNA index system (CODIS) and non-CODIS short tandem repeat loci in Goiás, Central Brazil.

PubMed

Rodovalho, R G; Santos, G S; Cavalcanti, L M; Moura, B F S M; Rodrigues, E L; Lima, P R; Gigonzac, M A D; Vieira, T C

2015-07-03

In studies of human identification, obtaining a high standard of outcomes and satisfactory conclusions are directly related to the use of highly polymorphic molecular markers. In addition to the combined DNA index system (CODIS) group, it is also important to implement non-CODIS markers into the analysis, as they increase the power of discrimination. During the identification process, it is essential to consider the genetic variation among distinct groups of populations, as the allele frequencies are directly associated with the power of discrimination. However, the population of Goiás, a State located in Central Brazil, is characterized by a highly mixed population due to its diverse ethnic origins. In this study, a survey of the allelic frequencies in the Goiás population was carried out using a molecular assembly composed of 21 autosomal loci both from and external to the CODIS group. The new data, for some of the markers used, were statistically similar to those from previous studies. This consistency means that the use of these markers might serve as a parameter for future population comparisons. The results from these analyses further our knowledge of the study of human identification.

A Non-destructive Terahertz Spectroscopy-Based Method for Transgenic Rice Seed Discrimination via Sparse Representation

NASA Astrophysics Data System (ADS)

Hu, Xiaohua; Lang, Wenhui; Liu, Wei; Xu, Xue; Yang, Jianbo; Zheng, Lei

2017-08-01

Terahertz (THz) spectroscopy technique has been researched and developed for rapid and non-destructive detection of food safety and quality due to its low-energy and non-ionizing characteristics. The objective of this study was to develop a flexible identification model to discriminate transgenic and non-transgenic rice seeds based on terahertz (THz) spectroscopy. To extract THz spectral features and reduce the feature dimension, sparse representation (SR) is employed in this work. A sufficient sparsity level is selected to train the sparse coding of the THz data, and the random forest (RF) method is then applied to obtain a discrimination model. The results show that there exist differences between transgenic and non-transgenic rice seeds in THz spectral band and, comparing with Least squares support vector machines (LS-SVM) method, SR-RF is a better model for discrimination (accuracy is 95% in prediction set, 100% in calibration set, respectively). The conclusion is that SR may be more useful in the application of THz spectroscopy to reduce dimension and the SR-RF provides a new, effective, and flexible method for detection and identification of transgenic and non-transgenic rice seeds with THz spectral system.

A New Method for Estimating the Effective Population Size from Allele Frequency Changes

PubMed Central

Pollak, Edward

1983-01-01

A new procedure is proposed for estimating the effective population size, given that information is available on changes in frequencies of the alleles at one or more independently segregating loci and the population is observed at two or more separate times. Approximate expressions are obtained for the variances of the new statistic, as well as others, also based on allele frequency changes, that have been discussed in the literature. This analysis indicates that the new statistic will generally have a smaller variance than the others. Estimates of effective population sizes and of the standard errors of the estimates are computed for data on two fly populations that have been discussed in earlier papers. In both cases, there is evidence that the effective population size is very much smaller than the minimum census size of the population. PMID:17246147

Enantioseparation of cetirizine by chromatographic methods and discrimination by 1H-NMR.

PubMed

Taha, Elham A; Salama, Nahla N; Wang, Shudong

2009-03-01

Cetirizine is an antihistaminic drug used to prevent and treat allergic conditions. It is currently marketed as a racemate. The H1-antagonist activity of cetirizine is primarily due to (R)-levocetirizine. This has led to the introduction of (R)-levocetirizine into clinical practice, and the chiral switching is expected to be more selective and safer. The present work represents three methods for the analysis and chiral discrimination of cetirizine. The first method was based on the enantioseparation of cetirizine on silica gel TLC plates using different chiral selectors as mobile phase additives. The mobile phase enabling successful resolution was acetonitrile-water 17: 3, (v/v) containing 1 mM of chiral selector, namely hydroxypropyl-beta-cyclodextrin, chondroitin sulphate or vancomycin hydrochloride. The second method was a validated high performance liquid chromatography (HPLC), based on stereoselective separation of cetirizine and quantitative determination of its eutomer (R)-levocetirizine on a monolithic C18 column using hydroxypropyl-beta-cyclodextrin as a chiral mobile phase additive. The resolved peaks of (R)-levocetirizine and (S)-dextrocetirizine were confirmed by further mass spectrometry. The third method used a (1)H-NMR technique to characterize cetirizine and (R)-levocetirizine. These methods are selective and accurate, and can be easily applied for chiral discrimination and determination of cetirizine in drug substance and drug product in quality control laboratory. Moreover, chiral purity testing of (R)-levocetirizine can also be monitored by the chromatographic methods. Copyright 2009 John Wiley & Sons, Ltd.

Examination of Allelic Variation at the Hexokinase Loci of DROSOPHILA PSEUDOOBSCURA and D. PERSIMILIS by Different Methods

PubMed Central

Beckenbach, Andrew T.; Prakash, Satya

1977-01-01

Recently a number of electrophoretic techniques have been applied to reveal the presence of additional genetic variation among the electrophoretic mobility classes of the highly polymorphic xanthine dehydrogenase (XDH ) and esterase-5 (est-5) loci. We examined the hexokinase loci of Drosophila pseudoobscura and D. persimilis using a variety of techniques to determine whether further allelic variation could be revealed for these much less polymorphic loci and to analyze the nature of the known variation at the hexokinase-1 (hex-1) locus. The following studies were conducted: 135 strains of the two species from six localities were examined with buffer pH ranging from 5.5 to 10.0; 40 strains of D. pseudoobscura and 9 strains of D. persimilis from Mather were studied using starch gel concentrations ranging from 8.5 to 15.5% and were examined for differences in heat stability and reactivity to the thiol reagent pCMSA; strains were also tested for susceptibility to urea denaturation and differences in relative activities. Major findings of the work are: (1) No additional allelic variation could be detected at any of the hexokinase loci by applying these techniques. The finding of abundant hidden genetic variation in XDH and est-5 does not extend to all enzyme loci. (2) Evidence from studies using pCMSA indicates that the hex-1 alleles 0.6, 0.8, 1.0 and 1.2 of the two species form a series of unit charge steps. Since the 0.94 allele of D. persimilis has mobility intermediate between 0.8 and 1.0, it is argued that routine electrophoretic techniques are sensitive to at least some conservative amino acid substitutions. (3) Strong correlations were found at the hex-1 locus between low allelic frequency, reduced relative activity and reduced stability to heat and urea denaturation. Since the three sibling species, D. pseudoobscura, D. persimilis and D. miranda, all appear to share a common high frequency allele (1.0) at that locus, these findings are taken as evidence that the

Comparison of allele-specific PCR, created restriction-site PCR, and PCR with primer-introduced restriction analysis methods used for screening complex vertebral malformation carriers in Holstein cattle

PubMed Central

Altınel, Ahmet

2017-01-01

Complex vertebral malformation (CVM) is an inherited, autosomal recessive disorder of Holstein cattle. The aim of this study was to compare sensitivity, specificity, positive and negative predictive values, accuracy, and rapidity of allele-specific polymerase chain reaction (AS-PCR), created restriction-site PCR (CRS-PCR), and PCR with primer-introduced restriction analysis (PCR-PIRA), three methods used in identification of CVM carriers in a Holstein cattle population. In order to screen for the G>T mutation in the solute carrier family 35 member A3 (SLC35A3) gene, DNA sequencing as the gold standard method was used. The prevalence of carriers and the mutant allele frequency were 3.2% and 0.016, respectively, among Holstein cattle in the Thrace region of Turkey. Among the three methods, the fastest but least accurate was AS-PCR. Although the rapidity of CRS-PCR and PCR-PIRA were nearly equal, the accuracy of PCR-PIRA was higher than that of CRS-PCR. Therefore, among the three methods, PCR-PIRA appears to be the most efficacious for screening of mutant alleles when identifying CVM carriers in a Holstein cattle population. PMID:28927256

Digital pulse shape discrimination methods for n-γ separation in an EJ-301 liquid scintillation detector

NASA Astrophysics Data System (ADS)

Wan, Bo; Zhang, Xue-Ying; Chen, Liang; Ge, Hong-Lin; Ma, Fei; Zhang, Hong-Bin; Ju, Yong-Qin; Zhang, Yan-Bin; Li, Yan-Yan; Xu, Xiao-Wei

2015-11-01

A digital pulse shape discrimination system based on a programmable module NI-5772 has been established and tested with an EJ-301 liquid scintillation detector. The module was operated by running programs developed in LabVIEW, with a sampling frequency up to 1.6 GS/s. Standard gamma sources 22Na, 137Cs and 60Co were used to calibrate the EJ-301 liquid scintillation detector, and the gamma response function was obtained. Digital algorithms for the charge comparison method and zero-crossing method have been developed. The experimental results show that both digital signal processing (DSP) algorithms can discriminate neutrons from γ-rays. Moreover, the zero-crossing method shows better n-γ discrimination at 80 keVee and lower, whereas the charge comparison method gives better results at higher thresholds. In addition, the figure-of-merit (FOM) for detectors of two different dimensions were extracted at 9 energy thresholds, and it was found that the smaller detector presented better n-γ separation for fission neutrons. Supported by National Natural Science Foundation of China (91226107, 11305229) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA03030300)

Odour-based kin discrimination in the cooperatively breeding meerkat.

PubMed

Leclaire, Sarah; Nielsen, Johanna F; Thavarajah, Nathan K; Manser, Marta; Clutton-Brock, Tim H

2013-02-23

Kin recognition is a useful ability for animals, facilitating cooperation among relatives and avoidance of excessive kin competition or inbreeding. In meerkats, Suricata suricatta, encounters between unfamiliar kin are relatively frequent, and kin recognition by phenotype matching is expected to avoid inbreeding with close relatives. Here, we investigate whether female meerkats are able to discriminate the scent of unfamiliar kin from unfamiliar non-kin. Dominant females were presented with anal gland secretion from unfamiliar individuals that varied in their relatedness. Our result indicates that females spent more time investigating the scent of related than unrelated unfamiliar individuals, suggesting that females may use a phenotype matching mechanism (or recognition alleles) to discriminate the odour of their kin from the odour of their non-kin. Our study provides a key starting point for further investigations into the use of kin recognition for inbreeding avoidance in the widely studied meerkat.

Evaluation of hierarchical agglomerative cluster analysis methods for discrimination of primary biological aerosol

NASA Astrophysics Data System (ADS)

Crawford, I.; Ruske, S.; Topping, D. O.; Gallagher, M. W.

2015-07-01

In this paper we present improved methods for discriminating and quantifying Primary Biological Aerosol Particles (PBAP) by applying hierarchical agglomerative cluster analysis to multi-parameter ultra violet-light induced fluorescence (UV-LIF) spectrometer data. The methods employed in this study can be applied to data sets in excess of 1×106 points on a desktop computer, allowing for each fluorescent particle in a dataset to be explicitly clustered. This reduces the potential for misattribution found in subsampling and comparative attribution methods used in previous approaches, improving our capacity to discriminate and quantify PBAP meta-classes. We evaluate the performance of several hierarchical agglomerative cluster analysis linkages and data normalisation methods using laboratory samples of known particle types and an ambient dataset. Fluorescent and non-fluorescent polystyrene latex spheres were sampled with a Wideband Integrated Bioaerosol Spectrometer (WIBS-4) where the optical size, asymmetry factor and fluorescent measurements were used as inputs to the analysis package. It was found that the Ward linkage with z-score or range normalisation performed best, correctly attributing 98 and 98.1 % of the data points respectively. The best performing methods were applied to the BEACHON-RoMBAS ambient dataset where it was found that the z-score and range normalisation methods yield similar results with each method producing clusters representative of fungal spores and bacterial aerosol, consistent with previous results. The z-score result was compared to clusters generated with previous approaches (WIBS AnalysiS Program, WASP) where we observe that the subsampling and comparative attribution method employed by WASP results in the overestimation of the fungal spore concentration by a factor of 1.5 and the underestimation of bacterial aerosol concentration by a factor of 5. We suggest that this likely due to errors arising from misatrribution due to poor

Evolutionary dynamics of sporophytic self-incompatibility alleles in plants.

PubMed

Schierup, M H; Vekemans, X; Christiansen, F B

1997-10-01

The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed.

The Sociology of Discrimination: Racial Discrimination in Employment, Housing, Credit, and Consumer Markets

PubMed Central

Pager, Devah; Shepherd, Hana

2010-01-01

Persistent racial inequality in employment, housing, and a wide range of other social domains has renewed interest in the possible role of discrimination. And yet, unlike in the pre–civil rights era, when racial prejudice and discrimination were overt and widespread, today discrimination is less readily identifiable, posing problems for social scientific conceptualization and measurement. This article reviews the relevant literature on discrimination, with an emphasis on racial discrimination in employment, housing, credit markets, and consumer interactions. We begin by defining discrimination and discussing relevant methods of measurement. We then provide an overview of major findings from studies of discrimination in each of the four domains; and, finally, we turn to a discussion of the individual, organizational, and structural mechanisms that may underlie contemporary forms of discrimination. This discussion seeks to orient readers to some of the key debates in the study of discrimination and to provide a roadmap for those interested in building upon this long and important line of research. PMID:20689680

Perceived discrimination, humiliation, and mental health: a mixed-methods study among Haitian migrants in the Dominican Republic.

PubMed

Keys, Hunter M; Kaiser, Bonnie N; Foster, Jennifer W; Burgos Minaya, Rosa Y; Kohrt, Brandon A

2015-01-01

Many Haitian migrants live and work as undocumented laborers in the Dominican Republic. This study examines the legacy of anti-Haitian discrimination in the Dominican Republic and association of discrimination with mental health among Haitian migrants. This study used mixed methods to generate hypotheses for associations between discrimination and mental health of Haitian migrants in the Dominican Republic. In-depth interviews were conducted with 21 Haitian and 18 Dominican community members and clinicians. One hundred and twenty-seven Haitian migrants participated in a pilot cross-sectional community survey. Instruments included culturally adapted Kreyòl versions of the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) and a locally developed function impairment scale. Haitian migrants described humiliation (imilyasyon) as a reason for mental distress and barrier to health care. Dominicans reported that discrimination (discriminación) was not a current social problem and attributed negative social interactions to sociocultural, behavioral, and biological differences between Dominicans and Haitians. These qualitative findings were supported in the quantitative analyses. Perceived discrimination was significantly associated with depression severity and functional impairment. Perceived mistreatment by Dominicans was associated with a 6.6-point increase in BDI score (90% confidence interval [CI]: 3.29, 9.9). Knowing someone who was interrogated or deported was associated with a 3.4-point increase in BAI score (90% CI: 0.22, 6.64). Both qualitative and quantitative methods suggest that perceived discrimination and the experience of humiliation contribute to Haitian migrant mental ill-health and limit access to health care. Future research should evaluate these associations and identify intervention pathways for both improved treatment access and reduction of discrimination-related health risk factors.

Novel methods for the molecular discrimination of Fasciola spp. on the basis of nuclear protein-coding genes.

PubMed

Shoriki, Takuya; Ichikawa-Seki, Madoka; Suganuma, Keisuke; Naito, Ikunori; Hayashi, Kei; Nakao, Minoru; Aita, Junya; Mohanta, Uday Kumar; Inoue, Noboru; Murakami, Kenji; Itagaki, Tadashi

2016-06-01

Fasciolosis is an economically important disease of livestock caused by Fasciola hepatica, Fasciola gigantica, and aspermic Fasciola flukes. The aspermic Fasciola flukes have been discriminated morphologically from the two other species by the absence of sperm in their seminal vesicles. To date, the molecular discrimination of F. hepatica and F. gigantica has relied on the nucleotide sequences of the internal transcribed spacer 1 (ITS1) region. However, ITS1 genotypes of aspermic Fasciola flukes cannot be clearly differentiated from those of F. hepatica and F. gigantica. Therefore, more precise and robust methods are required to discriminate Fasciola spp. In this study, we developed PCR restriction fragment length polymorphism and multiplex PCR methods to discriminate F. hepatica, F. gigantica, and aspermic Fasciola flukes on the basis of the nuclear protein-coding genes, phosphoenolpyruvate carboxykinase and DNA polymerase delta, which are single locus genes in most eukaryotes. All aspermic Fasciola flukes used in this study had mixed fragment pattern of F. hepatica and F. gigantica for both of these genes, suggesting that the flukes are descended through hybridization between the two species. These molecular methods will facilitate the identification of F. hepatica, F. gigantica, and aspermic Fasciola flukes, and will also prove useful in etiological studies of fasciolosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Allelic Prevalence of ABO Blood Group Genes in Iranian Azari Population

PubMed Central

Nojavan, Mohammad; Shamsasenjan, Karrim; Movassaghpour, Ali Akbar; Akbarzadehlaleh, Parvin; Torabi, Seyd Esmail; Ghojazadeh, Morteza

2012-01-01

Introduction ABO blood group system is the most important blood group in transfusion and has been widely used in population studies. Several molecular techniques for ABO allele’s detection are widely used for distinguishing various alleles of glycosyl transferase locus on chromosome 9. Methods 744 randomly selected samples from Azari donors of East Azerbaijan province (Iran) were examined using well-adjusted multiplex allele- specific PCR ABO genotyping technique. Results The results were consistent for all individuals. The ABO blood group genotype of 744 healthy Azari blood donors was: 25.8% AA/AO (2), 7.6% AO (1), 1.6% BB, 11.3% B0 (1), 10% AB, 9.3% 0(1)0(1) and 15.3%0(1)0(2). The highest genotype frequency belonged to O01/O02 genotype (15.3%) and the lowest frequency belonged to A101/A102 genotype (0.4%). Conclusions: The frequencies of ABO alleles didn’t show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). Conclusions The frequencies of ABO alleles didn’t show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). PMID:23678461

Street Lighting Infrastructure Assessment Using Discriminant and GIS Method on Mount Merapi Evacuation Road

NASA Astrophysics Data System (ADS)

Izdihar, R. P.; Maryono, M.; Widjonarko, W.; Rahayu, S.

2018-02-01

This research aims to assess street lighting infrastructure in rural-urban of Mount Merapi Evacuation road. Three evacuation road/corridor; Mriyan-Boyolali, Wonodoyo-Boyolali and Samiran-Boyolali are selected as case study. By using discriminant this study examine 6 variables namely type of lamp, physical component, height, time, power and cons consumption. In addition this study also using GIS method to assessing geographical feature as of previous result. According to the discriminant analysis, the characteristic of street lighting could be distinguished as two characteristic, while from the GIS assessment, the study found three characteristic of geographical street lighting feature.

Independent components analysis to increase efficiency of discriminant analysis methods (FDA and LDA): Application to NMR fingerprinting of wine.

PubMed

Monakhova, Yulia B; Godelmann, Rolf; Kuballa, Thomas; Mushtakova, Svetlana P; Rutledge, Douglas N

2015-08-15

Discriminant analysis (DA) methods, such as linear discriminant analysis (LDA) or factorial discriminant analysis (FDA), are well-known chemometric approaches for solving classification problems in chemistry. In most applications, principle components analysis (PCA) is used as the first step to generate orthogonal eigenvectors and the corresponding sample scores are utilized to generate discriminant features for the discrimination. Independent components analysis (ICA) based on the minimization of mutual information can be used as an alternative to PCA as a preprocessing tool for LDA and FDA classification. To illustrate the performance of this ICA/DA methodology, four representative nuclear magnetic resonance (NMR) data sets of wine samples were used. The classification was performed regarding grape variety, year of vintage and geographical origin. The average increase for ICA/DA in comparison with PCA/DA in the percentage of correct classification varied between 6±1% and 8±2%. The maximum increase in classification efficiency of 11±2% was observed for discrimination of the year of vintage (ICA/FDA) and geographical origin (ICA/LDA). The procedure to determine the number of extracted features (PCs, ICs) for the optimum DA models was discussed. The use of independent components (ICs) instead of principle components (PCs) resulted in improved classification performance of DA methods. The ICA/LDA method is preferable to ICA/FDA for recognition tasks based on NMR spectroscopic measurements. Copyright © 2015 Elsevier B.V. All rights reserved.

Simulation of introgression of the polled allele into the Holstein breed via conventional breeding versus gene editing

USDA-ARS?s Scientific Manuscript database

The objective of this study was to simulate the introgression of the polled allele into a dairy cattle population and compare the impact of using the methods of conventional breeding versus gene editing to increase the frequency of the polled allele. The rate of minor allele frequency (MAF) change, ...

Allelic genealogies in sporophytic self-incompatibility systems in plants.

PubMed

Schierup, M H; Vekemans, X; Christiansen, F B

1998-11-01

Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed.

Geophysical technique for mineral exploration and discrimination based on electromagnetic methods and associated systems

DOEpatents

Zhdanov,; Michael, S [Salt Lake City, UT

2008-01-29

Mineral exploration needs a reliable method to distinguish between uneconomic mineral deposits and economic mineralization. A method and system includes a geophysical technique for subsurface material characterization, mineral exploration and mineral discrimination. The technique introduced in this invention detects induced polarization effects in electromagnetic data and uses remote geophysical observations to determine the parameters of an effective conductivity relaxation model using a composite analytical multi-phase model of the rock formations. The conductivity relaxation model and analytical model can be used to determine parameters related by analytical expressions to the physical characteristics of the microstructure of the rocks and minerals. These parameters are ultimately used for the discrimination of different components in underground formations, and in this way provide an ability to distinguish between uneconomic mineral deposits and zones of economic mineralization using geophysical remote sensing technology.

Evaluation of hierarchical agglomerative cluster analysis methods for discrimination of primary biological aerosol

NASA Astrophysics Data System (ADS)

Crawford, I.; Ruske, S.; Topping, D. O.; Gallagher, M. W.

2015-11-01

In this paper we present improved methods for discriminating and quantifying primary biological aerosol particles (PBAPs) by applying hierarchical agglomerative cluster analysis to multi-parameter ultraviolet-light-induced fluorescence (UV-LIF) spectrometer data. The methods employed in this study can be applied to data sets in excess of 1 × 106 points on a desktop computer, allowing for each fluorescent particle in a data set to be explicitly clustered. This reduces the potential for misattribution found in subsampling and comparative attribution methods used in previous approaches, improving our capacity to discriminate and quantify PBAP meta-classes. We evaluate the performance of several hierarchical agglomerative cluster analysis linkages and data normalisation methods using laboratory samples of known particle types and an ambient data set. Fluorescent and non-fluorescent polystyrene latex spheres were sampled with a Wideband Integrated Bioaerosol Spectrometer (WIBS-4) where the optical size, asymmetry factor and fluorescent measurements were used as inputs to the analysis package. It was found that the Ward linkage with z-score or range normalisation performed best, correctly attributing 98 and 98.1 % of the data points respectively. The best-performing methods were applied to the BEACHON-RoMBAS (Bio-hydro-atmosphere interactions of Energy, Aerosols, Carbon, H2O, Organics and Nitrogen-Rocky Mountain Biogenic Aerosol Study) ambient data set, where it was found that the z-score and range normalisation methods yield similar results, with each method producing clusters representative of fungal spores and bacterial aerosol, consistent with previous results. The z-score result was compared to clusters generated with previous approaches (WIBS AnalysiS Program, WASP) where we observe that the subsampling and comparative attribution method employed by WASP results in the overestimation of the fungal spore concentration by a factor of 1.5 and the underestimation of

A LDR-PCR approach for multiplex polymorphisms genotyping of severely degraded DNA with fragment sizes <100 bp.

PubMed

Zhang, Zhen; Wang, Bao-Jie; Guan, Hong-Yu; Pang, Hao; Xuan, Jin-Feng

2009-11-01

Reducing amplicon sizes has become a major strategy for analyzing degraded DNA typical of forensic samples. However, amplicon sizes in current mini-short tandem repeat-polymerase chain reaction (PCR) and mini-sequencing assays are still not suitable for analysis of severely degraded DNA. In this study, we present a multiplex typing method that couples ligase detection reaction with PCR that can be used to identify single nucleotide polymorphisms and small-scale insertion/deletions in a sample of severely fragmented DNA. This method adopts thermostable ligation for allele discrimination and subsequent PCR for signal enhancement. In this study, four polymorphic loci were used to assess the ability of this technique to discriminate alleles in an artificially degraded sample of DNA with fragment sizes <100 bp. Our results showed clear allelic discrimination of single or multiple loci, suggesting that this method might aid in the analysis of extremely degraded samples in which allelic drop out of larger fragments is observed.

Short mucin 6 alleles are associated with H pylori infection

PubMed Central

Nguyen, Thai V; Janssen, Marcel JR; Gritters, Paulien; te Morsche, René HM; Drenth, Joost PH; van Asten, Henri; Laheij, Robert JF; Jansen, Jan BMJ

2006-01-01

AIM: To investigate the relationship between mucin 6 (MUC6) VNTR length and H pylori infection. METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (PvuII) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by 14C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (≤ 13.5 kbp) and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)]. RESULTS: 160 patients were studied (mean age 43 years, 36% were males, 58% H pylori positive). MUC6 PvuII-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6 genotype, 43% (24/56), 57% (25/58) and 76% (11/46) were infected with H pylori, respectively (P = 0.003). CONCLUSION: Short MUC6 alleles are associated with H pylori infection. PMID:17009402

Theoretical vs. empirical discriminability: the application of ROC methods to eyewitness identification.

PubMed

Wixted, John T; Mickes, Laura

2018-01-01

Receiver operating characteristic (ROC) analysis was introduced to the field of eyewitness identification 5 years ago. Since that time, it has been both influential and controversial, and the debate has raised an issue about measuring discriminability that is rarely considered. The issue concerns the distinction between empirical discriminability (measured by area under the ROC curve) vs. underlying/theoretical discriminability (measured by d' or variants of it). Under most circumstances, the two measures will agree about a difference between two conditions in terms of discriminability. However, it is possible for them to disagree, and that fact can lead to confusion about which condition actually yields higher discriminability. For example, if the two conditions have implications for real-world practice (e.g., a comparison of competing lineup formats), should a policymaker rely on the area-under-the-curve measure or the theory-based measure? Here, we illustrate the fact that a given empirical ROC yields as many underlying discriminability measures as there are theories that one is willing to take seriously. No matter which theory is correct, for practical purposes, the singular area-under-the-curve measure best identifies the diagnostically superior procedure. For that reason, area under the ROC curve informs policy in a way that underlying theoretical discriminability never can. At the same time, theoretical measures of discriminability are equally important, but for a different reason. Without an adequate theoretical understanding of the relevant task, the field will be in no position to enhance empirical discriminability.

New RNAi strategy for selective suppression of a mutant allele in polyglutamine disease.

PubMed

Kubodera, Takayuki; Yokota, Takanori; Ishikawa, Kinya; Mizusawa, Hidehiro

2005-12-01

In gene therapy of dominantly inherited diseases with small interfering RNA (siRNA), mutant allele specific suppression may be necessary for diseases in which the defective gene normally has an important role. It is difficult, however, to design a mutant allele-specific siRNA for trinucleotide repeat diseases in which the difference of sequences is only repeat length. To overcome this problem, we use a new RNA interference (RNAi) strategy for selective suppression of mutant alleles. Both mutant and wild-type alleles are inhibited by the most effective siRNA, and wild-type protein is restored using the wild-type mRNA modified to be resistant to the siRNA. Here, we applied this method to spinocerebellar ataxia type 6 (SCA6). We discuss its feasibility and problems for future gene therapy.

Protective effect of the APOE-e3 allele in Alzheimer's disease

PubMed Central

de-Almada, B.V.P.; de-Almeida, L.D.; Camporez, D.; de-Moraes, M.V.D.; Morelato, R.L.; Perrone, A.M.S.; Belcavello, L.; Louro, I.D.; de-Paula, F.

2011-01-01

Although several alleles of susceptibility to Alzheimer's disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95%CI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95%CI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to estabilish a profile of risk for AD in the population from Vitória, ES. PMID:22068907

Early detection of nonnative alleles in fish populations: When sample size actually matters

USGS Publications Warehouse

Croce, Patrick Della; Poole, Geoffrey C.; Payne, Robert A.; Gresswell, Bob

2017-01-01

Reliable detection of nonnative alleles is crucial for the conservation of sensitive native fish populations at risk of introgression. Typically, nonnative alleles in a population are detected through the analysis of genetic markers in a sample of individuals. Here we show that common assumptions associated with such analyses yield substantial overestimates of the likelihood of detecting nonnative alleles. We present a revised equation to estimate the likelihood of detecting nonnative alleles in a population with a given level of admixture. The new equation incorporates the effects of the genotypic structure of the sampled population and shows that conventional methods overestimate the likelihood of detection, especially when nonnative or F-1 hybrid individuals are present. Under such circumstances—which are typical of early stages of introgression and therefore most important for conservation efforts—our results show that improved detection of nonnative alleles arises primarily from increasing the number of individuals sampled rather than increasing the number of genetic markers analyzed. Using the revised equation, we describe a new approach to determining the number of individuals to sample and the number of diagnostic markers to analyze when attempting to monitor the arrival of nonnative alleles in native populations.

Multivariate methods to visualise colour-space and colour discrimination data.

PubMed

Hastings, Gareth D; Rubin, Alan

2015-01-01

Despite most modern colour spaces treating colour as three-dimensional (3-D), colour data is usually not visualised in 3-D (and two-dimensional (2-D) projection-plane segments and multiple 2-D perspective views are used instead). The objectives of this article are firstly, to introduce a truly 3-D percept of colour space using stereo-pairs, secondly to view colour discrimination data using that platform, and thirdly to apply formal statistics and multivariate methods to analyse the data in 3-D. This is the first demonstration of the software that generated stereo-pairs of RGB colour space, as well as of a new computerised procedure that investigated colour discrimination by measuring colour just noticeable differences (JND). An initial pilot study and thorough investigation of instrument repeatability were performed. Thereafter, to demonstrate the capabilities of the software, five colour-normal and one colour-deficient subject were examined using the JND procedure and multivariate methods of data analysis. Scatter plots of responses were meaningfully examined in 3-D and were useful in evaluating multivariate normality as well as identifying outliers. The extent and direction of the difference between each JND response and the stimulus colour point was calculated and appreciated in 3-D. Ellipsoidal surfaces of constant probability density (distribution ellipsoids) were fitted to response data; the volumes of these ellipsoids appeared useful in differentiating the colour-deficient subject from the colour-normals. Hypothesis tests of variances and covariances showed many statistically significant differences between the results of the colour-deficient subject and those of the colour-normals, while far fewer differences were found when comparing within colour-normals. The 3-D visualisation of colour data using stereo-pairs, as well as the statistics and multivariate methods of analysis employed, were found to be unique and useful tools in the representation and study

Human minisatellite alleles detectable only after PCR amplification.

PubMed

Armour, J A; Crosier, M; Jeffreys, A J

1992-01-01

We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange

PubMed Central

Hmelo, Laura R.; Borlee, Bradley R.; Almblad, Henrik; Love, Michelle E.; Randall, Trevor E.; Tseng, Boo Shan; Lin, Chuyang; Irie, Yasuhiko; Storek, Kelly M.; Yang, Jaeun Jane; Siehnel, Richard J.; Howell, P. Lynne; Singh, Pradeep K.; Tolker-Nielsen, Tim; Parsek, Matthew R.; Schweizer, Herbert P.; Harrison, Joe J.

2016-01-01

Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knockins, as well as single nucleotide insertions, deletions and substitutions in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selection are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNA. The entire procedure requires ~2 weeks. PMID:26492139

Joint recognition and discrimination in nonlinear feature space

NASA Astrophysics Data System (ADS)

Talukder, Ashit; Casasent, David P.

1997-09-01

A new general method for linear and nonlinear feature extraction is presented. It is novel since it provides both representation and discrimination while most other methods are concerned with only one of these issues. We call this approach the maximum representation and discrimination feature (MRDF) method and show that the Bayes classifier and the Karhunen- Loeve transform are special cases of it. We refer to our nonlinear feature extraction technique as nonlinear eigen- feature extraction. It is new since it has a closed-form solution and produces nonlinear decision surfaces with higher rank than do iterative methods. Results on synthetic databases are shown and compared with results from standard Fukunaga- Koontz transform and Fisher discriminant function methods. The method is also applied to an automated product inspection problem (discrimination) and to the classification and pose estimation of two similar objects (representation and discrimination).

Rapid identification of tomato Sw-5 resistance-breaking isolates of Tomato spotted wilt virus using high resolution melting and TaqMan SNP Genotyping assays as allelic discrimination techniques.

PubMed

di Rienzo, Valentina; Bubici, Giovanni; Montemurro, Cinzia; Cillo, Fabrizio

2018-01-01

In tomato, resistance to Tomato spotted wilt virus (TSWV) is conferred by the dominant gene, designated Sw-5. Virulent Sw-5 resistance breaking (SRB) mutants of TSWV have been reported on Sw-5 tomato cultivars. Two different PCR-based allelic discrimination techniques, namely Custom TaqMan™ SNP Genotyping and high-resolution melting (HRM) assays, were developed and compared for their ability to distinguish between avirulent (Sw-5 non-infecting, SNI) and SRB biotypes. TaqMan assays proved to be more sensitive (threshold of detection in a range of 50-70 TSWV RNA copies) and more reliable than HRM, assigning 25 TSWV isolates to their correct genotype with an accuracy of 100%. Moreover, the TaqMan SNP assays were further improved developing a rapid and simple protocol that included crude leaf extraction for RNA template preparations. On the other hand, HRM assays showed higher levels of sensitivity than TaqMan when used to co-detect both biotypes in different artificial mixtures. These diagnostic assays contributed to gain preliminary information on the epidemiology of TSWV isolates in open field conditions. In fact, the presented data suggest that SRB isolates are present as stable populations established year round, persisting on both winter (globe artichoke) and summer (tomato) crops, in the same cultivated areas of Southern Italy.

Two Methods for Teaching Simple Visual Discriminations to Learners with Severe Disabilities

ERIC Educational Resources Information Center

Graff, Richard B.; Green, Gina

2004-01-01

Simple discriminations are involved in many functional skills; additionally, they are components of conditional discriminations (identity and arbitrary matching-to-sample), which are involved in a wide array of other important performances. Many individuals with severe disabilities have difficulty acquiring simple discriminations with standard…

Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

PubMed

Remington, David L

2015-12-01

Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

A new method for fingerprinting sediments source contributions using distances from discriminant function analysis

USDA-ARS?s Scientific Manuscript database

Mixing models have been used to predict sediment source contributions. The inherent problem of the mixing models limited the number of sediment sources. The objective of this study is to develop and evaluate a new method using Discriminant Function Analysis (DFA) to fingerprint sediment source contr...

Existence of the rdl mutant alleles among the anopheles malaria vector in Indonesia

PubMed Central

2012-01-01

Background The gamma-aminobutyric acid (GABA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide. GABA-receptors, with a naturally occurring amino acid substitution, A302S/G in the putative ion-channel lining region, confer resistance to cyclodiene insecticides that includes aldrin, chlordane, dieldrin, heptachlor, endrin and endosulphan. Methods A total of 154 mosquito samples from 10 provinces of malaria-endemic areas across Indonesia (Aceh, North Sumatra, Bangka Belitung, Lampung, Central Java, East Nusa Tenggara, West Nusa Tenggara, West Sulawesi, Molucca and North Molucca) were obtained and identified by species, using morphological characteristic. The DNA was individually extracted using chelex-ion exchanger and the DNA obtained was used for analyses using sequencing method. Results Molecular analysis indicated 11% of the total 154 Anopheles samples examined, carried Rdl mutant alleles. All of the alleles were found in homozygous form. Rdl 302S allele was observed in Anopheles vagus (from Central Java, Lampung, and West Nusa Tenggara), Anopheles aconitus (from Central Java), Anopheles barbirostris (from Central Java and Lampung), Anopheles sundaicus (from North Sumatra and Lampung), Anopheles nigerrimus (from North Sumatra), whereas the 302 G allele was only found in Anopheles farauti from Molucca. Conclusion The existence of the Rdl mutant allele indicates that, either insecticide pressure on the Anopheles population in these areas might still be ongoing (though not directly associated with the malaria control programme) or that the mutant form of the Rdl allele is relatively stable in the absence of insecticide. Nonetheless, the finding suggests that integrated pest management is warranted in malaria-endemic areas where insecticides are widely used for other purposes. PMID:22364613

A pulse-shape discrimination method for improving Gamma-ray spectrometry based on a new digital shaping filter

NASA Astrophysics Data System (ADS)

Qin, Zhang-jian; Chen, Chuan; Luo, Jun-song; Xie, Xing-hong; Ge, Liang-quan; Wu, Qi-fan

2018-04-01

It is a usual practice for improving spectrum quality by the mean of designing a good shaping filter to improve signal-noise ratio in development of nuclear spectroscopy. Another method is proposed in the paper based on discriminating pulse-shape and discarding the bad pulse whose shape is distorted as a result of abnormal noise, unusual ballistic deficit or bad pulse pile-up. An Exponentially Decaying Pulse (EDP) generated in nuclear particle detectors can be transformed into a Mexican Hat Wavelet Pulse (MHWP) and the derivation process of the transform is given. After the transform is performed, the baseline drift is removed in the new MHWP. Moreover, the MHWP-shape can be discriminated with the three parameters: the time difference between the two minima of the MHWP, and the two ratios which are from the amplitude of the two minima respectively divided by the amplitude of the maximum in the MHWP. A new type of nuclear spectroscopy was implemented based on the new digital shaping filter and the Gamma-ray spectra were acquired with a variety of pulse-shape discrimination levels. It had manifested that the energy resolution and the peak-Compton ratio were both improved after the pulse-shape discrimination method was used.

Heuristics to Facilitate Understanding of Discriminant Analysis.

ERIC Educational Resources Information Center

Van Epps, Pamela D.

This paper discusses the principles underlying discriminant analysis and constructs a simulated data set to illustrate its methods. Discriminant analysis is a multivariate technique for identifying the best combination of variables to maximally discriminate between groups. Discriminant functions are established on existing groups and used to…

Allelic Analysis of Sheath Blight Resistance with Association Mapping in Rice

PubMed Central

Jia, Limeng; Yan, Wengui; Zhu, Chengsong; Agrama, Hesham A.; Jackson, Aaron; Yeater, Kathleen; Li, Xiaobai; Huang, Bihu; Hu, Biaolin; McClung, Anna; Wu, Dianxing

2012-01-01

Sheath blight (ShB) caused by the soil-borne pathogen Rhizoctonia solani is one of the most devastating diseases in rice world-wide. Global attention has focused on examining individual mapping populations for quantitative trait loci (QTLs) for ShB resistance, but to date no study has taken advantage of association mapping to examine hundreds of lines for potentially novel QTLs. Our objective was to identify ShB QTLs via association mapping in rice using 217 sub-core entries from the USDA rice core collection, which were phenotyped with a micro-chamber screening method and genotyped with 155 genome-wide markers. Structure analysis divided the mapping panel into five groups, and model comparison revealed that PCA5 with genomic control was the best model for association mapping of ShB. Ten marker loci on seven chromosomes were significantly associated with response to the ShB pathogen. Among multiple alleles in each identified loci, the allele contributing the greatest effect to ShB resistance was named the putative resistant allele. Among 217 entries, entry GSOR 310389 contained the most putative resistant alleles, eight out of ten. The number of putative resistant alleles presented in an entry was highly and significantly correlated with the decrease of ShB rating (r = −0.535) or the increase of ShB resistance. Majority of the resistant entries that contained a large number of the putative resistant alleles belonged to indica, which is consistent with a general observation that most ShB resistant accessions are of indica origin. These findings demonstrate the potential to improve breeding efficiency by using marker-assisted selection to pyramid putative resistant alleles from various loci in a cultivar for enhanced ShB resistance in rice. PMID:22427867

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus.

PubMed

Liu, Q; Bu, D-F; Li, D; Zhu, X-J

2008-03-01

Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.

Estimation of mating system parameters in plant populations using marker loci with null alleles.

PubMed

Ross, H A

1986-06-01

An Expectation-Maximization (EM)-algorithm procedure is presented that extends Cheliak et al. (1983) method of maximum-likelihood estimation of mating system parameters of mixed mating system models. The extension permits the estimation of the rate of self-fertilization (s) and allele frequencies (Pi) at loci in outcrossing pollen, at marker loci having recessive null alleles. The algorithm makes use of maternal and filial genotypic arrays obtained by the electrophoretic analysis of cohorts of progeny. The genotypes of maternal plants must be known. Explicit equations are given for cases when the genotype of the maternal gamete inherited by a seed can (gymnosperms) or cannot (angiosperms) be determined. The procedure can accommodate any number of codominant alleles, but only one recessive null allele at each locus. An example, using actual data from Pinus banksiana, is presented to illustrate the application of this EM algorithm to the estimation of mating system parameters using marker loci having both codominant and recessive alleles.

Study of a Vocal Feature Selection Method and Vocal Properties for Discriminating Four Constitution Types

PubMed Central

Kim, Keun Ho; Ku, Boncho; Kang, Namsik; Kim, Young-Su; Jang, Jun-Su; Kim, Jong Yeol

2012-01-01

The voice has been used to classify the four constitution types, and to recognize a subject's health condition by extracting meaningful physical quantities, in traditional Korean medicine. In this paper, we propose a method of selecting the reliable variables from various voice features, such as frequency derivative features, frequency band ratios, and intensity, from vowels and a sentence. Further, we suggest a process to extract independent variables by eliminating explanatory variables and reducing their correlation and remove outlying data to enable reliable discriminant analysis. Moreover, the suitable division of data for analysis, according to the gender and age of subjects, is discussed. Finally, the vocal features are applied to a discriminant analysis to classify each constitution type. This method of voice classification can be widely used in the u-Healthcare system of personalized medicine and for improving diagnostic accuracy. PMID:22529874

Fast-HPLC Fingerprinting to Discriminate Olive Oil from Other Edible Vegetable Oils by Multivariate Classification Methods.

PubMed

Jiménez-Carvelo, Ana M; González-Casado, Antonio; Pérez-Castaño, Estefanía; Cuadros-Rodríguez, Luis

2017-03-01

A new analytical method for the differentiation of olive oil from other vegetable oils using reversed-phase LC and applying chemometric techniques was developed. A 3 cm short column was used to obtain the chromatographic fingerprint of the methyl-transesterified fraction of each vegetable oil. The chromatographic analysis took only 4 min. The multivariate classification methods used were k-nearest neighbors, partial least-squares (PLS) discriminant analysis, one-class PLS, support vector machine classification, and soft independent modeling of class analogies. The discrimination of olive oil from other vegetable edible oils was evaluated by several classification quality metrics. Several strategies for the classification of the olive oil were used: one input-class, two input-class, and pseudo two input-class.

An Inexpensive and Automated Method for Presenting Olfactory or Tactile Stimuli to Rats in a Two-Choice Discrimination Task

ERIC Educational Resources Information Center

Iversen, Iver H.

2008-01-01

An inexpensive and automated method for presentation of olfactory or tactile stimuli in a two-choice task for rats was implemented with the use of a computer-controlled bidirectional motor. The motor rotated a disk that presented two stimuli of different texture for tactile discrimination, or different odor for olfactory discrimination. Because…

Nucleation and Spread of an Invasive Allele

NASA Astrophysics Data System (ADS)

Korniss, Gyorgy; Caraco, Thomas

2005-03-01

We analyze a prototypical discrete spatial model for the spread of an invasive allele when individuals compete preemptively for common limiting resources. Initially, the population is genetically monomorphic with the resident allele at high density. The invasive allele is introduced through rare, but recurrent, mutation. The mutant allele is the better competitor (has an individual-level advantage) but its spread is limited by the local availability of resources. We find that each successful introduction of the mutant leads to strong spatial clustering. Spatial patterns in simulation resemble nucleation and subsequent growth, articulately described by Avrami's law in sufficiently large systemsootnotetextG. Korniss and T. Caraco, J. Theor. Biol. (in press, 2004); http://www.rpi.edu/ korniss/Research/JTB04.pdf.

Haplotypic Background of a Private Allele at High Frequency in the Americas

PubMed Central

Schroeder, Kari B.; Jakobsson, Mattias; Crawford, Michael H.; Schurr, Theodore G.; Boca, Simina M.; Conrad, Donald F.; Tito, Raul Y.; Osipova, Ludmilla P.; Tarskaia, Larissa A.; Zhadanov, Sergey I.; Wall, Jeffrey D.; Pritchard, Jonathan K.; Malhi, Ripan S.; Smith, David G.; Rosenberg, Noah A.

2009-01-01

Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the “American Modal Haplotype” (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all

Component-based subspace linear discriminant analysis method for face recognition with one training sample

NASA Astrophysics Data System (ADS)

Huang, Jian; Yuen, Pong C.; Chen, Wen-Sheng; Lai, J. H.

2005-05-01

Many face recognition algorithms/systems have been developed in the last decade and excellent performances have also been reported when there is a sufficient number of representative training samples. In many real-life applications such as passport identification, only one well-controlled frontal sample image is available for training. Under this situation, the performance of existing algorithms will degrade dramatically or may not even be implemented. We propose a component-based linear discriminant analysis (LDA) method to solve the one training sample problem. The basic idea of the proposed method is to construct local facial feature component bunches by moving each local feature region in four directions. In this way, we not only generate more samples with lower dimension than the original image, but also consider the face detection localization error while training. After that, we propose a subspace LDA method, which is tailor-made for a small number of training samples, for the local feature projection to maximize the discrimination power. Theoretical analysis and experiment results show that our proposed subspace LDA is efficient and overcomes the limitations in existing LDA methods. Finally, we combine the contributions of each local component bunch with a weighted combination scheme to draw the recognition decision. A FERET database is used for evaluating the proposed method and results are encouraging.

Assigning breed origin to alleles in crossbred animals.

PubMed

Vandenplas, Jérémie; Calus, Mario P L; Sevillano, Claudia A; Windig, Jack J; Bastiaansen, John W M

2016-08-22

For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. The BOA approach accurately assigns

New Geophysical Technique for Mineral Exploration and Mineral Discrimination Based on Electromagnetic Methods

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

Michael S. Zhdanov

2005-03-09

The research during the first year of the project was focused on developing the foundations of a new geophysical technique for mineral exploration and mineral discrimination, based on electromagnetic (EM) methods. The proposed new technique is based on examining the spectral induced polarization effects in electromagnetic data using modern distributed acquisition systems and advanced methods of 3-D inversion. The analysis of IP phenomena is usually based on models with frequency dependent complex conductivity distribution. One of the most popular is the Cole-Cole relaxation model. In this progress report we have constructed and analyzed a different physical and mathematical model ofmore » the IP effect based on the effective-medium theory. We have developed a rigorous mathematical model of multi-phase conductive media, which can provide a quantitative tool for evaluation of the type of mineralization, using the conductivity relaxation model parameters. The parameters of the new conductivity relaxation model can be used for discrimination of the different types of rock formations, which is an important goal in mineral exploration. The solution of this problem requires development of an effective numerical method for EM forward modeling in 3-D inhomogeneous media. During the first year of the project we have developed a prototype 3-D IP modeling algorithm using the integral equation (IP) method. Our IE forward modeling code INTEM3DIP is based on the contraction IE method, which improves the convergence rate of the iterative solvers. This code can handle various types of sources and receivers to compute the effect of a complex resistivity model. We have tested the working version of the INTEM3DIP code for computer simulation of the IP data for several models including a southwest US porphyry model and a Kambalda-style nickel sulfide deposit. The numerical modeling study clearly demonstrates how the various complex resistivity models manifest differently in the

Molecular diversity of HLA-Cw alleles in the Maratha community of Mumbai, Maharashtra, western India.

PubMed

Shankarkumar, U; Ghosh, K; Mohanty, D

2005-08-01

Recent advances suggest a significant role for the HLA-C locus as a target of alloreactions after bone marrow transplantation. The biological importance of products of the HLA-C locus, both as transplant antigens and as ligands for natural killer (NK) cells, is well established. A total of 10 different serologically defined HLA-Cw antigen specificities (Cw1-Cw10) are encoded by the C locus; however, there are now 151 different alleles that can be identified by molecular methods. Serological definition of Cw alleles therefore includes 20-50% blanks, which cannot be detected by the available antisera. We used the molecular method of polymerase chain reaction (PCR)-based sequence-specific amplification and probe hybridization to define Cw alleles in 91 individuals from the Maratha community, and compared the data with data for 92 serologically typed Maratha individuals from India. We identified Cw*12, Cw*14, Cw*15, Cw*16 and Cw*18, along with the serologically identified Cw*01, Cw*02, Cw*03, Cw*04, Cw*06 and Cw*07 alleles. The HLA-Cw blank allele frequency in the Maratha was reduced from 0.5706 to 0.00. Furthermore, by using a molecular technique, it was possible to identify novel allele subtypes, such as Cw*0104, Cw*0203 and Cw*0707, and a high frequency of Cw* 1801 in the Maratha community compared with other Indian and world populations. Our results will have clinical implications in related and unrelated HLA-matched bone marrow transplantation in India.

Orthogonal sparse linear discriminant analysis

NASA Astrophysics Data System (ADS)

Liu, Zhonghua; Liu, Gang; Pu, Jiexin; Wang, Xiaohong; Wang, Haijun

2018-03-01

Linear discriminant analysis (LDA) is a linear feature extraction approach, and it has received much attention. On the basis of LDA, researchers have done a lot of research work on it, and many variant versions of LDA were proposed. However, the inherent problem of LDA cannot be solved very well by the variant methods. The major disadvantages of the classical LDA are as follows. First, it is sensitive to outliers and noises. Second, only the global discriminant structure is preserved, while the local discriminant information is ignored. In this paper, we present a new orthogonal sparse linear discriminant analysis (OSLDA) algorithm. The k nearest neighbour graph is first constructed to preserve the locality discriminant information of sample points. Then, L2,1-norm constraint on the projection matrix is used to act as loss function, which can make the proposed method robust to outliers in data points. Extensive experiments have been performed on several standard public image databases, and the experiment results demonstrate the performance of the proposed OSLDA algorithm.

Development and validation of a discriminative dissolution method for atorvastatin calcium tablets using in vivo data by LC and UV methods.

PubMed

Machado, J C; Lange, A D; Todeschini, V; Volpato, N M

2014-02-01

A dissolution method to analyze atorvastatin tablets using in vivo data for RP and test pilot (PB) was developed and validated. The appropriate conditions were determined after solubility tests using different media, and sink conditions were established. The conditions used were equipment paddle at 50 rpm and 900 mL of potassium phosphate buffer pH 6.0 as dissolution medium. In vivo release profiles were obtained from the bioequivalence study of RP and the generic candidate PB. The fraction of dose absorbed was calculated using the Loo-Riegelman method. It was necessary to use a scale factor of time similar to 6.0, to associate the values of absorbed fraction and dissolved fraction, obtaining an in vivo-in vitro correlation level A. The dissolution method to quantify the amount of drug dissolved was validated using high-performance liquid chromatography and ultraviolet spectrophotometry, and validated according to the USP protocol. The discriminative power of dissolution conditions was assessed using two different pilot batches of atorvastatin tablets (PA and PB) and RP. The dissolution test was validated and may be used as a discriminating method in quality control and in the development of the new formulations.

Color measurement and discrimination

NASA Technical Reports Server (NTRS)

Wandell, B. A.

1985-01-01

Theories of color measurement attempt to provide a quantative means for predicting whether two lights will be discriminable to an average observer. All color measurement theories can be characterized as follows: suppose lights a and b evoke responses from three color channels characterized as vectors, v(a) and v(b); the vector difference v(a) - v(b) corresponds to a set of channel responses that would be generated by some real light, call it *. According to theory a and b will be discriminable when * is detectable. A detailed development and test of the classic color measurement approach are reported. In the absence of a luminance component in the test stimuli, a and b, the theory holds well. In the presence of a luminance component, the theory is clearly false. When a luminance component is present discrimination judgements depend largely on whether the lights being discriminated fall in separate, categorical regions of color space. The results suggest that sensory estimation of surface color uses different methods, and the choice of method depends upon properties of the image. When there is significant luminance variation a categorical method is used, while in the absence of significant luminance variation judgments are continuous and consistant with the measurement approach.

The loss-of-allele assay for ES cell screening and mouse genotyping.

PubMed

Frendewey, David; Chernomorsky, Rostislav; Esau, Lakeisha; Om, Jinsop; Xue, Yingzi; Murphy, Andrew J; Yancopoulos, George D; Valenzuela, David M

2010-01-01

Targeting vectors used to create directed mutations in mouse embryonic stem (ES) cells consist, in their simplest form, of a gene for drug selection flanked by mouse genomic sequences, the so-called homology arms that promote site-directed homologous recombination between the vector and the target gene. The VelociGene method for the creation of targeted mutations in ES cells employs targeting vectors, called BACVecs, that are based on bacterial artificial chromosomes. Compared with conventional short targeting vectors, BacVecs provide two major advantages: (1) their much larger homology arms promote high targeting efficiencies without the need for isogenicity or negative selection strategies; and (2) they enable deletions and insertions of up to 100kb in a single targeting event, making possible gene-ablating definitive null alleles and other large-scale genomic modifications. Because of their large arm sizes, however, BACVecs do not permit screening by conventional assays, such as long-range PCR or Southern blotting, that link the inserted targeting vector to the targeted locus. To exploit the advantages of BACVecs for gene targeting, we inverted the conventional screening logic in developing the loss-of-allele (LOA) assay, which quantifies the number of copies of the native locus to which the mutation was directed. In a correctly targeted ES cell clone, the LOA assay detects one of the two native alleles (for genes not on the X or Y chromosome), the other allele being disrupted by the targeted modification. We apply the same principle in reverse as a gain-of-allele assay to quantify the copy number of the inserted targeting vector. The LOA assay reveals a correctly targeted clone as having lost one copy of the native target gene and gained one copy of the drug resistance gene or other inserted marker. The combination of these quantitative assays makes LOA genotyping unequivocal and amenable to automated scoring. We use the quantitative polymerase chain reaction

How discriminating are discriminative instruments?

PubMed

Hankins, Matthew

2008-05-27

The McMaster framework introduced by Kirshner & Guyatt is the dominant paradigm for the development of measures of health status and health-related quality of life (HRQL). The framework defines the functions of such instruments as evaluative, predictive or discriminative. Evaluative instruments are required to be sensitive to change (responsiveness), but there is no corresponding index of the degree to which discriminative instruments are sensitive to cross-sectional differences. This paper argues that indices of validity and reliability are not sufficient to demonstrate that a discriminative instrument performs its function of discriminating between individuals, and that the McMaster framework would be augmented by the addition of a separate index of discrimination. The coefficient proposed by Ferguson (Delta) is easily adapted to HRQL instruments and is a direct, non-parametric index of the degree to which an instrument distinguishes between individuals. While Delta should prove useful in the development and evaluation of discriminative instruments, further research is required to elucidate the relationship between the measurement properties of discrimination, reliability and responsiveness.

Noncontact discrimination of animal and human blood with vacuum blood vessel and factors affect the discrimination

NASA Astrophysics Data System (ADS)

Zhang, Linna; Zhang, Shengzhao; Sun, Meixiu; Li, Hongxiao; Li, Yingxin; Fu, Zhigang; Guan, Yang; Li, Gang; Lin, Ling

2017-03-01

Discrimination of human and nonhuman blood is crucial for import-export ports and inspection and quarantine departments. Current methods are usually destructive, complicated and time-consuming. We had previously demonstrated that visible diffuse reflectance spectroscopy combining PLS-DA method can successfully realize human blood discrimination. In that research, the spectra were measured with the fiber probe under the surface of blood samples. However, open sampling may pollute the blood samples. Virulence factors in blood samples can also endanger inspectors. In this paper, we explored the classification effect with the blood samples measured in the original containers-vacuum blood vessel. Furthermore, we studied the impact of different conditions of blood samples, such as coagulation and hemolysis, on the prediction ability of the discrimination model. The calibration model built with blood samples in different conditions displayed a satisfactory prediction result. This research demonstrated that visible and near-infrared diffuse reflectance spectroscopy method was potential for noncontact discrimination of human blood.

Multiplex Allele-Specific Amplification from Whole Blood for Detecting Multiple Polymorphisms Simultaneously

PubMed Central

Zhu, Jianjie; Chen, Lanxin; Mao, Yong; Zhou, Huan

2013-01-01

Allele-specific amplification on the basis of polymerase chain reaction (PCR) has been widely used for single-nucleotide polymorphism (SNP) genotyping. However, the extraction of PCR-compatible genomic DNA from whole blood is usually required. This process is complicated and tedious, and is prone to cause cross-contamination between samples. To facilitate direct PCR amplification from whole blood without the extraction of genomic DNA, we optimized the pH value of PCR solution and the concentrations of magnesium ions and facilitator glycerol. Then, we developed multiplex allele-specific amplifications from whole blood and applied them to a case–control study. In this study, we successfully established triplex, five-plex, and eight-plex allele-specific amplifications from whole blood for determining the distribution of genotypes and alleles of 14 polymorphisms in 97 gastric cancer patients and 141 healthy controls. Statistical analysis results showed significant association of SNPs rs9344, rs1799931, and rs1800629 with the risk of gastric cancer. This method is accurate, time-saving, cost-effective, and easy-to-do, especially suitable for clinical prediction of disease susceptibility. PMID:23072573

Schizophrenia and neurotrophin-3 alleles.

PubMed

Jŏnsson, E; Brené, S; Zhang, X R; Nimgaonkar, V L; Tylec, A; Schalling, M; Sedvall, G

1997-05-01

Studies of brain anatomy and premorbid functioning indicate that schizophrenia may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3 (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located in the promoter region was found to be associated with schizophrenia in a Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association with schizophrenic patients with a putative neurodevelopmental form of the disease. We examined Swedish schizophrenic patients (n = 109) and control subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent exonic polymorphism (at Pro55). No significant difference was found between the two groups. However, in a meta-analysis including the present and previous studies of Caucasian subjects, the A3/147-bp allele frequency was found to be significantly higher in the schizophrenic patients. In the present study, carriers of the A3/147 bp allele tended to have an earlier age of onset and to display more extrapyramidal symptoms. In the silent exonic polymorphism (at Pro55), female schizophrenic patients had higher adenine and lower guanine allele frequencies than control female subjects. Together with previous studies, the results provide some support for an association between the NT-3 gene and certain forms of schizophrenia. This warrants further investigation of NT-3 and other neurotrophic factors with additional polymorphisms and larger patient samples.

Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection

PubMed Central

KC, R.; Srivastava, A.; Wilkowski, J. M.; Richter, C. E.; Shavit, J. A.; Burke, D. T.; Bielas, S. L.

2016-01-01

CRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies. PMID:27557703

THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites

PubMed Central

Chang, Hsiao-Han; Worby, Colin J.; Yeka, Adoke; Nankabirwa, Joaniter; Kamya, Moses R.; Staedke, Sarah G.; Hubbart, Christina; Amato, Roberto; Kwiatkowski, Dominic P.

2017-01-01

As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available. Estimates limited to monogenomic infections may not be representative, however, and when the average COI is high, they can be difficult or impossible to obtain. Therefore, we developed THE REAL McCOIL, Turning HEterozygous SNP data into Robust Estimates of ALelle frequency, via Markov chain Monte Carlo, and Complexity Of Infection using Likelihood, to incorporate polygenomic samples and simultaneously estimate allele frequency and COI. This approach was tested via simulations then applied to SNP data from cross-sectional surveys performed in three Ugandan sites with varying malaria transmission. We show that THE REAL McCOIL consistently outperforms COIL on simulated data, particularly when most infections are polygenomic. Using field data we show that, unlike with COIL, we can distinguish epidemiologically relevant differences in COI between and within these sites. Surprisingly, for example, we estimated high average COI in a peri-urban subregion with lower transmission intensity, suggesting that many of these cases were imported from surrounding regions with higher transmission intensity. THE REAL McCOIL therefore provides a robust tool for understanding the molecular epidemiology of malaria across transmission settings. PMID

HLA-DR2-associated DRB1 and DRB5 alleles and haplotypes in Koreans.

PubMed

Song, E Y; Kang, S J; Lee, Y J; Park, M H

2000-09-01

There are considerable racial differences in the distribution of HLA-DR2-associated DRB1 and DRB5 alleles and the characteristics of linkage disequilibrium between these alleles. In this study, the frequencies of DR2-associated DRB1 and DRB5 alleles and related haplotypes were analyzed in 186 DR2-positive individuals out of 800 normal Koreans registered for unrelated bone marrow donors. HLA class I antigen typing was performed by the serological method and DRB1 and DRB5 genotyping by the PCR-single strand conformational polymorphism method. Only 3 alleles were detected for DR2-associated DRB1 and DRB5 genes, respectively: DRB1(*)1501 (gene frequency 8.0%), (*)1502 (3.2%), (*)1602 (0.9%); DRB5(*)0101 (8.0%), (*)0102 (3.2%), and (*)0202 (0.9%). DRB1-DRB5 haplotype analysis showed an exclusive association between these alleles: DRB1*1501-DRB5*0101 (haplotype frequency 8.0%), DRB1(*)1502-DRB5(*)0102 (3.2%), and DRB1(*)1602-DRB5(*)0202 (0.9%). The 5 most common DR2-associated A-B-DRB1 haplotypes occurring at frequencies of > or = 0.5% were A24-B52-DRB1(*)1502 (1.8%), A2-B62-DRB1(*)1501, A2-B54-DRB1(*)1501, A26-B61-DRB1(*)1501, and A24-B51-DRB1(*)1501. The remarkable homogeneity in the haplotypic associations between DR2-associated DRB1 and DRB5 alleles in Koreans would be advantageous for organ transplantation compared with other ethnic groups showing considerable heterogeneity in the distribution of DRB1-DRB5 haplotypes.

Improved neutron-gamma discrimination for a 3He neutron detector using subspace learning methods

DOE PAGES

Wang, C. L.; Funk, L. L.; Riedel, R. A.; ...

2017-02-10

3He gas based neutron linear-position-sensitive detectors (LPSDs) have been applied for many neutron scattering instruments. Traditional Pulse-Height Analysis (PHA) for Neutron-Gamma Discrimination (NGD) resulted in the neutron-gamma efficiency ratio on the orders of 10 5-10 6. The NGD ratios of 3He detectors need to be improved for even better scientific results from neutron scattering. Digital Signal Processing (DSP) analyses of waveforms were proposed for obtaining better NGD ratios, based on features extracted from rise-time, pulse amplitude, charge integration, a simplified Wiener filter, and the cross-correlation between individual and template waveforms of neutron and gamma events. Fisher linear discriminant analysis (FLDA)more » and three multivariate analyses (MVAs) of the features were performed. The NGD ratios are improved by about 10 2-10 3 times compared with the traditional PHA method. Finally, our results indicate the NGD capabilities of 3He tube detectors can be significantly improved with subspace-learning based methods, which may result in a reduced data-collection time and better data quality for further data reduction.« less

Allele Age Under Non-Classical Assumptions is Clarified by an Exact Computational Markov Chain Approach.

PubMed

De Sanctis, Bianca; Krukov, Ivan; de Koning, A P Jason

2017-09-19

Determination of the age of an allele based on its population frequency is a well-studied problem in population genetics, for which a variety of approximations have been proposed. We present a new result that, surprisingly, allows the expectation and variance of allele age to be computed exactly (within machine precision) for any finite absorbing Markov chain model in a matter of seconds. This approach makes none of the classical assumptions (e.g., weak selection, reversibility, infinite sites), exploits modern sparse linear algebra techniques, integrates over all sample paths, and is rapidly computable for Wright-Fisher populations up to N e  = 100,000. With this approach, we study the joint effect of recurrent mutation, dominance, and selection, and demonstrate new examples of "selective strolls" where the classical symmetry of allele age with respect to selection is violated by weakly selected alleles that are older than neutral alleles at the same frequency. We also show evidence for a strong age imbalance, where rare deleterious alleles are expected to be substantially older than advantageous alleles observed at the same frequency when population-scaled mutation rates are large. These results highlight the under-appreciated utility of computational methods for the direct analysis of Markov chain models in population genetics.

Detecting Small Amounts of Gene Flow from Phylogenies of Alleles

PubMed Central

Slatkin, M.

1989-01-01

The method of coalescents is used to find the probability that none of the ancestors of alleles sampled from a population are immigrants. If that is the case for samples from two or more populations, then there would be concordance between the phylogenies of those alleles and the geographic locations from which they are drawn. This type of concordance has been found in several studies of mitochondrial DNA from natural populations. It is shown that if the number of sequences sampled from each population is reasonably large (10 or more), then this type of concordance suggests that the average number of individuals migrating between populations is likely to be relatively small (Nm < 1) but the possibility of occasional migrants cannot be excluded. The method is applied to the data of E. Bermingham and J. C. Avise on mtDNA from the bowfin, Amia calva. PMID:2714639

Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis lyrata.

PubMed

Bechsgaard, J; Bataillon, T; Schierup, M H

2004-05-01

Self-incompatibility in Arabidopsis lyrata is sporophytically controlled by the multi-allelic S-locus. Self-incompatibility alleles (S-alleles) are under strong negative frequency dependent selection because pollen carrying common S-alleles have fewer mating opportunities. Population genetics theory predicts that deleterious alleles can accumulate if linked to the S-locus. This was tested by studying segregation of S-alleles in 11 large full sib families in A. lyrata. Significant segregation distortion leading to an up to fourfold difference in transmission rates was found in six families. Differences in transmission rates were not significantly different in reciprocal crosses and the distortions observed were compatible with selection acting at the gametic stage alone. The S-allele with the largest segregation advantage is also the most recessive, and is very common in natural populations concordant with its apparent segregation advantage. These results imply that frequencies of S-alleles in populations of A. lyrata cannot be predicted based on simple models of frequency-dependent selection alone.

Analysis of the discriminative methods for diagnosis of benign and malignant solitary pulmonary nodules based on serum markers.

PubMed

Wang, Wanping; Liu, Mingyue; Wang, Jing; Tian, Rui; Dong, Junqiang; Liu, Qi; Zhao, Xianping; Wang, Yuanfang

2014-01-01

Screening indexes of tumor serum markers for benign and malignant solitary pulmonary nodules (SPNs) were analyzed to find the optimum method for diagnosis. Enzyme-linked immunosorbent assays, an automatic immune analyzer and radioimmunoassay methods were used to examine the levels of 8 serum markers in 164 SPN patients, and the sensitivity for differential diagnosis of malignant or benign SPN was compared for detection using a single plasma marker or a combination of markers. The results for serological indicators that closely relate to benign and malignant SPNs were screened using the Fisher discriminant analysis and a non-conditional logistic regression analysis method, respectively. The results were then verified by the k-means clustering analysis method. The sensitivity when using a combination of serum markers to detect SPN was higher than that using a single marker. By Fisher discriminant analysis, cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and breast cancer antigen (CA153), which relate to the benign and malignant SPNs, were screened. Through non-conditional logistic regression analysis, CYFRA21-1, SCC and CA153 were obtained. Using the k-means clustering analysis, the cophenetic correlation coefficient (0.940) obtained by the Fisher discriminant analysis was higher than that obtained with logistic regression analysis (0.875). This study indicated that the Fisher discriminant analysis functioned better in screening out serum markers to recognize the benign and malignant SPN. The combined detection of CYFRA21-1, CA125, SCC and CA153 is an effective way to distinguish benign and malignant SPN, and will find an important clinical application in the early diagnosis of SPN. © 2014 S. Karger GmbH, Freiburg.

The convergent and discriminant validity of burnout measures in sport: a multi-trait/multi-method analysis.

PubMed

Cresswell, Scott L; Eklund, Robert C

2006-02-01

Athlete burnout research has been hampered by the lack of an adequate measurement tool. The Athlete Burnout Questionnaire (ABQ) and the Maslach Burnout Inventory General Survey (MBI-GS) are two recently developed self-report instruments designed to assess burnout. The convergent and discriminant validity of the ABQ and MBI-GS were assessed through multi-trait/multi-method analysis with a sporting population. Overall, the ABQ and the MBI-GS displayed acceptable convergent validity with matching subscales highly correlated, and satisfactory internal discriminant validity with lower correlations between non-matching subscales. Both scales also indicated an adequate discrimination between the concepts of burnout and depression. These findings add support to previous findings in non-sporting populations that depression and burnout are separate constructs. Based on the psychometric results, construct validity analysis and practical considerations, the results support the use of the ABQ to assess athlete burnout.

Allelic variants of hereditary prions: The bimodularity principle.

PubMed

Tikhodeyev, Oleg N; Tarasov, Oleg V; Bondarev, Stanislav A

2017-01-02

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.

Genetic sensitivity to emotional cues, racial discrimination and depressive symptoms among African–American adolescent females

PubMed Central

Sales, Jessica M.; Brown, Jennifer L.; Swartzendruber, Andrea L.; Smearman, Erica L.; Brody, Gene H.; DiClemente, Ralph

2015-01-01

Psychosocial stress, including stress resulting from racial discrimination (RD), has been associated with elevated depressive symptoms. However, individuals vary in their reactivity to stress, with some variability resulting from genetic differences. Specifically, genetic variation within the linked promoter region of the serotonin transporter gene (5-HTTLPR) is related to heightened reactivity to emotional environmental cues. Likewise, variations within this region may interact with stressful life events (e.g., discrimination) to influence depressive symptoms, but this has not been empirically examined in prior studies. The objective of this study was to examine whether variation in the 5-HTTLPR gene interacts with RD to predict depressive symptoms among a sample of African–American adolescent females. Participants were 304 African–American adolescent females enrolled in a sexually transmitted disease prevention trial. Participants completed a baseline survey assessing psychosocial factors including RD (low vs. high) and depressive symptomatology (low vs. high) and provided a saliva sample for genotyping the risk polymorphism 5-HTTLPR (s allele present vs. not present). In a logistic regression model adjusting for psychosocial correlates of depressive symptoms, an interaction between RD and 5-HTTLPR group was significantly associated with depressive symptomatology (AOR = 3.79, 95% CI: 1.20–11.98, p = 0.02). Follow-up tests found that high RD was significantly associated with greater odds of high depressive symptoms only for participants with the s allele. RD and 5-HTTLPR status interact to differentially impact depressive symptoms among African–American adolescent females. Efforts to decrease depression among minority youth should include interventions which address RD and strengthen factors (e.g., coping, emotion regulation, building support systems) which protect youth from the psychological costs of discrimination. PMID:26157407

QuASAR-MPRA: accurate allele-specific analysis for massively parallel reporter assays.

PubMed

Kalita, Cynthia A; Moyerbrailean, Gregory A; Brown, Christopher; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

2018-03-01

The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRAs), have been used to functionally validate non-coding variants. However, we are still missing high-quality and robust data analysis tools for these datasets. We have further developed our method for allele-specific analysis QuASAR (quantitative allele-specific analysis of reads) to analyze allele-specific signals in barcoded read counts data from MPRA. Using this approach, we can take into account the uncertainty on the original plasmid proportions, over-dispersion, and sequencing errors. The provided allelic skew estimate and its standard error also simplifies meta-analysis of replicate experiments. Additionally, we show that a beta-binomial distribution better models the variability present in the allelic imbalance of these synthetic reporters and results in a test that is statistically well calibrated under the null. Applying this approach to the MPRA data, we found 602 SNPs with significant (false discovery rate 10%) allele-specific regulatory function in LCLs. We also show that we can combine MPRA with QuASAR estimates to validate existing experimental and computational annotations of regulatory variants. Our study shows that with appropriate data analysis tools, we can improve the power to detect allelic effects in high-throughput reporter assays. http://github.com/piquelab/QuASAR/tree/master/mpra. fluca@wayne.edu or rpique@wayne.edu. Supplementary data are available online at Bioinformatics. © The Author (2017). Published by

Sequence-Based Genotyping of Expressed Swine Leukocyte Antigen Class I Alleles by Next-Generation Sequencing Reveal Novel Swine Leukocyte Antigen Class I Haplotypes and Alleles in Belgian, Danish, and Kenyan Fattening Pigs and Göttingen Minipigs.

PubMed

Sørensen, Maria Rathmann; Ilsøe, Mette; Strube, Mikael Lenz; Bishop, Richard; Erbs, Gitte; Hartmann, Sofie Bruun; Jungersen, Gregers

2017-01-01

The need for typing of the swine leukocyte antigen (SLA) is increasing with the expanded use of pigs as models for human diseases and organ-transplantation experiments, their use in infection studies, and for design of veterinary vaccines. Knowledge of SLA sequences is furthermore a prerequisite for the prediction of epitope binding in pigs. The low number of known SLA class I alleles and the limited knowledge of their prevalence in different pig breeds emphasizes the need for efficient SLA typing methods. This study utilizes an SLA class I-typing method based on next-generation sequencing of barcoded PCR amplicons. The amplicons were generated with universal primers and predicted to resolve 68-88% of all known SLA class I alleles dependent on amplicon size. We analyzed the SLA profiles of 72 pigs from four different pig populations; Göttingen minipigs and Belgian, Kenyan, and Danish fattening pigs. We identified 67 alleles, nine previously described haplotypes and 15 novel haplotypes. The highest variation in SLA class I profiles was observed in the Danish pigs and the lowest among the Göttingen minipig population, which also have the highest percentage of homozygote individuals. Highlighting the fact that there are still numerous unknown SLA class I alleles to be discovered, a total of 12 novel SLA class I alleles were identified. Overall, we present new information about known and novel alleles and haplotypes and their prevalence in the tested pig populations.

New accelerometric method to discriminate between asymptomatic subjects and patients with medial knee osteoarthritis during 3-d gait.

PubMed

Turcot, Katia; Aissaoui, Rachid; Boivin, Karine; Pelletier, Michel; Hagemeister, Nicola; de Guise, Jacques A

2008-04-01

This study presents a new method to estimate 3-D linear accelerations at tibial and femoral functional coordinate systems. The method combines the use of 3-D accelerometers, 3-D gyroscopes and reflective markers rigidly fixed on an exoskeleton and, a functional postural calibration method. Marker positions were tracked by a six-camera optoelectronic system (VICON 460, Oxford Metrics). The purpose of this study was to determine if this method could discriminate between medial osteoarthritic and asymptomatic knees during gait. Nine patients with osteoarthritic knees and nine asymptomatic control subjects were included in this study. Eighteen parameters representing maximal, minimal, and range of acceleration values were extracted during the loading and preswing to mid-swing phase periods, and were compared in both groups. Results show good discriminative capacity of the new method. Eight parameters were significantly different between both groups. The proposed method has the potential to be used in comprehending and monitoring gait strategy in patients with osteoarthritic knee.

Cargo and Container X-Ray Inspection with Intra-Pulse Multi-Energy Method for Material Discrimination

NASA Astrophysics Data System (ADS)

Saverskiy, Aleksandr Y.; Dinca, Dan-Cristian; Rommel, J. Martin

The Intra-Pulse Multi-Energy (IPME) method of material discrimination mitigates main disadvantages of the traditional "interlaced" approach: ambiguity caused by sampling different regions of cargo and reduction of effective scanning speed. A novel concept of creating multi-energy probing pulses using a standing-wave structure allows maintaining a constant energy spectrum while changing the time duration of each sub-pulse and thus enables adaptive cargo inspection. Depending on the cargo density, the dose delivered to the inspected object is optimized for best material discrimination, maximum material penetration, or lowest dose to cargo. A model based on Monte-Carlo simulation and experimental reference points were developed for the optimization of inspection conditions.

Credit scoring analysis using kernel discriminant

NASA Astrophysics Data System (ADS)

Widiharih, T.; Mukid, M. A.; Mustafid

2018-05-01

Credit scoring model is an important tool for reducing the risk of wrong decisions when granting credit facilities to applicants. This paper investigate the performance of kernel discriminant model in assessing customer credit risk. Kernel discriminant analysis is a non- parametric method which means that it does not require any assumptions about the probability distribution of the input. The main ingredient is a kernel that allows an efficient computation of Fisher discriminant. We use several kernel such as normal, epanechnikov, biweight, and triweight. The models accuracy was compared each other using data from a financial institution in Indonesia. The results show that kernel discriminant can be an alternative method that can be used to determine who is eligible for a credit loan. In the data we use, it shows that a normal kernel is relevant to be selected for credit scoring using kernel discriminant model. Sensitivity and specificity reach to 0.5556 and 0.5488 respectively.

HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity

PubMed Central

Stephens, Camilla; López-Nevot, Miguel-Ángel; Ruiz-Cabello, Francisco; Ulzurrun, Eugenia; Soriano, Germán; Romero-Gómez, Manuel; Moreno-Casares, Antonia; Lucena, M. Isabel; Andrade, Raúl J.

2013-01-01

Background and Aim The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases. Methods High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls. Results The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy’s Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07). Conclusions HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients. PMID:23874514

ClusPro: an automated docking and discrimination method for the prediction of protein complexes.

PubMed

Comeau, Stephen R; Gatchell, David W; Vajda, Sandor; Camacho, Carlos J

2004-01-01

Predicting protein interactions is one of the most challenging problems in functional genomics. Given two proteins known to interact, current docking methods evaluate billions of docked conformations by simple scoring functions, and in addition to near-native structures yield many false positives, i.e. structures with good surface complementarity but far from the native. We have developed a fast algorithm for filtering docked conformations with good surface complementarity, and ranking them based on their clustering properties. The free energy filters select complexes with lowest desolvation and electrostatic energies. Clustering is then used to smooth the local minima and to select the ones with the broadest energy wells-a property associated with the free energy at the binding site. The robustness of the method was tested on sets of 2000 docked conformations generated for 48 pairs of interacting proteins. In 31 of these cases, the top 10 predictions include at least one near-native complex, with an average RMSD of 5 A from the native structure. The docking and discrimination method also provides good results for a number of complexes that were used as targets in the Critical Assessment of PRedictions of Interactions experiment. The fully automated docking and discrimination server ClusPro can be found at http://structure.bu.edu

Mining the human phenome using allelic scores that index biological intermediates.

PubMed

Evans, David M; Brion, Marie Jo A; Paternoster, Lavinia; Kemp, John P; McMahon, George; Munafò, Marcus; Whitfield, John B; Medland, Sarah E; Montgomery, Grant W; Timpson, Nicholas J; St Pourcain, Beate; Lawlor, Debbie A; Martin, Nicholas G; Dehghan, Abbas; Hirschhorn, Joel; Smith, George Davey

2013-10-01

It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure

Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins.

PubMed

Quadros, Rolen M; Miura, Hiromi; Harms, Donald W; Akatsuka, Hisako; Sato, Takehito; Aida, Tomomi; Redder, Ronald; Richardson, Guy P; Inagaki, Yutaka; Sakai, Daisuke; Buckley, Shannon M; Seshacharyulu, Parthasarathy; Batra, Surinder K; Behlke, Mark A; Zeiner, Sarah A; Jacobi, Ashley M; Izu, Yayoi; Thoreson, Wallace B; Urness, Lisa D; Mansour, Suzanne L; Ohtsuka, Masato; Gurumurthy, Channabasavaiah B

2017-05-17

Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models. Although CRISPR-based strategies were reported to create conditional and targeted-insertion alleles via one-step delivery of targeting components directly to zygotes, these strategies are quite inefficient. Here we describe Easi-CRISPR (Efficient additions with ssDNA inserts-CRISPR), a targeting strategy in which long single-stranded DNA donors are injected with pre-assembled crRNA + tracrRNA + Cas9 ribonucleoprotein (ctRNP) complexes into mouse zygotes. We show for over a dozen loci that Easi-CRISPR generates correctly targeted conditional and insertion alleles in 8.5-100% of the resulting live offspring. Easi-CRISPR solves the major problem of animal genome engineering, namely the inefficiency of targeted DNA cassette insertion. The approach is robust, succeeding for all tested loci. It is versatile, generating both conditional and targeted insertion alleles. Finally, it is highly efficient, as treating an average of only 50 zygotes is sufficient to produce a correctly targeted allele in up to 100% of live offspring. Thus, Easi-CRISPR offers a comprehensive means of building large-scale Cre-LoxP animal resources.

Racial/Ethnic Workplace Discrimination

PubMed Central

Chavez, Laura J.; Ornelas, India J.; Lyles, Courtney R.; Williams, Emily C.

2014-01-01

Background Experiences of discrimination are associated with tobacco and alcohol use, and work is a common setting where individuals experience racial/ethnic discrimination. Few studies have evaluated the association between workplace discrimination and these behaviors, and none have described associations across race/ethnicity. Purpose To examine the association between workplace discrimination and tobacco and alcohol use in a large, multistate sample of U.S. adult respondents to the Behavioral Risk Factor Surveillance System survey Reactions to Race Module (2004–2010). Methods Multivariable logistic regression analyses evaluated cross-sectional associations between self-reported workplace discrimination and tobacco (current and daily smoking) and alcohol use (any and heavy use, and binge drinking) among all participants and stratified by race/ethnicity, adjusting for relevant covariates. Data were analyzed in 2013. Results Among respondents, 70,080 completed the workplace discrimination measure. Discrimination was more common among black non-Hispanic (21%), Hispanic (12%), and other race respondents (11%) than white non-Hispanics (4%) (p<0.001). In the total sample, discrimination was associated with current smoking (risk ratio [RR]=1.32, 95% CI=1.19, 1.47), daily smoking (RR=1.41, 95% CI=1.24, 1.61), and heavy drinking (RR=1.11, 95% CI=1.01, 1.22), but not binge or any drinking. Among Hispanics, workplace discrimination was associated with increased heavy and binge drinking, but not any alcohol use or smoking. Workplace discrimination among black non-Hispanics and white Non-Hispanics was associated with increased current and daily smoking, but not alcohol outcomes. Conclusions Workplace discrimination is common, associated with smoking and alcohol use, and merits further policy attention given the impact of these behaviors on morbidity and mortality. PMID:25441232

India Allele Finder: a web-based annotation tool for identifying common alleles in next-generation sequencing data of Indian origin.

PubMed

Zhang, Jimmy F; James, Francis; Shukla, Anju; Girisha, Katta M; Paciorkowski, Alex R

2017-06-27

We built India Allele Finder, an online searchable database and command line tool, that gives researchers access to variant frequencies of Indian Telugu individuals, using publicly available fastq data from the 1000 Genomes Project. Access to appropriate population-based genomic variant annotation can accelerate the interpretation of genomic sequencing data. In particular, exome analysis of individuals of Indian descent will identify population variants not reflected in European exomes, complicating genomic analysis for such individuals. India Allele Finder offers improved ease-of-use to investigators seeking to identify and annotate sequencing data from Indian populations. We describe the use of India Allele Finder to identify common population variants in a disease quartet whole exome dataset, reducing the number of candidate single nucleotide variants from 84 to 7. India Allele Finder is freely available to investigators to annotate genomic sequencing data from Indian populations. Use of India Allele Finder allows efficient identification of population variants in genomic sequencing data, and is an example of a population-specific annotation tool that simplifies analysis and encourages international collaboration in genomics research.

Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

PubMed Central

Kukurba, Kimberly R.; Zhang, Rui; Li, Xin; Smith, Kevin S.; Knowles, David A.; How Tan, Meng; Piskol, Robert; Lek, Monkol; Snyder, Michael; MacArthur, Daniel G.; Li, Jin Billy; Montgomery, Stephen B.

2014-01-01

Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants. PMID:24786518

Characterization of the treefrog null allele, 1991

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

Guttman, S.I.

1992-04-01

Spring peeper (Hyla crucifer) tadpoles collected from the waste storage area during the Biological and Ecological Site Characterization of the Feed Materials Production Center (FEMP) in 1986 and 1987 appeared to be unique. A null (inactive) allele was found at the glucose phosphate isomerase enzyme locus in significant frequencies (approximately 20%) each year; this allele did not appear to occur in the offsite sample collected approximately 15km from the FEMP. Null alleles at this locus have not been reported in other amphibian populations; when they have been found in other organisms they have invariably been lethal in the homozygous condition.

Detection of MPLW515L/K Mutations and Determination of Allele Frequencies with a Single-Tube PCR Assay

PubMed Central

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner. PMID:25144224

Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

PubMed

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

Combination of Eight Alleles at Four Quantitative Trait Loci Determines Grain Length in Rice

PubMed Central

Zeng, Yuxiang; Ji, Zhijuan; Wen, Zhihua; Liang, Yan; Yang, Changdeng

2016-01-01

Grain length is an important quantitative trait in rice (Oryza sativa L.) that influences both grain yield and exterior quality. Although many quantitative trait loci (QTLs) for grain length have been identified, it is still unclear how different alleles from different QTLs regulate grain length coordinately. To explore the mechanisms of QTL combination in the determination of grain length, five mapping populations, including two F2 populations, an F3 population, an F7 recombinant inbred line (RIL) population, and an F8 RIL population, were developed from the cross between the U.S. tropical japonica variety ‘Lemont’ and the Chinese indica variety ‘Yangdao 4’ and grown under different environmental conditions. Four QTLs (qGL-3-1, qGL-3-2, qGL-4, and qGL-7) for grain length were detected using both composite interval mapping and multiple interval mapping methods in the mapping populations. In each locus, there was an allele from one parent that increased grain length and another allele from another parent that decreased it. The eight alleles in the four QTLs were analyzed to determine whether these alleles act additively across loci, and lead to a linear relationship between the predicted breeding value of QTLs and phenotype. Linear regression analysis suggested that the combination of eight alleles determined grain length. Plants carrying more grain length-increasing alleles had longer grain length than those carrying more grain length-decreasing alleles. This trend was consistent in all five mapping populations and demonstrated the regulation of grain length by the four QTLs. Thus, these QTLs are ideal resources for modifying grain length in rice. PMID:26942914

Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

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

Poduslo, S.E.; Schwankhaus, J.D.

1994-09-01

A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal,more » and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.« less

Confidence intervals for population allele frequencies: the general case of sampling from a finite diploid population of any size.

PubMed

Fung, Tak; Keenan, Kevin

2014-01-01

The estimation of population allele frequencies using sample data forms a central component of studies in population genetics. These estimates can be used to test hypotheses on the evolutionary processes governing changes in genetic variation among populations. However, existing studies frequently do not account for sampling uncertainty in these estimates, thus compromising their utility. Incorporation of this uncertainty has been hindered by the lack of a method for constructing confidence intervals containing the population allele frequencies, for the general case of sampling from a finite diploid population of any size. In this study, we address this important knowledge gap by presenting a rigorous mathematical method to construct such confidence intervals. For a range of scenarios, the method is used to demonstrate that for a particular allele, in order to obtain accurate estimates within 0.05 of the population allele frequency with high probability (> or = 95%), a sample size of > 30 is often required. This analysis is augmented by an application of the method to empirical sample allele frequency data for two populations of the checkerspot butterfly (Melitaea cinxia L.), occupying meadows in Finland. For each population, the method is used to derive > or = 98.3% confidence intervals for the population frequencies of three alleles. These intervals are then used to construct two joint > or = 95% confidence regions, one for the set of three frequencies for each population. These regions are then used to derive a > or = 95%% confidence interval for Jost's D, a measure of genetic differentiation between the two populations. Overall, the results demonstrate the practical utility of the method with respect to informing sampling design and accounting for sampling uncertainty in studies of population genetics, important for scientific hypothesis-testing and also for risk-based natural resource management.

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

PubMed Central

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-01-01

Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

The distribution of apolipoprotein E alleles in Scottish perinatal deaths

PubMed Central

Becher, J‐C; Keeling, J W; McIntosh, N; Wyatt, B; Bell, J

2006-01-01

Background The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer's disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investigated. Methods ApoE genotyping was undertaken in a Scottish cohort of perinatal deaths (n = 261), some of whom had prenatal brain damage. The distribution of ApoE alleles in perinatal deaths was compared with that in healthy liveborn infants and in adults in Scotland. Results ApoE e2 was over‐represented in 251 perinatal deaths (13% v 8% in healthy newborns, odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.13 to 2.36 and 13% v 8% in adults, OR = 1.67, 95% CI 1.16 to 2.41), both in liveborn and stillborn perinatal deaths. In contrast, the prevalence of ApoE e4 was raised in healthy liveborn infants (19%) compared with stillbirths (13%, OR = 1.59, 95% CI 1.11 to 2.26) and with adults (15%, OR = 1.35, 95% CI 1.04 to 1.76). However, no correlation was found between ApoE genotype and the presence or absence of perinatal brain damage. Conclusions This study shows a shift in ApoE allelic distribution in early life compared with adults. The raised prevalence of ApoE e2 associated with perinatal death suggests that this allele is detrimental to pregnancy outcome, whereas ApoE e4 may be less so. However, ApoE genotype did not appear to influence the vulnerability for perinatal hypoxic/ischaemic brain damage, in agreement with findings in adult brains and in animal models. PMID:16183800

Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming

PubMed Central

Jeffries, Aaron Richard; Uwanogho, Dafe Aghogho; Cocks, Graham; Perfect, Leo William; Dempster, Emma; Mill, Jonathan; Price, Jack

2016-01-01

Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter. PMID:27539784

Pulse shape discrimination and classification methods for continuous depth of interaction encoding PET detectors.

PubMed

Roncali, Emilie; Phipps, Jennifer E; Marcu, Laura; Cherry, Simon R

2012-10-21

In previous work we demonstrated the potential of positron emission tomography (PET) detectors with depth-of-interaction (DOI) encoding capability based on phosphor-coated crystals. A DOI resolution of 8 mm full-width at half-maximum was obtained for 20 mm long scintillator crystals using a delayed charge integration linear regression method (DCI-LR). Phosphor-coated crystals modify the pulse shape to allow continuous DOI information determination, but the relationship between pulse shape and DOI is complex. We are therefore interested in developing a sensitive and robust method to estimate the DOI. Here, linear discriminant analysis (LDA) was implemented to classify the events based on information extracted from the pulse shape. Pulses were acquired with 2×2×20 mm(3) phosphor-coated crystals at five irradiation depths and characterized by their DCI values or Laguerre coefficients. These coefficients were obtained by expanding the pulses on a Laguerre basis set and constituted a unique signature for each pulse. The DOI of individual events was predicted using LDA based on Laguerre coefficients (Laguerre-LDA) or DCI values (DCI-LDA) as discriminant features. Predicted DOIs were compared to true irradiation depths. Laguerre-LDA showed higher sensitivity and accuracy than DCI-LDA and DCI-LR and was also more robust to predict the DOI of pulses with higher statistical noise due to low light levels (interaction depths further from the photodetector face). This indicates that Laguerre-LDA may be more suitable to DOI estimation in smaller crystals where lower collected light levels are expected. This novel approach is promising for calculating DOI using pulse shape discrimination in single-ended readout depth-encoding PET detectors.

Pulse Shape Discrimination and Classification Methods for Continuous Depth of Interaction Encoding PET Detectors

PubMed Central

Roncali, Emilie; Phipps, Jennifer E.; Marcu, Laura; Cherry, Simon R.

2012-01-01

In previous work we demonstrated the potential of positron emission tomography (PET) detectors with depth-of-interaction (DOI) encoding capability based on phosphor-coated crystals. A DOI resolution of 8 mm full-width at half-maximum was obtained for 20 mm long scintillator crystals using a delayed charge integration linear regression method (DCI-LR). Phosphor-coated crystals modify the pulse shape to allow continuous DOI information determination, but the relationship between pulse shape and DOI is complex. We are therefore interested in developing a sensitive and robust method to estimate the DOI. Here, linear discriminant analysis (LDA) was implemented to classify the events based on information extracted from the pulse shape. Pulses were acquired with 2 × 2 × 20 mm3 phosphor-coated crystals at five irradiation depths and characterized by their DCI values or Laguerre coefficients. These coefficients were obtained by expanding the pulses on a Laguerre basis set and constituted a unique signature for each pulse. The DOI of individual events was predicted using LDA based on Laguerre coefficients (Laguerre-LDA) or DCI values (DCI-LDA) as discriminant features. Predicted DOIs were compared to true irradiation depths. Laguerre-LDA showed higher sensitivity and accuracy than DCI-LDA and DCI-LR and was also more robust to predict the DOI of pulses with higher statistical noise due to low light levels (interaction depths further from the photodetector face). This indicates that Laguerre-LDA may be more suitable to DOI estimation in smaller crystals where lower collected light levels are expected. This novel approach is promising for calculating DOI using pulse shape discrimination in single-ended readout depth-encoding PET detectors. PMID:23010690

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

PubMed

Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

2015-09-01

Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

PubMed Central

Baker, Christopher L.; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M.; Paigen, Kenneth

2015-01-01

Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9 +/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape. PMID:26368021

From Discrimination to Internalized Mental Illness Stigma: The Mediating Roles of Anticipated Discrimination and Anticipated Stigma

PubMed Central

Quinn, Diane M.; Williams, Michelle K.; Weisz, Bradley M.

2015-01-01

Objective Internalizing mental illness stigma is related to poorer well-being, but less is known about the factors that predict levels of internalized stigma. This study explored how experiences of discrimination relate to greater anticipation of discrimination and devaluation in the future, and how anticipation of stigma, in turn predicts greater stigma internalization. Method Participants were 105 adults with mental illness who self-reported their experiences of discrimination based on their mental illness, their anticipation of discrimination and social devaluation from others in the future, and their level of internalized stigma. Participants were approached in several locations and completed surveys on laptop computers. Results Correlational analyses indicated that more experiences of discrimination due to one’s mental illness were related to increased anticipated discrimination in the future, increased anticipated social stigma from others, and greater internalized stigma. Multiple serial mediator analyses showed that the effect of experiences of discrimination on internalized stigma was fully mediated by increased anticipated discrimination and anticipated stigma. Conclusion and Implications for Practice Experiences of discrimination over the lifetime may influence not only how much future discrimination people with mental illness are concerned with but also how much they internalize negative feelings about the self. Mental health professionals may need to address concerns with future discrimination and devaluation in order to decrease internalized stigma. PMID:25844910

Quasi-equilibrium theory for the distribution of rare alleles in a subdivided population: justification and implications.

PubMed

Burr, T L

2000-05-01

This paper examines a quasi-equilibrium theory of rare alleles for subdivided populations that follow an island-model version of the Wright-Fisher model of evolution. All mutations are assumed to create new alleles. We present four results: (1) conditions for the theory to apply are formally established using properties of the moments of the binomial distribution; (2) approximations currently in the literature can be replaced with exact results that are in better agreement with our simulations; (3) a modified maximum likelihood estimator of migration rate exhibits the same good performance on island-model data or on data simulated from the multinomial mixed with the Dirichlet distribution, and (4) a connection between the rare-allele method and the Ewens Sampling Formula for the infinite-allele mutation model is made. This introduces a new and simpler proof for the expected number of alleles implied by the Ewens Sampling Formula. Copyright 2000 Academic Press.

SSR allelic variation in almond (Prunus dulcis Mill.).

PubMed

Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

2006-01-01

Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

Mutant maize variety containing the glt1-1 allele

DOEpatents

Nelson, O.E.; Pan, D.

1994-07-19

A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating. 2 figs.

Mutant maize variety containing the glt1-1 allele

DOEpatents

Nelson, Oliver E.; Pan, David

1994-01-01

A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating.

Reduced Height (Rht) Alleles Affect Wheat Grain Quality.

PubMed

Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

2016-01-01

The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05) reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the

Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.

PubMed

Jeffries, Aaron Richard; Uwanogho, Dafe Aghogho; Cocks, Graham; Perfect, Leo William; Dempster, Emma; Mill, Jonathan; Price, Jack

2016-10-01

Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter. © 2016 Jeffries et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield.

PubMed

Guo, Mei; Rupe, Mary A; Wei, Jun; Winkler, Chris; Goncalves-Butruille, Marymar; Weers, Ben P; Cerwick, Sharon F; Dieter, Jo Ann; Duncan, Keith E; Howard, Richard J; Hou, Zhenglin; Löffler, Carlos M; Cooper, Mark; Simmons, Carl R

2014-01-01

Crop improvement for yield and drought tolerance is challenging due to the complex genetic nature of these traits and environmental dependencies. This study reports that transgenic over-expression of Zea mays AR GOS1 (ZAR1) enhanced maize organ growth, grain yield, and drought-stress tolerance. The ZAR1 transgene exhibited environmental interactions, with yield increase under Temperate Dry and yield reduction under Temperate Humid or High Latitude environments. Native ZAR1 allele variation associated with drought-stress tolerance. Two founder alleles identified in the mid-maturity germplasm of North America now predominate in Pioneer's modern breeding programme, and have distinct proteins, promoters and expression patterns. These two major alleles show heterotic group partitioning, with one predominant in Pioneer's female and the other in the male heterotic groups, respectively. These two alleles also associate with favourable crop performance when heterozygous. Allele-specific transgene testing showed that, of the two alleles discussed here, each allele differed in their impact on yield and environmental interactions. Moreover, when transgenically stacked together the allelic pair showed yield and environmental performance advantages over either single allele, resembling heterosis effects. This work demonstrates differences in transgenic efficacy of native alleles and the differences reflect their association with hybrid breeding performance.

Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield

PubMed Central

Guo, Mei

2014-01-01

Crop improvement for yield and drought tolerance is challenging due to the complex genetic nature of these traits and environmental dependencies. This study reports that transgenic over-expression of Zea mays ARGOS1 (ZAR1) enhanced maize organ growth, grain yield, and drought-stress tolerance. The ZAR1 transgene exhibited environmental interactions, with yield increase under Temperate Dry and yield reduction under Temperate Humid or High Latitude environments. Native ZAR1 allele variation associated with drought-stress tolerance. Two founder alleles identified in the mid-maturity germplasm of North America now predominate in Pioneer’s modern breeding programme, and have distinct proteins, promoters and expression patterns. These two major alleles show heterotic group partitioning, with one predominant in Pioneer’s female and the other in the male heterotic groups, respectively. These two alleles also associate with favourable crop performance when heterozygous. Allele-specific transgene testing showed that, of the two alleles discussed here, each allele differed in their impact on yield and environmental interactions. Moreover, when transgenically stacked together the allelic pair showed yield and environmental performance advantages over either single allele, resembling heterosis effects. This work demonstrates differences in transgenic efficacy of native alleles and the differences reflect their association with hybrid breeding performance. PMID:24218327

Application of the multiplex PCR method for discrimination of Artemisia iwayomogi from other Artemisia herbs.

PubMed

Lee, Mi Young; Doh, Eui Jeong; Kim, Eung Soo; Kim, Young Wha; Ko, Byong Seob; Oh, Seung-Eun

2008-04-01

Some plants classified in the genus Artemisia are used for medicinal purposes. In particular, A. iwayomogi, which is referred to as 'Haninjin,' is used as an important medicinal material in traditional Korean medicine. However, A. capillaris, and both A. argyi and A. princeps, referred to as 'Injinho' and 'Aeyup,' respectively, are used for purposes other than those for which 'Haninjin' is utilized. However, it is occasionally difficult to differentiate 'Haninjin' from 'Injinho' and/or 'Aeyup' on the basis of their morphological features, particularly when in the dried and/or sliced form. Therefore, the development of a reliable method by which to discriminate 'Haninjin' from other Artemisia herbs, especially 'Injinho' and 'Aeyup,' is clearly necessary. We recently determined that the RAPD (random amplified polymorphic DNA) technique can be used to discriminate efficiently between some Artemisia herbs. In particular, when applied to RAPD, the non-specific UBC primer 391 (5'-GCG AAC CTC G-3') was demonstrated to amplify PCR products specific to A. iwayomogi. Based on the nucleotide sequences of the PCR product, we designed a 2F1 (5'-ACC TCG GAC CTA AAT ACA-3')/ 2F3 (5'-TTA TGA TTC ATG TTC AAT TC-3') primer set to amplify a SCAR (sequence-characterized amplified region) marker of A. iwayomogi. Employing this primer set, along with two other primer sets amplifying SCAR markers of 'Aeyup' (A. argyi and A. princeps) and both 'Injinho' (A. capillaris) and A. japonica, which are classified into the same subgroup in a phenogram constructed from RAPD analysis, we developed a multiplex PCR method by which A. iwayomogi could be discriminated with certainty from other Artemisia herbs. Via this method, we determined not only whether the tested Artemisia herb was A. iwayomogi, but also which Artemisia herbs were tested concurrently with A. iwayomogi.

Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia.

PubMed

Overgaard, Martin; Pedersen, Susanne Møller

2017-10-26

Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms. Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC). Normative data for six prolactin assays included the range of values (2.5th-97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively. Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.

Huntington disease reduced penetrance alleles occur at high frequency in the general population

PubMed Central

Kay, Chris; Collins, Jennifer A.; Miedzybrodzka, Zosia; Madore, Steven J.; Gordon, Erynn S.; Gerry, Norman; Davidson, Mark; Slama, Ramy A.

2016-01-01

Objective: To directly estimate the frequency and penetrance of CAG repeat alleles associated with Huntington disease (HD) in the general population. Methods: CAG repeat length was evaluated in 7,315 individuals from 3 population-based cohorts from British Columbia, the United States, and Scotland. The frequency of ≥36 CAG alleles was assessed out of a total of 14,630 alleles. The general population frequency of reduced penetrance alleles (36–39 CAG) was compared to the prevalence of patients with HD with genetically confirmed 36–39 CAG from a multisource clinical ascertainment in British Columbia, Canada. The penetrance of 36–38 CAG repeat alleles for HD was estimated for individuals ≥65 years of age and compared against previously reported clinical penetrance estimates. Results: A total of 18 of 7,315 individuals had ≥36 CAG, revealing that approximately 1 in 400 individuals from the general population have an expanded CAG repeat associated with HD (0.246%). Individuals with CAG 36–37 genotypes are the most common (36, 0.096%; 37, 0.082%; 38, 0.027%; 39, 0.000%; ≥40, 0.041%). General population CAG 36–38 penetrance rates are lower than penetrance rates extrapolated from clinical cohorts. Conclusion: HD alleles with a CAG repeat length of 36–38 occur at high frequency in the general population. The infrequent diagnosis of HD at this CAG length is likely due to low penetrance. Another important contributing factor may be reduced ascertainment of HD in those of older age. PMID:27335115

A genotype probability index for multiple alleles and haplotypes.

PubMed

Percy, A; Kinghorn, B P

2005-12-01

We use linear algebra to calculate an index of information content in genotype probabilities which has previously been calculated using trigonometry. The new method can be generalized allowing the index to be calculated for loci with more than two alleles. Applications of this index include its use in genotyping strategies, strategies to manage genetic disorders and in estimation of genotype effects.

Sensory Gating and Alpha-7 Nicotinic Receptor Gene Allelic Variants in Schizoaffective Disorder, Bipolar Type

PubMed Central

Martin, Laura F.; Leonard, Sherry; Hall, Mei-Hua; Tregellas, Jason R.; Freedman, Robert; Olincy, Ann

2011-01-01

Objectives Single nucleotide allelic variants in the promoter region of the chromosome 15 alpha-7 acetylcholine nicotinic receptor gene (CHRNA7) are associated with both schizophrenia and the P50 auditory evoked potential sensory gating deficit. The purpose of this study was to determine if CHRNA7 promoter allelic variants are also associated with abnormal P50 ratios in persons with schizoaffective disorder, bipolar type. Methods P50 auditory evoked potentials were recorded in a paired stimulus paradigm in 17 subjects with schizoaffective disorder, bipolar type. The P50 test to conditioning ratio was used as the measure of sensory gating. Mutation screening of the CHRNA7 promoter region was performed on the subjects’ DNA samples. Comparisons to previously obtained data from persons with schizophrenia and controls were made. Results Subjects with schizophrenia, regardless of allele status, had an abnormal mean P50 ratio. Subjects with schizoaffective disorder, bipolar type and a variant allele had an abnormal mean P50 ratio, whereas those schizoaffective subjects with the common alleles had a normal mean P50 ratio. Normal control subjects had a normal mean ratio, but controls with variant alleles had higher P50 ratios. Conclusions In persons with bipolar type schizoaffective disorder, CHRNA7 promoter region allelic variants are linked to the capacity to inhibit the P50 auditory evoked potential and thus are associated with a type of illness genetically and biologically more similar to schizophrenia. PMID:17192894

Perceived age discrimination in older adults

PubMed Central

Rippon, Isla; Kneale, Dylan; de Oliveira, Cesar; Demakakos, Panayotes; Steptoe, Andrew

2014-01-01

Objectives: to examine perceived age discrimination in a large representative sample of older adults in England. Methods: this cross-sectional study of over 7,500 individuals used data from the fifth wave of the English Longitudinal Study of Ageing (ELSA), a longitudinal cohort study of men and women aged 52 years and older in England. Wave 5 asked respondents about the frequency of five everyday discriminatory situations. Participants who attributed any experiences of discrimination to their age were treated as cases of perceived age discrimination. Multivariable logistic regression analysis was used to estimate the odds ratios of experiencing perceived age discrimination in relation to selected sociodemographic factors. Results: approximately a third (33.3%) of all respondents experienced age discrimination, rising to 36.8% in those aged 65 and over. Perceived age discrimination was associated with older age, higher education, lower levels of household wealth and being retired or not in employment. The correlates of age discrimination across the five discriminatory situations were similar. Conclusion: understanding age discrimination is vital if we are to develop appropriate policies and to target future interventions effectively. These findings highlight the scale of the challenge of age discrimination for older adults in England and illustrate that those groups are particularly vulnerable to this form of discrimination. PMID:24077751

Workplace discrimination: experiences of practicing physicians.

PubMed Central

Coombs, Alice A. Tolbert; King, Roderick K.

2005-01-01

BACKGROUND: In response to a growing concern regarding physician discrimination in the workplace, this study was developed to: (1) describe the types of discrimination that exist for the practicing physician and (2) determine which groups of physicians are more likely to experience the various forms of discrimination. METHODS: Surveys were mailed to 1930 practicing physicians in Massachusetts. Participants were asked if they had encountered discrimination, how significant the discrimination was against a specific group, the frequency of personal discrimination, and the type of discrimination. Factor analysis identified four types of discrimination: career advancement, punitive behaviors, practice barriers and hiring barriers. RESULTS: A total of 445 responses were received (a 24% response rate). Sixty-three percent of responding physicians had experienced some form of discrimination. Respondents were women (46%), racial/ethnic minorities (42%) and international medical graduates (IMGs) (40%). In addition, 26% of those classified as white were also IMGs. Over 60% of respondents believed discrimination against IMGs was very or somewhat significant. Almost 27% of males acknowledged that gender bias against females was very or somewhat significant. IMGs were more likely to indicate that discrimination against IMGs was significant in their current organization. Of U.S. medical graduates (USMGs) 44% reported that discrimination against IMGs in their current organization was significant. Nonwhites were more likely to report that discrimination based on race/ethnicity was significant. Nearly 29% of white respondents also believed that such discrimination was very or somewhat significant. CONCLUSIONS: Physicians practicing in academic, research, and private practice sectors experience discrimination based on gender, ethnic/racial, and IMG status. Images Figure 3 Figure 4 Figure 5 PMID:15868767

Allelic differences within and among sister spores of the arbuscular mycorrhizal fungus Glomus etunicatum suggest segregation at sporulation.

PubMed

Boon, Eva; Zimmerman, Erin; St-Arnaud, Marc; Hijri, Mohamed

2013-01-01

Arbuscular mycorrhizal fungi (AMF) are root-inhabiting fungi that form mutualistic symbioses with their host plants. AMF are made up of coenocytic networks of hyphae through which nuclei and organelles can freely migrate. In this study, we investigated the possibility of a genetic bottleneck and segregation of allelic variation at sporulation for a low-copy Polymerase1-like gene, PLS. Specifically, our objectives were (1) to estimate what allelic diversity is passed on to a single spore (2) to determine whether this diversity is less than the total amount of variation found in all spores (3) to investigate whether there is any differential segregation of allelic variation. We inoculated three tomato plants with a single spore of Glomus etunicatum each and after six months sampled between two and three daughter spores per tomato plant. Pyrosequencing PLS amplicons in eight spores revealed high levels of allelic diversity; between 43 and 152 alleles per spore. We corroborated the spore pyrosequencing results with Sanger- and pyrosequenced allele distributions from the original parent isolate. Both sequencing methods retrieved the most abundant alleles from the offspring spore allele distributions. Our results indicate that individual spores contain only a subset of the total allelic variation from the pooled spores and parent isolate. Patterns of allele diversity between spores suggest the possibility for segregation of PLS alleles among spores. We conclude that a genetic bottleneck could potentially occur during sporulation in AMF, with resulting differences in genetic variation among sister spores. We suggest that the effects of this bottleneck may be countered by anastomosis (hyphal fusion) between related hyphae.

Allele frequency changes due to hitch-hiking in genomic selection programs

PubMed Central

2014-01-01

Background Genomic selection makes it possible to reduce pedigree-based inbreeding over best linear unbiased prediction (BLUP) by increasing emphasis on own rather than family information. However, pedigree inbreeding might not accurately reflect loss of genetic variation and the true level of inbreeding due to changes in allele frequencies and hitch-hiking. This study aimed at understanding the impact of using long-term genomic selection on changes in allele frequencies, genetic variation and level of inbreeding. Methods Selection was performed in simulated scenarios with a population of 400 animals for 25 consecutive generations. Six genetic models were considered with different heritabilities and numbers of QTL (quantitative trait loci) affecting the trait. Four selection criteria were used, including selection on own phenotype and on estimated breeding values (EBV) derived using phenotype-BLUP, genomic BLUP and Bayesian Lasso. Changes in allele frequencies at QTL, markers and linked neutral loci were investigated for the different selection criteria and different scenarios, along with the loss of favourable alleles and the rate of inbreeding measured by pedigree and runs of homozygosity. Results For each selection criterion, hitch-hiking in the vicinity of the QTL appeared more extensive when accuracy of selection was higher and the number of QTL was lower. When inbreeding was measured by pedigree information, selection on genomic BLUP EBV resulted in lower levels of inbreeding than selection on phenotype BLUP EBV, but this did not always apply when inbreeding was measured by runs of homozygosity. Compared to genomic BLUP, selection on EBV from Bayesian Lasso led to less genetic drift, reduced loss of favourable alleles and more effectively controlled the rate of both pedigree and genomic inbreeding in all simulated scenarios. In addition, selection on EBV from Bayesian Lasso showed a higher selection differential for mendelian sampling terms than selection on

Complex and multi-allelic copy number variation in human disease

PubMed Central

McCarroll, Steven A.

2015-01-01

Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels—alleles, allele frequencies, structural features—that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs’ low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV–disease relationships that remain to be discovered. PMID:26163405

An evolutionary approach to major histocompatibility diversity based on allele supertypes.

PubMed

Naugler, Christopher; Liwski, Robert

2008-01-01

Human leukocyte antigens are traditionally classified by serologic or molecular techniques into a bewildering variety of alleles. It is generally believed that this allelic diversity is maintained by selection pressures for inbreeding avoidance and/or maximal immune system diversity. While the usual antigen-based classification of individual alleles may be most appropriate in the artificial situation of tissue transplantation, we hypothesize that a functional classification based on allele supertypes may represent a more biologically relevant way to view MHC diversity in the contexts of mate choice and disease pathogenesis. Furthermore, immune system diversity could be quantitatively estimated by calculating a Supertype Diversity Index (SDI) which is the number of different MHC supertypes possessed by an individual. This hypothesis generates a number of testable predictions. First, it predicts that a reduced inherited diversity of MHC allele supertypes may predispose to the development of malignancies because of a decreased native ability to present different tumor-associated antigens. Furthermore, specific autoimmune diseases may be associated with the presence or absence of a particular MHC supertype rather than a particular MHC haplotype. In transplant medicine, it is possible that unmatched alleles may trigger a weaker foreign antigen response if they are matched by allele supertype. Finally, there have been several studies documenting dissortative mating in humans for dissimilar MHC alleles. We predict that natural selection should favor maximization of the heterozygosity of allele supertypes instead of the heterozygosity of individual alleles and that the previously observed dissortative mating may actually be an adaptive strategy to maximize allele supertype diversity.

Pyrosequencing-based quantitative measurement of CALR mutation allele burdens and their clinical implications in patients with myeloproliferative neoplasms.

PubMed

Oh, Yejin; Song, Ik-Chan; Kim, Jimyung; Kwon, Gye Cheol; Koo, Sun Hoe; Kim, Seon Young

2018-05-01

We developed a pyrosequencing-based method for the quantification of CALR mutations and compared the results using Sanger sequencing, fragment length analysis (FLA), digital-droplet PCR (ddPCR), and next-generation sequencing (NGS). Method validation studies were performed using cloned plasmid controls. Samples from 24 patients with myeloproliferative neoplasms were evaluated. Among the 24 patients, 15 had CALR mutations (7 type 1, 2 type 2, and 6 other mutations). The type 1 or type 2 mutation-positive results from pyrosequencing exhibited 100% concordance with the Sanger sequencing results. One novel CALR mutation was not detected by pyrosequencing. The CALR mutation allele burdens measured by pyrosequencing were slightly lower than those measured by FLA but slightly higher than the results obtained using ddPCR. Pyrosequencing exhibited high correlations with both methods. The mutation allele burdens estimated by NGS were significantly lower than those measured by pyrosequencing. An increased CALR mutation allele burden was associated with overt primary myelofibrosis. Patients with >70% mutation allele burdens in myeloid cells had a significantly longer time from diagnosis (P = 0.007), more bone marrow fibrosis (P = 0.010), and lower hemoglobin (P = 0.007). Pyrosequencing was a useful rapid sequencing method to determine the burden of CALR mutations. Copyright © 2018 Elsevier B.V. All rights reserved.

Reduced Height (Rht) Alleles Affect Wheat Grain Quality

PubMed Central

Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

2016-01-01

The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0–450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05) reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the

An improved assay for the determination of Huntington`s disease allele size

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

Reeves, C.; Klinger, K.; Miller, G.

1994-09-01

The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra-more » or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.« less

Evolutionary renovation of L/M opsin polymorphism confers a fruit discrimination advantage to ateline New World monkeys

PubMed Central

Matsumoto, Yoshifumi; Hiramatsu, Chihiro; Matsushita, Yuka; Ozawa, Norihiro; Ashino, Ryuichi; Nakata, Makiko; Kasagi, Satoshi; Di Fiore, Anthony; Schaffner, Colleen M; Aureli, Filippo; Melin, Amanda D; Kawamura, Shoji

2014-01-01

New World monkeys exhibit prominent colour vision variation due to allelic polymorphism of the long-to-middle wavelength (L/M) opsin gene. The known spectral variation of L/M opsins in primates is broadly determined by amino acid composition at three sites: 180, 277 and 285 (the ‘three-sites’ rule). However, two L/M opsin alleles found in the black-handed spider monkeys (Ateles geoffroyi) are known exceptions, presumably due to novel mutations. The spectral separation of the two L/M photopigments is 1.5 times greater than expected based on the ‘three-sites’ rule. Yet the consequence of this for the visual ecology of the species is unknown, as is the evolutionary mechanism by which spectral shift was achieved. In this study, we first examine L/M opsins of two other Atelinae species, the long-haired spider monkeys (A. belzebuth) and the common woolly monkeys (Lagothrix lagotricha). By a series of site-directed mutagenesis, we show that a mutation Y213D (tyrosine to aspartic acid at site 213) in the ancestral opsin of the two alleles enabled N294K, which occurred in one allele of the ateline ancestor and increased the spectral separation between the two alleles. Second, by modelling the chromaticity of dietary fruits and background leaves in a natural habitat of spider monkeys, we demonstrate that chromatic discrimination of fruit from leaves is significantly enhanced by these mutations. This evolutionary renovation of L/M opsin polymorphism in atelines illustrates a previously unappreciated dynamism of opsin genes in shaping primate colour vision. PMID:24612406

A pseudodeficiency allele (D152N) of the human {beta}-glucuronidase gene

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

Vervoort, R.; Liebaers, I.; Lissens, W.

1995-10-01

We present evidence that a 480G{r_arrow}A transition in the coding region of the {Beta}glucuronidase gene, which results in an aspartic-acid-to-asparagine substitution at amino acid position 152 (D152N), produces a pseudodeficiency allele (GUSBp) that leads to greatly reduced levels of {Beta}-glucuronidase activity without apparent deleterious consequences. The 48OG{r_arrow}A mutation was found initially in the pseudodeficient mother of a child with mucopolysaccharidosis VII (MPSVII), but it was not on her disease-causing allele, which carried the L176F mutation. The 480G{r_arrow}A change was also present in an unrelated individual with another MPSVII allele who had unusually low {Beta}-glucuronidase activity, but whose clinical symptoms weremore » probably unrelated to {Beta}-glucuronidase deficiency. This individual also had an R357X mutation, probably on his second allele. We screened 100 unrelated normal individuals for the 480G{r_arrow}A mutation with a PCR method and detected one carrier. Reduced {Beta}-glucuronidase activity following transfection of COS cells with the D152N cDNA supported the causal relationship between the D152N allele and pseudodeficiency. The mutation reduced the fraction of expressed enzyme that was secreted. Pulse-chase experiments indicated that the reduced activity in COS cells was due to accelerated intracellular turnover of the D152N enzyme. They also suggested that a potential glycosylation site created by the mutation is utilized in {approximately}50% of the enzyme expressed. 25 refs., 3 figs., 3 tabs.« less

Competitive allele-specific TaqMan PCR (Cast-PCR) is a sensitive, specific and fast method for BRAF V600 mutation detection in Melanoma patients

PubMed Central

Barbano, Raffaela; Pasculli, Barbara; Coco, Michelina; Fontana, Andrea; Copetti, Massimiliano; Rendina, Michelina; Valori, Vanna Maria; Graziano, Paolo; Maiello, Evaristo; Fazio, Vito Michele; Parrella, Paola

2015-01-01

BRAF codon 600 mutation testing of melanoma patients is mandatory for the choice of the most appropriate therapy in the clinical setting. Competitive allele specific TaqMan PCR (Cast-PCR) technology allows not only the selective amplification of minor alleles, but it also blocks the amplification of non-mutant allele. We genotyped codon 600 of the BRAF gene in 54 patients’ samples by Cast-PCR and bidirectional direct sequence analysis. All the mutations detected by sequencing were also identified by Cast-PCR. In addition, Cast-PCR assay detected four samples carrying mutations and was able to clearly identify two mutations of uncertain interpretation by Sanger sequencing. The limit of detection of Cast-PCR was evaluated by constructing dilution curves of BRAFV600E and BRAFV600K mutated clinical samples mixed with a not-mutated specimens. Both mutations could be detected until a 1:100 mutated/not mutated ratio. Cloning and sequencing of the clones was used to confirm mutations on representative discrepant cases. Cast PCR performances were not affected by intratumour heterogeneity, and less affected by melanin content. Our results indicate that Cast-PCR is a reliable diagnostic tool for the identification of melanoma patients as eligible to be treated with TKIs and might be implemented in the clinical setting as elective screening method. PMID:26690267

Allelic variants of hereditary prions: The bimodularity principle

PubMed Central

Tikhodeyev, Oleg N.; Tarasov, Oleg V.; Bondarev, Stanislav A.

2017-01-01

ABSTRACT Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either “canonical” (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as “gene” and “allele” to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor. PMID:28281926

A discriminant function model as an alternative method to spirometry for COPD screening in primary care settings in China.

PubMed

Cui, Jiangyu; Zhou, Yumin; Tian, Jia; Wang, Xinwang; Zheng, Jingping; Zhong, Nanshan; Ran, Pixin

2012-12-01

COPD is often underdiagnosed in a primary care setting where the spirometry is unavailable. This study was aimed to develop a simple, economical and applicable model for COPD screening in those settings. First we established a discriminant function model based on Bayes' Rule by stepwise discriminant analysis, using the data from 243 COPD patients and 112 non-COPD subjects from our COPD survey in urban and rural communities and local primary care settings in Guangdong Province, China. We then used this model to discriminate COPD in additional 150 subjects (50 non-COPD and 100 COPD ones) who had been recruited by the same methods as used to have established the model. All participants completed pre- and post-bronchodilator spirometry and questionnaires. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria. The sensitivity and specificity of the discriminant function model was assessed. THE ESTABLISHED DISCRIMINANT FUNCTION MODEL INCLUDED NINE VARIABLES: age, gender, smoking index, body mass index, occupational exposure, living environment, wheezing, cough and dyspnoea. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, accuracy and error rate of the function model to discriminate COPD were 89.00%, 82.00%, 4.94, 0.13, 86.66% and 13.34%, respectively. The accuracy and Kappa value of the function model to predict COPD stages were 70% and 0.61 (95% CI, 0.50 to 0.71). This discriminant function model may be used for COPD screening in primary care settings in China as an alternative option instead of spirometry.

Existence of the rdl mutant alleles among the anopheles malaria vector in Indonesia.

PubMed

Asih, Puji Bs; Syahrani, Lepa; Rozi, Ismail Ep; Pratama, Nandha R; Marantina, Sylvia S; Arsyad, Dian S; Mangunwardoyo, Wibowo; Hawley, William; Laihad, Ferdinand; Shinta; Sukowati, Supratman; Lobo, Neil F; Syafruddin, Din

2012-02-25

The gamma-aminobutyric acid (GABA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide. GABA-receptors, with a naturally occurring amino acid substitution, A302S/G in the putative ion-channel lining region, confer resistance to cyclodiene insecticides that includes aldrin, chlordane, dieldrin, heptachlor, endrin and endosulphan. A total of 154 mosquito samples from 10 provinces of malaria-endemic areas across Indonesia (Aceh, North Sumatra, Bangka Belitung, Lampung, Central Java, East Nusa Tenggara, West Nusa Tenggara, West Sulawesi, Molucca and North Molucca) were obtained and identified by species, using morphological characteristic. The DNA was individually extracted using chelex-ion exchanger and the DNA obtained was used for analyses using sequencing method. Molecular analysis indicated 11% of the total 154 Anopheles samples examined, carried Rdl mutant alleles. All of the alleles were found in homozygous form. Rdl 302S allele was observed in Anopheles vagus (from Central Java, Lampung, and West Nusa Tenggara), Anopheles aconitus (from Central Java), Anopheles barbirostris (from Central Java and Lampung), Anopheles sundaicus (from North Sumatra and Lampung), Anopheles nigerrimus (from North Sumatra), whereas the 302 G allele was only found in Anopheles farauti from Molucca. The existence of the Rdl mutant allele indicates that, either insecticide pressure on the Anopheles population in these areas might still be ongoing (though not directly associated with the malaria control programme) or that the mutant form of the Rdl allele is relatively stable in the absence of insecticide. Nonetheless, the finding suggests that integrated pest management is warranted in malaria-endemic areas where insecticides are widely used for other purposes.

A novel HLA-B allele, B*5214, detected in a Taiwanese volunteer bone marrow donor using a sequence-based typing method.

PubMed

Chen, M J; Chu, C C; Shyr, M H; Lin, C L; Lin, P Y; Yang, K L

2010-02-01

HLA-B*5214, a novel rare allele of HLA-B*52 variant, was found in a Taiwanese volunteer bone marrow donor by sequence-based typing method. The sequence of B*5214 is identical to that of B*520101 in exon 2 but differs from B*520101 in exon 3 at nucleotide positions 419 A-->T and 435 A-->G. Alteration of these two nucleotides resulted an amino acid substitution at amino acid residue 116 Y-->F ( TAC-->TTC) and a silent exchange at residue 121 K-->K (AAA-->AAG).

The utility of placing recollection in opposition to familiarity in early discrimination of healthy aging and very mild dementia of the Alzheimer’s type

PubMed Central

Tse, Chi-Shing; Balota, David A.; Moynan, Sarah C.; Duchek, Janet M.; Jacoby, Larry L.

2009-01-01

The present study explored the ability to control familiarity-based information in a memory exclusion paradigm in healthy young, older adults, and early-stage DAT individuals. We compared the predictive power of memory exclusion performance to standard psychometric performance in discriminating between healthy aging and the earliest detectable form of DAT and between APOe4-present and APOe4-absent genotype in healthy control individuals. Participants responded “yes” to words that were previously semantically encoded, and “no” to other words. The number of targets and distractors on the read “distractor” list was manipulated to investigate the degree to which aging and DAT influence the ability to recollect specific details of study episodes in the face of distractor familiarity due to repetition. Memory exclusion performance (as reflected by d′) decreased across participant groups (young > healthy old control > very mild DAT). Logistic regression analyses showed that d′ increased the discriminative power for healthy older adults vs. very mild DAT individuals above and beyond standard psychometric measures. Memory exclusion d′ was also lower for healthy control individuals with APOe4 allele, compared to those without the APOe4 allele after partialing out baseline psychometric performance. Discussion focuses on the importance of attentional control systems in memory retrieval and the utility of the opposition paradigm for early discrimination between healthy and pathological aging. PMID:20063946

Allelic Differences within and among Sister Spores of the Arbuscular Mycorrhizal Fungus Glomus etunicatum Suggest Segregation at Sporulation

PubMed Central

St-Arnaud, Marc; Hijri, Mohamed

2013-01-01

Arbuscular mycorrhizal fungi (AMF) are root-inhabiting fungi that form mutualistic symbioses with their host plants. AMF are made up of coenocytic networks of hyphae through which nuclei and organelles can freely migrate. In this study, we investigated the possibility of a genetic bottleneck and segregation of allelic variation at sporulation for a low-copy Polymerase1-like gene, PLS. Specifically, our objectives were (1) to estimate what allelic diversity is passed on to a single spore (2) to determine whether this diversity is less than the total amount of variation found in all spores (3) to investigate whether there is any differential segregation of allelic variation. We inoculated three tomato plants with a single spore of Glomus etunicatum each and after six months sampled between two and three daughter spores per tomato plant. Pyrosequencing PLS amplicons in eight spores revealed high levels of allelic diversity; between 43 and 152 alleles per spore. We corroborated the spore pyrosequencing results with Sanger- and pyrosequenced allele distributions from the original parent isolate. Both sequencing methods retrieved the most abundant alleles from the offspring spore allele distributions. Our results indicate that individual spores contain only a subset of the total allelic variation from the pooled spores and parent isolate. Patterns of allele diversity between spores suggest the possibility for segregation of PLS alleles among spores. We conclude that a genetic bottleneck could potentially occur during sporulation in AMF, with resulting differences in genetic variation among sister spores. We suggest that the effects of this bottleneck may be countered by anastomosis (hyphal fusion) between related hyphae. PMID:24386173

The interleukin-10-1082 'A' allele and abdominal aortic aneurysms.

PubMed

Bown, Matthew J; Lloyd, Geraint M; Sandford, Rebecca M; Thompson, John R; London, Nicholas J M; Samani, Nilesh J; Sayers, Robert D

2007-10-01

Abdominal aortic aneurysms (AAA) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with AAA in a small study. The aim of this study was to determine whether this polymorphism is associated with AAA and also examine its effect on the growth of small AAA. A case control study was performed. A total of 389 patients with AAA and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small AAA (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the AAA group (P = .006). In the AAA group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for AAA was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with AAA if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small AAA. This study demonstrates that the IL-10-1082 'A' allele is associated with AAA, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than AAA per se.

Use of the LUS in sequence allele designations to facilitate probabilistic genotyping of NGS-based STR typing results.

PubMed

Just, Rebecca S; Irwin, Jodi A

2018-05-01

Some of the expected advantages of next generation sequencing (NGS) for short tandem repeat (STR) typing include enhanced mixture detection and genotype resolution via sequence variation among non-homologous alleles of the same length. However, at the same time that NGS methods for forensic DNA typing have advanced in recent years, many caseworking laboratories have implemented or are transitioning to probabilistic genotyping to assist the interpretation of complex autosomal STR typing results. Current probabilistic software programs are designed for length-based data, and were not intended to accommodate sequence strings as the product input. Yet to leverage the benefits of NGS for enhanced genotyping and mixture deconvolution, the sequence variation among same-length products must be utilized in some form. Here, we propose use of the longest uninterrupted stretch (LUS) in allele designations as a simple method to represent sequence variation within the STR repeat regions and facilitate - in the nearterm - probabilistic interpretation of NGS-based typing results. An examination of published population data indicated that a reference LUS region is straightforward to define for most autosomal STR loci, and that using repeat unit plus LUS length as the allele designator can represent greater than 80% of the alleles detected by sequencing. A proof of concept study performed using a freely available probabilistic software demonstrated that the LUS length can be used in allele designations when a program does not require alleles to be integers, and that utilizing sequence information improves interpretation of both single-source and mixed contributor STR typing results as compared to using repeat unit information alone. The LUS concept for allele designation maintains the repeat-based allele nomenclature that will permit backward compatibility to extant STR databases, and the LUS lengths themselves will be concordant regardless of the NGS assay or analysis tools

Rotary pin-in-maze discriminator

DOEpatents

Benavides, Gilbert L.

1997-01-01

A discriminator apparatus and method that discriminates between a unique signal and any other (incorrect) signal. The unique signal is a sequence of events; each event can assume one of two possible event states. Given the unique signal, a maze wheel is allowed to rotate fully in one direction. Given an incorrect signal, both the maze wheel and a pin wheel lock in position.

Color model and method for video fire flame and smoke detection using Fisher linear discriminant

NASA Astrophysics Data System (ADS)

Wei, Yuan; Jie, Li; Jun, Fang; Yongming, Zhang

2013-02-01

Video fire detection is playing an increasingly important role in our life. But recent research is often based on a traditional RGB color model used to analyze the flame, which may be not the optimal color space for fire recognition. It is worse when we research smoke simply using gray images instead of color ones. We clarify the importance of color information for fire detection. We present a fire discriminant color (FDC) model for flame or smoke recognition based on color images. The FDC models aim to unify fire color image representation and fire recognition task into one framework. With the definition of between-class scatter matrices and within-class scatter matrices of Fisher linear discriminant, the proposed models seek to obtain one color-space-transform matrix and a discriminate projection basis vector by maximizing the ratio of these two scatter matrices. First, an iterative basic algorithm is designed to get one-component color space transformed from RGB. Then, a general algorithm is extended to generate three-component color space for further improvement. Moreover, we propose a method for video fire detection based on the models using the kNN classifier. To evaluate the recognition performance, we create a database including flame, smoke, and nonfire images for training and testing. The test experiments show that the proposed model achieves a flame verification rate receiver operating characteristic (ROC I) of 97.5% at a false alarm rate (FAR) of 1.06% and a smoke verification rate (ROC II) of 91.5% at a FAR of 1.2%, and lots of fire video experiments demonstrate that our method reaches a high accuracy for fire recognition.

ovoD Co-selection: A Method for Enriching CRISPR/Cas9-Edited Alleles in Drosophila.

PubMed

Ewen-Campen, Ben; Perrimon, Norbert

2018-06-22

Screening for successful CRISPR/Cas9 editing events remains a time consuming technical bottleneck in the field of Drosophila genome editing. This step can be particularly laborious for events that do not cause a visible phenotype, or those which occur at relatively low frequency. A promising strategy to enrich for desired CRISPR events is to co-select for an independent CRISPR event that produces an easily detectable phenotype. Here, we describe a simple negative co-selection strategy involving CRISPR-editing of a dominant female sterile allele, ovo D1 In this system (" ovo D co-selection"), the only functional germ cells in injected females are those that have been edited at the ovo D1 locus, and thus all offspring of these flies have undergone editing of at least one locus. We demonstrate that ovo D co-selection can be used to enrich for knock-out mutagenesis via nonhomologous end-joining (NHEJ), and for knock-in alleles via homology-directed repair (HDR). Altogether, our results demonstrate that ovoD co-selection reduces the amount of screening necessary to isolate desired CRISPR events in Drosophila. Copyright © 2018, G3: Genes, Genomes, Genetics.

KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

NASA Astrophysics Data System (ADS)

Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

2016-03-01

KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E35 could kill more target cells lacking their ligands than NK cells with the weaker -Q35 alleles, indicating better licensing of KIR2DL2/L3+ NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

Quality assessment of data discrimination using self-organizing maps.

PubMed

Mekler, Alexey; Schwarz, Dmitri

2014-10-01

One of the important aspects of the data classification problem lies in making the most appropriate selection of features. The set of variables should be small and, at the same time, should provide reliable discrimination of the classes. The method for the discriminating power evaluation that enables a comparison between different sets of variables will be useful in the search for the set of variables. A new approach to feature selection is presented. Two methods of evaluation of the data discriminating power of a feature set are suggested. Both of the methods implement self-organizing maps (SOMs) and the newly introduced exponents of the degree of data clusterization on the SOM. The first method is based on the comparison of intraclass and interclass distances on the map. Another method concerns the evaluation of the relative number of best matching unit's (BMUs) nearest neighbors of the same class. Both methods make it possible to evaluate the discriminating power of a feature set in cases when this set provides nonlinear discrimination of the classes. Current algorithms in program code can be downloaded for free at http://mekler.narod.ru/Science/Articles_support.html, as well as the supporting data files. Copyright © 2014 Elsevier Inc. All rights reserved.

Rotary pin-in-maze discriminator

DOEpatents

Benavides, G.L.

1997-05-06

A discriminator apparatus and method that discriminates between a unique signal and any other (incorrect) signal are disclosed. The unique signal is a sequence of events; each event can assume one of two possible event states. Given the unique signal, a maze wheel is allowed to rotate fully in one direction. Given an incorrect signal, both the maze wheel and a pin wheel lock in position. 4 figs.

Discriminative staining methods for the nervous system: luxol fast blue--periodic acid-Schiff--hematoxylin triple stain and subsidiary staining methods.

PubMed

Goto, N

1987-09-01

This paper describes a new series of staining methods which can discriminatively demonstrate every structure of the nervous system, including axons and capillaries, in animal and human materials. Methods described in this paper consist of one primary stain, luxol fast blue-periodic acid Schiff-hematoxylin (LPH) and six different subsidiary staining methods. The LPH triple stain can precisely differentiate the following structures: neurons (Nissl bodies, cytoplasm, nuclear membrane and nucleolus), various kinds of nuclei (glia, ependyma, endothelium, leucocyte, connective tissue, etc.), myelin sheaths, neuronal processes (axons and dendrites), reacted glial cell bodies (protoplasmic astrocytes, foamy cells, etc.), blood vessels (arteries, veins and capillaries), meninges, intervening connective tissue, erythrocytes, lipofuscin granules, amyloid bodies, and others. Subsidiary staining methods are also described briefly. Applications are discussed in the context of staining technology and neuromorphological research.

Single step PCR for detection of allelic variation of MDR1 gene (P-glycoprotein) among three ethnic groups in Malaysia.

PubMed

Teh, L K; Lee, W L; Amir, J; Salleh, M Z; Ismail, R

2007-06-01

P-glycoprotein (PgP) is the most extensively studied ATP-binding cassette (ABC) coded by MDR1 gene. To date, 29 single nucleotide polymorphisms (SNPs) have been identified; but only SNP C3435T has been correlated with intestinal PgP expression levels and shown to influence the absorption of orally taken drugs that are PgP substrates. Individuals homozygous for the T allele have more than fourfold lower PgP expression compared with C/C individuals. We developed a one step primer based allele specific PCR method to detect SNP at C3435T to investigate the distribution of this genotype in the local population. DNA was extracted from 5 mL of whole blood using standard salting-out method. Primers were designed specific to 3' end which amplify the variants of C3435T. The method was validated by direct DNA sequencing. Seven hundred and sixty-three healthy blood donors comprising of three major ethnic groups in Malaysia were recruited and DNA subjected to genotyping of C3435T using this method. The method was found to be robust and reproducible in detecting SNP of C3435T. Interethnic variations in genotype and allele frequency were observed in PgP among the ethnic groups. In comparison to both the Caucasians and the other Asian countries, the Malay and Chinese showed a higher frequency of allele C (50-60%); while the Indian exhibits a lower frequency (40%), similar to other Indian populations. Using a new simple method to investigate the distribution of C3435T, we found that the allele frequency of MDR1 showed variablity between the different ethnic groups within the Malaysian population.

An efficient method for generation of bi-allelic null mutant mouse embryonic stem cells and its application for investigating epigenetic modifiers

PubMed Central

Cho, Lily Ting-yin; Andrews, Robert; Carroll, Thomas; Iyer, Vivek; Tate, Peri; Rosen, Barry; Stunnenberg, Hendrik G.; Fisher, Amanda G.; Skarnes, William C.

2017-01-01

Abstract Mouse embryonic stem (ES) cells are a popular model system to study biological processes, though uncovering recessive phenotypes requires inactivating both alleles. Building upon resources from the International Knockout Mouse Consortium (IKMC), we developed a targeting vector for second allele inactivation in conditional-ready IKMC ‘knockout-first’ ES cell lines. We applied our technology to several epigenetic regulators, recovering bi-allelic targeted clones with a high efficiency of 60% and used Flp recombinase to restore expression in two null cell lines to demonstrate how our system confirms causality through mutant phenotype reversion. We designed our strategy to select against re-targeting the ‘knockout-first’ allele and identify essential genes in ES cells, including the histone methyltransferase Setdb1. For confirmation, we exploited the flexibility of our system, enabling tamoxifen inducible conditional gene ablation while controlling for genetic background and tamoxifen effects. Setdb1 ablated ES cells exhibit severe growth inhibition, which is not rescued by exogenous Nanog expression or culturing in naive pluripotency ‘2i’ media, suggesting that the self-renewal defect is mediated through pluripotency network independent pathways. Our strategy to generate null mutant mouse ES cells is applicable to thousands of genes and repurposes existing IKMC Intermediate Vectors. PMID:28981838

Silvicultural management and the manipulation of rare alleles

Treesearch

Paul G. Schaberg; Gary J. Hawley; Donald H. DeHayes; Samuel E. Nijensohn

2004-01-01

Because rare alleles provide a means for adaptation to environmental change they are often considered important to long-term forest health. Through the selective removal of trees (and genes), silvicultural management may alter the genetic structure of forests, with rare alleles perhaps being uniquely vulnerable to manipulation due to their low frequencies or...

Transfusion strategy for weak D type 4.0 based on RHD alleles and RH haplotypes in Tunisia

PubMed Central

Ouchari, Mouna; Srivastava, Kshitij; Romdhane, Houda; Yacoub, Saloua Jemni; Flegel, Willy Albert

2017-01-01

Background With more than 460 RHD alleles, this gene is the most complex and polymorphic among all blood group systems. The Tunisian population has the largest known prevalence of weak D type 4.0 alleles, occurring in 1 of 105 RH haplotypes. We aimed to establish a rationale for the transfusion strategy of weak D type 4.0 in Tunisia. Study design and methods Donors were randomly screened for the serological weak D phenotype. The RHD coding sequence and parts of the introns were sequenced. To establish the RH haplotype, the RHCE gene was tested for characteristic single nucleotide positions. Results We determined all RHD alleles and the RH haplotypes coding for the serologic weak D phenotype among 13,431 Tunisian donations. A serologic weak D phenotype was found in 67 individuals (0.50%). Among them, 60 carried a weak D type 4 allele: 53 weak D type 4.0, 6 weak D type 4.2.2 (DAR), and 1 weak D type 4.1. Another 4 donors had 1 variant allele each: DVII, weak D type 1, weak D type 3, and weak D type 100, while 3 donors showed a normal RHD sequence. The weak D type 4.0 was most often linked to RHCE*ceVS.04.01, weak D type 4.2.2 to RHCE*ceAR, and weak D type 4.1 to RHCE*ceVS.02, while the other RHD alleles were linked to one of the common RHCE alleles. Conclusions Among the weak D phenotypes in Tunisia, no novel RHD allele was found and almost 90% were caused by alleles of the weak D type 4 cluster, of which 88% represented the weak D type 4.0 allele. Based on established RH haplotypes for variant RHD and RHCE alleles and the lack of adverse clinical reports, we recommend D positive transfusions for patients with weak D type 4.0 in Tunisia. PMID:29193104

A novel and rapid diagnostic method for discriminating between feces of sika deer and Japanese serow by loop-mediated isothermal amplification.

PubMed

Aikawa, T; Horino, S; Ichihara, Y

2015-08-01

Severe damages to natural vegetation, agriculture, and forestry caused by overpopulation of sika deer (Cervus nippon) have markedly increased in Japan in recent years. To devise a population management plan of sika deer, information on the distribution and population size of the animal in each region is indispensable. An easy and effective method to obtain this information is to count the fecal pellets in the field. However, the habitat of sika deer in Japan overlaps that of Japanese serow (Capricornis crispus). Additionally, it is difficult to discriminate between the feces of both animals. Here, we present a rapid and precise diagnostic method for discriminating between the feces of sika deer and Japanese serow using loop-mediated isothermal amplification (LAMP) targeting cytochrome b gene in the mitochondrial DNA. Our results showed that the LAMP can discriminate between the feces of sika deer and Japanese serow, and the method is simpler and more sensitive than the conventional molecular diagnostic method. Since LAMP method does not require special skills for molecular biology techniques, even the field researchers who have never done a molecular experiment can easily carry out the protocol. In addition, the entire protocol, from DNA extraction from fecal pellet to identification of species, takes only about 75 min and does not require expensive equipment. Hence, this diagnostic method is simple, fast, and accessible to anyone. As such, the method can be a useful tool to estimate distribution and population size of sika deer.

The utility of placing recollection in opposition to familiarity in early discrimination of healthy aging and very mild dementia of the Alzheimer's type.

PubMed

Tse, Chi-Shing; Balota, David A; Moynan, Sarah C; Duchek, Janet M; Jacoby, Larry L

2010-01-01

This study explored the ability to control familiarity-based information in a memory exclusion paradigm in healthy young, older adults, and early stage DAT individuals. We compared the predictive power of memory exclusion performance to standard psychometric performance in discriminating between aging and the earliest stage of DAT and between APOe4-present and APOe4-absent genotype in healthy control individuals. Participants responded "yes" to words that were previously semantically encoded, and "no" to words that were previously read aloud and to new words. The number of targets and distractors on the read "distractor" list was manipulated to investigate the degree to which aging and DAT influence the ability to recollect in the face of distractor familiarity due to repetition. Memory exclusion performance was better for healthy older adults than very mild DAT individuals and better for healthy control individuals with APOe4 allele than those without APOe4 allele even after controlling for standard psychometric performance. Discussion focuses on the importance of attentional control systems in memory retrieval and the utility of the opposition paradigm for discriminating healthy versus pathological aging. Copyright 2009 APA, all rights reserved.

Molecular identification of rare FY*Null and FY*X alleles in Caucasian thalassemic family from Sardinia.

PubMed

Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

2015-10-01

Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Allelic Prevalence of ABO Blood Group Genes in Iranian Azari Population.

PubMed

Nojavan, Mohammad; Shamsasenjan, Karrim; Movassaghpour, Ali Akbar; Akbarzadehlaleh, Parvin; Torabi, Seyd Esmail; Ghojazadeh, Morteza

2012-01-01

ABO blood group system is the most important blood group in transfusion and has been widely used in population studies. Several molecular techniques for ABO allele's detection are widely used for distinguishing various alleles of glycosyl transferase locus on chromosome 9. 744 randomly selected samples from Azari donors of East Azerbaijan province (Iran) were examined using well-adjusted multiplex allele- specific PCR ABO genotyping technique. The results were consistent for all individuals. The ABO blood group genotype of 744 healthy Azari blood donors was: 25.8% AA/AO (2), 7.6% AO (1), 1.6% BB, 11.3% B0 (1), 10% AB, 9.3% 0(1)0(1) and 15.3%0(1)0(2). The highest genotype frequency belonged to O01/O02 genotype (15.3%) and the lowest frequency belonged to A101/A102 genotype (0.4%). The frequencies of ABO alleles didn't show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). The frequencies of ABO alleles didn't show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05).

Forensic applicability of multi-allelic InDels with mononucleotide homopolymer structures.

PubMed

Zhang, Shu; Zhu, Qiang; Chen, Xiaogang; Zhao, Yuancun; Zhao, Xiaohong; Yang, Yiwen; Gao, Zehua; Fang, Ting; Wang, Yufang; Zhang, Ji

2018-04-27

Insertion/deletion polymorphisms (InDels), which possess the characteristics of low mutation rates and a short amplicon size, have been regarded as promising markers for forensic DNA analysis. InDels can be classified as bi-allelic or multi-allelic, depending on the number of alleles. Many studies have explored the use of bi-allelic InDels in forensic applications, such as individual identification and ancestry inference. However, multi-allelic InDels have received relatively little attention. In this study, InDels with 2-6 alleles and a minor allele frequency ≥0.01, in Chinese Southern Han (CHS), were retrieved from the 1000 Genomes Project Phase III. Based on the structural analysis of all retrieved InDels, 17 multi-allelic markers with mononucleotide homopolymer structures were selected and combined in one multiplex PCR reaction system. Sensitivity, species specificity and applicability in forensic case work of the multiplex were analyzed. A total of 218 unrelated individuals from a Chinese Han population were genotyped. The combined discriminatory power (CDP), the combined match probability (CMP) and the cumulative probability of exclusion (CPE) were 0.9999999999609, 3.91E-13 and 0.9956, respectively. The results demonstrated that this InDel multiplex panel was highly informative in the investigated population and most of the 26 populations of the 1000 Genomes Project. The data also suggested that multi-allelic InDel markers with monomeric base pair expansions are useful for forensic applications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity.

PubMed

Sata, F; Sapone, A; Elizondo, G; Stocker, P; Miller, V P; Zheng, W; Raunio, H; Crespi, C L; Gonzalez, F J

2000-01-01

To determine the existence of mutant and variant CgammaP3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression. A bacterial artificial chromosome that contains the complete CgammaP3A4 gene was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation. To investigate the existence of mutant and variant CgammaP3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human CgammaP3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human CgammaP3A4 gene, designated CgammaP3A4*1B, was found in the three different racial groups. The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The CgammaP3A4*1B allele was not found in Chinese subjects. A second variant allele, designated CgammaP3A4*2, having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 P450 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme but was not significantly different from the wild-type enzyme for testosterone 6beta-hydroxylation. Another rare allele, designated CgammaP3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. These are the first examples of potential function polymorphisms resulting from missense mutations in

The assessment of biases in the acoustic discrimination of individuals

PubMed Central

Šálek, Martin

2017-01-01

Animal vocalizations contain information about individual identity that could potentially be used for the monitoring of individuals. However, the performance of individual discrimination is subjected to many biases depending on factors such as the amount of identity information, or methods used. These factors need to be taken into account when comparing results of different studies or selecting the most cost-effective solution for a particular species. In this study, we evaluate several biases associated with the discrimination of individuals. On a large sample of little owl male individuals, we assess how discrimination performance changes with methods of call description, an increasing number of individuals, and number of calls per male. Also, we test whether the discrimination performance within the whole population can be reliably estimated from a subsample of individuals in a pre-screening study. Assessment of discrimination performance at the level of the individual and at the level of call led to different conclusions. Hence, studies interested in individual discrimination should optimize methods at the level of individuals. The description of calls by their frequency modulation leads to the best discrimination performance. In agreement with our expectations, discrimination performance decreased with population size. Increasing the number of calls per individual linearly increased the discrimination of individuals (but not the discrimination of calls), likely because it allows distinction between individuals with very similar calls. The available pre-screening index does not allow precise estimation of the population size that could be reliably monitored. Overall, projects applying acoustic monitoring at the individual level in population need to consider limitations regarding the population size that can be reliably monitored and fine-tune their methods according to their needs and limitations. PMID:28486488

The Maintenance of Single-Locus Polymorphism. IV. Models with Mutation from Existing Alleles

PubMed Central

Spencer, H. G.; Marks, R. W.

1992-01-01

The ability of viability selection to maintain allelic polymorphism is investigated using a constructionist approach. In extensions to the models we have previously proposed, a population is bombarded with a series of mutations whose fitnesses in conjunction with other alleles are functions of the corresponding fitnesses with a particular allele, the parent allele, already in the population. Allele frequencies are iterated simultaneously, thus allowing alleles to be driven to extinction by selection. Such models allow very high levels of polymorphism to evolve: up to 38 alleles in one case. Alleles that are lethal as homozygotes can evolve to surprisingly high frequencies. The joint evolution of allele frequencies and viabilities highlights the necessity to consider more than the current morphology of a population. Comparisons are made with the neutral theory of evolution and it is suggested that failure to reject neutrality using the Ewens-Watterson test cannot be regarded as evidence for the neutral theory. PMID:1732162

The maintenance of single-locus polymorphism. IV. Models with mutation from existing alleles.

PubMed

Spencer, H G; Marks, R W

1992-01-01

The ability of viability selection to maintain allelic polymorphism is investigated using a constructionist approach. In extensions to the models we have previously proposed, a population is bombarded with a series of mutations whose fitnesses in conjunction with other alleles are functions of the corresponding fitnesses with a particular allele, the parent allele, already in the population. Allele frequencies are iterated simultaneously, thus allowing alleles to be driven to extinction by selection. Such models allow very high levels of polymorphism to evolve: up to 38 alleles in one case. Alleles that are lethal as homozygotes can evolve to surprisingly high frequencies. The joint evolution of allele frequencies and viabilities highlights the necessity to consider more than the current morphology of a population. Comparisons are made with the neutral theory of evolution and it is suggested that failure to reject neutrality using the Ewens-Watterson test cannot be regarded as evidence for the neutral theory.

Independent regulation of the two Pax5 alleles during B-cell development.

PubMed

Nutt, S L; Vambrie, S; Steinlein, P; Kozmik, Z; Rolink, A; Weith, A; Busslinger, M

1999-04-01

The developmental control genes of the Pax family are frequently associated with mouse mutants and human disease syndromes. The function of these transcription factors is sensitive to gene dosage, as mutation of one allele or a modest increase in gene number results in phenotypic abnormalities. Pax5 has an important role in B-cell and midbrain development. By following the expression of individual Pax5 alleles at the single-cell level, we demonstrate here that Pax5 is subject to allele-specific regulation during B-lymphopoiesis. Pax5 is predominantly transcribed from only one allele in early progenitors and mature B cells, whereas it switches to a biallelic transcription mode in immature B cells. The allele-specific regulation of Pax5 is stochastic, reversible, independent of parental origin and correlates with synchronous replication, in contrast with imprinted and other monoallelically expressed genes. As a consequence, B-lymphoid tissues are mosaics with respect to the transcribed Pax5 allele, and thus mutation of one allele in heterozygous mice results in deletion of the cell population expressing the mutant allele due to loss of Pax5 function at the single-cell level. Similar allele-specific regulation may be a common mechanism causing the haploinsufficiency and frequent association of other Pax genes with human disease.

JAK2V617F mutation is associated with special alleles in essential thrombocythemia.

PubMed

Hsiao, Hui-Hua; Liu, Yi-Chang; Tsai, Hui-Jen; Lee, Ching-Ping; Hsu, Jui-Feng; Lin, Sheng-Fung

2011-03-01

Janus kinase 2 mutation (JAK2V617F) has been identified in myeloproliferative neoplasms. Furthermore, special single nucleoside polymorphisms (SNPs) have been found to be associated with the JAK2V617F mutation. Therefore, the associations among JAK2V617F and special SNPs and the allelic location between them were investigated in patients with essential thrombocythemia (ET). A total of 61 patients with ET and 106 healthy individuals were enrolled. The PCR-RFLP method was applied to investigate the pattern of three SNPs, rs10974944, rs12343867, and rs12340895. Allele-specific PCR was used to examine the allelic location between rs10974944 and JAK2V617F. Among the patients with ET, 34 (55.7%, 34/61) were JAK2V617F positive (heterozygous) while the other 27 (44.3%, 27/61) were negative, and there were no MPLW515L/K mutations noted. The pattern of special SNPs in JAK2V617F(+) was significantly different from that in normal individuals (p <0.05), while there was no difference between JAK2V617F(-) patients and normal individuals. Allele-specific PCR showed high association of a cis-location between the special G-allele of rs10974944 and JAK2V617F(+). Based on this small numbered study, the results show the association between special SNPs and JAK2V617F mutation and a cis-location between the special G-allelic form of rs10974944 and the JAK2V617F mutation. These data highlight a close relationship between them in patients with ET.

Perceived racial, socioeconomic and gender discrimination and its impact on contraceptive choice.

PubMed

Kossler, Karla; Kuroki, Lindsay M; Allsworth, Jenifer E; Secura, Gina M; Roehl, Kimberly A; Peipert, Jeffrey F

2011-09-01

The study was conducted to determine whether perceived racial, economic and gender discrimination has an impact on contraception use and choice of method. We analyzed the first 2,500 women aged 14-45 years enrolled in the Contraceptive CHOICE Project, a prospective cohort study aimed to reduce barriers to obtaining long-acting reversible contraception. Items from the "Experiences of Discrimination" (EOD) scale measured experienced race-, gender- and economic-based discrimination. Overall, 57% of women reported a history of discrimination. Thirty-three percent reported gender- or race-based discrimination, and 24% reported discrimination attributed to socioeconomic status (SES). Prior to study enrollment, women reporting discrimination were more likely to report any contraception use (61% vs. 52%, p<.001) but were more likely to use less effective methods (e.g., barrier methods, natural family planning or withdrawal; 41% vs. 32%, p<.001). In adjusted analyses, gender-, race- or SES-based discrimination were associated with increased current use of less effective methods [adjusted risk ratio (aRR) 1.22, 95% confidence interval (CI) 1.06-1.41; aRR 1.25, CI 1.08-1.45; aRR 1.23, CI 1.06-1.43, respectively]. After enrollment, 66% of women with a history of experience of discrimination chose a long-acting reversible contraceptive method (intrauterine device or implantable) and 35% chose a depo-medroxyprogesterone acetate or contraceptive pill, patch or ring. Discrimination negatively impacts a woman's use of contraception. However, after financial and structural barriers to contraceptive use were eliminated, women with EOD overwhelmingly selected effective methods of contraception. Future interventions to improve access and utilization of contraception should focus on eliminating barriers and targeting interventions that encompass race-, gender- and economic-based discrimination. Copyright © 2011 Elsevier Inc. All rights reserved.

Marker-assisted selection for recognizing wheat mutant genotypes carrying HMW glutenin alleles related to baking quality.

PubMed

Zamani, Mohammad Javad; Bihamta, Mohammad Reza; Naserian Khiabani, Behnam; Tahernezhad, Zahra; Hallajian, Mohammad Taher; Shamsi, Marzieh Varasteh

2014-01-01

Allelic diversity of HMW glutenin loci in several studies revealed that allelic combinations affect dough quality. Dx5 + Dy10 subunits are related to good baking quality and Dx2 + Dy12 are related to undesirable baking quality. One of the most regular methods to evaluate the baking quality is SDS-PAGE which is used to improve baking quality labs. Marker-assisted selection is the method which can recognize the alleles related to baking quality and this method is based on polymerase chain reaction. 10 pairs of specific primers related to Dx2, Dx2.1, Dx5, Dy10, and Dy12 subunits were used for recognizing baking quality of some wheat varieties and some mutant genotypes. Only 5 pairs of them could show the specific bands. All subunits were recognized by the primers except Dx2.1. Some of the primers were extracted from previous studies and the others were designed based on D genome subunits of wheat. SDS-PAGE method accomplished having confidence in these marker's results. To realize the effect of mutation, seed storage proteins were measured. It showed that mutation had effect on the amount of seed storage protein on the mutant seeds (which showed polymorphism).

Discriminative graph embedding for label propagation.

PubMed

Nguyen, Canh Hao; Mamitsuka, Hiroshi

2011-09-01

In many applications, the available information is encoded in graph structures. This is a common problem in biological networks, social networks, web communities and document citations. We investigate the problem of classifying nodes' labels on a similarity graph given only a graph structure on the nodes. Conventional machine learning methods usually require data to reside in some Euclidean spaces or to have a kernel representation. Applying these methods to nodes on graphs would require embedding the graphs into these spaces. By embedding and then learning the nodes on graphs, most methods are either flexible with different learning objectives or efficient enough for large scale applications. We propose a method to embed a graph into a feature space for a discriminative purpose. Our idea is to include label information into the embedding process, making the space representation tailored to the task. We design embedding objective functions that the following learning formulations become spectral transforms. We then reformulate these spectral transforms into multiple kernel learning problems. Our method, while being tailored to the discriminative tasks, is efficient and can scale to massive data sets. We show the need of discriminative embedding on some simulations. Applying to biological network problems, our method is shown to outperform baselines.

Perceived racial, socioeconomic and gender discrimination and its impact on contraceptive choice

PubMed Central

Kossler, Karla; Kuroki, Lindsay M.; Allsworth, Jenifer E.; Secura, Gina M.; Roehl, Kimberly A.; Peipert, Jeffrey F.

2012-01-01

Background The study was conducted to determine whether perceived racial, economic, and gender discrimination has an impact on contraception use and choice of method. Methods We analyzed the first 2,500 women, aged 14–45 years enrolled in the Contraceptive CHOICE Project, a prospective cohort study aimed to reduce barriers to long-acting reversible contraception. Items from the “Experiences of Discrimination” (EOD) scale measured experienced race-, gender-, and economic-based discrimination. Results Overall, 57% of women reported a history of discrimination. Thirty-three percent reported gender- or race-based discrimination and 24% reported discrimination attributed to socioeconomic status (SES). Prior to study enrollment, women reporting discrimination were more likely to report any contraception use (61% vs. 51%, p<0.001), but were more likely to use less effective methods (e.g., barrier methods, natural family planning or withdrawal; 41% vs. 32%, p<0.001). In adjusted analyses, gender-, race- or SES-based discrimination were associated with increased current use of less effective methods (adjusted risk ratio (aRR) 1.22, CI 1.06–1.41; aRR 1.25, CI 1.08–1.45; aRR 1.23, CI 1.06–1.43, respectively). After enrollment, 67% of women with history of experience of discrimination chose a long-acting reversible contraceptive method (intrauterine device or implantable) and 33% chose a depo-medroxyprogesterone acetate or contraceptive pill, patch or ring. Conclusions Discrimination negatively impacts a woman’s use of contraception. However, after financial and structural barriers to contraceptive use were eliminated, women with EOD overwhelmingly selected effective methods of contraception. Future interventions to improve access and utilization of contraception should focus on eliminating barriers and targeting interventions that encompass race-, gender-, and economic-based discrimination. PMID:21843693

Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

PubMed

Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

2003-02-01

Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone.

Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

PubMed Central

Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

2003-01-01

Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone. PMID:12618417

First example of an FY*01 allele associated with weakened expression of Fya on red blood cells.

PubMed

Arndt, Patricia A; Horn, Trina; Keller, Jessica A; Heri, Suzanne M; Keller, Margaret A

2015-01-01

Duffy antigens are important in immunohematology. the reference allele for the Duffy gene (FY) is FY*02, which encodes Fy(b). An A>G single nucleotide polymorphism (SNP) at coding nucleotide (c.) 125 in exon 2 defines the FY*01 allele, which encodes the antithetical Fy(a). A C>T SNP at c.265 in the FY*02 allele is associated with weakening of Fy(b) expression on red blood cells (R BCs) (called Fy(x)). until recently, this latter change had not been described on a FY*01 background allele. Phenotype-matched units were desired for a multi-transfused Vietnamese fetus with α-thalassemia. Genotyping of the fetus using a microarray assay that interrogates three SNPs (c.1-67, c.125, and c.265) in FY yielded indeterminate results for the predicted Duffy phenotype. Genomic sequencing of FY exon 2 showed that the fetal sample had one wild-type FY*01 allele and one new FY*01 allele with the c.265C>T SNP, which until recently had only been found on the FY*02 allele. Genotyping performed on samples from the proband's parents indicated that the father had the same FY genotype as the fetus. Flow cytometry, which has been previously demonstrated as a useful method to study antigen strength on cells, was used to determine if this new FY*01 allele was associated with reduced Fy(a) expression on the father's RBCs. Median fluorescence intensity of the father's RBCs (after incubation with anti-FY(a) and fluorescein-labeled anti-IgG) was similar to known FY*01 heterozygotes. and significantly weaker than known FY*01 homozygotes. In conclusion, the fetus and father both had one normal FY*01 allele and one new FY*01W.01, is associated with weakened expression of Fy(a) on RBCs.

New Discriminant Method for Identifying the Aggressive Disease Phenotype of Non-alcoholic Fatty Liver Disease.

PubMed

Kawamura, Yusuke; Ikeda, Kenji; Arase, Yasuji; Fujiyama, Shunichiro; Hosaka, Tetsuya; Kobayashi, Masahiro; Saitoh, Satoshi; Sezaki, Hitomi; Akuta, Norio; Suzuki, Fumitaka; Suzuki, Yoshiyuki; Kumada, Hiromitsu

2017-01-01

Objective To detect the aggressive phenotype (AP) of non-alcoholic fatty liver disease (NAFLD) based on the initial laboratory data and clinical characteristics. Methods We enrolled 144 patients with histologically proven NAFLD. For the first analysis, 24 NAFLD patients underwent repeat biopsy to establish a discriminant formula for predicting the AP of NAFLD (D-APN). The AP was defined by NAFLD that had been maintained or progressed to a fibrotic stage beyond stage 2. In the second analysis, we analyzed the distribution of the AP in each stage of disease and the incidence of the PNPLA3 rs738409 GG genotype in AP in 120 other patients. Results After the analysis, the following function was found to discriminate the disease phenotype: z=0.150×body mass index (kg/m 2 )+0.085×age (years)+1.112×ln (AST) (IU/L)+0.127×ln (m-AST)-12.96. A positive result indicates the AP of NAFLD. The discriminant functions had a positive predictive value of 94% and a negative predictive value of 71%. The distribution of the AP and the incidence of the PNPLA3 GG genotype in the AP in each stage of the disease among the 120 patients were as follows: non-alcoholic fatty liver, 30%/33%; non-alcoholic steatohepatitis (NASH) stage 1, 53%/26%; stage 2, 71%/70%; stage 3, 92%/57%; and stage 4, 93%/64%; there was a significant increase in the incidence of the AP as the disease progressed (p<0.001). Conclusion The new discriminant formula was useful for predicting disease progression potential in NAFLD patients and the incidence of the PNPLA3 GG genotype was elevated according to the distribution of AP.

ASSORTATIVE MATING CAN IMPEDE OR FACILITATE FIXATION OF UNDERDOMINANT ALLELES

PubMed Central

NEWBERRY, MITCHELL G; MCCANDLISH, DAVID M; PLOTKIN, JOSHUA B

2017-01-01

Underdominant mutations have fixed between divergent species, yet classical models suggest that rare underdominant alleles are purged quickly except in small or subdivided populations. We predict that underdominant alleles that also influence mate choice, such as those affecting coloration patterns visible to mates and predators alike, can fix more readily. We analyze a mechanistic model of positive assortative mating in which individuals have n chances to sample compatible mates. This one-parameter model naturally spans random mating (n =1) and complete assortment (n → ∞), yet it produces sexual selection whose strength depends non-monotonically on n. This sexual selection interacts with viability selection to either inhibit or facilitate fixation. As mating opportunities increase, underdominant alleles fix as frequently as neutral mutations, even though sexual selection and underdominance independently each suppress rare alleles. This mechanism allows underdominant alleles to fix in large populations and illustrates how life history can affect evolutionary change. PMID:27497738

Assortative mating can impede or facilitate fixation of underdominant alleles.

PubMed

Newberry, Mitchell G; McCandlish, David M; Plotkin, Joshua B

2016-12-01

Underdominant mutations have fixed between divergent species, yet classical models suggest that rare underdominant alleles are purged quickly except in small or subdivided populations. We predict that underdominant alleles that also influence mate choice, such as those affecting coloration patterns visible to mates and predators alike, can fix more readily. We analyze a mechanistic model of positive assortative mating in which individuals have n chances to sample compatible mates. This one-parameter model naturally spans random mating (n=1) and complete assortment (n→∞), yet it produces sexual selection whose strength depends non-monotonically on n. This sexual selection interacts with viability selection to either inhibit or facilitate fixation. As mating opportunities increase, underdominant alleles fix as frequently as neutral mutations, even though sexual selection and underdominance independently each suppress rare alleles. This mechanism allows underdominant alleles to fix in large populations and illustrates how life history can affect evolutionary change. Copyright © 2016 Elsevier Inc. All rights reserved.

The DosiMap, a new 2D scintillating dosimeter for IMRT quality assurance: characterization of two Cerenkov discrimination methods.

PubMed

Frelin, A M; Fontbonne, J M; Ban, G; Colin, J; Labalme, M; Batalla, A; Vela, A; Boher, P; Braud, M; Leroux, T

2008-05-01

New radiation therapy techniques such as IMRT present significant efficiency due to their highly conformal dose distributions. A consequence of the complexity of their dose distributions (high gradients, small irradiation fields, low dose distribution, ...) is the requirement for better precision quality assurance than in classical radiotherapy in order to compare the conformation of the delivered dose with the planned dose distribution and to guarantee the quality of the treatment. Currently this control is mostly performed by matrices of ionization chambers, diode detectors, dosimetric films, portal imaging, or dosimetric gels. Another approach is scintillation dosimetry, which has been developed in the last 15 years mainly through scintillating fiber devices. Despite having many advantages over other methods it is still at an experimental level for routine dosimetry because the Cerenkov radiation produced under irradiation represents an important stem effect. A new 2D water equivalent scintillating dosimeter, the DosiMap, and two different Cerenkov discrimination methods were developed with the collaboration of the Laboratoire de Physique Corpusculaire of Caen, the Comprehensive Cancer Center François Baclesse, and the ELDIM Co., in the frame of the MAESTRO European project. The DosiMap consists of a plastic scintillating sheet placed inside a transparent polystyrene phantom. The light distribution produced under irradiation is recorded by a CCD camera. Our first Cerenkov discrimination technique is subtractive. It uses a chessboard pattern placed in front of the scintillator, which provides a background signal containing only Cerenkov light. Our second discrimination technique is colorimetric. It performs a spectral analysis of the light signal, which allows the unfolding of the Cerenkov radiation and the scintillation. Tests were carried out with our DosiMap prototype and the performances of the two discrimination methods were assessed. The comparison of the

DRD4 dopamine receptor allelic diversity in various primate species

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

Adamson, M.; Higley, D.; O`Brien, S.

The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypesmore » in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.« less

Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage.

PubMed

Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

2016-07-01

Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

An efficient method for generation of bi-allelic null mutant mouse embryonic stem cells and its application for investigating epigenetic modifiers.

PubMed

Fisher, Cynthia L; Marks, Hendrik; Cho, Lily Ting-Yin; Andrews, Robert; Wormald, Sam; Carroll, Thomas; Iyer, Vivek; Tate, Peri; Rosen, Barry; Stunnenberg, Hendrik G; Fisher, Amanda G; Skarnes, William C

2017-12-01

Mouse embryonic stem (ES) cells are a popular model system to study biological processes, though uncovering recessive phenotypes requires inactivating both alleles. Building upon resources from the International Knockout Mouse Consortium (IKMC), we developed a targeting vector for second allele inactivation in conditional-ready IKMC 'knockout-first' ES cell lines. We applied our technology to several epigenetic regulators, recovering bi-allelic targeted clones with a high efficiency of 60% and used Flp recombinase to restore expression in two null cell lines to demonstrate how our system confirms causality through mutant phenotype reversion. We designed our strategy to select against re-targeting the 'knockout-first' allele and identify essential genes in ES cells, including the histone methyltransferase Setdb1. For confirmation, we exploited the flexibility of our system, enabling tamoxifen inducible conditional gene ablation while controlling for genetic background and tamoxifen effects. Setdb1 ablated ES cells exhibit severe growth inhibition, which is not rescued by exogenous Nanog expression or culturing in naive pluripotency '2i' media, suggesting that the self-renewal defect is mediated through pluripotency network independent pathways. Our strategy to generate null mutant mouse ES cells is applicable to thousands of genes and repurposes existing IKMC Intermediate Vectors. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

PubMed Central

Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

2014-01-01

Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people

PubMed Central

Bennett, D; Schneider, J; Wilson, R; Bienias, J; Berry-Kravis, E; Arnold, S

2005-01-01

Background: The neurobiological changes underlying the association of the apolipoprotein E (APOE) e4 allele with level of cognition are poorly understood. Objective: To test the hypothesis that amyloid load can account for (mediate) the association of the APOE e4 allele with level of cognition assessed proximate to death. Methods: There were 44 subjects with clinically diagnosed Alzheimer's disease and 50 without dementia, who had participated in the Religious Orders Study. They underwent determination of APOE allele status, had comprehensive cognitive testing in the last year of life, and brain autopsy at death. The percentage area of cortex occupied by amyloid beta and the density of tau positive neurofibrillary tangles were quantified from six brain regions and averaged to yield summary measures of amyloid load and neurofibrillary tangles. Multiple regression analyses were used to examine whether amyloid load could account for the effect of allele status on level of cognition, controlling for age, sex, and education. Results: Possession of at least one APOE e4 allele was associated with lower level of cognitive function proximate to death (p = 0.04). The effect of the e4 allele was reduced by nearly 60% and was no longer significant after controlling for the effect of amyloid load, whereas there was a robust inverse association between amyloid and cognition (p = 0.001). Because prior work had suggested that neurofibrillary tangles could account for the association of amyloid on cognition, we next examined whether amyloid could account for the effect of allele status on tangles. In a series of regression analyses, e4 was associated with density of tangles (p = 0.002), but the effect of the e4 allele was reduced by more than 50% and was no longer significant after controlling for the effect of amyloid load. Conclusion: These findings are consistent with a sequence of events whereby the e4 allele works through amyloid deposition and subsequent tangle formation to

Reflections on discrimination and health in India.

PubMed

Srivatsan, R

2015-01-01

This is a speculative paper on the structure of caste-based discrimination in India. It sketches the field by a) proposing four empirical and historical examples of discrimination in different medical situations; b) suggesting an analytical framework composed of domain, register, temporality and intensity of discrimination; c) proposing that in the Indian historical context, discrimination masks itself, hiding its character behind the veneer of secular ideas; d) arguing that discrimination is not some unfortunate residue of backwardness in modern society that will go away, but is the force of social hierarchy transforming itself into a fully modern capitalist culture. The paper then arrives at the understanding that discrimination is pandemic across India. The conclusion suggests that in India today, we need proposals, hypotheses and arguments that help us establish the ethical framework for meaningful empirical research that sociological studies of medical ethics and the epidemiology of discrimination can pursue. Its method is that of logical and speculative argument based on experience, with examples of different forms of discrimination to clarify the point being made. No specific research was undertaken for this purpose since the paper is not empirically based.

Origin Discrimination of Osmanthus fragrans var. thunbergii Flowers using GC-MS and UPLC-PDA Combined with Multivariable Analysis Methods.

PubMed

Zhou, Fei; Zhao, Yajing; Peng, Jiyu; Jiang, Yirong; Li, Maiquan; Jiang, Yuan; Lu, Baiyi

2017-07-01

Osmanthus fragrans flowers are used as folk medicine and additives for teas, beverages and foods. The metabolites of O. fragrans flowers from different geographical origins were inconsistent in some extent. Chromatography and mass spectrometry combined with multivariable analysis methods provides an approach for discriminating the origin of O. fragrans flowers. To discriminate the Osmanthus fragrans var. thunbergii flowers from different origins with the identified metabolites. GC-MS and UPLC-PDA were conducted to analyse the metabolites in O. fragrans var. thunbergii flowers (in total 150 samples). Principal component analysis (PCA), soft independent modelling of class analogy analysis (SIMCA) and random forest (RF) analysis were applied to group the GC-MS and UPLC-PDA data. GC-MS identified 32 compounds common to all samples while UPLC-PDA/QTOF-MS identified 16 common compounds. PCA of the UPLC-PDA data generated a better clustering than PCA of the GC-MS data. Ten metabolites (six from GC-MS and four from UPLC-PDA) were selected as effective compounds for discrimination by PCA loadings. SIMCA and RF analysis were used to build classification models, and the RF model, based on the four effective compounds (caffeic acid derivative, acteoside, ligustroside and compound 15), yielded better results with the classification rate of 100% in the calibration set and 97.8% in the prediction set. GC-MS and UPLC-PDA combined with multivariable analysis methods can discriminate the origin of Osmanthus fragrans var. thunbergii flowers. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Identification of novel alleles of the rice blast resistance gene Pi54

NASA Astrophysics Data System (ADS)

Vasudevan, Kumar; Gruissem, Wilhelm; Bhullar, Navreet K.

2015-10-01

Rice blast is one of the most devastating rice diseases and continuous resistance breeding is required to control the disease. The rice blast resistance gene Pi54 initially identified in an Indian cultivar confers broad-spectrum resistance in India. We explored the allelic diversity of the Pi54 gene among 885 Indian rice genotypes that were found resistant in our screening against field mixture of naturally existing M. oryzae strains as well as against five unique strains. These genotypes are also annotated as rice blast resistant in the International Rice Genebank database. Sequence-based allele mining was used to amplify and clone the Pi54 allelic variants. Nine new alleles of Pi54 were identified based on the nucleotide sequence comparison to the Pi54 reference sequence as well as to already known Pi54 alleles. DNA sequence analysis of the newly identified Pi54 alleles revealed several single polymorphic sites, three double deletions and an eight base pair deletion. A SNP-rich region was found between a tyrosine kinase phosphorylation site and the nucleotide binding site (NBS) domain. Together, the newly identified Pi54 alleles expand the allelic series and are candidates for rice blast resistance breeding programs.

Microcounseling Skill Discrimination Scale: A Methodological Note

ERIC Educational Resources Information Center

Stokes, Joseph; Romer, Daniel

1977-01-01

Absolute ratings on the Microcounseling Skill Discrimination Scale (MSDS) confound the individual's use of the rating scale and actual ability to discriminate effective and ineffective counselor behaviors. This note suggests methods of scoring the MSDS that will eliminate variability attributable to response language and improve the validity of…

[Study on the classification of dominant pathogens related to febrile respiratory syndrome, based on the method of Bayes discriminant analysis].

PubMed

Li, X C; Li, J S; Meng, L; Bai, Y N; Yu, D S; Liu, X N; Liu, X F; Jiang, X J; Ren, X W; Yang, X T; Shen, X P; Zhang, J W

2017-08-10

Objective: To understand the dominant pathogens of febrile respiratory syndrome (FRS) patients in Gansu province and to establish the Bayes discriminant function in order to identify the patients infected with the dominant pathogens. Methods: FRS patients were collected in various sentinel hospitals of Gansu province from 2009 to 2015 and the dominant pathogens were determined by describing the composition of pathogenic profile. Significant clinical variables were selected by stepwise discriminant analysis to establish the Bayes discriminant function. Results: In the detection of pathogens for FRS, both influenza virus and rhinovirus showed higher positive rates than those caused by other viruses (13.79%, 8.63%), that accounting for 54.38%, 13.73% of total viral positive patients. Most frequently detected bacteria would include Streptococcus pneumoniae , and haemophilus influenza (44.41%, 18.07%) that accounting for 66.21% and 24.55% among the bacterial positive patients. The original-validated rate of discriminant function, established by 11 clinical variables, was 73.1%, with the cross-validated rate as 70.6%. Conclusion: Influenza virus, Rhinovirus, Streptococcus pneumoniae and Haemophilus influenzae were the dominant pathogens of FRS in Gansu province. Results from the Bayes discriminant analysis showed both higher accuracy in the classification of dominant pathogens, and applicative value for FRS.

Molecular and morphological approaches in discrimination of endangered Probarbus jullieni of Malaysia and Thailand stocks.

PubMed

Bhassu, S; Abd Rashid, Z

2009-09-01

The population structure of Probarbus jullieni from Malaysia and Thailand stocks was based on seven microsatellite primers and truss network measurements. Truss morphometric measurements were made on Temoleh, Probarbus jullieni to demonstrate the degree of speciation that can be induced by both biotic and abiotic conditions and contribute to the definition of different stocks of Probarbus sp. At the momment no relevant information on stock definition has been produced recently concerning Probarbus spp., which is now in IUCN threatened red list. We also summarize the possible discriminant morphological characteristics that shows differentiation between Malaysia and Thailand stocks. We also compare the levels of morphology and genetic differences for Malaysian stocks throughout one year of sampling to determine whether sampling season and possible sexual dimorphism can be detected in this fishes. A total of 25 different alleles were found across the two populations by the seven microsatellites, of which 21 and 19 alleles were detected in Pahang, Malaysia and Thailand, respectively At the population level, the mean number of alleles of Pahang (3.4991) per locus was higher than that (3.1665) of Thailand. From both molecular and morphometric measurements showed that there were two distinct populations. However the differences between these two populations showed that they belong to the same species with least degree of separation

Direct testing for allele-specific expression differences between conditions

USDA-ARS?s Scientific Manuscript database

Genetic differences in cis regulatory regions contribute to the phenotypic variation observed in natural and human populations, including beneficial, potentially adaptive, traits as well as disease states. The two alleles in a diploid cell can differ in their allele-specific expression leading to al...

Genetic Discrimination

MedlinePlus

... the News Canadian 41 st Parliament Passes New Law, S-201 "Genetic Non-Discrimination Act" Canadian lawmakers passed ... Title II). Read more Genetic Discrimination and Other Laws Genetic Discrimination and Other Laws includes the Health ...

MATRIX DISCRIMINANT ANALYSIS WITH APPLICATION TO COLORIMETRIC SENSOR ARRAY DATA

PubMed Central

Suslick, Kenneth S.

2014-01-01

With the rapid development of nano-technology, a “colorimetric sensor array” (CSA) which is referred to as an optical electronic nose has been developed for the identification of toxicants. Unlike traditional sensors which rely on a single chemical interaction, CSA can measure multiple chemical interactions by using chemo-responsive dyes. The color changes of the chemo-responsive dyes are recorded before and after exposure to toxicants and serve as a template for classification. The color changes are digitalized in the form of a matrix with rows representing dye effects and columns representing the spectrum of colors. Thus, matrix-classification methods are highly desirable. In this article, we develop a novel classification method, matrix discriminant analysis (MDA), which is a generalization of linear discriminant analysis (LDA) for the data in matrix form. By incorporating the intrinsic matrix-structure of the data in discriminant analysis, the proposed method can improve CSA’s sensitivity and more importantly, specificity. A penalized MDA method, PMDA, is also introduced to further incorporate sparsity structure in discriminant function. Numerical studies suggest that the proposed MDA and PMDA methods outperform LDA and other competing discriminant methods for matrix predictors. The asymptotic consistency of MDA is also established. R code and data are available online as supplementary material. PMID:26783371

Exploring new alleles for frost tolerance in winter rye.

PubMed

Erath, Wiltrud; Bauer, Eva; Fowler, D Brian; Gordillo, Andres; Korzun, Viktor; Ponomareva, Mira; Schmidt, Malthe; Schmiedchen, Brigitta; Wilde, Peer; Schön, Chris-Carolin

2017-10-01

Rye genetic resources provide a valuable source of new alleles for the improvement of frost tolerance in rye breeding programs. Frost tolerance is a must-have trait for winter cereal production in northern and continental cropping areas. Genetic resources should harbor promising alleles for the improvement of frost tolerance of winter rye elite lines. For frost tolerance breeding, the identification of quantitative trait loci (QTL) and the choice of optimum genome-based selection methods are essential. We identified genomic regions involved in frost tolerance of winter rye by QTL mapping in a biparental population derived from a highly frost tolerant selection from the Canadian cultivar Puma and the European elite line Lo157. Lines per se and their testcrosses were phenotyped in a controlled freeze test and in multi-location field trials in Russia and Canada. Three QTL on chromosomes 4R, 5R, and 7R were consistently detected across environments. The QTL on 5R is congruent with the genomic region harboring the Frost resistance locus 2 (Fr-2) in Triticeae. The Puma allele at the Fr-R2 locus was found to significantly increase frost tolerance. A comparison of predictive ability obtained from the QTL-based model with different whole-genome prediction models revealed that besides a few large, also small QTL effects contribute to the genomic variance of frost tolerance in rye. Genomic prediction models assigning a high weight to the Fr-R2 locus allow increasing the selection intensity for frost tolerance by genome-based pre-selection of promising candidates.

Association between diabetes type 1 and DQB1 alleles in a case-control study conducted in Montevideo, Uruguay.

PubMed

Mimbacas, Adriana; Pérez-Bravo, Francisco; Hidalgo, Pedro C; Javiel, Gerardo; Pisciottano, Carmen; Grignola, Rosario; Jorge, Ana María; Gallino, Juan Pablo; Gasagoite, Jackeline; Cardoso, Horacio

2003-03-31

We studied HLA DQB1 allele frequencies and the relative risk (RR) of various genotypes in 72 type 1 diabetic patients and 40 control individuals in Uruguay. This is a tri-racial (Caucasian, Black and Indo-American) mixed population. The products of the polymerase chain reaction amplifications were hybridized with oligonucleotides by allele-specific oligonucleotide reverse or dot blot methods. Significant differences between these two groups were observed only for allele DQB1*0302 (35%, RR = 7.34, P<0.001). The frequency of the alleles carrying a non-aspartic acid residue at position 57 was significantly higher in the diabetic patients (85 vs 53%, P<0.001). In contrast, the frequency of Asp alleles was negatively associated with type 1 diabetes (RR = 0.20, P<0.001). The genotype DQB1*0302/DQB1*0201 (33%, RR = 5.41, P<0.05) was positively associated with this disease. The genotype frequencies associated with type 1 diabetes in our population were significantly different from what is known for Caucasian and Black populations as well as compared with another admixed population, from Chile.

Kernel Partial Least Squares for Nonlinear Regression and Discrimination

NASA Technical Reports Server (NTRS)

Rosipal, Roman; Clancy, Daniel (Technical Monitor)

2002-01-01

This paper summarizes recent results on applying the method of partial least squares (PLS) in a reproducing kernel Hilbert space (RKHS). A previously proposed kernel PLS regression model was proven to be competitive with other regularized regression methods in RKHS. The family of nonlinear kernel-based PLS models is extended by considering the kernel PLS method for discrimination. Theoretical and experimental results on a two-class discrimination problem indicate usefulness of the method.

Allele-specific Characterization of Alanine: Glyoxylate Aminotransferase Variants Associated with Primary Hyperoxaluria

PubMed Central

Lage, Melissa D.; Pittman, Adrianne M. C.; Roncador, Alessandro; Cellini, Barbara; Tucker, Chandra L.

2014-01-01

Primary Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type) and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele. PMID:24718375

Allelic database and accession divergence of a Brazilian mango collection based on microsatellite markers.

PubMed

Dos Santos Ribeiro, I C N; Lima Neto, F P; Santos, C A F

2012-12-19

Allelic patterns and genetic distances were examined in a collection of 103 foreign and Brazilian mango (Mangifera indica) accessions in order to develop a reference database to support cultivar protection and breeding programs. An UPGMA dendrogram was generated using Jaccard's coefficients from a distance matrix based on 50 alleles of 12 microsatellite loci. The base pair number was estimated by the method of inverse mobility. The cophenetic correlation was 0.8. The accessions had a coefficient of similarity from 30 to 100%, which reflects high genetic variability. Three groups were observed in the UPGMA dendrogram; the first group was formed predominantly by foreign accessions, the second group was formed by Brazilian accessions, and the Dashehari accession was isolated from the others. The 50 microsatellite alleles did not separate all 103 accessions, indicating that there are duplicates in this mango collection. These 12 microsatellites need to be validated in order to establish a reliable set to identify mango cultivars.

Japaneseplex: A forensic SNP assay for identification of Japanese people using Japanese-specific alleles.

PubMed

Yuasa, Isao; Akane, Atsushi; Yamamoto, Toshimichi; Matsusue, Aya; Endoh, Minoru; Nakagawa, Mayumi; Umetsu, Kazuo; Ishikawa, Takaki; Iino, Morio

2018-04-24

It is sometimes necessary to determine whether a forensic biological sample came from a Japanese person. In this study, we developed a 60-locus SNP assay designed for the differentiation of Japanese people from other East Asians using entirely and nearly Japanese-specific alleles. This multiplex assay consisted of 6 independent PCR reactions followed by single nucleotide extension. The average number and standard deviation of Japanese-specific alleles possessed by an individual were 0.81 ± 0.93 in 108 Koreans from Seoul, 8.87 ± 2.89 in 103 Japanese from Tottori, 17.20 ± 3.80 in 88 Japanese from Okinawa, and 0 in 220 Han Chinese from Wuxi and Changsha. The Koreans had 0-4 Japanese-specific alleles per individual, whereas the Japanese had 4-26 Japanese-specific alleles. Almost all Japanese were distinguished from the Koreans and other people by the factorial correspondence and principal component analyses. The Snipper program was also useful to estimate the degree of Japaneseness. The method described here was successfully applied to the differentiation of Japanese from non-Japanese people in forensic cases. This Japanese-specific SNP assay was named Japaneseplex. Copyright © 2018 Elsevier B.V. All rights reserved.

A multiple maximum scatter difference discriminant criterion for facial feature extraction.

PubMed

Song, Fengxi; Zhang, David; Mei, Dayong; Guo, Zhongwei

2007-12-01

Maximum scatter difference (MSD) discriminant criterion was a recently presented binary discriminant criterion for pattern classification that utilizes the generalized scatter difference rather than the generalized Rayleigh quotient as a class separability measure, thereby avoiding the singularity problem when addressing small-sample-size problems. MSD classifiers based on this criterion have been quite effective on face-recognition tasks, but as they are binary classifiers, they are not as efficient on large-scale classification tasks. To address the problem, this paper generalizes the classification-oriented binary criterion to its multiple counterpart--multiple MSD (MMSD) discriminant criterion for facial feature extraction. The MMSD feature-extraction method, which is based on this novel discriminant criterion, is a new subspace-based feature-extraction method. Unlike most other subspace-based feature-extraction methods, the MMSD computes its discriminant vectors from both the range of the between-class scatter matrix and the null space of the within-class scatter matrix. The MMSD is theoretically elegant and easy to calculate. Extensive experimental studies conducted on the benchmark database, FERET, show that the MMSD out-performs state-of-the-art facial feature-extraction methods such as null space method, direct linear discriminant analysis (LDA), eigenface, Fisherface, and complete LDA.

Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.

PubMed

Takeuchi, Hikaru; Tomita, Hiroaki; Taki, Yasuyuki; Kikuchi, Yoshie; Ono, Chiaki; Yu, Zhiqian; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2015-04-15

The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases. Copyright © 2015. Published by Elsevier Inc.

Discriminative object tracking via sparse representation and online dictionary learning.

PubMed

Xie, Yuan; Zhang, Wensheng; Li, Cuihua; Lin, Shuyang; Qu, Yanyun; Zhang, Yinghua

2014-04-01

We propose a robust tracking algorithm based on local sparse coding with discriminative dictionary learning and new keypoint matching schema. This algorithm consists of two parts: the local sparse coding with online updated discriminative dictionary for tracking (SOD part), and the keypoint matching refinement for enhancing the tracking performance (KP part). In the SOD part, the local image patches of the target object and background are represented by their sparse codes using an over-complete discriminative dictionary. Such discriminative dictionary, which encodes the information of both the foreground and the background, may provide more discriminative power. Furthermore, in order to adapt the dictionary to the variation of the foreground and background during the tracking, an online learning method is employed to update the dictionary. The KP part utilizes refined keypoint matching schema to improve the performance of the SOD. With the help of sparse representation and online updated discriminative dictionary, the KP part are more robust than the traditional method to reject the incorrect matches and eliminate the outliers. The proposed method is embedded into a Bayesian inference framework for visual tracking. Experimental results on several challenging video sequences demonstrate the effectiveness and robustness of our approach.

Discriminant Validity Assessment: Use of Fornell & Larcker criterion versus HTMT Criterion

NASA Astrophysics Data System (ADS)

Hamid, M. R. Ab; Sami, W.; Mohmad Sidek, M. H.

2017-09-01

Assessment of discriminant validity is a must in any research that involves latent variables for the prevention of multicollinearity issues. Fornell and Larcker criterion is the most widely used method for this purpose. However, a new method has emerged for establishing the discriminant validity assessment through heterotrait-monotrait (HTMT) ratio of correlations method. Therefore, this article presents the results of discriminant validity assessment using these methods. Data from previous study was used that involved 429 respondents for empirical validation of value-based excellence model in higher education institutions (HEI) in Malaysia. From the analysis, the convergent, divergent and discriminant validity were established and admissible using Fornell and Larcker criterion. However, the discriminant validity is an issue when employing the HTMT criterion. This shows that the latent variables under study faced the issue of multicollinearity and should be looked into for further details. This also implied that the HTMT criterion is a stringent measure that could detect the possible indiscriminant among the latent variables. In conclusion, the instrument which consisted of six latent variables was still lacking in terms of discriminant validity and should be explored further.

Strategies for mapping heterogeneous recessive traits by allele-sharing methods.

PubMed Central

Feingold, E; Siegmund, D O

1997-01-01

We investigate strategies for detecting linkage of recessive and partially recessive traits, using sibling pairs and inbred individuals. We assume that a genomewide search is being conducted and that locus heterogeneity of the trait is likely. For sibling pairs, we evaluate the efficiency of different statistics under the assumption that one does not know the true degree of recessiveness of the trait. We recommend a sibling-pair statistic that is a linear compromise between two previously suggested statistics. We also compare the power of sibling pairs to that of more distant relatives, such as cousins. For inbred individuals, we evaluate the power of offspring of different types of matings and compare them to sibling pairs. Over a broad range of trait etiologies, sibling pairs are more powerful than inbred individuals, but for traits caused by very rare alleles, particularly in the case of heterogeneity, inbred individuals can be much more powerful. The models we develop can also be used to examine specific situations other than those we look at. We present this analysis in the idealized context of a dense set of highly polymorphic markers. In general, incorporation of real-world complexities makes inbred individuals, particularly offspring of distant relatives, look slightly less useful than our results imply. PMID:9106544

[Discrimination of Rice Syrup Adulterant of Acacia Honey Based Using Near-Infrared Spectroscopy].

PubMed

Zhang, Yan-nan; Chen, Lan-zhen; Xue, Xiao-feng; Wu, Li-ming; Li, Yi; Yang, Juan

2015-09-01

At present, the rice syrup as a low price of the sweeteners was often adulterated into acacia honey and the adulterated honeys were sold in honey markets, while there is no suitable and fast method to identify honey adulterated with rice syrup. In this study, Near infrared spectroscopy (NIR) combined with chemometric methods were used to discriminate authenticity of honey. 20 unprocessed acacia honey samples from the different honey producing areas, mixed? with different proportion of rice syrup, were prepared of seven different concentration gradient? including 121 samples. The near infrared spectrum (NIR) instrument and spectrum processing software have been applied in the? spectrum? scanning and data conversion on adulterant samples, respectively. Then it was analyzed by Principal component analysis (PCA) and canonical discriminant analysis methods in order to discriminating adulterated honey. The results showed that after principal components analysis, the first two principal components accounted for 97.23% of total variation, but the regionalism of the score plot of the first two PCs was not obvious, so the canonical discriminant analysis was used to make the further discrimination, all samples had been discriminated correctly, the first two discriminant functions accounted for 91.6% among the six canonical discriminant functions, Then the different concentration of adulterant samples can be discriminated correctly, it illustrate that canonical discriminant analysis method combined with NIR spectroscopy is not only feasible but also practical for rapid and effective discriminate of the rice syrup adulterant of acacia honey.

An ancillary method in urine cytology: Nucleolar/nuclear volume ratio for discrimination between benign and malignant urothelial cells.

PubMed

Tone, Kiyoshi; Kojima, Keiko; Hoshiai, Keita; Kumagai, Naoya; Kijima, Hiroshi; Kurose, Akira

2016-06-01

The essential of urine cytology for the diagnosis and the follow-up of urothelial neoplasia has been widely recognized. However, there are some cases in which a definitive diagnosis cannot be made due to difficulty in discriminating between benign and malignant. This study evaluated the practicality of nucleolar/nuclear volume ratio (%) for the discrimination. Using Papanicolaou-stained slides, 253 benign urothelial cells and 282 malignant urothelial cells were selected and divided into a benign urothelial cell and an urothelial carcinoma (UC) cell groups. Three suspicious cases and four cases in which discrimination between benign and malignant was difficult were prepared for verification test. Subject cells were decolorized and stained with 4',6-diamidino-2-phenylindole for detection of the nuclei and the nucleoli. Z-stack method was performed to analyze. When the cutoff point of 1.514% discriminating benign urothelial cells and UC cells from nucleolar/nuclear volume ratio (%) was utilized, the sensitivity was 56.0%, the specificity was 88.5%, the positive predictive value was 84.5%, and the negative predictive value was 64.4%. Nuclear and nucleolar volume, number of the nucleoli, and nucleolar/nuclear volume ratio (%) were significantly higher in the UC cell group than in the benign urothelial cell group (P <0.001). In the verification test using the nucleolar/nuclear ratio (%), four of the seven cases were concordant with the final diagnosis. This study analyzed the nuclear and nucleolar volume to establish an index for discrimination of benign and malignant urothelial cells, providing possible additional information in urine cytology. Diagn. Cytopathol. 2016;44:483-491. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles.

PubMed

Robinson, James; Guethlein, Lisbeth A; Cereb, Nezih; Yang, Soo Young; Norman, Paul J; Marsh, Steven G E; Parham, Peter

2017-06-01

HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles. This analysis required development of suites of methods, having general applicability, for comparing and analyzing large numbers of homologous sequences. At least three amino-acid substitutions are present at every position in the polymorphic α1 and α2 domains of HLA-A, -B and -C. A minority of positions have an incidence >1% for the 'second' most frequent nucleotide, comprising 70 positions in HLA-A, 85 in HLA-B and 54 in HLA-C. The majority of these positions have three or four alternative nucleotides. These positions were subject to positive selection and correspond to binding sites for peptides and receptors. Most alleles of HLA class I (>80%) are very rare, often identified in one person or family, and they differ by point mutation from older, more common alleles. These alleles with single nucleotide polymorphisms reflect the germ-line mutation rate. Their frequency predicts the human population harbors 8-9 million HLA class I variants. The common alleles of human populations comprise 42 core alleles, which represent all selected polymorphism, and recombinants that have assorted this polymorphism.

Distinguishing functional polymorphism from random variation in the sequences of >10,000 HLA-A, -B and -C alleles

PubMed Central

Cereb, Nezih; Yang, Soo Young; Marsh, Steven G. E.; Parham, Peter

2017-01-01

HLA class I glycoproteins contain the functional sites that bind peptide antigens and engage lymphocyte receptors. Recently, clinical application of sequence-based HLA typing has uncovered an unprecedented number of novel HLA class I alleles. Here we define the nature and extent of the variation in 3,489 HLA-A, 4,356 HLA-B and 3,111 HLA-C alleles. This analysis required development of suites of methods, having general applicability, for comparing and analyzing large numbers of homologous sequences. At least three amino-acid substitutions are present at every position in the polymorphic α1 and α2 domains of HLA-A, -B and -C. A minority of positions have an incidence >1% for the ‘second’ most frequent nucleotide, comprising 70 positions in HLA-A, 85 in HLA-B and 54 in HLA-C. The majority of these positions have three or four alternative nucleotides. These positions were subject to positive selection and correspond to binding sites for peptides and receptors. Most alleles of HLA class I (>80%) are very rare, often identified in one person or family, and they differ by point mutation from older, more common alleles. These alleles with single nucleotide polymorphisms reflect the germ-line mutation rate. Their frequency predicts the human population harbors 8–9 million HLA class I variants. The common alleles of human populations comprise 42 core alleles, which represent all selected polymorphism, and recombinants that have assorted this polymorphism. PMID:28650991

Hyperspectral interventional imaging for enhanced tissue visualization and discrimination combining band selection methods.

PubMed

Nouri, Dorra; Lucas, Yves; Treuillet, Sylvie

2016-12-01

Hyperspectral imaging is an emerging technology recently introduced in medical applications inasmuch as it provides a powerful tool for noninvasive tissue characterization. In this context, a new system was designed to be easily integrated in the operating room in order to detect anatomical tissues hardly noticed by the surgeon's naked eye. Our LCTF-based spectral imaging system is operative over visible, near- and middle-infrared spectral ranges (400-1700 nm). It is dedicated to enhance critical biological tissues such as the ureter and the facial nerve. We aim to find the best three relevant bands to create a RGB image to display during the intervention with maximal contrast between the target tissue and its surroundings. A comparative study is carried out between band selection methods and band transformation methods. Combined band selection methods are proposed. All methods are compared using different evaluation criteria. Experimental results show that the proposed combined band selection methods provide the best performance with rich information, high tissue separability and short computational time. These methods yield a significant discrimination between biological tissues. We developed a hyperspectral imaging system in order to enhance some biological tissue visualization. The proposed methods provided an acceptable trade-off between the evaluation criteria especially in SWIR spectral band that outperforms the naked eye's capacities.

Vigilance in the discrimination-stress model for Black Americans

PubMed Central

Himmelstein, Mary S.; Young, Danielle M.; Sanchez, Diana T.; Jackson, James S.

2015-01-01

Objective Daily events of discrimination are important factors in understanding health disparities. Vigilant coping, or protecting against anticipated discrimination by monitoring and modifying behaviour, is an understudied mechanism that may link discrimination and health outcomes. This study investigates how responding to everyday discrimination with anticipatory vigilance relates to the health of Black men and women. Methods Black adults (N = 221) from the Detroit area completed measures of discrimination, adverse life events, vigilance coping, stress, depressive symptoms and self-reported health. Results Vigilance coping strategies mediated the relationship between discrimination and stress. Multi-group path analysis revealed that stress in turn was associated with increased depression in men and women. Self-reported health consequences of stress differed between men and women. Conclusions Vigilance coping mediates the link between discrimination and stress, and stress has consequences for health outcomes resulting from discrimination. More research is needed to understand other underlying contributors to discrimination, stress and poor health outcomes as well as to create potential interventions to ameliorate health outcomes in the face of discrimination-related stress. PMID:25247925

Estimating Time to the Common Ancestor for a Beneficial Allele

PubMed Central

Smith, Joel; Coop, Graham; Stephens, Matthew; Novembre, John

2018-01-01

Abstract The haplotypes of a beneficial allele carry information about its history that can shed light on its age and the putative cause for its increase in frequency. Specifically, the signature of an allele’s age is contained in the pattern of variation that mutation and recombination impose on its haplotypic background. We provide a method to exploit this pattern and infer the time to the common ancestor of a positively selected allele following a rapid increase in frequency. We do so using a hidden Markov model which leverages the length distribution of the shared ancestral haplotype, the accumulation of derived mutations on the ancestral background, and the surrounding background haplotype diversity. Using simulations, we demonstrate how the inclusion of information from both mutation and recombination events increases accuracy relative to approaches that only consider a single type of event. We also show the behavior of the estimator in cases where data do not conform to model assumptions, and provide some diagnostics for assessing and improving inference. Using the method, we analyze population-specific patterns in the 1000 Genomes Project data to estimate the timing of adaptation for several variants which show evidence of recent selection and functional relevance to diet, skin pigmentation, and morphology in humans. PMID:29361025

Nomenclature for alleles of the thiopurine methyltransferase gene

PubMed Central

Appell, Malin L.; Berg, Jonathan; Duley, John; Evans, William E.; Kennedy, Martin A.; Lennard, Lynne; Marinaki, Tony; McLeod, Howard L.; Relling, Mary V.; Schaeffeler, Elke; Schwab, Matthias; Weinshilboum, Richard; Yeoh, Allen E.J.; McDonagh, Ellen M.; Hebert, Joan M.; Klein, Teri E.; Coulthard, Sally A.

2013-01-01

The drug-metabolizing enzyme thiopurine methyltransferase (TPMT) has become one of the best examples of pharmacogenomics to be translated into routine clinical practice. TPMT metabolizes the thiopurines 6-mercaptopurine, 6-thioguanine, and azathioprine, drugs that are widely used for treatment of acute leukemias, inflammatory bowel diseases, and other disorders of immune regulation. Since the discovery of genetic polymorphisms in the TPMT gene, many sequence variants that cause a decreased enzyme activity have been identified and characterized. Increasingly, to optimize dose, pretreatment determination of TPMT status before commencing thiopurine therapy is now routine in many countries. Novel TPMT sequence variants are currently numbered sequentially using PubMed as a source of information; however, this has caused some problems as exemplified by two instances in which authors’ articles appeared on PubMed at the same time, resulting in the same allele numbers given to different polymorphisms. Hence, there is an urgent need to establish an order and consensus to the numbering of known and novel TPMT sequence variants. To address this problem, a TPMT nomenclature committee was formed in 2010, to define the nomenclature and numbering of novel variants for the TPMT gene. A website (http://www.imh.liu.se/tpmtalleles) serves as a platform for this work. Researchers are encouraged to submit novel TPMT alleles to the committee for designation and reservation of unique allele numbers. The committee has decided to renumber two alleles: nucleotide position 106 (G > A) from TPMT*24 to TPMT*30 and position 611 (T > C, rs79901429) from TPMT*28 to TPMT*31. Nomenclature for all other known alleles remains unchanged. PMID:23407052

Tissue-specific patterns of allelically-skewed DNA methylation

PubMed Central

Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

2016-01-01

ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

MICA diversity and linkage disequilibrium with HLA-B alleles in renal-transplant candidates in southern Brazil.

PubMed

Yamakawa, Roger Haruki; Saito, Patrícia Keiko; Gelmini, Geórgia Fernanda; da Silva, José Samuel; Bicalho, Maria da Graça; Borelli, Sueli Donizete

2017-01-01

The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located centromerically to the human leukocyte antigen (HLA)-B. The short distance between these loci in the MHC indicates the presence of linkage disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and this polymorphism has not been well documented in different populations. In this study, we estimated the allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence-specific primer method (PCR-SSO), combined with the Luminex technology. A total of 19 MICA allele groups were identified. The most frequent allele groups were MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35 (5.63%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc = 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469). This study provided information on the distribution of MICA polymorphisms and linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant candidates. This information should help to determine the mechanisms of susceptibility to different diseases in patients with chronic kidney disease, and to elucidate the mechanisms involved in allograft rejection associated with MICA polymorphisms in a Brazilian population.

Prejudice and discrimination from mental health service providers.

PubMed

Nemec, Patricia B; Swarbrick, Margaret; Legere, Lyn

2015-06-01

This column describes the experience of prejudice and discrimination that some mental health service users encounter in their interactions with service providers and organizations. The intent of this column is to highlight potential action steps to address the negative beliefs and attitudes of service providers that contribute to prejudice and discrimination. This description draws from published material and the authors' experience. If the most effective approaches to reduce public prejudice and discrimination toward people diagnosed with a mental illness are education and contact, then those methods may be useful methods to help mental health service providers view and engage persons served from a strengths-based recovery and wellness orientation. (c) 2015 APA, all rights reserved).

Allelic variation contributes to bacterial host specificity

DOE PAGES

Yue, Min; Han, Xiangan; Masi, Leon De; ...

2015-10-30

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

A parallel spatiotemporal saliency and discriminative online learning method for visual target tracking in aerial videos.

PubMed

Aghamohammadi, Amirhossein; Ang, Mei Choo; A Sundararajan, Elankovan; Weng, Ng Kok; Mogharrebi, Marzieh; Banihashem, Seyed Yashar

2018-01-01

Visual tracking in aerial videos is a challenging task in computer vision and remote sensing technologies due to appearance variation difficulties. Appearance variations are caused by camera and target motion, low resolution noisy images, scale changes, and pose variations. Various approaches have been proposed to deal with appearance variation difficulties in aerial videos, and amongst these methods, the spatiotemporal saliency detection approach reported promising results in the context of moving target detection. However, it is not accurate for moving target detection when visual tracking is performed under appearance variations. In this study, a visual tracking method is proposed based on spatiotemporal saliency and discriminative online learning methods to deal with appearance variations difficulties. Temporal saliency is used to represent moving target regions, and it was extracted based on the frame difference with Sauvola local adaptive thresholding algorithms. The spatial saliency is used to represent the target appearance details in candidate moving regions. SLIC superpixel segmentation, color, and moment features can be used to compute feature uniqueness and spatial compactness of saliency measurements to detect spatial saliency. It is a time consuming process, which prompted the development of a parallel algorithm to optimize and distribute the saliency detection processes that are loaded into the multi-processors. Spatiotemporal saliency is then obtained by combining the temporal and spatial saliencies to represent moving targets. Finally, a discriminative online learning algorithm was applied to generate a sample model based on spatiotemporal saliency. This sample model is then incrementally updated to detect the target in appearance variation conditions. Experiments conducted on the VIVID dataset demonstrated that the proposed visual tracking method is effective and is computationally efficient compared to state-of-the-art methods.

Contextual Advantage for State Discrimination

NASA Astrophysics Data System (ADS)

Schmid, David; Spekkens, Robert W.

2018-02-01

Finding quantitative aspects of quantum phenomena which cannot be explained by any classical model has foundational importance for understanding the boundary between classical and quantum theory. It also has practical significance for identifying information processing tasks for which those phenomena provide a quantum advantage. Using the framework of generalized noncontextuality as our notion of classicality, we find one such nonclassical feature within the phenomenology of quantum minimum-error state discrimination. Namely, we identify quantitative limits on the success probability for minimum-error state discrimination in any experiment described by a noncontextual ontological model. These constraints constitute noncontextuality inequalities that are violated by quantum theory, and this violation implies a quantum advantage for state discrimination relative to noncontextual models. Furthermore, our noncontextuality inequalities are robust to noise and are operationally formulated, so that any experimental violation of the inequalities is a witness of contextuality, independently of the validity of quantum theory. Along the way, we introduce new methods for analyzing noncontextuality scenarios and demonstrate a tight connection between our minimum-error state discrimination scenario and a Bell scenario.

New prediction model for probe specificity in an allele-specific extension reaction for haplotype-specific extraction (HSE) of Y chromosome mixtures.

PubMed

Rothe, Jessica; Watkins, Norman E; Nagy, Marion

2012-01-01

Allele-specific extension reactions (ASERs) use 3' terminus-specific primers for the selective extension of completely annealed matches by polymerase. The ability of the polymerase to extend non-specific 3' terminal mismatches leads to a failure of the reaction, a process that is only partly understood and predictable, and often requires time-consuming assay design. In our studies we investigated haplotype-specific extraction (HSE) for the separation of male DNA mixtures. HSE is an ASER and provides the ability to distinguish between diploid chromosomes from one or more individuals. Here, we show that the success of HSE and allele-specific extension depend strongly on the concentration difference between complete match and 3' terminal mismatch. Using the oligonucleotide-modeling platform Visual Omp, we demonstrated the dependency of the discrimination power of the polymerase on match- and mismatch-target hybridization between different probe lengths. Therefore, the probe specificity in HSE could be predicted by performing a relative comparison of different probe designs with their simulated differences between the duplex concentration of target-probe match and mismatches. We tested this new model for probe design in more than 300 HSE reactions with 137 different probes and obtained an accordance of 88%.

Population differentiation in allele frequencies of obesity-associated SNPs.

PubMed

Mao, Linyong; Fang, Yayin; Campbell, Michael; Southerland, William M

2017-11-10

Obesity is emerging as a global health problem, with more than one-third of the world's adult population being overweight or obese. In this study, we investigated worldwide population differentiation in allele frequencies of obesity-associated SNPs (single nucleotide polymorphisms). We collected a total of 225 obesity-associated SNPs from a public database. Their population-level allele frequencies were derived based on the genotype data from 1000 Genomes Project (phase 3). We used hypergeometric model to assess whether the effect allele at a given SNP is significantly enriched or depleted in each of the 26 populations surveyed in the 1000 Genomes Project with respect to the overall pooled population. Our results indicate that 195 out of 225 SNPs (86.7%) possess effect alleles significantly enriched or depleted in at least one of the 26 populations. Populations within the same continental group exhibit similar allele enrichment/depletion patterns whereas inter-continental populations show distinct patterns. Among the 225 SNPs, 15 SNPs cluster in the first intron region of the FTO gene, which is a major gene associated with body-mass index (BMI) and fat mass. African populations exhibit much smaller blocks of LD (linkage disequilibrium) among these15 SNPs while European and Asian populations have larger blocks. To estimate the cumulative effect of all variants associated with obesity, we developed the personal composite genetic risk score for obesity. Our results indicate that the East Asian populations have the lowest averages of the composite risk scores, whereas three European populations have the highest averages. In addition, the population-level average of composite genetic risk scores is significantly correlated (R 2 = 0.35, P = 0.0060) with obesity prevalence. We have detected substantial population differentiation in allele frequencies of obesity-associated SNPs. The results will help elucidate the genetic basis which may contribute to population

Relation between minimum-error discrimination and optimum unambiguous discrimination

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

Qiu Daowen; SQIG-Instituto de Telecomunicacoes, Departamento de Matematica, Instituto Superior Tecnico, Universidade Tecnica de Lisboa, Avenida Rovisco Pais PT-1049-001, Lisbon; Li Lvjun

2010-09-15

In this paper, we investigate the relationship between the minimum-error probability Q{sub E} of ambiguous discrimination and the optimal inconclusive probability Q{sub U} of unambiguous discrimination. It is known that for discriminating two states, the inequality Q{sub U{>=}}2Q{sub E} has been proved in the literature. The main technical results are as follows: (1) We show that, for discriminating more than two states, Q{sub U{>=}}2Q{sub E} may not hold again, but the infimum of Q{sub U}/Q{sub E} is 1, and there is no supremum of Q{sub U}/Q{sub E}, which implies that the failure probabilities of the two schemes for discriminating somemore » states may be narrowly or widely gapped. (2) We derive two concrete formulas of the minimum-error probability Q{sub E} and the optimal inconclusive probability Q{sub U}, respectively, for ambiguous discrimination and unambiguous discrimination among arbitrary m simultaneously diagonalizable mixed quantum states with given prior probabilities. In addition, we show that Q{sub E} and Q{sub U} satisfy the relationship that Q{sub U{>=}}(m/m-1)Q{sub E}.« less

Disturbance by optimal discrimination

NASA Astrophysics Data System (ADS)

Kawakubo, Ryûitirô; Koike, Tatsuhiko

2018-03-01

We discuss the disturbance by measurements which unambiguously discriminate between given candidate states. We prove that such an optimal measurement necessarily changes distinguishable states indistinguishable when the inconclusive outcome is obtained. The result was previously shown by Chefles [Phys. Lett. A 239, 339 (1998), 10.1016/S0375-9601(98)00064-4] under restrictions on the class of quantum measurements and on the definition of optimality. Our theorems remove these restrictions and are also applicable to infinitely many candidate states. Combining with our previous results, one can obtain concrete mathematical conditions for the resulting states. The method may have a wide variety of applications in contexts other than state discrimination.

Spectral Regression Discriminant Analysis for Hyperspectral Image Classification

NASA Astrophysics Data System (ADS)

Pan, Y.; Wu, J.; Huang, H.; Liu, J.

2012-08-01

Dimensionality reduction algorithms, which aim to select a small set of efficient and discriminant features, have attracted great attention for Hyperspectral Image Classification. The manifold learning methods are popular for dimensionality reduction, such as Locally Linear Embedding, Isomap, and Laplacian Eigenmap. However, a disadvantage of many manifold learning methods is that their computations usually involve eigen-decomposition of dense matrices which is expensive in both time and memory. In this paper, we introduce a new dimensionality reduction method, called Spectral Regression Discriminant Analysis (SRDA). SRDA casts the problem of learning an embedding function into a regression framework, which avoids eigen-decomposition of dense matrices. Also, with the regression based framework, different kinds of regularizes can be naturally incorporated into our algorithm which makes it more flexible. It can make efficient use of data points to discover the intrinsic discriminant structure in the data. Experimental results on Washington DC Mall and AVIRIS Indian Pines hyperspectral data sets demonstrate the effectiveness of the proposed method.

In silico and experimental evaluation of DNA-based detection methods for the ability to discriminate almond from other Prunus spp.

PubMed

Brežná, Barbara; Šmíd, Jiří; Costa, Joana; Radvanszky, Jan; Mafra, Isabel; Kuchta, Tomáš

2015-04-01

Ten published DNA-based analytical methods aiming at detecting material of almond (Prunus dulcis) were in silico evaluated for potential cross-reactivity with other stone fruits (Prunus spp.), including peach, apricot, plum, cherry, sour cherry and Sargent cherry. For most assays, the analysis of nucleotide databases suggested none or insufficient discrimination of at least some stone fruits. On the other hand, the assay targeting non-specific lipid transfer protein (Röder et al., 2011, Anal Chim Acta 685:74-83) was sufficiently discriminative, judging from nucleotide alignments. Empirical evaluation was performed for three of the published methods, one modification of a commercial kit (SureFood allergen almond) and one attempted novel method targeting thaumatin-like protein gene. Samples of leaves and kernels were used in the experiments. The empirical results were favourable for the method from Röder et al. (2011) and a modification of SureFood allergen almond kit, both showing cross-reactivity <10(-3) compared to the model almond. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genome-wide identification of allele-specific expression (ASE) in response to Marek's disease virus infection using next generation sequencing.

PubMed

Maceachern, Sean; Muir, William M; Crosby, Seth; Cheng, Hans H

2011-06-03

Marek's disease (MD), a T cell lymphoma induced by the highly oncogenic α-herpesvirus Marek's disease virus (MDV), is the main chronic infectious disease concern threatening the poultry industry. Enhancing genetic resistance to MD in commercial poultry is an attractive method to augment MD vaccines, which is currently the control method of choice. In order to optimally implement this control strategy through marker-assisted selection (MAS) and to gain biological information, it is necessary to identify specific genes that influence MD incidence. A genome-wide screen for allele-specific expression (ASE) in response to MDV infection was conducted. The highly inbred ADOL chicken lines 6 (MD resistant) and 7 (MD susceptible) were inter-mated in reciprocal crosses and half of the progeny challenged with MDV. Splenic RNA pools at a single time after infection for each treatment group point were generated, sequenced using a next generation sequencer, then analyzed for allele-specific expression (ASE). To validate and extend the results, Illumina GoldenGate assays for selected cSNPs were developed and used on all RNA samples from all 6 time points following MDV challenge. RNA sequencing resulted in 11-13+ million mappable reads per treatment group, 1.7+ Gb total sequence, and 22,655 high-confidence cSNPs. Analysis of these cSNPs revealed that 5360 cSNPs in 3773 genes exhibited statistically significant allelic imbalance. Of the 1536 GoldenGate assays, 1465 were successfully scored with all but 19 exhibiting evidence for allelic imbalance. ASE is an efficient method to identify potentially all or most of the genes influencing this complex trait. The identified cSNPs can be further evaluated in resource populations to determine their allelic direction and size of effect on genetic resistance to MD as well as being directly implemented in genomic selection programs. The described method, although demonstrated in inbred chicken lines, is applicable to all traits in any

Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

NASA Astrophysics Data System (ADS)

Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

1993-04-01

Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

Discrimination of Mirror-Image shapes by Young Children

ERIC Educational Resources Information Center

Thompson, G. Brian

1975-01-01

Conducted two experiments which employed discrimination learning methods to test predictions related to the difficulty of discrimination of lateral reversals and of inversions when shapes are presented: (1) successively, (2) simultaneously in lateral alignment, and (3) simultaneously in vertical alignment. Subjects were 6-year-old children. (SDH)

Health Care Workplace Discrimination and Physician Turnover

PubMed Central

Nunez-Smith, Marcella; Pilgrim, Nanlesta; Wynia, Matthew; Desai, Mayur M.; Bright, Cedric; Krumholz, Harlan M.; Bradley, Elizabeth H.

2013-01-01

Objective To examine the association between physician race/ethnicity, workplace discrimination, and physician job turnover. Methods Cross-sectional, national survey conducted in 2006–2007 of practicing physicians [n = 529] randomly identified via the American Medical Association Masterfile and The National Medical Association membership roster. We assessed the relationships between career racial/ethnic discrimination at work and several career-related dependent variables, including 2 measures of physician turnover, career satisfaction, and contemplation of career change. We used standard frequency analyses, odds ratios and χ2 statistics, and multivariate logistic regression modeling to evaluate these associations. Results Physicians who self-identified as nonmajority were significantly more likely to have left at least 1 job because of workplace discrimination (black, 29%; Asian, 24%; other race, 21%; Hispanic/Latino, 20%; white, 9%). In multivariate models, having experienced racial/ethnic discrimination at work was associated with high job turnover [adjusted odes ratio, 2.7; 95% CI, 1.4–4.9]. Among physicians who experienced work-place discrimination, only 45% of physicians were satisfied with their careers (vs 88% among those who had not experienced workplace discrimination, p value < .01], and 40% were con-templating a career change (vs 10% among those who had not experienced workplace discrimination, p value < .001). Conclusion Workplace discrimination is associated with physician job turnover, career dissatisfaction, and contemplation of career change. These findings underscore the importance of monitoring for workplace discrimination and responding when opportunities for intervention and retention still exist. PMID:20070016

Unsupervised spike sorting based on discriminative subspace learning.

PubMed

Keshtkaran, Mohammad Reza; Yang, Zhi

2014-01-01

Spike sorting is a fundamental preprocessing step for many neuroscience studies which rely on the analysis of spike trains. In this paper, we present two unsupervised spike sorting algorithms based on discriminative subspace learning. The first algorithm simultaneously learns the discriminative feature subspace and performs clustering. It uses histogram of features in the most discriminative projection to detect the number of neurons. The second algorithm performs hierarchical divisive clustering that learns a discriminative 1-dimensional subspace for clustering in each level of the hierarchy until achieving almost unimodal distribution in the subspace. The algorithms are tested on synthetic and in-vivo data, and are compared against two widely used spike sorting methods. The comparative results demonstrate that our spike sorting methods can achieve substantially higher accuracy in lower dimensional feature space, and they are highly robust to noise. Moreover, they provide significantly better cluster separability in the learned subspace than in the subspace obtained by principal component analysis or wavelet transform.

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

PubMed

Chan, Elizabeth A W; Teng, Grace; Corbett, Elizabeth; Choudhury, Kingshuk Roy; Bassing, Craig H; Schatz, David G; Krangel, Michael S

2013-11-26

Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4(-)CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins.

Perceived Discrimination and Heavy Episodic Drinking among African American Youth: Differences by Age and Reason for Discrimination

PubMed Central

Jackson, Kristina; Wang, Heng; Miles, Thomas T.; Mather, Frances; Shankar, Arti

2015-01-01

Purpose To examine whether associations between perceived discrimination and heavy episodic drinking (HED) varies by age and by discrimination type (e.g., racial, age, physical appearance) among African American youth. Methods National data from the Panel Study of Income Dynamics Transition to Adulthood Study were analyzed. Youth participated in up to four interviews (2005, 2007, 2009, 2011; n=657) between ages 18–25. Respondents reported past-year engagement in HED (4 or more drinks for females, 5 or more drinks for males), and frequency of discriminatory acts experienced (e.g., receiving poor service, being treated with less courtesy). Categorical latent growth curve models, including perceived discrimination types (racial, age, and physical appearance) as a time-varying predictors of HED, were run in MPlus. Controls for gender, birth cohort, living arrangement in adolescence, familial wealth, parental alcohol use, and college attendance were explored. Results The average HED trajectory was curvilinear (increasing followed by flattening), while perceived discrimination remained flat with age. In models including controls, odds of HED were significantly higher than average around ages 20–21 with greater frequency of perceived racial discrimination; associations were not significant at other ages. Discrimination attributed to age or physical appearance was not associated with HED at any age. Conclusions Perceived racial discrimination may be a particularly salient risk factor for HED around the ages of transition to legal access to alcohol among African American youth. Interventions to reduce discrimination or its impact could be targeted before this transition to ameliorate the negative outcomes associated with HED. PMID:26499858

A comparison of discrimination learning in touchscreen and 2-choice swim tank using an allelic series of Huntington's disease mice.

PubMed

Glynn, Dervila; Skillings, Elizabeth A; Morton, A Jennifer

2016-05-30

Progressive cognitive impairments are a major, debilitating symptom of neurodegenerative disorders such as Alzheimer's disease (AD) and Huntington's disease (HD). Developing treatments to slow or prevent cognitive decline is a key challenge for these fields. Unfortunately, preclinical therapeutic testing has not kept pace with molecular advances, and the methods for systematic cognitive testing in mice remain largely unchanged. Although higher throughput semi-automated systems exist, the lack of a 'positive control' (i.e. a drug or treatment that works) makes it challenging to test their sensitivity and predict usefulness for preclinical drug testing. We used an allelic series of transgenic HD mice to test the sensitivity and flexibility of two cognitive testing systems; a semi-automated touchscreen system and a traditional water-based task, the 2-choice swim tank. We found significant differences in performance of HD mice with different CAG repeats, with timing and severity of deficits dependent on CAG repeat length. We also found deficits in long-term memory retention that have not been reported previously. Both systems were useful for detecting deficits, and were sensitive enough to detect small changes (10-20%) in cognitive performance. While the touchscreen system is more sensitive and can identify deficits up to 10 weeks earlier than the 2-choice swim tank, both tests detected similar patterns of deficit progression in HD mice, regardless of CAG repeat length. Thus, although it has its limitations, the 2-choice swim tank remains a simple, cheap and accessible system for assessing cognitive function. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in Border Collie dogs.

PubMed

Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

2012-01-01

P-glycoprotein, encoded by the MDR1 or ABCB1 gene, is an integral component of the blood-brain barrier as an efflux pump for xenobiotics crucial in limiting drug uptake into the central nervous system. Dogs homozygous for a 4-base pair deletion of the canine MDR1 gene show altered expression or function of P-glycoprotein, resulting in neurotoxicosis after administration of the substrate drugs. In the present study, the usefulness of microchip electrophoresis for genotyping assays detecting this deletion mutation was evaluated. Mutagenically separated polymerase chain reaction (MS-PCR) and real-time PCR assays were newly developed and evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies dogs in Japan to determine the allele frequency in this breed. Microchip electrophoresis showed advantages in detection sensitivity and time saving over other modes of electrophoresis. The MS-PCR assay clearly discriminated all genotypes. Real-time PCR assay was most suitable for a large-scale survey due to its high throughput and rapidity. The genotyping survey demonstrated that the carrier and mutant allele frequencies were 0.49% and 0.25%, respectively, suggesting that the mutant allele frequency in Border Collies is markedly low compared to that in the susceptible dog breeds such as rough and smooth Collies.

Human Drug Discrimination: A Primer and Methodological Review

PubMed Central

Bolin, B. Levi; Alcorn, Joseph L.; Reynolds, Anna R.; Lile, Joshua A.; Rush, Craig R.

2016-01-01

Drug-discrimination procedures empirically evaluate the control that internal drug states exert over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs. Historically, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have also been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This review gives some general history and background concerning the major theoretical concepts and principles of drug-discrimination research as well as its relevance to substance-use disorders. This article also provides a procedural overview and discusses key methodological issues that must be considered when designing and conducting a human drug-discrimination study. Although drug discrimination is unequivocally one of the most sophisticated and useful behavioral assays to investigate the underlying neuropharmacology of drugs in vivo, enthusiasm for its use has steadily declined in the last decade and a half. We conclude by commenting on the current state of drug-discrimination research and suggest potential avenues for future drug-discrimination research. PMID:27454673

Human drug discrimination: A primer and methodological review.

PubMed

Bolin, B Levi; Alcorn, Joseph L; Reynolds, Anna R; Lile, Joshua A; Rush, Craig R

2016-08-01

Drug-discrimination procedures empirically evaluate the control that internal drug states exert over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs. Historically, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have also been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This review gives some general history and background concerning the major theoretical concepts and principles of drug-discrimination research as well as its relevance to substance-use disorders. This article also provides a procedural overview and discusses key methodological issues that must be considered when designing and conducting a human drug-discrimination study. Although drug discrimination is unequivocally one of the most sophisticated and useful behavioral assays to investigate the underlying neuropharmacology of drugs in vivo, enthusiasm for its use has steadily declined in the last decade and a half. We conclude by commenting on the current state of drug-discrimination research and suggest potential avenues for future drug-discrimination research. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Study on bayes discriminant analysis of EEG data.

PubMed

Shi, Yuan; He, DanDan; Qin, Fang

2014-01-01

In this paper, we have done Bayes Discriminant analysis to EEG data of experiment objects which are recorded impersonally come up with a relatively accurate method used in feature extraction and classification decisions. In accordance with the strength of α wave, the head electrodes are divided into four species. In use of part of 21 electrodes EEG data of 63 people, we have done Bayes Discriminant analysis to EEG data of six objects. Results In use of part of EEG data of 63 people, we have done Bayes Discriminant analysis, the electrode classification accuracy rates is 64.4%. Bayes Discriminant has higher prediction accuracy, EEG features (mainly αwave) extract more accurate. Bayes Discriminant would be better applied to the feature extraction and classification decisions of EEG data.

Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

PubMed

Montag, Judith; Syring, Mandy; Rose, Julia; Weber, Anna-Lena; Ernstberger, Pia; Mayer, Anne-Kathrin; Becker, Edgar; Keyser, Britta; Dos Remedios, Cristobal; Perrot, Andreas; van der Velden, Jolanda; Francino, Antonio; Navarro-Lopez, Francesco; Ho, Carolyn Yung; Brenner, Bernhard; Kraft, Theresia

2017-08-01

HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

Variant Alleles, Triallelic Patterns, and Point Mutations Observed in Nuclear Short Tandem Repeat Typing of Populations in Bosnia and Serbia

PubMed Central

Huel, René L. M.; Bašić, Lara; Madacki-Todorović, Kamelija; Smajlović, Lejla; Eminović, Izet; Berbić, Irfan; Miloš, Ana; Parsons, Thomas J.

2007-01-01

Aim To present a compendium of off-ladder alleles and other genotyping irregularities relating to rare/unexpected population genetic variation, observed in a large short tandem repeat (STR) database from Bosnia and Serbia. Methods DNA was extracted from blood stain cards relating to reference samples from a population of 32 800 individuals from Bosnia and Serbia, and typed using Promega’s PowerPlex®16 STR kit. Results There were 31 distinct off-ladder alleles were observed in 10 of the 15 STR loci amplified from the PowerPlex®16 STR kit. Of these 31 alleles, 3 have not been previously reported. Furthermore, 16 instances of triallelic patterns were observed in 9 of the 15 loci. Primer binding site mismatches that affected amplification were observed in two loci, D5S818 and D8S1179. Conclusion Instances of deviations from manufacturer’s allelic ladders should be expected and caution taken to properly designate the correct alleles in large DNA databases. Particular care should be taken in kinship matching or paternity cases as incorrect designation of any of these deviations from allelic ladders could lead to false exclusions. PMID:17696304

Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

PubMed

Loat, C S; Craig, G; Plomin, R; Craig, I W

2006-09-01

The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

Learning Robust and Discriminative Subspace With Low-Rank Constraints.

PubMed

Li, Sheng; Fu, Yun

2016-11-01

In this paper, we aim at learning robust and discriminative subspaces from noisy data. Subspace learning is widely used in extracting discriminative features for classification. However, when data are contaminated with severe noise, the performance of most existing subspace learning methods would be limited. Recent advances in low-rank modeling provide effective solutions for removing noise or outliers contained in sample sets, which motivates us to take advantage of low-rank constraints in order to exploit robust and discriminative subspace for classification. In particular, we present a discriminative subspace learning method called the supervised regularization-based robust subspace (SRRS) approach, by incorporating the low-rank constraint. SRRS seeks low-rank representations from the noisy data, and learns a discriminative subspace from the recovered clean data jointly. A supervised regularization function is designed to make use of the class label information, and therefore to enhance the discriminability of subspace. Our approach is formulated as a constrained rank-minimization problem. We design an inexact augmented Lagrange multiplier optimization algorithm to solve it. Unlike the existing sparse representation and low-rank learning methods, our approach learns a low-dimensional subspace from recovered data, and explicitly incorporates the supervised information. Our approach and some baselines are evaluated on the COIL-100, ALOI, Extended YaleB, FERET, AR, and KinFace databases. The experimental results demonstrate the effectiveness of our approach, especially when the data contain considerable noise or variations.

HLA-B*3531, a hybrid of B35 and B61, implications for diagnostic approaches to alleles with complex ancestral compositions.

PubMed

Elsner, H-A; Himmel, A; Steitz, M; Hammer, P; Schmitz, G; Ballas, M; Blasczyk, R

2002-07-01

The serological characterization of allelic variants that have been generated by large-scale interallelic recombination events indicates which residues may be involved in the formation of epitopes crucial for serological recognition. The allelic product of HLA-B*3531 is composed of B35 in its alpha1 domain and of B61(40) in its alpha2 domain. Both specificities are only weakly detectable with available sera. Allelic products with 'mixed' serology also represent a challenge to DNA-based HLA typing methods, as only the sequence motif of one ancestral allele may be recognized. In this case the hidden specificity would not be considered in the matching process and might not be recognized as an antigen 'unacceptable' to the recipient.

Multimodal Discriminative Binary Embedding for Large-Scale Cross-Modal Retrieval.

PubMed

Wang, Di; Gao, Xinbo; Wang, Xiumei; He, Lihuo; Yuan, Bo

2016-10-01

Multimodal hashing, which conducts effective and efficient nearest neighbor search across heterogeneous data on large-scale multimedia databases, has been attracting increasing interest, given the explosive growth of multimedia content on the Internet. Recent multimodal hashing research mainly aims at learning the compact binary codes to preserve semantic information given by labels. The overwhelming majority of these methods are similarity preserving approaches which approximate pairwise similarity matrix with Hamming distances between the to-be-learnt binary hash codes. However, these methods ignore the discriminative property in hash learning process, which results in hash codes from different classes undistinguished, and therefore reduces the accuracy and robustness for the nearest neighbor search. To this end, we present a novel multimodal hashing method, named multimodal discriminative binary embedding (MDBE), which focuses on learning discriminative hash codes. First, the proposed method formulates the hash function learning in terms of classification, where the binary codes generated by the learned hash functions are expected to be discriminative. And then, it exploits the label information to discover the shared structures inside heterogeneous data. Finally, the learned structures are preserved for hash codes to produce similar binary codes in the same class. Hence, the proposed MDBE can preserve both discriminability and similarity for hash codes, and will enhance retrieval accuracy. Thorough experiments on benchmark data sets demonstrate that the proposed method achieves excellent accuracy and competitive computational efficiency compared with the state-of-the-art methods for large-scale cross-modal retrieval task.

Population-specific documentation of pharmacogenomic markers and their allelic frequencies in FINDbase.

PubMed

Georgitsi, Marianthi; Viennas, Emmanouil; Gkantouna, Vassiliki; Christodoulopoulou, Elena; Zagoriti, Zoi; Tafrali, Christina; Ntellos, Fotios; Giannakopoulou, Olga; Boulakou, Athanassia; Vlahopoulou, Panagiota; Kyriacou, Eva; Tsaknakis, John; Tsakalidis, Athanassios; Poulas, Konstantinos; Tzimas, Giannis; Patrinos, George P

2011-01-01

Population and ethnic group-specific allele frequencies of pharmacogenomic markers are poorly documented and not systematically collected in structured data repositories. We developed the Frequency of Inherited Disorders Pharmacogenomics database (FINDbase-PGx), a separate module of the FINDbase, aiming to systematically document pharmacogenomic allele frequencies in various populations and ethnic groups worldwide. We critically collected and curated 214 scientific articles reporting pharmacogenomic markers allele frequencies in various populations and ethnic groups worldwide. Subsequently, in order to host the curated data, support data visualization and data mining, we developed a website application, utilizing Microsoft™ PivotViewer software. Curated allelic frequency data pertaining to 144 pharmacogenomic markers across 14 genes, representing approximately 87,000 individuals from 150 populations worldwide, are currently included in FINDbase-PGx. A user-friendly query interface allows for easy data querying, based on numerous content criteria, such as population, ethnic group, geographical region, gene, drug and rare allele frequency. FINDbase-PGx is a comprehensive database, which, unlike other pharmacogenomic knowledgebases, fulfills the much needed requirement to systematically document pharmacogenomic allelic frequencies in various populations and ethnic groups worldwide.

Modified bases enable high-efficiency oligonucleotide-mediated allelic replacement via mismatch repair evasion

PubMed Central

Wang, Harris H.; Xu, George; Vonner, Ashley J.; Church, George

2011-01-01

Genome engineering using single-stranded oligonucleotides is an efficient method for generating small chromosomal and episomal modifications in a variety of host organisms. The efficiency of this allelic replacement strategy is highly dependent on avoidance of the endogenous mismatch repair (MMR) machinery. However, global MMR inactivation generally results in significant accumulation of undesired background mutations. Here, we present a novel strategy using oligos containing chemically modified bases (2′-Fluoro-Uridine, 5-Methyl-deoxyCytidine, 2,6-Diaminopurine or Iso-deoxyGuanosine) in place of the standard T, C, A or G to avoid mismatch detection and repair, which we tested in Escherichia coli. This strategy increases transient allelic-replacement efficiencies by up to 20-fold, while maintaining a 100-fold lower background mutation level. We further show that the mismatched bases between the full length oligo and the chromosome are often not incorporated at the target site, probably due to nuclease activity at the 5′ and 3′ termini of the oligo. These results further elucidate the mechanism of oligo-mediated allelic replacement (OMAR) and enable improved methodologies for efficient, large-scale engineering of genomes. PMID:21609953

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2

PubMed Central

Chan, Elizabeth A. W.; Teng, Grace; Corbett, Elizabeth; Choudhury, Kingshuk Roy; Bassing, Craig H.; Schatz, David G.; Krangel, Michael S.

2013-01-01

Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4−CD8− thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins. PMID:24218622

Identification, genetic localization, and allelic diversity of selectively amplified microsatellite polymorphic loci in lettuce and wild relatives (Lactuca spp.).

PubMed

Witsenboer, H; Michelmore, R W; Vogel, J

1997-12-01

Selectively amplified microsatellite polymorphic locus (SAMPL) analysis is a method of amplifying microsatellite loci using generic PCR primers. SAMPL analysis uses one AFLP primer in combination with a primer complementary to microsatellite sequences. SAMPL primers based on compound microsatellite sequences provided the clearest amplification patterns. We explored the potential of SAMPL analysis in lettuce to detect PCR-based codominant microsatellite markers. Fifty-eight SAMPLs were identified and placed on the genetic map. Seventeen were codominant. SAMPLs were dispersed with RFLP markers on 11 of the 12 main linkage groups in lettuce, indicating that they have a similar genomic distribution. Some but not all fragments amplified by SAMPL analysis were confirmed to contain microsatellite sequences by Southern hybridization. Forty-five cultivars of lettuce and five wild species of Lactuca were analyzed to determine the allelic diversity for codominant SAMPLs. From 3 to 11 putative alleles were found for each SAMPL; 2-6 alleles were found within Lactuca sativa and 1-3 alleles were found among the crisphead genotypes, the most genetically homogeneous plant type of L. sativa. This allelic diversity is greater than that found for RFLP markers. Numerous new alleles were observed in the wild species; however, there were frequent null alleles. Therefore, SAMPL analysis is more applicable to intraspecific than to interspecific comparisons. A phenetic analysis based on SAMPLs resulted in a dendrogram similar to those based on RFLP and AFLP markers.

Discrimination in a General Algebraic Setting

PubMed Central

Fine, Benjamin; Lipschutz, Seymour; Spellman, Dennis

2015-01-01

Discriminating groups were introduced by G. Baumslag, A. Myasnikov, and V. Remeslennikov as an outgrowth of their theory of algebraic geometry over groups. Algebraic geometry over groups became the main method of attack on the solution of the celebrated Tarski conjectures. In this paper we explore the notion of discrimination in a general universal algebra context. As an application we provide a different proof of a theorem of Malcev on axiomatic classes of Ω-algebras. PMID:26171421

Characterization of Greenbeard Genes Involved in Long-Distance Kind Discrimination in a Microbial Eukaryote

PubMed Central

Heller, Jens; Zhao, Jiuhai; Rosenfield, Gabriel; Kowbel, David J.; Gladieux, Pierre; Glass, N. Louise

2016-01-01

Microorganisms are capable of communication and cooperation to perform social activities. Cooperation can be enforced using kind discrimination mechanisms in which individuals preferentially help or punish others, depending on genetic relatedness only at certain loci. In the filamentous fungus Neurospora crassa, genetically identical asexual spores (germlings) communicate and fuse in a highly regulated process, which is associated with fitness benefits during colony establishment. Recognition and chemotropic interactions between isogenic germlings requires oscillation of the mitogen-activated protein kinase (MAPK) signal transduction protein complex (NRC-1, MEK-2, MAK-2, and the scaffold protein HAM-5) to specialized cell fusion structures termed conidial anastomosis tubes. Using a population of 110 wild N. crassa isolates, we investigated germling fusion between genetically unrelated individuals and discovered that chemotropic interactions are regulated by kind discrimination. Distinct communication groups were identified, in which germlings within one communication group interacted at high frequency, while germlings from different communication groups avoided each other. Bulk segregant analysis followed by whole genome resequencing identified three linked genes (doc-1, doc-2, and doc-3), which were associated with communication group phenotype. Alleles at doc-1, doc-2, and doc-3 fell into five haplotypes that showed transspecies polymorphism. Swapping doc-1 and doc-2 alleles from different communication group strains was necessary and sufficient to confer communication group affiliation. During chemotropic interactions, DOC-1 oscillated with MAK-2 to the tips of conidial anastomosis tubes, while DOC-2 was statically localized to the plasma membrane. Our data indicate that doc-1, doc-2, and doc-3 function as “greenbeard” genes, involved in mediating long-distance kind recognition that involves actively searching for one’s own type, resulting in cooperation

HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides.

PubMed

Kidnapillai, S; Sirisena, N D; Dissanayake, V H

2016-06-01

This preliminary study aims to describe the HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides (SA). An anonymised database of 373 Sri Lankan patients with SA referred for HLA-B27 testing was retrospectively analysed. Eighty five (22.8%) patients were positive for the HLA-B27 allele. A male preponderance was observed among the positives. The HLA-B27 allele frequency in this sample of patients with SA was relatively low compared to published studies in other populations. Further research is needed to identify the predominant subtypes of the allele to determine which subtypes are the most prevalent in a larger sample of Sri Lankan patients with SA, and to define their association with the specific types of SA.

Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis

PubMed Central

Goëb, Vincent; Dieudé, Philippe; Vittecoq, Olivier; Mejjad, Othmane; Ménard, Jean-François; Thomas, Marlène; Gilbert, Danièle; Boumier, Patrick; Pouplin, Sophie; Daragon, Alain; Fardellone, Patrice; Tron, François; Cornélis, François; Le Loët, Xavier

2005-01-01

Tumour necrosis factor (TNF)-α plays a key role in the pathogenesis of rheumatoid arthritis (RA). It binds to two receptors, namely TNF receptor (TNFR)I and TNFRII. Several studies have suggested an association between TNFRII 196R/R genotype and RA. The objective of the present study was to evaluate the predictive value of the TNFRII 196R allele for RA diagnosis and prognosis in a cohort of patients with very early arthritis. We followed up a total of 278 patients recruited from the community, who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for less than 6 months, and who had not received disease-modifying antirheumatic drugs or steroid therapy. At 2 years, patients were classified according to the American College of Rheumatology criteria. All patients were genotyped with respect to TNFRII 196M/R polymorphism. Radiographs of hands and feet (read according to the modified Sharp method) and the Health Assessment Questionnaire were used to quantify structural and functional severity. The cohort of 278 patients was found to include 156 and 122 RA and non-RA patients, respectively. The TNFRII 196R allele was found to be associated with RA (P = 0.002). However, progression of radiographic severity and Health Assessment Questionnaire scores over 1 year did not differ between carriers of the 196R allele and noncarriers. Our findings suggest that the TNFRII 196R allele may be associated with RA diagnosis but that it does not predict early radiographic progression or functional severity in patients with very early, unclassified arthritis. PMID:16207322

Detection of MPL mutations by a novel allele-specific PCR-based strategy.

PubMed

Furtado, Larissa V; Weigelin, Helmut C; Elenitoba-Johnson, Kojo S J; Betz, Bryan L

2013-11-01

MPL mutation testing is recommended in patients with suspected primary myelofibrosis or essential thrombocythemia who lack the JAK2 V617F mutation. MPL mutations can occur at allelic levels below 15%, which may escape detection by commonly used mutation screening methods such as Sanger sequencing. We developed a novel multiplexed allele-specific PCR assay capable of detecting most recurrent MPL exon 10 mutations associated with primary myelofibrosis and essential thrombocythemia (W515L, W515K, W515A, and S505N) down to a sensitivity of 2.5% mutant allele. Test results were reviewed from 15 reference cases and 1380 consecutive specimens referred to our laboratory for testing. Assay performance was compared to Sanger sequencing across a series of 58 specimens with MPL mutations. Positive cases consisted of 45 with W515L, 6 with S505N, 5 with W515K, 1 with W515A, and 1 with both W515L and S505N. Seven cases had mutations below 5% that were undetected by Sanger sequencing. Ten additional cases had mutation levels between 5% and 15% that were not consistently detected by sequencing. All results were easily interpreted in the allele-specific test. This assay offers a sensitive and reliable solution for MPL mutation testing. Sanger sequencing appears insufficiently sensitive for robust MPL mutation detection. Our data also suggest the relative frequency of S505N mutations may be underestimated, highlighting the necessity for inclusion of this mutation in MPL test platforms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Meta-analytic review of the development of face discrimination in infancy: Face race, face gender, infant age, and methodology moderate face discrimination.

PubMed

Sugden, Nicole A; Marquis, Alexandra R

2017-11-01

Infants show facility for discriminating between individual faces within hours of birth. Over the first year of life, infants' face discrimination shows continued improvement with familiar face types, such as own-race faces, but not with unfamiliar face types, like other-race faces. The goal of this meta-analytic review is to provide an effect size for infants' face discrimination ability overall, with own-race faces, and with other-race faces within the first year of life, how this differs with age, and how it is influenced by task methodology. Inclusion criteria were (a) infant participants aged 0 to 12 months, (b) completing a human own- or other-race face discrimination task, (c) with discrimination being determined by infant looking. Our analysis included 30 works (165 samples, 1,926 participants participated in 2,623 tasks). The effect size for infants' face discrimination was small, 6.53% greater than chance (i.e., equal looking to the novel and familiar). There was a significant difference in discrimination by race, overall (own-race, 8.18%; other-race, 3.18%) and between ages (own-race: 0- to 4.5-month-olds, 7.32%; 5- to 7.5-month-olds, 9.17%; and 8- to 12-month-olds, 7.68%; other-race: 0- to 4.5-month-olds, 6.12%; 5- to 7.5-month-olds, 3.70%; and 8- to 12-month-olds, 2.79%). Multilevel linear (mixed-effects) models were used to predict face discrimination; infants' capacity to discriminate faces is sensitive to face characteristics including race, gender, and emotion as well as the methods used, including task timing, coding method, and visual angle. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Rapid ABO genotyping by high-speed droplet allele-specific PCR using crude samples.

PubMed

Taira, Chiaki; Matsuda, Kazuyuki; Takeichi, Naoya; Furukawa, Satomi; Sugano, Mitsutoshi; Uehara, Takeshi; Okumura, Nobuo; Honda, Takayuki

2018-01-01

ABO genotyping has common tools for personal identification of forensic and transplantation field. We developed a new method based on a droplet allele-specific PCR (droplet-AS-PCR) that enabled rapid PCR amplification. We attempted rapid ABO genotyping using crude DNA isolated from dried blood and buccal cells. We designed allele-specific primers for three SNPs (at nucleotides 261, 526, and 803) in exons 6 and 7 of the ABO gene. We pretreated dried blood and buccal cells with proteinase K, and obtained crude DNAs without DNA purification. Droplet-AS-PCR allowed specific amplification of the SNPs at the three loci using crude DNA, with results similar to those for DNA extracted from fresh peripheral blood. The sensitivity of the methods was 5%-10%. The genotyping of extracted DNA and crude DNA were completed within 8 and 9 minutes, respectively. The genotypes determined by the droplet-AS-PCR method were always consistent with those obtained by direct sequencing. The droplet-AS-PCR method enabled rapid and specific amplification of three SNPs of the ABO gene from crude DNA treated with proteinase K. ABO genotyping by the droplet-AS-PCR has the potential to be applied to various fields including a forensic medicine and transplantation medical care. © 2017 Wiley Periodicals, Inc.

The Influence of Discrimination on Smoking Cessation among Latinos

PubMed Central

Kendzor, Darla E.; Businelle, Michael S.; Reitzel, Lorraine R.; Castro, Yessenia; Vidrine, Jennifer I.; Mazas, Carlos A.; Cinciripini, Paul M.; Lam, Cho Y.; Adams, Claire E.; Correa-Fernández, Virmarie; Cano, Miguel Ángel; Wetter, David W.

2014-01-01

Background: Although studies have shown a cross-sectional link between discrimination and smoking, the prospective influence of discrimination on smoking cessation has yet to be evaluated. Thus, the purpose of the current study was to determine the influence of everyday and major discrimination on smoking cessation among Latinos making a quit attempt. Methods: Participants were 190 Spanish speaking smokers of Mexican Heritage recruited from the Houston, TX metropolitan area who participated in the study between 2009 and 2012. Logistic regression analyses were conducted to evaluate the associations of everyday and major discrimination with smoking abstinence at 26 weeks post-quit. Results: Most participants reported at least some everyday discrimination (64.4%), and at least one major discrimination event (56%) in their lifetimes. Race/ethnicity/nationality was the most commonly perceived reason for both everyday and major discrimination. Everyday discrimination was not associated with post-quit smoking status. However, experiencing a greater number of major discrimination events was associated with a reduced likelihood of achieving 7-day point prevalence smoking abstinence, OR = .51, p = .004, and continuous smoking abstinence, OR = .29, p = .018, at 26 weeks post-quit. Conclusions: Findings highlight the high frequency of exposure to discrimination among Latinos, and demonstrate the negative impact of major discrimination events on a smoking cessation attempt. Efforts are needed to attenuate the detrimental effects of major discrimination events on smoking cessation outcomes. PMID:24485880

Extensive variation between tissues in allele specific expression in an outbred mammal.

PubMed

Chamberlain, Amanda J; Vander Jagt, Christy J; Hayes, Benjamin J; Khansefid, Majid; Marett, Leah C; Millen, Catriona A; Nguyen, Thuy T T; Goddard, Michael E

2015-11-23

Allele specific gene expression (ASE), with the paternal allele more expressed than the maternal allele or vice versa, appears to be a common phenomenon in humans and mice. In other species the extent of ASE is unknown, and even in humans and mice there are several outstanding questions. These include; to what extent is ASE tissue specific? how often does the direction of allele expression imbalance reverse between tissues? how often is only one of the two alleles expressed? is there a genome wide bias towards expression of the paternal or maternal allele; and finally do genes that are nearby on a chromosome share the same direction of ASE? Here we use gene expression data (RNASeq) from 18 tissues from a single cow to investigate each of these questions in turn, and then validate some of these findings in two tissues from 20 cows. Between 40 and 100 million sequence reads were generated per tissue across three replicate samples for each of the eighteen tissues from the single cow (the discovery dataset). A bovine gene expression atlas was created (the first from RNASeq data), and differentially expressed genes in each tissue were identified. To analyse ASE, we had access to unambiguously phased genotypes for all heterozygous variants in the cow's whole genome sequence, where these variants were homozygous in the whole genome sequence of her sire, and as a result we were able to map reads to parental genomes, to determine SNP and genes showing ASE in each tissue. In total 25,251 heterozygous SNP within 7985 genes were tested for ASE in at least one tissue. ASE was pervasive, 89 % of genes tested had significant ASE in at least one tissue. This large proportion of genes displaying ASE was confirmed in the two tissues in a validation dataset. For individual tissues the proportion of genes showing significant ASE varied from as low as 8-16 % of those tested in thymus to as high as 71-82 % of those tested in lung. There were a number of cases where the direction of

A parallel spatiotemporal saliency and discriminative online learning method for visual target tracking in aerial videos

PubMed Central

2018-01-01

Visual tracking in aerial videos is a challenging task in computer vision and remote sensing technologies due to appearance variation difficulties. Appearance variations are caused by camera and target motion, low resolution noisy images, scale changes, and pose variations. Various approaches have been proposed to deal with appearance variation difficulties in aerial videos, and amongst these methods, the spatiotemporal saliency detection approach reported promising results in the context of moving target detection. However, it is not accurate for moving target detection when visual tracking is performed under appearance variations. In this study, a visual tracking method is proposed based on spatiotemporal saliency and discriminative online learning methods to deal with appearance variations difficulties. Temporal saliency is used to represent moving target regions, and it was extracted based on the frame difference with Sauvola local adaptive thresholding algorithms. The spatial saliency is used to represent the target appearance details in candidate moving regions. SLIC superpixel segmentation, color, and moment features can be used to compute feature uniqueness and spatial compactness of saliency measurements to detect spatial saliency. It is a time consuming process, which prompted the development of a parallel algorithm to optimize and distribute the saliency detection processes that are loaded into the multi-processors. Spatiotemporal saliency is then obtained by combining the temporal and spatial saliencies to represent moving targets. Finally, a discriminative online learning algorithm was applied to generate a sample model based on spatiotemporal saliency. This sample model is then incrementally updated to detect the target in appearance variation conditions. Experiments conducted on the VIVID dataset demonstrated that the proposed visual tracking method is effective and is computationally efficient compared to state-of-the-art methods. PMID:29438421

[A new human leukocyte antigen class I allele, HLA- B*52:11].

PubMed

Li, Xiao-feng; Zhang, Xu; Zhang, Kun-lian; Chen, Yang; Liu, Xian-zhi; Li, Jian-ping

2011-12-01

To identify and confirm a novel HLA allele. A new human leukocyte antigen class I allele was found during routine HLA genotyping by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) and sequencing-based typing (SBT). The novel HLA-B*52 allele was identical to B*52:01:01 with an exception of one base substitution at position 583 of exon 3 where a C was changed to T resulting in codon 195 changed from CAC(H) to TAC(Y). A new HLA class I allele, B*52:11, is identified, and is named officially by the WHO Nomenclature Committee.

Allele Surfing Promotes Microbial Adaptation from Standing Variation

PubMed Central

Gralka, Matti; Stiewe, Fabian; Farrell, Fred; Möbius, Wolfram; Waclaw, Bartek; Hallatschek, Oskar

2016-01-01

The coupling of ecology and evolution during range expansions enables mutations to establish at expanding range margins and reach high frequencies. This phenomenon, called allele surfing, is thought to have caused revolutions in the gene pool of many species, most evidently in microbial communities. It has remained unclear, however, under which conditions allele surfing promotes or hinders adaptation. Here, using microbial experiments and simulations, we show that, starting with standing adaptive variation, range expansions generate a larger increase in mean fitness than spatially uniform population expansions. The adaptation gain results from ‘soft’ selective sweeps emerging from surfing beneficial mutations. The rate of these surfing events is shown to sensitively depend on the strength of genetic drift, which varies among strains and environmental conditions. More generally, allele surfing promotes the rate of adaptation per biomass produced, which could help developing biofilms and other resource-limited populations to cope with environmental challenges. PMID:27307400

Haptic exploratory behavior during object discrimination: a novel automatic annotation method.

PubMed

Jansen, Sander E M; Bergmann Tiest, Wouter M; Kappers, Astrid M L

2015-01-01

In order to acquire information concerning the geometry and material of handheld objects, people tend to execute stereotypical hand movement patterns called haptic Exploratory Procedures (EPs). Manual annotation of haptic exploration trials with these EPs is a laborious task that is affected by subjectivity, attentional lapses, and viewing angle limitations. In this paper we propose an automatic EP annotation method based on position and orientation data from motion tracking sensors placed on both hands and inside a stimulus. A set of kinematic variables is computed from these data and compared to sets of predefined criteria for each of four EPs. Whenever all criteria for a specific EP are met, it is assumed that that particular hand movement pattern was performed. This method is applied to data from an experiment where blindfolded participants haptically discriminated between objects differing in hardness, roughness, volume, and weight. In order to validate the method, its output is compared to manual annotation based on video recordings of the same trials. Although mean pairwise agreement is less between human-automatic pairs than between human-human pairs (55.7% vs 74.5%), the proposed method performs much better than random annotation (2.4%). Furthermore, each EP is linked to a specific object property for which it is optimal (e.g., Lateral Motion for roughness). We found that the percentage of trials where the expected EP was found does not differ between manual and automatic annotation. For now, this method cannot yet completely replace a manual annotation procedure. However, it could be used as a starting point that can be supplemented by manual annotation.

Imputation of microsatellite alleles from dense SNP genotypes for parentage verification across multiple Bos taurus and Bos indicus breeds

PubMed Central

McClure, Matthew C.; Sonstegard, Tad S.; Wiggans, George R.; Van Eenennaam, Alison L.; Weber, Kristina L.; Penedo, Cecilia T.; Berry, Donagh P.; Flynn, John; Garcia, Jose F.; Carmo, Adriana S.; Regitano, Luciana C. A.; Albuquerque, Milla; Silva, Marcos V. G. B.; Machado, Marco A.; Coffey, Mike; Moore, Kirsty; Boscher, Marie-Yvonne; Genestout, Lucie; Mazza, Raffaele; Taylor, Jeremy F.; Schnabel, Robert D.; Simpson, Barry; Marques, Elisa; McEwan, John C.; Cromie, Andrew; Coutinho, Luiz L.; Kuehn, Larry A.; Keele, John W.; Piper, Emily K.; Cook, Jim; Williams, Robert; Van Tassell, Curtis P.

2013-01-01

To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ≤1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset. PMID:24065982

A new method for studying population genetics of cyst nematodes based on Pool-Seq and genomewide allele frequency analysis.

PubMed

Mimee, Benjamin; Duceppe, Marc-Olivier; Véronneau, Pierre-Yves; Lafond-Lapalme, Joël; Jean, Martine; Belzile, François; Bélair, Guy

2015-11-01

Cyst nematodes are important agricultural pests responsible for billions of dollars of losses each year. Plant resistance is the most effective management tool, but it requires a close monitoring of population genetics. Current technologies for pathotyping and genotyping cyst nematodes are time-consuming, expensive and imprecise. In this study, we capitalized on the reproduction mode of cyst nematodes to develop a simple population genetic analysis pipeline based on genotyping-by-sequencing and Pool-Seq. This method yielded thousands of SNPs and allowed us to study the relationships between populations of different origins or pathotypes. Validation of the method on well-characterized populations also demonstrated that it was a powerful and accurate tool for population genetics. The genomewide allele frequencies of 23 populations of golden nematode, from nine countries and representing the five known pathotypes, were compared. A clear separation of the pathotypes and fine genetic relationships between and among global populations were obtained using this method. In addition to being powerful, this tool has proven to be very time- and cost-efficient and could be applied to other cyst nematode species. © 2015 Her Majesty the Queen in Right of Canada Molecular Ecology Resources © 2015 John Wiley & Sons Ltd Reproduced with the permission of the Minister of Agriculture and Agri-food.

Airborne particulate discriminator

DOEpatents

Creek, Kathryn Louise [San Diego, CA; Castro, Alonso [Santa Fe, NM; Gray, Perry Clayton [Los Alamos, NM

2009-08-11

A method and apparatus for rapid and accurate detection and discrimination of biological, radiological, and chemical particles in air. A suspect aerosol of the target particulates is treated with a taggant aerosol of ultrafine particulates. Coagulation of the taggant and target particles causes a change in fluorescent properties of the cloud, providing an indication of the presence of the target.

[Discrimination of varieties of brake fluid using visual-near infrared spectra].

PubMed

Jiang, Lu-lu; Tan, Li-hong; Qiu, Zheng-jun; Lu, Jiang-feng; He, Yong

2008-06-01

A new method was developed to fast discriminate brands of brake fluid by means of visual-near infrared spectroscopy. Five different brands of brake fluid were analyzed using a handheld near infrared spectrograph, manufactured by ASD Company, and 60 samples were gotten from each brand of brake fluid. The samples data were pretreated using average smoothing and standard normal variable method, and then analyzed using principal component analysis (PCA). A 2-dimensional plot was drawn based on the first and the second principal components, and the plot indicated that the clustering characteristic of different brake fluid is distinct. The foregoing 6 principal components were taken as input variable, and the band of brake fluid as output variable to build the discriminate model by stepwise discriminant analysis method. Two hundred twenty five samples selected randomly were used to create the model, and the rest 75 samples to verify the model. The result showed that the distinguishing rate was 94.67%, indicating that the method proposed in this paper has good performance in classification and discrimination. It provides a new way to fast discriminate different brands of brake fluid.

[Allelic variation at high-molecular-weight glutenin subunit loci in Aegilops biuncialis Vis].

PubMed

Kozub, N A; Sozinov, I A; Ksinias, I N; Sozinov, A A

2011-09-01

Alleles at the high-molecular-weight glutenin subunit loci Glu-U1 and Glu-M(b)1 were analyzed in the tetraploid species Aegilops biuncialis (UUM(b)M(b)). The material for the investigation included the collection of 39 accessions of Ae. biuncialis from Ukraine (the Crimea), one Hellenic accession, one accession of unknown origin, F2 seeds from different crosses, as well as samples from natural populations from the Crimea. Ae. umbellulata and Ae. comosa accessions were used to allocate components of the HMW glutenin subunit patterns of Ae. biuncialis to U or M(b) genomes. Eight alleles were identified at the Glu-U1 locus and ten alleles were revealed at the Glu-M(b) 1 locus. Among alleles at the Glu-M(b) 1 locus ofAe. biuncialis there were two alleles controlling the y-type subunit only and one allele encoding the x-subunit only.

CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening.

PubMed

Chávez-Saldaña, Margarita; Yokoyama, Emiy; Lezana, José Luis; Carnevale, Alessandra; Macías, Miguel; Vigueras, Rosa M; López, Marisol; Orozco, Lorena

2010-01-01

Cystic fibrosis, the most common autosomal recessive disorder, is caused by defects in the CF transmembrane conductance regulator gene (CFTR) that encodes a chloride channel. To date, over 1,800 mutations have been described related to the causative gene of CF, showing a variable frequency among populations. In a previous extensive analysis of the CFTR locus in 97 Mexican patients, 34 different mutations (75% of CF alleles) were found using several strategies for mutation screening; however, 63% had at least an uncharacterized allele. Despite the combined technologies used, there are still a great number of unknown mutations in the Mexican population. Screening of the CFTR gene to provide additional evidence of the mutational wide spectrum responsible for CF in Mexican patients. In this study, the number of unrelated CF patients was increased to 230, 133 new cases and the 97 previously reported to include 63% with at least an uncharacterized allele. Additional tools were used to improve the detection rate of CF mutations, such as a commercial kit for 36 mutations plus a single chain conformational polymorphism method and DNA sequencing. By using a combination of these strategies we characterized 77.7% of all the CF alleles, resulting in a total of 46 different mutations detected, including the identification of 12 additional mutations (p.R334W, p.A455E, c.3120+1G > A, c.3272-26A > G, c.711+1G > T, p.Q552X, p.W1282X, c.IVS8-5T, p.R1162X and p.R347P, p.D1152H and p.T1036N). Although these 12 mutations have been reported in other populations, they have not yet been reported in Mexican patients. This report shows that Mexico has one of the widest spectra of CFTR mutations worldwide. The knowledge of the ethnic and geographic distribution of CFTR mutations in this population will allow the development of more effective methods for diagnosis and treatment.

Legitimating Racial Discrimination: Emotions, Not Beliefs, Best Predict Discrimination in a Meta-Analysis

PubMed Central

Talaska, Cara A.; Chaiken, Shelly

2013-01-01

Investigations of racial bias have emphasized stereotypes and other beliefs as central explanatory mechanisms and as legitimating discrimination. In recent theory and research, emotional prejudices have emerged as another, more direct predictor of discrimination. A new comprehensive meta-analysis of 57 racial attitude-discrimination studies finds a moderate relationship between overall attitudes and discrimination. Emotional prejudices are twices as closely related to racial discrimination as stereotypes and beliefs are. Moreover, emotional prejudices are closely related to both observed and self-reported discrimination, whereas stereotypes and beliefs are related only to self-reported discrimination. Implications for justifying discrimination are discussed. PMID:24052687

Discrimination of Aurantii Fructus Immaturus and Fructus Poniciri Trifoliatae Immaturus by Flow Injection UV Spectroscopy (FIUV) and 1H NMR using Partial Least-squares Discriminant Analysis (PLS-DA)

USDA-ARS?s Scientific Manuscript database

Two simple fingerprinting methods, flow-injection UV spectroscopy (FIUV) and 1H nuclear magnetic resonance (NMR), for discrimination of Aurantii FructusImmaturus and Fructus Poniciri TrifoliataeImmaturususing were described. Both methods were combined with partial least-squares discriminant analysis...

Graphical classification of DNA sequences of HLA alleles by deep learning.

PubMed

Miyake, Jun; Kaneshita, Yuhei; Asatani, Satoshi; Tagawa, Seiichi; Niioka, Hirohiko; Hirano, Takashi

2018-04-01

Alleles of human leukocyte antigen (HLA)-A DNAs are classified and expressed graphically by using artificial intelligence "Deep Learning (Stacked autoencoder)". Nucleotide sequence data corresponding to the length of 822 bp, collected from the Immuno Polymorphism Database, were compressed to 2-dimensional representation and were plotted. Profiles of the two-dimensional plots indicate that the alleles can be classified as clusters are formed. The two-dimensional plot of HLA-A DNAs gives a clear outlook for characterizing the various alleles.

Discrimination and subjective well-being: protective influences of membership in a discriminated category.

PubMed

Hnilica, Karel

2011-03-01

Research reveals that discrimination has harmful effects on health and quality of life. Among the most frequent types of discrimination pertains gender and age discrimination. Research results show that discriminatory behaviours based on gender afflict predominantly women; age discrimination afflicts mainly older adults. At the same time, it has been found that members of these traditionally discriminated categories often use strategies that mitigate the effects of discrimination. Discrimination will have detrimental effects on subjective well-being. But its effects will be most harmful for persons who are not members of the traditionally discriminated categories. These hypotheses were tested on data from three waves of the European Social Survey that the Czech Republic also participated in. Data were analyzed in a series of multilevel random coefficients regression analyses with respondents nested within states and states nested within years of study. Both perceived gender discrimination and perceived age discrimination have negative effects on subjective well-being. However, gender discrimination had more harmful effects on the subjective well-being of men than women and age discrimination had the most harmful effects on the subjective well-being of people in their middle ages, not the elderly ones. Discrimination does not need to have most harmful effects on the quality of life of members of the categories that are discriminated against most often.

Discrimination of coherent features in turbulent boundary layers by the entropy method

NASA Technical Reports Server (NTRS)

Corke, T. C.; Guezennec, Y. G.

1984-01-01

Entropy in information theory is defined as the expected or mean value of the measure of the amount of self-information contained in the ith point of a distribution series x sub i, based on its probability of occurrence p(x sub i). If p(x sub i) is the probability of the ith state of the system in probability space, then the entropy, E(X) = - sigma p(x sub i) logp (x sub i), is a measure of the disorder in the system. Based on this concept, a method was devised which sought to minimize the entropy in a time series in order to construct the signature of the most coherent motions. The constrained minimization was performed using a Lagrange multiplier approach which resulted in the solution of a simultaneous set of non-linear coupled equations to obtain the coherent time series. The application of the method to space-time data taken by a rake of sensors in the near-wall region of a turbulent boundary layer was presented. The results yielded coherent velocity motions made up of locally decelerated or accelerated fluid having a streamwise scale of approximately 100 nu/u(tau), which is in qualitative agreement with the results from other less objective discrimination methods.

Gene-based rare allele analysis identified a risk gene of Alzheimer's disease.

PubMed

Kim, Jong Hun; Song, Pamela; Lim, Hyunsun; Lee, Jae-Hyung; Lee, Jun Hong; Park, Sun Ah

2014-01-01

Alzheimer's disease (AD) has a strong propensity to run in families. However, the known risk genes excluding APOE are not clinically useful. In various complex diseases, gene studies have targeted rare alleles for unsolved heritability. Our study aims to elucidate previously unknown risk genes for AD by targeting rare alleles. We used data from five publicly available genetic studies from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the database of Genotypes and Phenotypes (dbGaP). A total of 4,171 cases and 9,358 controls were included. The genotype information of rare alleles was imputed using 1,000 genomes. We performed gene-based analysis of rare alleles (minor allele frequency≤3%). The genome-wide significance level was defined as meta P<1.8×10(-6) (0.05/number of genes in human genome = 0.05/28,517). ZNF628, which is located at chromosome 19q13.42, showed a genome-wide significant association with AD. The association of ZNF628 with AD was not dependent on APOE ε4. APOE and TREM2 were also significantly associated with AD, although not at genome-wide significance levels. Other genes identified by targeting common alleles could not be replicated in our gene-based rare allele analysis. We identified that rare variants in ZNF628 are associated with AD. The protein encoded by ZNF628 is known as a transcription factor. Furthermore, the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.

Neutron/Gamma-ray discrimination through measures of fit

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

Amiri, Moslem; Prenosil, Vaclav; Cvachovec, Frantisek

2015-07-01

Statistical tests and their underlying measures of fit can be utilized to separate neutron/gamma-ray pulses in a mixed radiation field. In this article, first the application of a sample statistical test is explained. Fit measurement-based methods require true pulse shapes to be used as reference for discrimination. This requirement makes practical implementation of these methods difficult; typically another discrimination approach should be employed to capture samples of neutrons and gamma-rays before running the fit-based technique. In this article, we also propose a technique to eliminate this requirement. These approaches are applied to several sets of mixed neutron and gamma-ray pulsesmore » obtained through different digitizers using stilbene scintillator in order to analyze them and measure their discrimination quality. (authors)« less

Association between the APOE ε4 Allele and Late-Onset Alzheimer's Disease in an Ecuadorian Mestizo Population

PubMed Central

Calero, Cristian; Vinueza, Rodrigo; Correa, Patricio; Carrera-Gonzalez, Andrea; Villegas, Franklin; Moreta, Germania; Paredes, Rosario

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease. It has two main pathological hallmarks: amyloid plaques and neurofibrillary tangles. The APOE ε4 allele has been recognized as the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD) in several populations worldwide, yet the risk varies by region and ethnicity. The aims of this study were to describe APOE allele and genotype frequencies and examine the relationship between the APOE ε4 allele and LOAD risk in an Ecuadorian Mestizo population. We carried out a case-control study comprising 56 individuals clinically diagnosed with probable AD (≥65 years of age) and 58 unrelated healthy control subjects (≥65 years of age). Genotyping was performed using the real-time PCR method. Our data showed that allelic and genotypic frequencies follow the trends observed in most worldwide populations. We also found a high-risk association between APOE ε4 allele carriers and LOAD (OR = 7.286; 95% CI = 2.824–18.799; p < 0.001). Therefore, we concluded that APOE ε4 must be considered an important genetic risk factor for LOAD in the Ecuadorian Mestizo population. Additionally, we suggest that in mixed populations the effects of admixture and ethnic identity should be differentiated when evaluating genetic contributions to Alzheimer's disease risk. PMID:29348964

Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis.

PubMed

Li, Bing-Yun; Yang, Yan-Mei; Liu, Yang; Sun, Jing; Ye, Yan; Liu, Xiao-Na; Liu, Hong-Xu; Sun, Zhen-Qi; Li, Mang; Cui, Jing; Sun, Dian-Jun; Gao, Yan-Hui

2017-01-01

Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea. We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms. Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094-0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025-0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199-0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029-0.472)]. Overall, subjects with 1.6-3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237-0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114-0.923)]. Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF.

Prolactin rs1341239 T allele may have protective role against the brick tea type skeletal fluorosis

PubMed Central

Li, Bing-Yun; Yang, Yan-Mei; Liu, Yang; Sun, Jing; Ye, Yan; Liu, Xiao-Na; Liu, Hong-Xu; Sun, Zhen-Qi; Li, Mang; Cui, Jing; Sun, Dian-Jun; Gao, Yan-Hui

2017-01-01

Objective Prolactin (PRL) has been reported to be associated with increased bone turnover, and increased bone turnover is also a feature of skeletal fluorosis (SF). Autocrine/paracrine production of PRL is regulated by the extrapituitary promoter and a polymorphism in the extrapituitary PRL promoter at -1149 (rs1341239) is associated with disturbances of bone metabolism in other diseases. Here, we have investigated the possibility that the rs1341239 polymorphism is associated with SF, which results from the consumption of brick tea. Design We conducted a cross-sectional study in Sinkiang, Qinghai, Inner Mongolia in China. Demography survey questionnaires were completed and physical examination and X-ray diagnoses were used to diagnose SF. Brick tea water fluoride intake (IF) and urinary fluoride (UF) were tested by an F-ion selective electrode method. A Sequenom MassARRAY system was used to determine PRL gene polymorphisms. Results Subjects who were younger than 45 years of age and carried the T allele had a significantly decreased risk of SF [OR = 0.279 (95%CI, 0.094–0.824)] compared to those carrying the homozygous G allele. This phenomenon was only observed in Kazakh subjects [OR = 0.127 (95%CI, 0.025–0.646)]. Kazakh females who carried T alleles has a decreased risk of SF [OR = 0.410 (95%CI, 0.199–0.847)]. For Kazakh subjects which IF is less than 3.5 mg/d, a decreased risk of SF was observed among the participants who carried T alleles [OR = 0.118 (95%CI, 0.029–0.472)]. Overall, subjects with 1.6–3.2 mg/L UF and carried T alleles had a significantly decreased risk of SF [OR = 0.476 (95%CI, 0.237–0.955)] compared to homozygous G allele carriers. This phenomenon was only observed in Kazakh subjects [OR = 0.324 (95%CI, 0.114–0.923)]. Conclusions Our results suggested that the PRL rs1341239 T allele decreases the risk of brick tea SF. PMID:28152004

Distribution of photoperiod-insensitive allele Ppd-A1a and its effect on heading time in Japanese wheat cultivars.

PubMed

Seki, Masako; Chono, Makiko; Nishimura, Tsutomu; Sato, Mikako; Yoshimura, Yasuhiro; Matsunaka, Hitoshi; Fujita, Masaya; Oda, Shunsuke; Kubo, Katashi; Kiribuchi-Otobe, Chikako; Kojima, Hisayo; Nishida, Hidetaka; Kato, Kenji

2013-09-01

The Ppd-A1 genotype of 240 Japanese wheat cultivars and 40 foreign cultivars was determined using a PCR-based method. Among Japanese cultivars, only 12 cultivars, all of which were Hokkaido winter wheat, carried the Ppd-A1a allele, while this allele was not found in Hokkaido spring wheat cultivars or Tohoku-Kyushu cultivars. Cultivars with a photoperiod-insensitive allele headed 6.9-9.8 days earlier in Kanto and 2.5 days earlier in Hokkaido than photoperiod-sensitive cultivars. The lower effect of photoperiod-insensitive alleles observed in Hokkaido could be due to the longer day-length at the spike formation stage compared with that in Kanto. Pedigree analysis showed that 'Purple Straw' and 'Tohoku 118' were donors of Ppd-A1a and Ppd-D1a in Hokkaido wheat cultivars, respectively. Wheat cultivars recently developed in Hokkaido carry photoperiod-insensitive alleles at a high frequency. For efficient utilization of Ppd-1 alleles in the Hokkaido wheat-breeding program, the effect of Ppd-1 on growth pattern and grain yield should be investigated. Ppd-A1a may be useful as a unique gene source for fine tuning the heading time in the Tohoku-Kyushu region since the effect of Ppd-A1a on photoperiod insensitivity appears to differ from the effect of Ppd-B1a and Ppd-D1a.

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

PubMed Central

Morgan, L; Crawshaw, S; Baker, P N; Brookfield, J F; Broughton Pipkin, F; Kalsheker, N

1998-01-01

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion. PMID:9719367

PyHLA: tests for the association between HLA alleles and diseases.

PubMed

Fan, Yanhui; Song, You-Qiang

2017-02-06

Recently, several tools have been designed for human leukocyte antigen (HLA) typing using single nucleotide polymorphism (SNP) array and next-generation sequencing (NGS) data. These tools provide high-throughput and cost-effective approaches for identifying HLA types. Therefore, tools for downstream association analysis are highly desirable. Although several tools have been designed for multi-allelic marker association analysis, they were designed only for microsatellite markers and do not scale well with increasing data volumes, or they were designed for large-scale data but provided a limited number of tests. We have developed a Python package called PyHLA, which implements several methods for HLA association analysis, to fill the gap. PyHLA is a tailor-made, easy to use, and flexible tool designed specifically for the association analysis of the HLA types imputed from genome-wide genotyping and NGS data. PyHLA provides functions for association analysis, zygosity tests, and interaction tests between HLA alleles and diseases. Monte Carlo permutation and several methods for multiple testing corrections have also been implemented. PyHLA provides a convenient and powerful tool for HLA analysis. Existing methods have been integrated and desired methods have been added in PyHLA. Furthermore, PyHLA is applicable to small and large sample sizes and can finish the analysis in a timely manner on a personal computer with different platforms. PyHLA is implemented in Python. PyHLA is a free, open source software distributed under the GPLv2 license. The source code, tutorial, and examples are available at https://github.com/felixfan/PyHLA.

Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population.

PubMed

Coffee, Erin M; Yerkes, Laura; Ewen, Elizabeth P; Zee, Tiffany; Tolan, Dean R

2010-02-01

Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Delta4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense mutations Delta4E4 and R59Op are the next most common alleles, with each having a frequency of 4%. Together, the frequencies of all seven alleles make up 65% of HFI-causing alleles in this population. Worldwide, these same alleles make up 82% of HFI-causing mutations. This difference indicates that screening for common HFI alleles is more difficult in the American population. Nevertheless, a genetic screen for diagnosing HFI in America can be improved by including all seven alleles studied here. Lastly, identification of HFI patients presenting with classic symptoms and who have homozygous null genotypes indicates that aldolase B is not required for proper development or metabolic maintenance.

Binocular contrast discrimination needs monocular multiplicative noise

PubMed Central

Ding, Jian; Levi, Dennis M.

2016-01-01

The effects of signal and noise on contrast discrimination are difficult to separate because of a singularity in the signal-detection-theory model of two-alternative forced-choice contrast discrimination (Katkov, Tsodyks, & Sagi, 2006). In this article, we show that it is possible to eliminate the singularity by combining that model with a binocular combination model to fit monocular, dichoptic, and binocular contrast discrimination. We performed three experiments using identical stimuli to measure the perceived phase, perceived contrast, and contrast discrimination of a cyclopean sine wave. In the absence of a fixation point, we found a binocular advantage in contrast discrimination both at low contrasts (<4%), consistent with previous studies, and at high contrasts (≥34%), which has not been previously reported. However, control experiments showed no binocular advantage at high contrasts in the presence of a fixation point or for observers without accommodation. We evaluated two putative contrast-discrimination mechanisms: a nonlinear contrast transducer and multiplicative noise (MN). A binocular combination model (the DSKL model; Ding, Klein, & Levi, 2013b) was first fitted to both the perceived-phase and the perceived-contrast data sets, then combined with either the nonlinear contrast transducer or the MN mechanism to fit the contrast-discrimination data. We found that the best model combined the DSKL model with early MN. Model simulations showed that, after going through interocular suppression, the uncorrelated noise in the two eyes became anticorrelated, resulting in less binocular noise and therefore a binocular advantage in the discrimination task. Combining a nonlinear contrast transducer or MN with a binocular combination model (DSKL) provides a powerful method for evaluating the two putative contrast-discrimination mechanisms. PMID:26982370

Binocular contrast discrimination needs monocular multiplicative noise.

PubMed

Ding, Jian; Levi, Dennis M

2016-01-01

The effects of signal and noise on contrast discrimination are difficult to separate because of a singularity in the signal-detection-theory model of two-alternative forced-choice contrast discrimination (Katkov, Tsodyks, & Sagi, 2006). In this article, we show that it is possible to eliminate the singularity by combining that model with a binocular combination model to fit monocular, dichoptic, and binocular contrast discrimination. We performed three experiments using identical stimuli to measure the perceived phase, perceived contrast, and contrast discrimination of a cyclopean sine wave. In the absence of a fixation point, we found a binocular advantage in contrast discrimination both at low contrasts (<4%), consistent with previous studies, and at high contrasts (≥34%), which has not been previously reported. However, control experiments showed no binocular advantage at high contrasts in the presence of a fixation point or for observers without accommodation. We evaluated two putative contrast-discrimination mechanisms: a nonlinear contrast transducer and multiplicative noise (MN). A binocular combination model (the DSKL model; Ding, Klein, & Levi, 2013b) was first fitted to both the perceived-phase and the perceived-contrast data sets, then combined with either the nonlinear contrast transducer or the MN mechanism to fit the contrast-discrimination data. We found that the best model combined the DSKL model with early MN. Model simulations showed that, after going through interocular suppression, the uncorrelated noise in the two eyes became anticorrelated, resulting in less binocular noise and therefore a binocular advantage in the discrimination task. Combining a nonlinear contrast transducer or MN with a binocular combination model (DSKL) provides a powerful method for evaluating the two putative contrast-discrimination mechanisms.

Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele.

PubMed

Medicina, Daniela; Montani, Nadia; Fra, Anna M; Tiberio, Laura; Corda, Luciano; Miranda, Elena; Pezzini, Alessandro; Bonetti, Fausta; Ingrassia, Rosaria; Scabini, Roberta; Facchetti, Fabio; Schiaffonati, Luisa

2009-08-01

Alpha1-antitrypsin (alpha(1)AT) deficiency is a hereditary disorder associated with reduced alpha(1)AT serum level, predisposing adults to pulmonary emphysema. Among the known mutations of the alpha(1)AT gene (SERPINA1) causing alpha(1)AT deficiency, a few alleles, particularly the Z allele, may also predispose adults to liver disease. We have characterized a new defective alpha(1)AT allele (c.745G>C) coding for a mutant alpha(1)AT (Gly225Arg), named P(brescia). The P(brescia) alpha(1)AT allele was first identified in combination with the rare defective M(würzburg) allele in an 11-year-old boy showing significantly reduced serum alpha(1)AT level. Subsequently, the P(brescia) allele was found in the heterozygous state with the normal M or the defective Z allele in nine and three adults respectively. In cellular models of the disease, we show that the P(brescia) mutant is retained in the endoplasmic reticulum as ordered polymers and is secreted more slowly than the normal M alpha(1)AT. This behaviour recapitulates the abnormal cellular handling and fate of the Z alpha(1)AT and suggests that the mutation present in the P(brescia) alpha(1)AT causes a conformational change of the protein which, by favouring polymer formation, is etiologic to both severe alpha(1)AT deficiency in the plasma and toxic protein-overload in the liver.

Phenotypic variability within the JAK2 V617F-positive MPD: The roles of progenitor cell and neutrophil allele burdens

PubMed Central

Moliterno, Alison R.; Williams, Donna M.; Rogers, Ophelia; Isaacs, Mary Ann; Spivak, Jerry L.

2008-01-01

(1) Objective The myeloproliferative disorders (MPD), polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) differ phenotypically but share the same JAK2V617F mutation. We examined the relationship of the quantitative JAK2V617F allele burden to MPD disease phenotype among the three MPD classes and within PV. (2) Methods We measured the JAK2V617F allele percentage in genomic DNA from neutrophils, CD34+ cells, and cloned progenitors in 212 JAK2V617F –positive MPD patients and correlated the allele burdens to both disease class and disease features. (3) Results In ET and PV, the mean CD34+ cell JAK2V617F allele burdens were lower than the corresponding neutrophil allele burdens, but these were equivalent in PMF. JAK2WT progenitors were present in ET and PV when the CD34+ JAK2V617F allele burden was lower than the neutrophil allele burden, but not in PV and PMF subjects in whom the CD34+ cell and neutrophil allele burdens were similar. CD34+ cell JAK2V617F clonal dominance, defined as coherence between the CD34+ cell and neutrophil JAK2V617F allele burdens, was present in 24% of ET, 56% of PV and 93% of PMF patients, and was independent of the CD34+ cell JAK2V617F genotype. Clonally-dominant PV patients had significantly longer disease durations, higher white cell counts and larger spleens than nondominant PV patients. (4) Conclusions We conclude that the extent of JAK2V617F CD34+ cell clonal dominance is associated with disease phenotype within the MPD, and in PV, is associated with extramedullary disease, leukocytosis and disease duration. PMID:18723264

Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality.

PubMed

Rajan, Kumar B; Aggarwal, Neelum T; Schneider, Julie A; Wilson, Robert S; Everson-Rose, Susan A; Evans, Denis A

2016-01-01

The apolipoprotein E (APOE) ε4 allele and stroke increase the risk of cognitive decline. However, the association of the APOE ε4 allele before and after stroke is not well understood. Using a prospective sample of 3444 (66% African Americans, 61% females, mean age=71.9 y) participants, we examined cognitive decline relative to stroke among those with and without the APOE ε4 allele. In our sample, 505 (15%) had incident stroke. Among participants without stroke, the ε4 allele was associated with increased cognitive decline compared to noncarriers (0.080 vs. 0.036 units/year; P<0.0001). Among participants without the ε4 allele, cognitive decline increased significantly after stroke compared to before stroke (0.115 vs. 0.039 units/year; P<0.0001). Interestingly, cognitive decline before and after stroke was not significantly different among those with the ε4 allele (0.091 vs. 0.102 units/year; P=0.32). Poor cognitive function was associated with higher risk of stroke (hazard ratio=1.41, 95% confidence interval, 1.25-1.58), but the APOE ε4 allele was not (P=0.66). The APOE ε4 allele, cognitive function, and incident stroke were associated with mortality. The association of stroke with cognitive decline appears to differ by the presence of the APOE ε4 allele, but no such interaction was observed for mortality.

Discrimination of gastrointestinal nematode eggs from crude fecal egg preparations by inhibitor-resistant conventional and real-time PCR.

PubMed

Demeler, Janina; Ramünke, Sabrina; Wolken, Sonja; Ianiello, Davide; Rinaldi, Laura; Gahutu, Jean Bosco; Cringoli, Giuseppe; von Samson-Himmelstjerna, Georg; Krücken, Jürgen

2013-01-01

Diagnosis of gastrointestinal nematodes relies predominantly on coproscopic methods such as flotation, Kato-Katz, McMaster or FLOTAC. Although FLOTAC allows accurate quantification, many nematode eggs can only be differentiated to genus or family level. Several molecular diagnostic tools discriminating closely related species suffer from high costs for DNA isolation from feces and limited sensitivity since most kits use only small amounts of feces (<1 g). A direct PCR from crude egg preparations was designed for full compatibility with FLOTAC to accurately quantify eggs per gram feces (epg) and determine species composition. Eggs were recovered from the flotation solution and concentrated by sieving. Lysis was achieved by repeated boiling and freezing cycles - only Trichuris eggs required additional mechanic disruption. Egg lysates were directly used as template for PCR with Phusion DNA polymerase which is particularly resistant to PCR inhibitors. Qualitative results were obtained with feces of goats, cattle, horses, swine, cats, dogs and mice. The finally established protocol was also compatible with quantitative real-time PCR in the presence of EvaGreen and no PCR inhibition was detectable when extracts were diluted at least fourfold. Sensitivity was comparable to DNA isolation protocols and spiked samples with five epg were reliably detected. For Toxocara cati a detection limit below one epg was demonstrated. It was possible to distinguish T. cati and Toxocara canis using high resolution melt (HRM) analysis, a rapid tool for species identification. In human samples, restriction fragment length polymorphism (RFLP) and HRM analysis were used to discriminate Necator americanus and Ancylostoma duodenale. The method is able to significantly improve molecular diagnosis of gastrointestinal nematodes by increasing speed and sensitivity while decreasing overall costs. For identification of species or resistance alleles, analysis of PCR products with many different post

Discrimination of Gastrointestinal Nematode Eggs from Crude Fecal Egg Preparations by Inhibitor-Resistant Conventional and Real-Time PCR

PubMed Central

Demeler, Janina; Ramünke, Sabrina; Wolken, Sonja; Ianiello, Davide; Rinaldi, Laura; Gahutu, Jean Bosco; Cringoli, Giuseppe; von Samson-Himmelstjerna, Georg; Krücken, Jürgen

2013-01-01

Diagnosis of gastrointestinal nematodes relies predominantly on coproscopic methods such as flotation, Kato-Katz, McMaster or FLOTAC. Although FLOTAC allows accurate quantification, many nematode eggs can only be differentiated to genus or family level. Several molecular diagnostic tools discriminating closely related species suffer from high costs for DNA isolation from feces and limited sensitivity since most kits use only small amounts of feces (<1 g). A direct PCR from crude egg preparations was designed for full compatibility with FLOTAC to accurately quantify eggs per gram feces (epg) and determine species composition. Eggs were recovered from the flotation solution and concentrated by sieving. Lysis was achieved by repeated boiling and freezing cycles – only Trichuris eggs required additional mechanic disruption. Egg lysates were directly used as template for PCR with Phusion DNA polymerase which is particularly resistant to PCR inhibitors. Qualitative results were obtained with feces of goats, cattle, horses, swine, cats, dogs and mice. The finally established protocol was also compatible with quantitative real-time PCR in the presence of EvaGreen and no PCR inhibition was detectable when extracts were diluted at least fourfold. Sensitivity was comparable to DNA isolation protocols and spiked samples with five epg were reliably detected. For Toxocara cati a detection limit below one epg was demonstrated. It was possible to distinguish T. cati and Toxocara canis using high resolution melt (HRM) analysis, a rapid tool for species identification. In human samples, restriction fragment length polymorphism (RFLP) and HRM analysis were used to discriminate Necator americanus and Ancylostoma duodenale. The method is able to significantly improve molecular diagnosis of gastrointestinal nematodes by increasing speed and sensitivity while decreasing overall costs. For identification of species or resistance alleles, analysis of PCR products with many different post

Varietal discrimination of hop pellets by near and mid infrared spectroscopy.

PubMed

Machado, Julio C; Faria, Miguel A; Ferreira, Isabel M P L V O; Páscoa, Ricardo N M J; Lopes, João A

2018-04-01

Hop is one of the most important ingredients of beer production and several varieties are commercialized. Therefore, it is important to find an eco-real-time-friendly-low-cost technique to distinguish and discriminate hop varieties. This paper describes the development of a method based on vibrational spectroscopy techniques, namely near- and mid-infrared spectroscopy, for the discrimination of 33 commercial hop varieties. A total of 165 samples (five for each hop variety) were analysed by both techniques. Principal component analysis, hierarchical cluster analysis and partial least squares discrimination analysis were the chemometric tools used to discriminate positively the hop varieties. After optimizing the spectral regions and pre-processing methods a total of 94.2% and 96.6% correct hop varieties discrimination were obtained for near- and mid-infrared spectroscopy, respectively. The results obtained demonstrate the suitability of these vibrational spectroscopy techniques to discriminate different hop varieties and consequently their potential to be used as an authenticity tool. Compared with the reference procedures normally used for hops variety discrimination these techniques are quicker, cost-effective, non-destructive and eco-friendly. Copyright © 2017 Elsevier B.V. All rights reserved.

Discrimination of germline V genes at different sequencing lengths and mutational burdens: A new tool for identifying and evaluating the reliability of V gene assignment.

PubMed

Zhang, Bochao; Meng, Wenzhao; Prak, Eline T Luning; Hershberg, Uri

2015-12-01

Immune repertoires are collections of lymphocytes that express diverse antigen receptor gene rearrangements consisting of Variable (V), (Diversity (D) in the case of heavy chains) and Joining (J) gene segments. Clonally related cells typically share the same germline gene segments and have highly similar junctional sequences within their third complementarity determining regions. Identifying clonal relatedness of sequences is a key step in the analysis of immune repertoires. The V gene is the most important for clone identification because it has the longest sequence and the greatest number of sequence variants. However, accurate identification of a clone's germline V gene source is challenging because there is a high degree of similarity between different germline V genes. This difficulty is compounded in antibodies, which can undergo somatic hypermutation. Furthermore, high-throughput sequencing experiments often generate partial sequences and have significant error rates. To address these issues, we describe a novel method to estimate which germline V genes (or alleles) cannot be discriminated under different conditions (read lengths, sequencing errors or somatic hypermutation frequencies). Starting with any set of germline V genes, this method measures their similarity using different sequencing lengths and calculates their likelihood of unambiguous assignment under different levels of mutation. Hence, one can identify, under different experimental and biological conditions, the germline V genes (or alleles) that cannot be uniquely identified and bundle them together into groups of specific V genes with highly similar sequences. Copyright © 2015 Elsevier B.V. All rights reserved.

Sub-pattern based multi-manifold discriminant analysis for face recognition

NASA Astrophysics Data System (ADS)

Dai, Jiangyan; Guo, Changlu; Zhou, Wei; Shi, Yanjiao; Cong, Lin; Yi, Yugen

2018-04-01

In this paper, we present a Sub-pattern based Multi-manifold Discriminant Analysis (SpMMDA) algorithm for face recognition. Unlike existing Multi-manifold Discriminant Analysis (MMDA) approach which is based on holistic information of face image for recognition, SpMMDA operates on sub-images partitioned from the original face image and then extracts the discriminative local feature from the sub-images separately. Moreover, the structure information of different sub-images from the same face image is considered in the proposed method with the aim of further improve the recognition performance. Extensive experiments on three standard face databases (Extended YaleB, CMU PIE and AR) demonstrate that the proposed method is effective and outperforms some other sub-pattern based face recognition methods.

Workplace Discrimination and Health Among Filipinos in the United States

PubMed Central

de Castro, Arnold B.; Gee, Gilbert C.; Takeuchi, David T.

2008-01-01

Objectives. We examined the association between work discrimination and morbidity among Filipinos in the United States, independent of more-global measures of discrimination. Methods. Data were collected from the Filipino American Community Epidemiological Survey. Our analysis focused on 1652 participants who were employed at the time of data collection, and we used negative binomial regression to determine the association between work discrimination and health conditions. Results. The report of workplace discrimination specific to being Filipino was associated with an increased number of health conditions. This association persisted even after we controlled for everyday discrimination, a general assessment of discrimination; job concerns, a general assessment of unpleasant work circumstances; having immigrated for employment reasons; job category; income; education; gender; and other sociodemographic factors. Conclusions. Racial discrimination in the workplace was positively associated with poor health among Filipino Americans after we controlled for reports of everyday discrimination and general concerns about one’s job. This finding shows the importance of considering the work setting as a source of discrimination and its effect on morbidity among racial minorities. PMID:18235069

Association of HLA class I alleles with aloplecia areata in Chinese Hans.

PubMed

Xiao, Feng-Li; Yang, Sen; Yan, Kai-lin; Cui, Yong; Liang, Yan-Hua; Zhou, Fu-Sheng; Du, Wen-Hui; Gao, Min; Sun, Liang-Dan; Fan, Xing; Chen, Jian-Jun; Wang, Pei-Guang; Zhu, Ya-Gang; Zhou, Shun-Ming; Zhang, Xue-Jun

2006-02-01

Some studies suggested that human HLA status may potentiate development of the AA phenotype and exists ethic differences. No report has been published about HLA class I alleles associated with AA in Chinese Hans. To study the distribution of HLA class I alleles and haplotypes in Chinese Hans AA patients and the relation of HLA class I profile with age of onset, severity, duration of current attack, past history and family history. The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with AA and 252 healthy controls in Chinese Hans. The frequencies of HLA-A*02, -A*03, -B*18, -B*27, -B*52 and -Cw*0704 were significantly higher in patients than in controls. The A*2-B*18, A*2-B*27, A*2-B*52, A*2-Cw*0704, B*18-Cw*0704, B*27-Cw*0704, B*52-Cw*0704 were found as high-risk haplotypes in developing AA in this study. The HLA-A*02 and -A*03 were observed increased frequencies in patients less than 50% hair loss, and HLA-B*27 equally in patients of 50-99% hair loss, alopecia totalis and alopecia universalis. The frequencies of HLA-A*02 and -B*27 were significantly raised in recurrent patients, and ones of HLA-A*02, -A*03 and -B*27 similarly in patients without a positive family history. This study demonstrated the positive association of HLA class I alleles and haplotypes with AA. There may be differences in genetic background in patients with different age of onset, grade of scalp hair loss, duration of current attack, a past history and a family history.

TBX6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis

PubMed Central

Wu, N.; Ming, X.; Xiao, J.; Wu, Z.; Chen, X.; Shinawi, M.; Shen, Y.; Yu, G.; Liu, J.; Xie, H.; Gucev, Z.S.; Liu, S.; Yang, N.; Al-Kateb, H.; Chen, J.; Zhang, Jian; Hauser, N.; Zhang, T.; Tasic, V.; Liu, P.; Su, X.; Pan, X.; Liu, C.; Wang, L.; Shen, Joseph; Shen, Jianxiong; Chen, Y.; Zhang, T.; Zhang, Jianguo; Choy, K.W.; Wang, Jun; Wang, Q.; Li, S.; Zhou, W.; Guo, J.; Wang, Y.; Zhang, C.; Zhao, H.; An, Y.; Zhao, Y.; Wang, Jiucun; Liu, Z.; Zuo, Y.; Tian, Y.; Weng, X.; Sutton, V.R.; Wang, H.; Ming, Y.; Kulkarni, S.; Zhong, T.P.; Giampietro, P.F.; Dunwoodie, S.L.; Cheung, S.W.; Zhang, X.; Jin, L.; Lupski, J.R.; Qiu, G.; Zhang, F.

2015-01-01

BACKGROUND Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. METHODS We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions. RESULTS We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. CONCLUSIONS Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. PMID:25564734

The genetic basis for fruit odor discrimination in Rhagoletis flies and its significance for sympatric host shifts.

PubMed

Dambroski, Hattie R; Linn, Charles; Berlocher, Stewart H; Forbes, Andrew A; Roelofs, Wendell; Feder, Jeffrey L

2005-09-01

Rhagoletis pomonella (Diptera: Tephritidae) use volatile compounds emitted from the surface of ripening fruit as important chemosensory cues for recognizing and distinguishing among alternative host plants. Host choice is of evolutionary significance in Rhagoletis because these flies mate on or near the fruit of their respective host plants. Differences in host choice based on fruit odor discrimination therefore result in differential mate choice and prezygotic reproductive isolation, facilitating sympatric speciation in the absence of geographic isolation. We test for a genetic basis for host fruit odor discrimination through an analysis of F2 and backcross hybrids constructed between apple-, hawthorn-, and flowering dogwood-infesting Rhagoletis flies. We recovered a significant proportion (30-65%) of parental apple, hawthorn, and dogwood fly response phenotypes in F2 hybrids, despite the general failure of F1 hybrids to reach odor source spheres. Segregation patterns in F2 and backcross hybrids suggest that only a modest number of allelic differences at a few loci may underlie host fruit odor discrimination. In addition, a strong bias was observed for F2 and backcross flies to orient to the natal fruit blend of their maternal grandmother, implying the existence of cytonuclear gene interactions. We explore the implications of our findings for the evolutionary dynamics of sympatric host race formation and speciation.

The Predicted Cross Value for Genetic Introgression of Multiple Alleles

PubMed Central

Han, Ye; Cameron, John N.; Wang, Lizhi; Beavis, William D.

2017-01-01

We consider the plant genetic improvement challenge of introgressing multiple alleles from a homozygous donor to a recipient. First, we frame the project as an algorithmic process that can be mathematically formulated. We then introduce a novel metric for selecting breeding parents that we refer to as the predicted cross value (PCV). Unlike estimated breeding values, which represent predictions of general combining ability, the PCV predicts specific combining ability. The PCV takes estimates of recombination frequencies as an input vector and calculates the probability that a pair of parents will produce a gamete with desirable alleles at all specified loci. We compared the PCV approach with existing estimated-breeding-value approaches in two simulation experiments, in which 7 and 20 desirable alleles were to be introgressed from a donor line into a recipient line. Results suggest that the PCV is more efficient and effective for multi-allelic trait introgression. We also discuss how operations research can be used for other crop genetic improvement projects and suggest several future research directions. PMID:28122824

Short mucin 6 alleles are associated with H pylori infection.

PubMed

Nguyen, Thai V; Janssen, Marcel; Gritters, Paulien; te Morsche, René H M; Drenth, Joost P H; van Asten, Henri; Laheij, Robert J F; Jansen, Jan B M J

2006-10-07

To investigate the relationship between mucin 6 (MUC6) VNTR length and H pylori infection. Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu II) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by (14)C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (< or = 13.5 kbp) and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)]. 160 patients were studied (mean age 43 years, 36% were males, 58% H pylori positive). MUC6 Pvu II-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6 genotype, 43% (24/56), 57% (25/58) and 76% (11/46) were infected with H pylori, respectively (P = 0.003). Short MUC6 alleles are associated with H pylori infection.

Hard and soft age discrimination: the dual nature of workplace discrimination.

PubMed

Stypinska, Justyna; Turek, Konrad

2017-03-01

The paper concentrates on the problem of age discrimination in the labour market and the way it can be conceptualised and measured in a multi-disciplinary way. The approach proposed here combines two understandings of age discrimination-a sociological and legal one, what allows for a fuller and expanded understanding of ageism in the workplace. At the heart of the study is a survey carried out in Poland with a sample of 1000 men and women aged 45-65 years. The study takes a deeper and innovative look into the issue of age discrimination in employment. Confirmatory factor analysis with WLSMV estimation and logistic regressions were used to test the hypotheses. The study shows that age discrimination in labour market can take on different forms: hard and soft, where the hard type of age discrimination mirrors the legally prohibited types of behaviours and those which relate to the actual decisions of employers which can impact on the employee's career development. The soft discrimination corresponds with those occurrences, which are not inscribed in the legal system per se, are occurring predominantly in the interpersonal sphere, but can nevertheless have negative consequences. Soft discrimination was experienced more often (28.6% of respondents) than hard discrimination (15.7%) with higher occurrences among women, persons in precarious job situation or residents of urban areas. The role of education was not confirmed to influence the levels of perceived age discrimination.

New Prediction Model for Probe Specificity in an Allele-Specific Extension Reaction for Haplotype-Specific Extraction (HSE) of Y Chromosome Mixtures

PubMed Central

Rothe, Jessica; Watkins, Norman E.; Nagy, Marion

2012-01-01

Allele-specific extension reactions (ASERs) use 3′ terminus-specific primers for the selective extension of completely annealed matches by polymerase. The ability of the polymerase to extend non-specific 3′ terminal mismatches leads to a failure of the reaction, a process that is only partly understood and predictable, and often requires time-consuming assay design. In our studies we investigated haplotype-specific extraction (HSE) for the separation of male DNA mixtures. HSE is an ASER and provides the ability to distinguish between diploid chromosomes from one or more individuals. Here, we show that the success of HSE and allele-specific extension depend strongly on the concentration difference between complete match and 3′ terminal mismatch. Using the oligonucleotide-modeling platform Visual Omp, we demonstrated the dependency of the discrimination power of the polymerase on match- and mismatch-target hybridization between different probe lengths. Therefore, the probe specificity in HSE could be predicted by performing a relative comparison of different probe designs with their simulated differences between the duplex concentration of target-probe match and mismatches. We tested this new model for probe design in more than 300 HSE reactions with 137 different probes and obtained an accordance of 88%. PMID:23049901

Enhanced low-template DNA analysis conditions and investigation of allele dropout patterns.

PubMed

Hedell, Ronny; Dufva, Charlotte; Ansell, Ricky; Mostad, Petter; Hedman, Johannes

2015-01-01

Forensic DNA analysis applying PCR enables profiling of minute biological samples. Enhanced analysis conditions can be applied to further push the limit of detection, coming with the risk of visualising artefacts and allele imbalances. We have evaluated the consecutive increase of PCR cycles from 30 to 35 to investigate the limitations of low-template (LT) DNA analysis, applying the short tandem repeat (STR) analysis kit PowerPlex ESX 16. Mock crime scene DNA extracts of four different quantities (from around 8-84 pg) were tested. All PCR products were analysed using 5, 10 and 20 capillary electrophoresis (CE) injection seconds. Bayesian models describing allele dropout patterns, allele peak heights and heterozygote balance were developed to assess the overall improvements in EPG quality with altered PCR/CE settings. The models were also used to evaluate the impact of amplicon length, STR marker and fluorescent label on the risk for allele dropout. The allele dropout probability decreased for each PCR cycle increment from 30 to 33 PCR cycles. Irrespective of DNA amount, the dropout probability was not affected by further increasing the number of PCR cycles. For the 42 and 84 pg samples, mainly complete DNA profiles were generated applying 32 PCR cycles. For the 8 and 17 pg samples, the allele dropouts decreased from 100% using 30 cycles to about 75% and 20%, respectively. The results for 33, 34 and 35 PCR cycles indicated that heterozygote balance and stutter ratio were mainly affected by DNA amount, and not directly by PCR cycle number and CE injection settings. We found 32 and 33 PCR cycles with 10 CE injection seconds to be optimal, as 34 and 35 PCR cycles did not improve allele detection and also included CE saturation problems. We find allele dropout probability differences between several STR markers. Markers labelled with the fluorescent dyes CXR-ET (red in electropherogram) and TMR-ET (shown as black) generally have higher dropout risks compared with those

Toward a fractal spectrum approach for neutron and gamma pulse shape discrimination

NASA Astrophysics Data System (ADS)

Liu, Ming-Zhe; Liu, Bing-Qi; Zuo, Zhuo; Wang, Lei; Zan, Gui-Bin; Tuo, Xian-Guo

2016-06-01

Accurately selecting neutron signals and discriminating γ signals from a mixed radiation field is a key research issue in neutron detection. This paper proposes a fractal spectrum discrimination approach by means of different spectral characteristics of neutrons and γ rays. Figure of merit and average discriminant error ratio are used together to evaluate the discrimination effects. Different neutron and γ signals with various noise and pulse pile-up are simulated according to real data in the literature. The proposed approach is compared with the digital charge integration and pulse gradient methods. It is found that the fractal approach exhibits the best discrimination performance, followed by the digital charge integration method and the pulse gradient method, respectively. The fractal spectrum approach is not sensitive to high frequency noise and pulse pile-up. This means that the proposed approach has superior performance for effective and efficient anti-noise and high discrimination in neutron detection. Supported by the National Natural Science Foundation of China (41274109), Sichuan Youth Science and Technology Innovation Research Team (2015TD0020), Scientific and Technological Support Program of Sichuan Province (2013FZ0022), and the Creative Team Program of Chengdu University of Technology.

Social Status Correlates of Reporting Racial Discrimination and Gender Discrimination among Racially Diverse Women

PubMed Central

Ro, Annie E.; Choi, Kyung-Hee

2009-01-01

The growing body of research on discrimination and health indicates a deleterious effect of discrimination on various health outcomes. However, less is known about the sociodemographic correlates of reporting racial discrimination and gender discrimination among racially diverse women. We examined the associations of social status characteristics with lifetime experiences of racial discrimination and gender discrimination using a racially-diverse sample of 754 women attending family planning clinics in Northern California (11.4% African American, 16.8% Latina, 10.1% Asian and 61.7% Caucasian). A multivariate analysis revealed that race, financial difficulty and marital status were significantly correlated with higher reports of racial discrimination, while race, education, financial difficulty and nativity were significantly correlated with gender discrimination scores. Our findings suggest that the social patterning of perceiving racial discrimination is somewhat different from that of gender discrimination. This has implications in the realm of discrimination research and applied interventions, as different forms of discrimination may have unique covariates that should be accounted for in research analysis or program design. PMID:19485231

Social status correlates of reporting gender discrimination and racial discrimination among racially diverse women.

PubMed

Ro, Annie E; Choi, Kyung-Hee

2009-01-01

The growing body of research on discrimination and health indicates a deleterious effect of discrimination on various health outcomes. However, less is known about the sociodemographic correlates of reporting racial discrimination and gender discrimination among racially diverse women. We examined the associations of social status characteristics with lifetime experiences of racial discrimination and gender discrimination using a racially-diverse sample of 754 women attending family planning clinics in North California (11.4% African American, 16.8% Latina, 10.1% Asian and 61.7% Caucasian). A multivariate analysis revealed that race, financial difficulty and marital status were significantly correlated with higher reports of racial discrimination, while race, education, financial difficulty and nativity were significantly correlated with gender discrimination scores. Our findings suggest that the social patterning of perceiving racial discrimination is somewhat different from that of gender discrimination. This has implications in the realm of discrimination research and applied interventions, as different forms of discrimination may have unique covariates that should be accounted for in research analysis or program design.

A manual and an automatic TERS based virus discrimination

NASA Astrophysics Data System (ADS)

Olschewski, Konstanze; Kämmer, Evelyn; Stöckel, Stephan; Bocklitz, Thomas; Deckert-Gaudig, Tanja; Zell, Roland; Cialla-May, Dana; Weber, Karina; Deckert, Volker; Popp, Jürgen

2015-02-01

Rapid techniques for virus identification are more relevant today than ever. Conventional virus detection and identification strategies generally rest upon various microbiological methods and genomic approaches, which are not suited for the analysis of single virus particles. In contrast, the highly sensitive spectroscopic technique tip-enhanced Raman spectroscopy (TERS) allows the characterisation of biological nano-structures like virions on a single-particle level. In this study, the feasibility of TERS in combination with chemometrics to discriminate two pathogenic viruses, Varicella-zoster virus (VZV) and Porcine teschovirus (PTV), was investigated. In a first step, chemometric methods transformed the spectral data in such a way that a rapid visual discrimination of the two examined viruses was enabled. In a further step, these methods were utilised to perform an automatic quality rating of the measured spectra. Spectra that passed this test were eventually used to calculate a classification model, through which a successful discrimination of the two viral species based on TERS spectra of single virus particles was also realised with a classification accuracy of 91%.Rapid techniques for virus identification are more relevant today than ever. Conventional virus detection and identification strategies generally rest upon various microbiological methods and genomic approaches, which are not suited for the analysis of single virus particles. In contrast, the highly sensitive spectroscopic technique tip-enhanced Raman spectroscopy (TERS) allows the characterisation of biological nano-structures like virions on a single-particle level. In this study, the feasibility of TERS in combination with chemometrics to discriminate two pathogenic viruses, Varicella-zoster virus (VZV) and Porcine teschovirus (PTV), was investigated. In a first step, chemometric methods transformed the spectral data in such a way that a rapid visual discrimination of the two examined viruses

Photoacoustic discrimination of vascular and pigmented lesions using classical and Bayesian methods

NASA Astrophysics Data System (ADS)

Swearingen, Jennifer A.; Holan, Scott H.; Feldman, Mary M.; Viator, John A.

2010-01-01

Discrimination of pigmented and vascular lesions in skin can be difficult due to factors such as size, subungual location, and the nature of lesions containing both melanin and vascularity. Misdiagnosis may lead to precancerous or cancerous lesions not receiving proper medical care. To aid in the rapid and accurate diagnosis of such pathologies, we develop a photoacoustic system to determine the nature of skin lesions in vivo. By irradiating skin with two laser wavelengths, 422 and 530 nm, we induce photoacoustic responses, and the relative response at these two wavelengths indicates whether the lesion is pigmented or vascular. This response is due to the distinct absorption spectrum of melanin and hemoglobin. In particular, pigmented lesions have ratios of photoacoustic amplitudes of approximately 1.4 to 1 at the two wavelengths, while vascular lesions have ratios of about 4.0 to 1. Furthermore, we consider two statistical methods for conducting classification of lesions: standard multivariate analysis classification techniques and a Bayesian-model-based approach. We study 15 human subjects with eight vascular and seven pigmented lesions. Using the classical method, we achieve a perfect classification rate, while the Bayesian approach has an error rate of 20%.

Pitfalls in genetic testing: a case of a SNP in primer-annealing region leading to allele dropout in BRCA1.

PubMed

Silva, Felipe Carneiro; Torrezan, Giovana Tardin; Brianese, Rafael Canfield; Stabellini, Raquel; Carraro, Dirce Maria

2017-07-01

Hereditary breast and ovarian cancer is characterized by mutations in BRCA1 or BRCA2 genes and PCR-based screening techniques, such as capillary sequencing and next-generation sequencing (NGS), are considered gold standard methods for detection of pathogenic mutations in these genes. Single-nucleotide polymorphisms (SNPs) constitute a vast source of variation in the human genome and represent a risk for misdiagnosis in genetic testing, since the presence of a SNP in primer-annealing sites may cause false negative results due to allele dropout. However, few reports are available and the frequency of this phenomenon in diagnostic assays remains unknown. In this article, we investigated the causes of a false negative capillary sequencing result in BRCA1 involving a mother-daughter dyad. Using several molecular strategies, including different DNA polymerases, primer redesign, allele-specific PCR and NGS, we established that the initial misdiagnosis was caused by a SNP located in the primer-annealing region, leading to allele dropout of the mutated allele. Assuming that this problem can also occur in any PCR-based method that are widely used in diagnostic settings, the clinical report presented here draws attention for one of the limitations of genetic testing in general, for which medical and laboratory communities need to be aware.

Identification of Low Molecular Weight Glutenin Alleles by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) in Common Wheat (Triticum aestivum L.).

PubMed

Wang, Aili; Liu, Li; Peng, Yanchun; Islam, Shahidul; Applebee, Marie; Appels, Rudi; Yan, Yueming; Ma, Wujun

2015-01-01

Low molecular weight glutenin subunits (LMW-GS) play an important role in determining dough properties and breadmaking quality. However, resolution of the currently used methodologies for analyzing LMW-GS is rather low which prevents an efficient use of genetic variations associated with these alleles in wheat breeding. The aim of the current study is to evaluate and develop a rapid, simple, and accurate method to differentiate LMW-GS alleles using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A set of standard single LMW-GS allele lines as well as a suite of well documented wheat cultivars were collected from France, CIMMYT, and Canada. Method development and optimization were focused on protein extraction procedures and MALDI-TOF instrument settings to generate reproducible diagnostic spectrum peak profiles for each of the known wheat LMW-GS allele. Results revealed a total of 48 unique allele combinations among the studied genotypes. Characteristic MALDI-TOF peak patterns were obtained for 17 common LMW-GS alleles, including 5 (b, a or c, d, e, f), 7 (a, b, c, d or i, f, g, h) and 5 (a, b, c, d, f) patterns or alleles for the Glu-A3, Glu-B3, and Glu-D3 loci, respectively. In addition, some reproducible MALDI-TOF peak patterns were also obtained that did not match with any known alleles. The results demonstrated a high resolution and throughput nature of MALDI-TOF technology in analyzing LMW-GS alleles, which is suitable for application in wheat breeding programs in processing a large number of wheat lines with high accuracy in limited time. It also suggested that the variation of LMW-GS alleles is more abundant than what has been defined by the current nomenclature system that is mainly based on SDS-PAGE system. The MALDI-TOF technology is useful to differentiate these variations. An international joint effort may be needed to assign allele symbols to these newly identified alleles and determine their effects on end

Identification of Low Molecular Weight Glutenin Alleles by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) in Common Wheat (Triticum aestivum L.)

PubMed Central

Islam, Shahidul; Applebee, Marie; Appels, Rudi; Yan, Yueming; Ma, Wujun

2015-01-01

Low molecular weight glutenin subunits (LMW-GS) play an important role in determining dough properties and breadmaking quality. However, resolution of the currently used methodologies for analyzing LMW-GS is rather low which prevents an efficient use of genetic variations associated with these alleles in wheat breeding. The aim of the current study is to evaluate and develop a rapid, simple, and accurate method to differentiate LMW-GS alleles using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A set of standard single LMW-GS allele lines as well as a suite of well documented wheat cultivars were collected from France, CIMMYT, and Canada. Method development and optimization were focused on protein extraction procedures and MALDI-TOF instrument settings to generate reproducible diagnostic spectrum peak profiles for each of the known wheat LMW-GS allele. Results revealed a total of 48 unique allele combinations among the studied genotypes. Characteristic MALDI-TOF peak patterns were obtained for 17 common LMW-GS alleles, including 5 (b, a or c, d, e, f), 7 (a, b, c, d or i, f, g, h) and 5 (a, b, c, d, f) patterns or alleles for the Glu-A3, Glu-B3, and Glu-D3 loci, respectively. In addition, some reproducible MALDI-TOF peak patterns were also obtained that did not match with any known alleles. The results demonstrated a high resolution and throughput nature of MALDI-TOF technology in analyzing LMW-GS alleles, which is suitable for application in wheat breeding programs in processing a large number of wheat lines with high accuracy in limited time. It also suggested that the variation of LMW-GS alleles is more abundant than what has been defined by the current nomenclature system that is mainly based on SDS-PAGE system. The MALDI-TOF technology is useful to differentiate these variations. An international joint effort may be needed to assign allele symbols to these newly identified alleles and determine their effects on end

Discrimination of isotrigon textures using the Rényi entropy of Allan variances.

PubMed

Gabarda, Salvador; Cristóbal, Gabriel

2008-09-01

We present a computational algorithm for isotrigon texture discrimination. The aim of this method consists in discriminating isotrigon textures against a binary random background. The extension of the method to the problem of multitexture discrimination is considered as well. The method relies on the fact that the information content of time or space-frequency representations of signals, including images, can be readily analyzed by means of generalized entropy measures. In such a scenario, the Rényi entropy appears as an effective tool, given that Rényi measures can be used to provide information about a local neighborhood within an image. Localization is essential for comparing images on a pixel-by-pixel basis. Discrimination is performed through a local Rényi entropy measurement applied on a spatially oriented 1-D pseudo-Wigner distribution (PWD) of the test image. The PWD is normalized so that it may be interpreted as a probability distribution. Prior to the calculation of the texture's PWD, a preprocessing filtering step replaces the original texture with its localized spatially oriented Allan variances. The anisotropic structure of the textures, as revealed by the Allan variances, turns out to be crucial later to attain a high discrimination by the extraction of Rényi entropy measures. The method has been empirically evaluated with a family of isotrigon textures embedded in a binary random background. The extension to the case of multiple isotrigon mosaics has also been considered. Discrimination results are compared with other existing methods.

A novel FY*A allele with the 265T and 298A SNPs formerly associated exclusively with the FY*B allele and weak Fy(b) antigen expression: implication for genotyping interpretative algorithms.

PubMed

Lopez, G H; Condon, J A; Wilson, B; Martin, J R; Liew, Y-W; Flower, R L; Hyland, C A

2015-01-01

An Australian Caucasian blood donor consistently presented a serology profile for the Duffy blood group as Fy(a+b+) with Fy(a) antigen expression weaker than other examples of Fy(a+b+) red cells. Molecular typing studies were performed to investigate the reason for the observed serology profile. Blood group genotyping was performed using a commercial SNP microarray platform. Sanger sequencing was performed using primer sets to amplify across exons 1 and 2 of the FY gene and using allele-specific primers. The propositus was genotyped as FY*A/B, FY*X heterozygote that predicted the Fy(a+b+(w) ) phenotype. Sequencing identified the 265T and 298A variants on the FY*A allele. This link between FY*A allele and 265T was confirmed by allele-specific PCR. The reduced Fy(a) antigen reactivity is attributed to a FY*A allele-carrying 265T and 298A variants previously defined in combination only with the FY*B allele and associated with weak Fy(b) antigen expression. This novel allele should be considered in genotyping interpretative algorithms for generating a predicted phenotype. © 2014 International Society of Blood Transfusion.

The role of perceived discrimination on active aging.

PubMed

Fernandez-Ballesteros, Rocio; Olmos, Ricardo; Santacreu, Marta; Bustillos, Antonio; Molina, Maria Angeles

2017-07-01

Among older adults, perceived age discrimination is highly associated with unhealthy outcomes and dissatisfaction. Active aging is a multidimensional concept described by a set of characteristics, particularly health, positive mood and control; most importantly, active aging is currently at the core of public policies. The aim of the present study was to test to what extent perceived discrimination influences active aging. Methods A total of 2005 older adults in three representative samples from regions of Germany, Mexico and Spain participated; they were tested on active aging and perceived discrimination. First, active aging was defined as high reported health, life satisfaction and self-perception of aging. Second, authors introduced the assumption that, in the total sample, structural equation modelling would confirm the hypothesis of a direct negative link between perceived age discrimination and active aging. Finally, multiple group comparison performed through structural equation modelling also provided support for the negative association between perceived discrimination and active aging proposed. In spite of the differences found among the three countries in both active aging variables and age discrimination perception, multiple group comparison indicates that regardless of the culture, perceived discrimination is a negative predictor of active aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Weighted Discriminative Dictionary Learning based on Low-rank Representation

NASA Astrophysics Data System (ADS)

Chang, Heyou; Zheng, Hao

2017-01-01

Low-rank representation has been widely used in the field of pattern classification, especially when both training and testing images are corrupted with large noise. Dictionary plays an important role in low-rank representation. With respect to the semantic dictionary, the optimal representation matrix should be block-diagonal. However, traditional low-rank representation based dictionary learning methods cannot effectively exploit the discriminative information between data and dictionary. To address this problem, this paper proposed weighted discriminative dictionary learning based on low-rank representation, where a weighted representation regularization term is constructed. The regularization associates label information of both training samples and dictionary atoms, and encourages to generate a discriminative representation with class-wise block-diagonal structure, which can further improve the classification performance where both training and testing images are corrupted with large noise. Experimental results demonstrate advantages of the proposed method over the state-of-the-art methods.

Identification of a synonymous polymorphism within the cytochrome P4502C9 gene that interferes with identification of the CYP2C9*2 allele.

PubMed

Womack, Edward P; Reynolds, Kristen K; Valdes, Roland; Linder, Mark W

2007-10-01

Cytochrome P450 2C9 (CYP4502C9) genotyping is useful in dosage adjustments for several critical drug therapies, including warfarin. Potential interference compromising these genotyping results could lead to inappropriate dose adjustments that may result in adverse drug reactions. During routine clinical CYP4502C9 genotyping using multiplex allele-specific primer extension, an ambiguous result was obtained for determination of the CYP2C9 430C>T substitution, which defines the CYP2C9*2 allele. In this one patient sample submitted for CYP2C9 genotyping, the ratio for the variant 430T allele signal to the total signal (C+T alleles) was 0.29. This is above the expected ratio to be classified as wild-type (<0.15) and below the minimum expected ratio (>0.3) when the genotype is heterozygous at the 430 position. The mean fluorescence intensity for the 430C allele was consistent with that observed in subjects who are heterozygous at this nucleotide position. However, the corresponding signal for the 430T allele indicated the absence of the CYP2C9*2 allele. This suggests the assay was not able to determine the correct nucleotide at position 430 for one of the two alleles in this patient. Subsequent sequencing to investigate the allele-specific primer extension failure revealed the presence of a rare C>T nucleotide substitution at position 429. We tested this subject's CYP2C9 genotype using AvaII restriction endonuclease digestion and found that this rare substitution causes false-positive identification of the CYP2C9*2 allele when using this method. We developed a DpnII endonuclease digestion assay to specifically detect the CYP2C9 429C>T substitution and tested 100 randomly selected samples obtained from unrelated individuals. The 429C>T polymorphism was not identified in this sample set, which indicates an allele frequency of less than 2.0% (95% confidence interval, 0.0-1.8%) in the general population. Despite the rarity of this polymorphism, it has important implications

Perceived Discrimination and Ethnic Identity Among Breast Cancer Survivors

PubMed Central

Campesino, Maureen; Saenz, Delia S.; Choi, Myunghan; Krouse, Robert S.

2012-01-01

Purpose/Objectives To examine ethnic identity and sociodemographic factors in minority patients' perceptions of healthcare discrimination in breast cancer care. Design Mixed methods. Setting Participants' homes in the metropolitan areas of Phoenix and Tucson, AZ. Sample 39 women treated for breast cancer in the past six years: 15 monolingual Spanish-speaking Latinas, 15 English-speaking Latinas, and 9 African Americans. Methods Two questionnaires were administered. Individual interviews with participants were conducted by nurse researchers. Quantitative, qualitative, and matrix analytic methods were used. Main Research Variables Ethnic identity and perceptions of discrimination. Findings Eighteen women (46%) believed race and spoken language affected the quality of health care. Perceived disrespect from providers was attributed to participant's skin color, income level, citizenship status, and ability to speak English. Discrimination was more likely to be described in a primary care context, rather than cancer care. Ethnic identity and early-stage breast cancer diagnosis were the only study variables significantly associated with perceived healthcare discrimination. Conclusions This article describes the first investigation examining ethnic identity and perceived discrimination in cancer care delivery. Replication of this study with larger samples is needed to better understand the role of ethnic identity and cancer stage in perceptions of cancer care delivery. Implications for Nursing Identification of ethnic-specific factors that influence patient's perspectives and healthcare needs will facilitate development of more effective strategies for the delivery of cross-cultural patient-centered cancer care. PMID:22374505

Segregation of male-sterility alleles across a species boundary.

PubMed

Weller, S G; Sakai, A K; Culley, T M; Duong, L; Danielson, R E

2014-02-01

Hybrid zones may serve as bridges permitting gene flow between species, including alleles influencing the evolution of breeding systems. Using greenhouse crosses, we assessed the likelihood that a hybrid zone could serve as a conduit for transfer of nuclear male-sterility alleles between a gynodioecious species and a hermaphroditic species with very rare females in some populations. Segregation patterns in progeny of crosses between rare females of hermaphroditic Schiedea menziesii and hermaphroditic plants of gynodioecious Schiedea salicaria heterozygous at the male-sterility locus, and between female S. salicaria and hermaphroditic plants from the hybrid zone, were used to determine whether male-sterility was controlled at the same locus in the parental species and the hybrid zone. Segregations of females and hermaphrodites in approximately equal ratios from many of the crosses indicate that the same nuclear male-sterility allele occurs in the parent species and the hybrid zone. These rare male-sterility alleles in S. menziesii may result from gene flow from S. salicaria through the hybrid zone, presumably facilitated by wind pollination in S. salicaria. Alternatively, rare male-sterility alleles might result from a reversal from gynodioecy to hermaphroditism in S. menziesii, or possibly de novo evolution of male sterility. Phylogenetic analysis indicates that some species of Schiedea have probably evolved separate sexes independently, but not in the lineage containing S. salicaria and S. menziesii. High levels of selfing and expression of strong inbreeding depression in S. menziesii, which together should favour females in populations, argue against a reversal from gynodioecy to hermaphroditism in S. menziesii. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

A study of the association of childhood asthma with HLA alleles in the population of Siliguri, West Bengal, India.

PubMed

Lama, M; Chatterjee, M; Chaudhuri, T K

2014-09-01

Asthma is a heterogeneous disease for which a strong genetic basis is firmly established. It is a complex disorder influenced by gene-environment interaction. Human leukocyte antigen (HLA) genes have been shown to be consistently associated with asthma and its related phenotypes in various populations. The aim of this study was to determine the frequency of the selected HLA classes I and II allelic groups in asthmatic and control groups. HLA typing was performed using polymerase chain reaction-sequence-specific typing (PCR-SSP) method. The allele frequency was estimated by direct counting. Frequency of each HLA allelic group was compared between asthmatic group and control group using χ(2) test. P-value was corrected by multiplying with the number of the allelic groups studied. Odds ratio (OR) and its corresponding 95% confidence interval (CI) for each allelic group were calculated using graphpad instat 3.10. The results of this study showed a significantly higher frequency of HLA-DRB1*03 in asthmatics than in controls (11.43% vs 3.64%, OR = 3.78, 95% CI = 1.61-8.85, P = 0.0025, Pcorr  < 0.05). Analysis of HLA alleles in low and high total serum immunoglobulin E (IgE) level in asthmatics revealed no significant association. HLA-DRB1*03 may be implicated in the susceptibility to asthma in the pediatric population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Distribution of photoperiod-insensitive allele Ppd-A1a and its effect on heading time in Japanese wheat cultivars

PubMed Central

Seki, Masako; Chono, Makiko; Nishimura, Tsutomu; Sato, Mikako; Yoshimura, Yasuhiro; Matsunaka, Hitoshi; Fujita, Masaya; Oda, Shunsuke; Kubo, Katashi; Kiribuchi-Otobe, Chikako; Kojima, Hisayo; Nishida, Hidetaka; Kato, Kenji

2013-01-01

The Ppd-A1 genotype of 240 Japanese wheat cultivars and 40 foreign cultivars was determined using a PCR-based method. Among Japanese cultivars, only 12 cultivars, all of which were Hokkaido winter wheat, carried the Ppd-A1a allele, while this allele was not found in Hokkaido spring wheat cultivars or Tohoku-Kyushu cultivars. Cultivars with a photoperiod-insensitive allele headed 6.9–9.8 days earlier in Kanto and 2.5 days earlier in Hokkaido than photoperiod-sensitive cultivars. The lower effect of photoperiod-insensitive alleles observed in Hokkaido could be due to the longer day-length at the spike formation stage compared with that in Kanto. Pedigree analysis showed that ‘Purple Straw’ and ‘Tohoku 118’ were donors of Ppd-A1a and Ppd-D1a in Hokkaido wheat cultivars, respectively. Wheat cultivars recently developed in Hokkaido carry photoperiod-insensitive alleles at a high frequency. For efficient utilization of Ppd-1 alleles in the Hokkaido wheat-breeding program, the effect of Ppd-1 on growth pattern and grain yield should be investigated. Ppd-A1a may be useful as a unique gene source for fine tuning the heading time in the Tohoku-Kyushu region since the effect of Ppd-A1a on photoperiod insensitivity appears to differ from the effect of Ppd-B1a and Ppd-D1a. PMID:24273426

Subject-based discriminative sparse representation model for detection of concealed information.

PubMed

Akhavan, Amir; Moradi, Mohammad Hassan; Vand, Safa Rafiei

2017-05-01

The use of machine learning approaches in concealed information test (CIT) plays a key role in the progress of this neurophysiological field. In this paper, we presented a new machine learning method for CIT in which each subject is considered independent of the others. The main goal of this study is to adapt the discriminative sparse models to be applicable for subject-based concealed information test. In order to provide sufficient discriminability between guilty and innocent subjects, we introduced a novel discriminative sparse representation model and its appropriate learning methods. For evaluation of the method forty-four subjects participated in a mock crime scenario and their EEG data were recorded. As the model input, in this study the recurrence plot features were extracted from single trial data of different stimuli. Then the extracted feature vectors were reduced using statistical dependency method. The reduced feature vector went through the proposed subject-based sparse model in which the discrimination power of sparse code and reconstruction error were applied simultaneously. Experimental results showed that the proposed approach achieved better performance than other competing discriminative sparse models. The classification accuracy, sensitivity and specificity of the presented sparsity-based method were about 93%, 91% and 95% respectively. Using the EEG data of a single subject in response to different stimuli types and with the aid of the proposed discriminative sparse representation model, one can distinguish guilty subjects from innocent ones. Indeed, this property eliminates the necessity of several subject EEG data in model learning and decision making for a specific subject. Copyright © 2017 Elsevier B.V. All rights reserved.

Discrimination of lymphoma using laser-induced breakdown spectroscopy conducted on whole blood samples

PubMed Central

Chen, Xue; Li, Xiaohui; Yang, Sibo; Yu, Xin; Liu, Aichun

2018-01-01

Lymphoma is a significant cancer that affects the human lymphatic and hematopoietic systems. In this work, discrimination of lymphoma using laser-induced breakdown spectroscopy (LIBS) conducted on whole blood samples is presented. The whole blood samples collected from lymphoma patients and healthy controls are deposited onto standard quantitative filter papers and ablated with a 1064 nm Q-switched Nd:YAG laser. 16 atomic and ionic emission lines of calcium (Ca), iron (Fe), magnesium (Mg), potassium (K) and sodium (Na) are selected to discriminate the cancer disease. Chemometric methods, including principal component analysis (PCA), linear discriminant analysis (LDA) classification, and k nearest neighbor (kNN) classification are used to build the discrimination models. Both LDA and kNN models have achieved very good discrimination performances for lymphoma, with an accuracy of over 99.7%, a sensitivity of over 0.996, and a specificity of over 0.997. These results demonstrate that the whole-blood-based LIBS technique in combination with chemometric methods can serve as a fast, less invasive, and accurate method for detection and discrimination of human malignancies. PMID:29541503

Inter-class sparsity based discriminative least square regression.