Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Databases, Genetic”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2006

Bayesian identification of admixture events using multilocus molecular markers.

Bayesian statistical methods for the estimation of hidden genetic structure of populations have gained considerable popularity in the recent years. Utilizing molecular marker data, Bayesian mixture models attempt to identify a hidden population structure by clustering individuals into genetically divergent groups, whereas admixture models target at separating the ancestral sources of the alleles observed in different individuals. We discuss the difficulties involved in the simultaneous estimation of the number of ancestral populations and the levels of admixture in studied individuals' genomes. To resolve this issue, we introduce a computationally efficient method for the identification of admixture events in the population history. Our approach is illustrated by analyses of several challenging real and simulated data sets. The software (baps), implementing the methods introduced here, is freely available at http://www.rni.helsinki.fi/~jic/bapspage.html.

Alleles↗
PubMed2006

The role of mutagenesis in defining genes in behaviour.

The study of human behavioural and psychiatric disorders benefits from the development of genetic models in mice and other organisms. Mouse mutants allow one to investigate the molecular basis of disease progression and to develop novel therapies. The number of potential mouse models is increasing dramatically through the implementation of mutagenesis screens for aberrant behavioural phenotypes. The alkylating agent N-ethyl-N-nitrosourea ENU is the mutagen of choice in these screens as it induces mutations at a very high rate. Progeny of chemically-mutagenised animals are screened either in systematic high-throughput test batteries or in specific low-throughput tests. Both approaches have been highly successful with large numbers of novel loci being identified and characterised. Many mutant lines are available for general research with phenotypes and genetic map positions on public websites. Of the mutant genes characterised, the majority have contributed to our knowledge of gene function in physiology and disease. The 'mutagenesis screening' approach continues to evolve through the design of new phenotyping strategies. The development of modifier screens in mice shows promise in the elucidation of complex phenotypes whereas the use of mutagenesis in combination with pharmacological agents targets specific neurochemical systems. Finally, the systematic screening approach has demonstrated that mutations are likely to affect more than one biological process.

Alkylating Agents↗
PubMed2005

Linkage analysis and association analysis in the presence of linkage using age at onset of COGA alcoholism data.

Complex disease mapping usually involves a combination of linkage and association techniques. Linkage analysis can scan the entire genome in a few hundred tests. Association tests may involve an even greater number of tests. However, association tests can localize the susceptibility genes more accurately. Using a recently developed combined linkage and association strategy, we analyzed a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data for the Genetic Analysis Workshop 14 (GAW14). In this analysis, we first employed linkage analysis based on frailty models that take into account age of onset information to establish which regions along the chromosome are likely to harbor disease susceptibility genes for alcohol dependence. Second, we used an association analysis by exploiting linkage disequilibrium to narrow down the peak regions. We also compare the methods with mean identity-by-descent tests and transmission/disequilibrium tests that do not use age of onset information.

Age of Onset↗
PubMed2004

The role of subspecies in obscuring avian biological diversity and misleading conservation policy.

Subspecies are often used in ways that require their evolutionary independence, for example as proxies for units of conservation. Mitochondrial DNA sequence data reveal that 97% of continentally distributed avian subspecies lack the population genetic structure indicative of a distinct evolutionary unit. Subspecies considered threatened or endangered, some of which have been targets of expensive restoration efforts, also generally lack genetic distinctiveness. Although sequence data show that species include 1.9 historically significant units on average, these units are not reflected by current subspecies nomenclature. Yet, it is these unnamed units and not named subspecies that should play a major role in guiding conservation efforts and in identifying biological diversity. Thus, a massive reorganization of classifications is required so that the lowest ranks, be they species or subspecies, reflect evolutionary diversity. Until such reorganization is accomplished, the subspecies rank will continue to hinder progress in taxonomy, evolutionary studies and especially conservation.

Animals↗
PubMed2005

Impact of human population history on distributions of individual-level genetic distance.

Summaries of human genomic variation shed light on human evolution and provide a framework for biomedical research. Variation is often summarised in terms of one or a few statistics (eg F(ST) and gene diversity). Now that multilocus genotypes for hundreds of autosomal loci are available for thousands of individuals, new approaches are applicable. Recently, trees of individuals and other clustering approaches have demonstrated the power of an individual-focused analysis. We propose analysing the distributions of genetic distances between individuals. Each distribution, or common ancestry profile (CAP), is unique to an individual, and does not require a priori assignment of individuals to populations. Here, we consider a range of models of population history and, using coalescent simulation, reveal the potential insights gained from a set of CAPs. Information lies in the shapes of individual profiles--sometimes captured by variance of individual CAPs--and the variation across profiles. Analysis of short tandem repeat genotype data for over 1,000 individuals from 52 populations is consistent with dramatic differences in population histories across human groups.

Databases, Genetic↗
PubMed2005

Genome-wide linkage and association mapping of disease genes with the GAW14 simulated datasets.

We combined the results of whole-genome linkage and association analyses to determine which markers were most strongly associated with Kofendrerd Personality Disorder. Using replicate 1 from the Genetic Analysis Workshop 14 Aipotu, Karangar, Danacaa, and New York City simulated populations, we determined that several markers showed significant linkage and association with disease status. We used both SNP and microsatellite markers to determine patterns and chromosomal regions of markers. Three consistently associated markers were C01R0050, C03R0280, and C10R0882. Using generalized linear mixed models, we modelled the effect of the three predefined phenotypic categories on disease status and concluded that the phenotypes defining the "anxiety-related" category best predicted the outcome.

Chromosome Mapping↗
PubMed2004

Genome-wide identification of genes likely to be involved in human genetic disease.

Sequence analysis of the group of proteins known to be associated with hereditary diseases allows the detection of key distinctive features shared within this group. The disease proteins are characterized by greater length of their amino acid sequence, a broader phylogenetic extent, and specific conservation and paralogy profiles compared with all human proteins. This unique property pattern provides insights into the global nature of hereditary diseases and moreover can be used to predict novel disease genes. We have developed a computational method that allows the detection of genes likely to be involved in hereditary disease in the human genome. The probability score assignments for the human genome are accessible at http://maine.ebi. ac.uk:8000/services/dgp.

Amino Acids↗
PubMed2004

Target SNP selection in complex disease association studies.

BACKGROUND: The massive amount of SNP data stored at public internet sites provides unprecedented access to human genetic variation. Selecting target SNP for disease-gene association studies is currently done more or less randomly as decision rules for the selection of functional relevant SNPs are not available. RESULTS: We implemented a computational pipeline that retrieves the genomic sequence of target genes, collects information about sequence variation and selects functional motifs containing SNPs. Motifs being considered are gene promoter, exon-intron structure, AU-rich mRNA elements, transcription factor binding motifs, cryptic and enhancer splice sites together with expression in target tissue. As a case study, 396 genes on chromosome 6p21 in the extended HLA region were selected that contributed nearly 20,000 SNPs. By computer annotation ~2,500 SNPs in functional motifs could be identified. Most of these SNPs are disrupting transcription factor binding sites but only those introducing new sites had a significant depressing effect on SNP allele frequency. Other decision rules concern position within motifs, the validity of SNP database entries, the unique occurrence in the genome and conserved sequence context in other mammalian genomes. CONCLUSION: Only 10% of all gene-based SNPs have sequence-predicted functional relevance making them a primary target for genotyping in association studies.

Amino Acid Substitution↗
PubMed2006

The gene for human IL-21 and genetic susceptibility to type 1 diabetes in the Japanese.

Type 1 diabetes is under polygenic control both in humans and the NOD mouse. Recently a possible role of IL-21 in the pathogenesis of type 1 diabetes was demonstrated in the NOD mouse. Furthermore, the murine IL-21 gene is mapped to the Idd3 interval, making the human IL-21 gene (IL21) a functional as well as positional candidate for susceptibility. We therefore screened sequence variants of IL21 and studied the association with type 1 diabetes. Preliminary data showed no association of IL21 polymorphisms with the disease, suggesting that IL21 plays little role in susceptibility to type 1 diabetes in Japanese.

Alleles↗
PubMed2004

TropGENE-DB, a multi-tropical crop information system.

TropGENE-DB, is a crop information system created to store genetic, molecular and phenotypic data of the numerous yet poorly documented tropical crop species. The most common data stored in TropGENE-DB are information on genetic resources (agro-morphological data, parentages, allelic diversity), molecular markers, genetic maps, results of quantitative trait loci analyses, data from physical mapping, sequences, genes, as well as the corresponding references. TropGENE-DB is organized on a crop basis with currently three running modules (sugarcane, cocoa and banana), with plans to create additional modules for rice, cotton, oil palm, coconut, rubber tree, pineapple, taro, yam and sorghum. The TropGENE-DB information system is accessible for consultation via the internet at http://tropgenedb.cirad.fr. Specific web consultation interfaces have been designed to allow quick consultations as well as complex queries.

Computational Biology↗
PubMed2005

The efficacy of short tandem repeat polymorphisms versus single-nucleotide polymorphisms for resolving population structure.

Accurately resolving population structure in a sample is important for both linkage and association studies. In this study we investigated the power of single-nucleotide polymorphisms (SNPs) in detecting population structure in a sample of 286 unrelated individuals. We varied the number of SNPs to determine how many are required to approach the degree of resolution obtained with the Collaborative Study on the Genetics of Alcoholism (COGA) short tandem repeat polymorphisms (STRPs). In addition, we selected SNPs with varying minor allele frequencies (MAFs) to determine whether low or high frequency SNPs are more efficient in resolving population structure. We conclude that a set of at least 100 evenly spaced SNPs with MAFs of 40-50% is required to resolve population structure in this dataset. If SNPs with lower MAFs are used, then more than 250 SNPs may be required to obtain reliable results.

Alcoholism↗
PubMed2006

An integrated in silico gene mapping strategy in inbred mice.

In recent years in silico analysis of common laboratory mice has been introduced and subsequently applied, in slightly different ways, as a methodology for gene mapping. Previously we have demonstrated some limitation of the methodology due to sporadic genetic correlations across the genome. Here, we revisit the three main aspects that affect in silico analysis. First, we report on the use of marker maps: we compared our existing 20,000 SNP map to the newly released 140,000 SNP map. Second, we investigated the effect of varying strain numbers on power to map QTL. Third, we introduced a novel statistical approach: a cladistic analysis, which is well suited for mouse genetics and has increased flexibility over existing in silico approaches. We have found that in our examples of complex traits, in silico analysis by itself does fail to uniquely identify quantitative trait gene (QTG)-containing regions. However, when combined with additional information, it may significantly help to prioritize candidate genes. We therefore recommend using an integrated work flow that uses other genomic information such as linkage regions, regions of shared ancestry, and gene expression information to obtain a list of candidate genes from the genome.

Algorithms↗
PubMed2005

Applying theological developments to bioethical issues such as genetic screening.

Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.

Bioethics↗
PubMed2019

Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants.

Variant interpretation in the era of massively parallel sequencing is challenging. Although many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here, we present the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE), a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in variant call format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4000 pediatric cancer patients and serves as a repository for the expert-reviewed results. PeCanPIE was originally developed for pediatric cancer but can be easily extended for use for nonpediatric cancers and noncancer genetic diseases. Although PeCanPIE's web-based interface was designed to be accessible to non-bioinformaticians, its back-end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.

Child↗
PubMed2006

Annotation of unknown yeast ORFs by correlation analysis of microarray data and extensive literature searches.

Changes in the expression of genes were used to elucidate the metabolic pathways and regulatory mechanisms that respond to environmental or genetic modifications. Results from previously published chemostat datasets were merged with novel data generated in the present study. ORFs displaying significant changes in expression that correlated with those of other ORFs were analysed using GO mapping tools and supplemented by literature information. The strategy developed was used to propose annotations for ORFs of unknown function. The following ORFs were assigned functions as a result of this study: YMR090w, YGL157w, YGR243w, YLR327c, YER121w, YFR017c, YGR067c, YKL187c, YGR236c (SPG1), YMR107w (SPG4), YMR206w, YER067w, YJL103c, YNL175C (NOP13) YJL200C, YDL070C (FMP16) and YGR173W.

Algorithms↗
PubMed2004

Cloning and characterization of the murine Vmd2 RFP-TM gene family.

Mutations in the human vitelliform macular dystrophy type 2 (VMD2) gene are known to cause autosomal dominant Best macular dystrophy (BMD), a degenerative disorder of the central retina. VMD2, together with VMD2L1, VMD2L2 and VMD2L3, belong to a closely related gene family characterized by several transmembrane (TM) spanning helical domains and an invariant arginine, phenylalanine and proline (RFP) tripeptide motif, thus termed VMD2 RFP-TM. The four genes are thought to encode a novel family of anion channels. We now report the cloning and characterization of the murine orthologs by combining biocomputational analyses and molecular genetic approaches. While the murine Vmd2, Vmd2l1 and Vmd2l3 genes are functional, murine Vmd2l2p was found to be a non-transcribed pseudogene. Expression profiling of the murine Vmd2 RFP-TM family members revealed tissue-restricted expression with predominant transcription of Vmd2 in testis, of Vmd2l1 in colon and of Vmd2l3 in heart. Differential splicing was observed for Vmd2l3 in a number of tissues (e.g. in brain, retina/RPE, kidney) although the functional importance of the splice variants remains to be determined.

Alternative Splicing↗
PubMed2005

Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data.

The beta 2 electroencephalogram (EEG) phenotype is used as a quantitative measure related to alcoholism, and evidence of linkage and association has previously been reported in the Collaborative Study on the Genetics of Alcoholism data. In this study, associations between the beta 2 EEG phenotype and single nucleotide polymorphisms from whole-genome Illumina and Affymetrix panels were investigated with the regression of offspring on mid-parent method to identify significant genetic effects and to estimate their heritability. Separate regressions on father and mother were performed to identify parent-specific effects. Estimates of the heritability of the beta 2 EEG phenotype were 0.68 +/- 0.12 and 0.52 +/- 0.07 based on father-offspring and mother-offspring pairs, respectively. Significant associations at the 0.0005 level, some of which were parent-specific, were found on chromosomes 1, 2, 5, 6, 7, 8, 11, 12, 15, 16, 17, 18, and 19 with heritability attributable to each SNP ranging from 0.01 to 8%.

Adolescent↗
PubMed2006

Longevity and the evolution of the mitochondrial DNA-coded proteins in mammals.

The amino acids sequences of the mitochondrial DNA-coded peptides of placental mammals evolved at different rates in different branches of the mammalian phylogenetic tree. Adaptive selection was suggested to account for the faster evolution of some mitochondrial DNA-coded proteins in several branches of the mammalian tree, but the driving force(s) for the accelerated evolution has not been elucidated. Mitochondria generate reactive oxygen species (ROS) that appear to constrain the life span of many species. Therefore, I tested the hypothesis that the evolution of mammalian longevity drives the accelerated evolution of mitochondrial DNA-coded peptides. Using rodents as an outgroup for a clad that included most placental mammals (excluding rodents and hedgehogs) the computed rates of amino acid substitution per site were positively correlated with genus longevity (maximal observed averaged life span) for most of the mitochondrial DNA-coded peptides. The substitution per site of ATP6, the proton conducting subunit of ATPsynthase, CYTB, the core subunit of ubiquinone oxidoreductase that participate in both electron and proton transport, and ND3, a subunit of NADH dehydrogenase, showed the strongest correlations with longevity. Additional confirmation for the hypothesis was obtained by the observation that the genetic distances between placental mammals species that belong to different orders are positively correlated with the sum of longevities of the species pairs. The substitutions per site for the entire amino acid sequence coded by the heavy strand mtDNA were also positively correlated with the average longevities of the placental mammals orders. These results support the hypothesis that the evolution of longevity in mammals drove the accelerated evolution of mtDNA-coded peptide. It is suggested that, in mammals, adaptive selection of mutations that decrease the rate of production of reactive oxygen species, directly or indirectly (e.g. by increasing proton leak), increases longevity.

Animals↗