Marcela K. Tello-Ruiz

WormBase: a multi-species resource for nematode biology and genomics.

WormBase (http://www.wormbase.org/) is the central data repository for information about Caenorhabditis elegans and related nematodes. As a model organism database, WormBase extends beyond the genomic sequence, integrating experimental results with extensively annotated views of the genome. The WormBase Consortium continues to expand the biological scope and utility of WormBase with the inclusion of large-scale genomic analyses, through active data and literature curation, through new analysis and visualization tools, and through refinement of the user interface. Over the past year, the nearly complete genomic sequence and comparative analyses of the closely related species Caenorhabditis briggsae have been integrated into WormBase, including gene predictions, ortholog assignments and a new synteny viewer to display the relationships between the two species. Extensive site-wide refinement of the user interface now provides quick access to the most frequently accessed resources and a consistent browsing experience across the site. Unified single-page views now provide complete summaries of commonly accessed entries like genes. These advances continue to increase the utility of WormBase for C.elegans researchers, as well as for those researchers exploring problems in functional and comparative genomics in the context of a powerful genetic system.

A Genomewide Admixture Map for Latino Populations

Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.

Gramene 2016: comparative plant genomics and pathway resources

Gramene (http://www.gramene.org) is an online resource for comparative functional genomics in crops and model plant species. Its two main frameworks are genomes (collaboration with Ensembl Plants) and pathways (The Plant Reactome and archival BioCyc databases). Since our last NAR update, the database website adopted a new Drupal management platform. The genomes section features 39 fully assembled reference genomes that are integrated using ontology-based annotation and comparative analyses, and accessed through both visual and programmatic interfaces. Additional community data, such as genetic variation, expression and methylation, are also mapped for a subset of genomes. The Plant Reactome pathway portal (http://plantreactome.gramene.org) provides a reference resource for analyzing plant metabolic and regulatory pathways. In addition to ∼200 curated rice reference pathways, the portal hosts gene homology-based pathway projections for 33 plant species. Both the genome and pathway browsers interface with the EMBL-EBIs Expression Atlas to enable the projection of baseline and differential expression data from curated expression studies in plants. Gramenes archive website (http://archive.gramene.org) continues to provide previously reported resources on comparative maps, markers and QTL. To further aid our users, we have also introduced a live monthly educational webinar series and a Gramene YouTube channel carrying video tutorials.

Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

Aims/hypothesisType 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case–control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained.MethodsWe genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures.ResultsAlthough European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p = 2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p = 0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p = 0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p = 0.02). Adjustment for BMI did not change the results.Conclusions/interpretationThe proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects.

Ensembl Genomes 2018: an integrated omics infrastructure for non-vertebrate species.

Abstract Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including genome sequence, gene models, transcript sequence, genetic variation, and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments and expansions. These include the incorporation of almost 20 000 additional genome sequences and over 35 000 tracks of RNA-Seq data, which have been aligned to genomic sequence and made available for visualization. Other advances since 2015 include the release of the database in Resource Description Framework (RDF) format, a large increase in community-derived curation, a new high-performance protein sequence search, additional cross-references, improved annotation of non-protein-coding genes, and the launch of pre-release and archival sites. Collectively, these changes are part of a continuing response to the increasing quantity of publicly-available genome-scale data, and the consequent need to archive, integrate, annotate and disseminate these using automated, scalable methods.

Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19

Evidence from four independent linkage studies and two meta-analyses of genome-wide data support the existence of a locus conferring susceptibility to inflammatory bowel diseases (IBD) in chromosomal region 19p. Identification of a susceptibility allele in this ∼28.5 Mb region with over 600 genes is a formidable task. To tackle this problem, we undertook two approaches: (1) haplotype-based candidate-gene screen, and (2) evaluation of previously reported associations. For the former, we selected genes with potential implication in IBD pathogenesis based on published functional and expression data, typed SNPs, constructed haplotypes, screened for association in 180 IBD trios, and followed up preliminary associations in 343 IBD patients and 207 control individuals. Overall, we analyzed 465 SNPs, and 260 haplotypes distributed across 56 candidate genes. We found suggestive evidence of association (nominal P<0.01) with four genes (C3, FCER2, IL12RB1, and CRLF1) in a screening stage, but were unable to confirm these preliminary observations at follow-up. In the second approach, we typed four nonsynonymous polymorphisms in genes C3 (R102G and L314P) and ICAM1 (G241R and K469E) in four independent cohorts totaling 2178 IBD cases. We evaluated these data together with previously published reports for three of these variants (C3-Gly102, ICAM1-Arg241, and ICAM1-Glu469), in a meta-analysis. Our pooled meta-analysis provides compelling evidence against association of these variants with disease. Overall, we performed the most comprehensive candidate-gene association study for IBD to date. The information hereby generated constitutes a valuable resource to investigate other common genetic immune diseases, such as celiac disease.

Linkage Disequilibrium Mapping of the Replicated Type 2 Diabetes Linkage Signal on Chromosome 1q

OBJECTIVE Linkage of the chromosome 1q21–25 region to type 2 diabetes has been demonstrated in multiple ethnic groups. We performed common variant fine-mapping across a 23-Mb interval in a multiethnic sample to search for variants responsible for this linkage signal. RESEARCH DESIGN AND METHODS In all, 5,290 single nucleotide polymorphisms (SNPs) were successfully genotyped in 3,179 type 2 diabetes case and control subjects from eight populations with evidence of 1q linkage. Samples were ascertained using strategies designed to enhance power to detect variants causal for 1q linkage. After imputation, we estimate ∼80% coverage of common variation across the region (r 2 > 0.8, Europeans). Association signals of interest were evaluated through in silico replication and de novo genotyping in ∼8,500 case subjects and 12,400 control subjects. RESULTS Association mapping of the 23-Mb region identified two strong signals, both of which were restricted to the subset of European-descent samples. The first mapped to the NOS1AP (CAPON) gene region (lead SNP: rs7538490, odds ratio 1.38 [95% CI 1.21–1.57], P = 1.4 × 10−6, in 999 case subjects and 1,190 control subjects); the second mapped within an extensive region of linkage disequilibrium that includes the ASH1L and PKLR genes (lead SNP: rs11264371, odds ratio 1.48 [1.18–1.76], P = 1.0 × 10−5, under a dominant model). However, there was no evidence for association at either signal on replication, and, across all data (>24,000 subjects), there was no indication that these variants were causally related to type 2 diabetes status. CONCLUSIONS Detailed fine-mapping of the 23-Mb region of replicated linkage has failed to identify common variant signals contributing to the observed signal. Future studies should focus on identification of causal alleles of lower frequency and higher penetrance.

Gramene: A Resource for Comparative Analysis of Plants Genomes and Pathways.

Gramene is an integrated informatics resource for accessing, visualizing, and comparing plant genomes and biological pathways. Originally targeting grasses, Gramene has grown to host annotations for economically important and research model crops, including wheat, potato, tomato, banana, grape, poplar, and Chlamydomonas. Its strength derives from the application of a phylogenetic framework for genome comparison and the use of ontologies to integrate structural and functional annotation data. This chapter outlines system requirements for end users and database hosting, data types and basic navigation within Gramene, and provides examples of how to (1) view a phylogenetic tree for a family of transcription factors, (2) explore genetic variation in the orthologues of a gene with a known trait association, and (3) upload, visualize, and privately share end user data into a new genome browser track.Moreover, this is the first publication describing Gramenes new web interface-intended to provide a simplified portal to the most complete and up-to-date set of plant genome and pathway annotations.

Gramene Database: Navigating Plant Comparative Genomics Resources.

Gramene (http://www.gramene.org) is an online, open source, curated resource for plant comparative genomics and pathway analysis designed to support researchers working in plant genomics, breeding, evolutionary biology, system biology, and metabolic engineering. It exploits phylogenetic relationships to enrich the annotation of genomic data and provides tools to perform powerful comparative analyses across a wide spectrum of plant species. It consists of an integrated portal for querying, visualizing and analyzing data for 44 plant reference genomes, genetic variation data sets for 12 species, expression data for 16 species, curated rice pathways and orthology-based pathway projections for 66 plant species including various crops. Here we briefly describe the functions and uses of the Gramene database.

Gramene 2018: unifying comparative genomics and pathway resources for plant research

Abstract Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramenes Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene–gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces.