Human Genomic Resources Research Articles

Benefit-Sharing by Design: A Call to Action for Human Genomics Research.

The ethical standards for the responsible conduct of human research have come a long way; however, concerns surrounding equity remain in human genetics and genomics research. Addressing these concerns will help society realize the full potential of human genomics research. One outstanding concern is the fair and equitable sharing of benefits from research on human participants. Several international bodies have recognized that benefit-sharing can be an effective tool for ethical research conduct, but international laws, including the Convention on Biological Diversity and its Nagoya Protocol on Access and Benefit-Sharing, explicitly exclude human genetic and genomic resources. These agreements face significant challenges that must be considered and anticipated if similar principles are applied in human genomics research. We propose that benefit-sharing from human genomics research can be a bottom-up effort and embedded into the existing research process. We propose the development of a "benefit-sharing by design" framework to address concerns of fairness and equity in the use of human genomic resources and samples and to learn from the aspirations and decade of implementation of the Nagoya Protocol.

Differentiated adaptative genetic architecture and language-related demographical history in South China inferred from 619 genomes from 56 populations

BackgroundThe underrepresentation of human genomic resources from Southern Chinese populations limited their health equality in the precision medicine era and complete understanding of their genetic formation, admixture, and adaptive features. Besides, linguistical and genetic evidence supported the controversial hypothesis of their origin processes. One hotspot case was from the Chinese Guangxi Pinghua Han people (GPH), whose language was significantly similar to Southern Chinese dialects but whose uniparental gene pool was phylogenetically associated with the indigenous Tai-Kadai (TK) people. Here, we analyzed genome-wide SNP data in 619 people from four language families and 56 geographically different populations, in which 261 people from 21 geographically distinct populations were first reported here.ResultsWe identified significant population stratification among ethnolinguistically diverse Guangxi populations, suggesting their differentiated genetic origin and admixture processes. GPH shared more alleles related to Zhuang than Southern Han Chinese but received more northern ancestry relative to Zhuang. Admixture models and estimates of genetic distances showed that GPH had a close genetic relationship with geographically close TK compared to Northern Han Chinese, supporting their admixture origin hypothesis. Further admixture time and demographic history reconstruction supported GPH was formed via admixture between Northern Han Chinese and Southern TK people. We identified robust signatures associated with lipid metabolisms, such as fatty acid desaturases (FADS) and medically relevant loci associated with Mendelian disorder (GJB2) and complex diseases. We also explored the shared and unique selection signatures of ethnically different but linguistically related Guangxi lineages and found some shared signals related to immune and malaria resistance.ConclusionsOur genetic analysis illuminated the language-related fine-scale genetic structure and provided robust genetic evidence to support the admixture hypothesis that can explain the pattern of observed genetic diversity and formation of GPH. This work presented one comprehensive analysis focused on the population history and demographical adaptative process, which provided genetic evidence for personal health management and disease risk prediction models from Guangxi people. Further large-scale whole-genome sequencing projects would provide the entire landscape of southern Chinese genomic diversity and their contributions to human health and disease traits.

The International Genome Sample Resource (IGSR) collection of open human genomic variation resources.

To sustain and develop the largest fully open human genomic resources the International Genome Sample Resource (IGSR) (https://www.internationalgenome.org) was established. It is built on the foundation of the 1000 Genomes Project, which created the largest openly accessible catalogue of human genomic variation developed from samples spanning five continents. IGSR (i) maintains access to 1000 Genomes Project resources, (ii) updates 1000 Genomes Project resources to the GRCh38 human reference assembly, (iii) adds new data generated on 1000 Genomes Project cell lines, (iv) shares data from samples with a similarly open consent to increase the number of samples and populations represented in the resources and (v) provides support to users of these resources. Among recent updates are the release of variation calls from 1000 Genomes Project data calculated directly on GRCh38 and the addition of high coverage sequence data for the 2504 samples in the 1000 Genomes Project phase three panel. The data portal, which facilitates web-based exploration of the IGSR resources, has been updated to include samples which were not part of the 1000 Genomes Project and now presents a unified view of data and samples across almost 5000 samples from multiple studies. All data is fully open and publicly accessible.

Database resources of the National Center for Biotechnology Information.

The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and retrieval operations for most of these data from 39 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include PubMed Data Management, RefSeq Functional Elements, genome data download, variation services API, Magic-BLAST, QuickBLASTp, and Identical Protein Groups. Resources that were updated in the past year include the genome data viewer, a human genome resources page, Gene, virus variation, OSIRIS, and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.

Beyond the genome (BTG) is a (PGDB) pathway genome database: HumanCyc

HumanCyc is a manually curated database of enzymatic reactions and metabolic pathways that can be used as a versatile reference resource or as a tool for analyzing ‘omics’ data sets in the context of metabolic pathways. The HumanCyc database was generated from the annotated genome using the Pathway Tools [1] software package written by SRI International (SRI). The software assists users in analyzing genomic data by predicting the metabolic network of an organism, presenting pathway and genome data in user-friendly and intuitive displays, and providing tools for missing enzyme identification, ‘omics’ data analyses and comparative studies. The HumanCyc website (http://humancyc.org/) and the downloadable HumanCyc software support a variety of query, visualization and analysis tools. Users can find and display existing metabolites, pathways and enzymes. Users can also define groups of metabolites or proteins and perform enrichment analysis of an ‘omics’ data set to determine over- represented substrates, pathways or enzymes. It is possible to color code a ‘zoomable’ human metabolic network diagram with metabolomic, proteomic or transcriptomic data for visual analysis of patterns in data sets. The software colors entities in the diagram to reflect their measured levels in useruploaded ‘omics’ data sets. By connecting metabolites to reactions to enzymes to genes, HumanCyc facilitates the integration of multiple ‘omics’ data types. It describes 255 human metabolic pathways, 3315 human enzymes, 1862 biochemical reactions, and 1359 human metabolites. HumanCyc is linked to human genome resources such as Ensembl, GeneCards, Entrez Gene, OMIM, PubChem and UniProt. Curation of the HumanCyc knowledge base is proceeding in conjunction with the Pharmacometabolomics Research Network (PMRN), a multi-year collaboration to develop tools and provide resources for the metabolomics community. To this end, we have focused on curation of information from the scientific literature concerning chemical compounds and enzymes of interest to the PMRN and the larger field of metabolomics, including pathways for metabolism of xenobiotics, nutrients and metabolites produced by the gut microbiome. HumanCyc is a component of the SRI maintained BioCyc databases, which number nearly 700, mostly prokaryotic and PGDBs. BioCyc databases contain 9000 compounds, including many produced by the human microbiome and plant dietary nutrients. Future work will include expansion of the BioCyc collection to keep pace with genome sequencing from the Human Microbiome Project and allow analysis of these Human Microbiome PGDBs and the impact of interspecies interactions on human metabolism.

The Bioinformatics Program at Washington University's Bernard Becker Medical Library

ABSTRACT The need for a Bioinformatics Program became apparent after repeated requests from researchers for bioinformatics resources and the University's announcement of BioMed 21, a $300 million biomedical science initiative to bring “new knowledge of the human genetic blueprint to the patient's bedside and change how illnesses are understood, diagnosed, and successfully treated.” A Bioinformatics Specialist with a strong background in the fields of Molecular Biology and Biostatistics was hired. Program development started in 2003. Initially, three core courses were developed: Sequence Similarity Search, Genetic Variation, and Human Genome Resources. Each of these courses was offered twice per semester. Additionally, partnerships were established within the University Medical School Community (e.g., the Genome Sequencing Center) to license and teach Spotfire's DecisionSite for Functional Genomics, a software package used to analyze microarray data. From March to May 2005, seven Spotfire classes were taught. Each Spotfire class consisted of seven hours of classroom work. Also, in-depth consultations were scheduled with faculty and researchers to address their specific needs. These consultations led to requests for other software packages to purchase and manage, including Lasergene and CSD (Cambridge Crystal Structure Database). Efforts to reach outside of the University Community were made through the development of a Bioinformatics Web site.

Alternate promoter and 5'-untranslated exon usage of the mouse adrenocorticotropin receptor gene in adipose tissue.

Mouse adrenocorticotropin receptor (ACTH-R/MC2R) messenger ribonucleic acid (mRNA) is expressed predominantly in the adrenal gland and, to a lesser extent, in adipose tissue. In this study, we found a novel 135-bp exon 1 (exon 1f) of the ACTH-R gene transcribed in mouse adipose tissue by RNA ligase-mediated rapid amplification of cDNA ends, which was located 1.4 kb downstream in the genome of previously-reported exon 1 (exon 1a) transcribed in the adrenal gland. The novel promoter region, 1.4 kb upstream of exon 1f contained three CCAAT boxes. RT-PCR analysis revealed that ACTH-R mRNA from adipose tissue and differentiated 3T3-L1 adipocytes exclusively contained exon 1f. Thus, the promoter region flanking to exon 1f is thought to be essential for adipose tissue, while that flanking to exon 1a is specific for the adrenal gland. A search for a similar sequence of mouse ACTH-R exon 1f and its flanking region in the human genome sequence database of GenBank Human Genome Resources did not reveal such a sequence in the region of the human ACTH-R gene. This may explain the absence of ACTH-R expression in human adipose tissue.

Internet resources for the clinical geneticist.

The Internet offers a number of resources to clinical geneticists. This review outlines some of these with special emphasis on sites present at the National Center for Biotechnology Information (NCBI) at the National Library of Medicine at the National Institutes of Health. Special attention is presented on how these various resources make use of PubMed, the premiere source of MEDLINE information on the Internet. Three NCBI resources are presented here. 1) 'Genes and diseases': a general curated series of web pages outlining various references to known genetic diseases with links to relevant on-line resources. 2) The Online Mendelian Inheritance in Man (OMIM) from Victor A. McKusick at Johns Hopkins University presents our current knowledge of all known human genetic diseases. 3) Human genome resources describe our current knowledge on the human genome project (HGP). A list of relevant uniform resource locators (URLs) is also included.