The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC) cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2) and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs). Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II-related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations). These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of ancestral blocks via recombination is a potential mechanism whereby certain DR-DQ allelic combinations, which presumably have favoured immunological functions, can spread across haplotypes and populations.
Pubmed ID: 16440057 RIS Download
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Database as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented August 22, 2016. A multi-country collaboration among scientists and funding agencies to develop a public resource where genetic similarities and differences in human beings are identified and catalogued. Using this information, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors. All of the information generated by the Project will be released into the public domain. Their goal is to compare the genetic sequences of different individuals to identify chromosomal regions where genetic variants are shared. Public and private organizations in six countries are participating in the International HapMap Project. Data generated by the Project can be downloaded with minimal constraints. HapMap project related data, software, and documentation include: bulk data on genotypes, frequencies, LD data, phasing data, allocated SNPs, recombination rates and hotspots, SNP assays, Perlegen amplicons, raw data, inferred genotypes, and mitochondrial and chrY haplogroups; Generic Genome Browser software; protocols and information on assay design, genotyping and other protocols used in the project; and documentation of samples/individuals and the XML format used in the project.
View all literature mentionsDatabase for sequences of the human major histocompatibility complex (HLA) and includes the official sequences for the WHO Nomenclature Committee For Factors of the HLA System. It currently contains 9,310 allele sequences (2013) along with detailed information concerning the material from which the sequence was derived and data on the validation of the sequences. It is established procedure for authors to submit the sequences directly to the IMGT/HLA Database for checking and assignment of an official name prior to publication, this avoids the problems associated with renaming published sequences and the confusion of multiple names for the same sequence. The need for reasonably rapid publication of new HLA allele sequences has necessitated an annual meeting of the WHO Nomenclature Committee for Factors of the HLA System. Additionally they now publish monthly HLA nomenclature updates both in journals and online to provide quick and easy access to new sequence information. The IMGT/HLA Database is part of the international ImMunoGeneTics project. In collaboration with the Imperial Cancer Research Fund (ICRF) and European Bioinformatics Institute (EBI) they have developed an Oracle database to house the HLA sequences in such a way as to allow users to present complex queries about the sequence, sequence features, references, contacts and allele designations to the database via a graphical user interface over the web. The IMGT/HLA Database Submission Tool allows direct submission of sequences to the WHO HLA Nomenclature Committee for Factors of the HLA System. The IMGT/HLA Database provides an FTP site for the retrieval of sequences in a number of pre-formatted files.
View all literature mentionsCentral repository for high quality frequently updated manual annotation of vertebrate finished genome sequence. Human, mouse and zebrafish are in the process of being completely annotated, whereas for other species the annotation is only of specific genomic regions of particular biological interest. The majority of the annotation is from the HAVANA group at the Welcome Trust Sanger Institute. Users can BLAST, search for specific text, export, and download data. Genomes and details of the projects for each species are available through the homepages for human mouse and zebrafish. The website is built upon code from the EnsEMBL (http://www.ensembl.org) project. Some Ensembl features are not available in Vega. From the users point of view perhaps the most significant of these is MartView. However due to their inclusion in Ensembl, Vega human and mouse data can be queried using Ensembl MartView. Vega contains annotation of the human MHC region in eight haplotypes, and the LRC region in three haplotypes. Vega also contains annotation on the Insulin Dependent Diabetes (IDD) regions on non-reference assemblies for mouse.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on August 26,2019. In October 2016, T1DBase has merged with its sister site ImmunoBase (https://immunobase.org). Documented on March 2020, ImmunoBase ownership has been transferred to Open Targets (https://www.opentargets.org). Results for all studies can be explored using Open Targets Genetics (https://genetics.opentargets.org). Database focused on genetics and genomics of type 1 diabetes susceptibility providing a curated and integrated set of datasets and tools, across multiple species, to support and promote research in this area. The current data scope includes annotated genomic sequences for suspected T1D susceptibility regions; genetic data; microarray data; and global datasets, generally from the literature, that are useful for genetics and systems biology studies. The site also includes software tools for analyzing the data.
View all literature mentionsFTP site to access Schizosaccharomyces pombe protein data.
View all literature mentionsSoftware package that provides a graphical summary of linkage disequilibrium in human genetic data. The graphical summary is well suited to the analysis of dense genetic maps, where contingency tables are cumbersome to interpret. An interface to the Simwalk2 application allows for the analysis of family data.
View all literature mentionsAn exploratory population genetics software environment able to handle large samples of molecular data (RFLPs, DNA sequences, microsatellites), while retaining the capacity of analyzing conventional genetic data (standard multi-locus data or mere allele frequency data). (entry from Genetic Analysis Software)
View all literature mentionsThe main purpose of the allelefrequencies.net website is to provide one central source, freely available to all. For the storage of allele frequencies from different polymorphic areas in the HUMAN genome. Users can contribute the results of their work into one common database, and can perform database searches on information already available. They have currently collected data in allele, haplotype and genotype format. The success of this website will depend on you to contribute your data. Sponsors: This resource is supported Royal Liverpool University. Keywords: Allele, Polymorphic, Genome, Database, Data, Haplotype, Genotype,
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