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https://www.sanger.ac.uk/collaboration/sequencing-idd-regions-nod-mouse-genome/
Genetic variations associated with type 1 diabetes identified by sequencing regions of the non-obese diabetic (NOD) mouse genome and comparing them with the same areas of a diabetes-resistant C57BL/6J reference mouse allowing identification of single nucleotide polymorphisms (SNPs) or other genomic variations putatively associated with diabetes in mice. Finished clones from the targeted insulin-dependent diabetes (Idd) candidate regions are displayed in the NOD clone sequence section of the website, where they can be downloaded either as individual clone sequences or larger contigs that make up the accession golden path (AGP). All sequences are publicly available via the International Nucleotide Sequence Database Collaboration. Two NOD mouse BAC libraries were constructed and the BAC ends sequenced. Clones from the DIL NOD BAC library constructed by RIKEN Genomic Sciences Centre (Japan) in conjunction with the Diabetes and Inflammation Laboratory (DIL) (University of Cambridge) from the NOD/MrkTac mouse strain are designated DIL. Clones from the CHORI-29 NOD BAC library constructed by Pieter de Jong (Children's Hospital, Oakland, California, USA) from the NOD/ShiLtJ mouse strain are designated CHORI-29. All NOD mouse BAC end-sequences have been submitted to the International Nucleotide Sequence Database Consortium (INSDC), deposited in the NCBI trace archive. They have generated a clone map from these two libraries by mapping the BAC end-sequences to the latest assembly of the C57BL/6J mouse reference genome sequence. These BAC end-sequence alignments can then be visualized in the Ensembl mouse genome browser where the alignments of both NOD BAC libraries can be accessed through the Distributed Annotation System (DAS). The Mouse Genomes Project has used the Illumina platform to sequence the entire NOD/ShiLtJ genome and this should help to position unaligned BAC end-sequences to novel non-reference regions of the NOD genome. Further information about the BAC end-sequences, such as their alignment, variation data and Ensembl gene coverage, can be obtained from the NOD mouse ftp site.
Proper citation: Sequencing of Idd regions in the NOD mouse genome (RRID:SCR_001483) Copy
Consortium of 50 research groups across the UK to harness the power of newly-available genotyping technologies to improve our understanding of the aetiological basis of several major causes of global disease. The consortium has gathered genotype data for up to 500,000 sites of genome sequence variation (single nucleotide polymorphisms or SNPs) in samples ascertained for the disease phenotypes. Analysis of the genome-wide association data generated has lead to the identification of many SNPs and genes showing evidence of association with disease susceptibility, some of which will be followed up in future studies. In addition, the Consortium has gained important insights into the technical, analytical, methodological and biological aspects of genome-wide association analysis. The core of the study comprised an analysis of 2,000 samples from each of seven diseases (type 1 diabetes, type 2 diabetes, coronary heart disease, hypertension, bipolar disorder, rheumatoid arthritis and Crohn's disease). For each disease, the case samples have been ascertained from sites widely distributed across Great Britain, allowing us to obtain considerable efficiencies by comparing each of these case populations to a common set of 3,000 nationally-ascertained controls also from England, Scotland and Wales. These controls come from two sources: 1,500 are representative samples from the 1958 British Birth Cohort and 1,500 are blood donors recruited by the three national UK Blood Services. One of the questions that the WTCCC study has addressed relates to the relative merits of these alternative strategies for the generation of representative population cohorts. Genotyping for this main Case Control study was conducted by Affymetrix using the (commercial) Affymetrix 500K chip. As part of this study a total of 17,000 samples were typed for 500,000 SNPs. There are two additional components to the study. First, the WTCCC award is part-funding a study of host resistance to infectious diseases in African populations. The same approach has been used to type 2,000 cases of tuberculosis (TB) and 2,000 cases of malaria, as well as 2,000 shared controls. As well as addressing diseases of major global significance, and extending WTCCC coverage into the area of infectious disease, the inclusion of samples of African origin has obvious benefits with respect to methodological aspects of genome-wide association analysis. Second, the WTCCC has, for four additional diseases (autoimmune thyroid disease, breast cancer, ankylosing spondylitis, multiple sclerosis), completed an analysis of 15,000 SNPs designed to represent a large proportion of the known non-synonymous coding SNPs across the genome. This analysis has been performed at the WTSI using a custom Infinium chip (Illumina). Data release The genotypic data of the control samples (1958 British Birth Cohort and UK Blood Service) and from seven diseases analyzed in the main study are now available to qualified researchers. Summary genotype statistics for these collections are available directly from the website. Access to the individual-level genotype data and summary genotype statistics is by application to the Consortium Data Access Committee (CDAC) and approval subject to a Data Access Agreement. WTCCC2: A further round of GWA studies were funded in April 2008. These include 15 WTCCC-collaborative studies and 12 independent studies be supported totaling approximately 120,000 samples. Many of the studies represent major international collaborative networks that have together assembled large sample collections. WTCCC2 will perform genome-wide association studies in 13 disease conditions: Ankylosing spondylitis, Barrett's oesophagus and oesophageal adenocarcinoma, glaucoma, ischaemic stroke, multiple sclerosis, pre-eclampsia, Parkinson's disease, psychosis endophenotypes, psoriasis, schizophrenia, ulcerative colitis and visceral leishmaniasis. WTCCC2 will also investigate the genetics of reading and mathematics abilities in children and the pharmacogenomics of statin response. Over 60,000 samples will be analyzed using either the Affymetrix v6.0 chip or the Illumina 660K chip. The WTCCC2 will also genotype 3,000 controls each from the 1958 British Birth cohort and the UK Blood Service control group, and the 6,000 controls will be genotyped on both the Affymetrix v6.0 and Illumina 1.2M chips. WTCCC3: The Wellcome Trust has provided support for a further round of GWA studies in January 2009. These include 5 WTCCC-collaborative studies to be carried out in WTCCC3 and 5 independent studies, across a range of diseases. Many of the studies represent major international collaborative networks that have together assembled large sample collections. WTCCC3 will perform genome-wide association studies in the following 4 disease conditions: primary biliary cirrhosis, anorexia nervosa, pre-eclampsia in UK subjects, and the interactions between donor and recipient DNA related to early and late renal transplant dysfunction. The WTCCC3 will also carry out a pilot in a study of the genetics of host control of HIV-1 infection. Over 40,000 samples will be analyzed using the Illumina 660K chip. The WTCCC3 will utilize the 6,000 control genotypes generated by the WTCCC2.
Proper citation: Wellcome Trust Case Control Consortium (RRID:SCR_001973) Copy
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