Showing papers by "Simon G. Gregory published in 2006"
Broad Institute1, University of Oxford2, Wellcome Trust Sanger Institute3, Wellcome Trust Centre for Human Genetics4, Utrecht University5, Science Applications International Corporation6, Illumina7, Duke University8, Brigham and Women's Hospital9, University of Cambridge10, Harvard University11, Imperial College London12, Université de Montréal13, Montreal Heart Institute14
TL;DR: The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
Abstract: The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
780 citations
TL;DR: The finished sequence and biological annotation of human chromosome 1 is reported, which reveals patterns of sequence variation that reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident.
Abstract: The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
249 citations
TL;DR: Using 1Mb‐spaced genome‐wide BAC arrays, the most significantly different genomic changes between favourable histology tumours that did not relapse, and did not, subsequently relapse were gains on 1q, and novel deletions at 12q24 and 18q21, respectively.
Abstract: Array CGH profiling of favourable histology Wilms tumours reveals novel gains and losses associated with relapse Despite the excellent survival of Wilms tumour patients treated with multimodality therapy, approximately 15% will suffer from tumour relapse, where response rates are markedly reduced. We have carried out microarray-based comparative genomic hybridisation on a series of 76 Wilms tumour samples, enriched for cases which recurred, to identify changes in DNA copy number associated with clinical outcome. Using 1Mb-spaced genome-wide BAC arrays, the most significantly different genomic changes between favourable histology tumours that did (n = 37), and did not (n = 39), subsequently relapse were gains on 1q, and novel deletions at 12q24 and 18q21. Further relapse-associated loci included losses at lq32.1, 2q36.3-2q37.1, and gain at 13q31. 1q gains correlated strongly with loss of 1p and/or 16q. In 3 of 11 cases with concurrent 1p(-)/1q(+), a breakpoint was identified at 1p13. Multiple low-level sub-megabase gains along the length of 1q were identified using chromosome 1 tiling-path arrays. One such recurrent region at 1q22-q23.1 included candidate genes RAB25, NES, CRABP2, HDGF and NTRK1, which were screened for mRNA expression using quantitative RT-PCR. These data provide a high-resolution catalogue of genomic copy number changes in relapsing favourable histology Wilms tumours. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
124 citations
TL;DR: This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is based on a two-step process, not a single step, like in the previous version of this paper.
Abstract: Nature 441, 315–321 (2006) We inadvertently omitted the names of the following authors: R. Banerjee, S. P. Bryant, D. C. Burford, W. D. H. Burrill, S. M. Clegg, P. Dhami, O. Dovey, L. M. Faulkner, S. M. Gribble, C. F. Langford, R. D. Pandian, K. M. Porter and E. Prigmore.
107 citations
TL;DR: A highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways is used to explore gene–gene interactions and disease susceptibility in a well-characterized African-American case–control MS data set, and the multifactor dimensionality reduction (MDR) test is applied to detect epistasis.
Abstract: Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans
61 citations
TL;DR: The overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma.
Abstract: Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17
28 citations
Journal Article•
18 citations
TL;DR: 1q44 is particularly interesting because of linkage evidence for this region in studies of both rheumatoid arthritis and systemic lupus erythematosus, and a peak LOD* score of 2.99 for the 1q44 region is identified and the linkage peak is substantially narrowed.
Abstract: Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage to chromosome 1q44
18 citations
TL;DR: The analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.
Abstract: Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1,540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene PVRL2. Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.
14 citations
Patent•
10 Nov 2006
TL;DR: In this article, the authors proposed a method for identifying an individual who has an altered risk for developing coronary artery disease (CAD) and then reducing the likelihood that a subject will develop CAD using reagents, nucleic acids and kits comprising nucleic acid containing a polymorphism in a CAD-determinative gene.
Abstract: The invention relates to predicting, or aiding in predicting, which individuals are at risk of developing coronary artery disease The invention provides a method for identifying an individual who has an altered risk for developing CAD The invention further relates to methods of reducing the likelihood that a subject will develop CAD The invention further provides reagents, nucleic acids and kits comprising nucleic acids containing a polymorphism in a CAD-determinative gene
9 citations
Journal Article•
Patent•
10 Nov 2006
TL;DR: The authors concerne egalement des methodes permettant de reduire la probabilite qu'un sujet developpe une coronaropathie, e.g., des reactifs, des acides nucleiques and des trousses comprenant des acide nucleiques contenant un polymorphisme dans un gene lie a la coronaropathy.
Abstract: L'invention concerne un moyen permettant de predire, ou d'aider a predire, quels sont les individus risquant de developper une coronaropathie. L'invention concerne plus precisement une methode permettant d'identifier un individu presentant un risque modifie de developper une coronaropathie. L'invention concerne egalement des methodes permettant de reduire la probabilite qu'un sujet developpe une coronaropathie. L'invention concerne egalement des reactifs, des acides nucleiques et des trousses comprenant des acides nucleiques contenant un polymorphisme dans un gene lie a la coronaropathie.