SEARCH:   Advanced

Blood, 1 November 2007, Vol. 110, No. 9, pp. 3326-3333. Prepublished online as a Blood First Edition Paper on August 8, 2007; DOI 10.1182/blood-2007-05-091561. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-091561v1 110/9/3326    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sellick, G. S. Articles by Houlston, R. S. Search for Related Content PubMed PubMed Citation Articles by Sellick, G. S. Articles by Houlston, R. S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 21, 2007 Accepted August 4, 2007 A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia Gabrielle S. Sellick, Lynn R. Goldin, Ruth W. Wild, Susan L. Slager, Laura Ressenti, Sara S. Strom, Martin J .S. Dyer, Francesca R. Mauro, Gerald E. Marti, Stephen Fuller, Matthew Lyttelton, Thomas J. Kipps, Michael J. Keating, Timothy G. Call, Daniel Catovsky, Neil Caporaso, and Richard S. Houlston* Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom Genetic Epidemiology Branch, Division of Cancer Epidemiology, National Cancer Institute, Bethesda, MD, United States Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, United States Moores Cancer Center, University of California, San Diego, CA, United States Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States MRC Toxicology Unit, Leicester University, Leicester, United Kingdom Divisionof Hematology, Dipartimento di Biotecnologie Cellulari ed Emotologia, Universita "La Sapienza", Rome, Italy Divisions of Cell and Gene Therapies, Flow and Image Cytometry Section, Center for Bioloics research and Evaluation, FDA, Bethesda, MD, United States Department of Medicine, Sydney University, Nepean Hospital, Penrith, NSW, Australia Department of Medicine, Kettering General Hospital, Kettering, United Kingdom Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego, CA, United States Division of Hematology, University of Texas M. D. Anderson Cancer Center, Houston, TX, United States Division of Hematology, Department of Medicine, Mayo Clinc College of Medicine, Rochester, MN, United States Section of Hemato-Oncology, Institute of Cancer Research, Sutton, Surrey, United Kingdom * Corresponding author; email: richard.houlston{at}icr.ac.uk. Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs we obtained a maximum NPL of 3.02 (P= 1.3 x 10-3) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD = 3.11; P= 7.7 x 10-5) which was significant at the genome-wide level. In addition, 2 other chromosomal positions 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1 displayed HLOD scores >2.1 (P < 0.002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Advances in genome-wide CLL linkage Stephan M. Tanner and John C. Byrd Blood 2007 110: 3094-3095. [Full Text] [PDF] This article has been cited by other articles: D. Crowther-Swanepoel, M. Qureshi, M. J. S. Dyer, E. Matutes, C. Dearden, D. Catovsky, and R. S. Houlston Genetic variation in CXCR4 and risk of chronic lymphocytic leukemia Blood, November 26, 2009; 114(23): 4843 - 4846. [Abstract] [Full Text] [PDF] S. Y. Kristinsson, L. R. Goldin, M. Bjorkholm, J. Koshiol, I. Turesson, and O. Landgren Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies Haematologica, November 1, 2009; 94(11): 1581 - 1589. [Abstract] [Full Text] [PDF] D. Crowther-Swanepoel and R. S. Houlston The molecular basis of familial chronic lymphocytic leukemia Haematologica, May 1, 2009; 94(5): 606 - 609. [Full Text] [PDF] L. R. Goldin, M. Bjorkholm, S. Y. Kristinsson, I. Turesson, and O. Landgren Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia Haematologica, May 1, 2009; 94(5): 647 - 653. [Abstract] [Full Text] [PDF] A. Enjuanes, Y. Benavente, F. Bosch, I. Martin-Guerrero, D. Colomer, S. Perez-Alvarez, O. Reina, M. T. Ardanaz, P. Jares, A. Garcia-Orad, et al. Genetic Variants in Apoptosis and Immunoregulation-Related Genes Are Associated with Risk of Chronic Lymphocytic Leukemia Cancer Res., December 15, 2008; 68(24): 10178 - 10186. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020