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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 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 Citation Map 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 Neoplasia Genomics Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia Gabrielle S. Sellick1, Lynn R. Goldin2, Ruth W. Wild1, Susan L. Slager3, Laura Ressenti4, Sara S. Strom5, Martin J. S. Dyer6, Francesca R. Mauro7, Gerald E. Marti8, Stephen Fuller9, Matthew Lyttelton10, Thomas J. Kipps11, Michael J. Keating12, Timothy G. Call13, Daniel Catovsky14, Neil Caporaso2, and Richard S. Houlston1 1 Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom; 2 Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; 3 Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN; 4 Moores Cancer Center, University of California, San Diego; 5 Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston; 6 Medical Research Council (MRC) Toxicology Unit, Leicester University, Leicester, United Kingdom; 7 Division of Hematology, Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Rome, Italy; 8 Flow and Image Cytometry Section, Divisions of Cell and Gene Therapies, Center for Biologics Research and Evaluation, Food and Drug Administration, Bethesda, MD; 9 Department of Medicine, Sydney University, Nepean Hospital, Penrith, Australia; 10 Kettering General Hospital, Kettering, United Kingdom; 11 Division of Hematology/Oncology, Moores Cancer Center, University of California, San Diego; 12 Division of Hematology, University of Texas M. D. Anderson Cancer Center, Houston; 13 Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN; 14 Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom 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 nonparametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P = .001) 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 higher than 2.1 (P < .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: 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]

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