Please use this identifier to cite or link to this item:
Title: A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia.
Authors: Sellick, Gabrielle S.
Goldin, Lynn R.
Wild, Ruth W.
Slager, Susan L.
Ressenti, Laura
Strom, Sara S.
Dyer, Martin J. S.
Mauro, Francesca R.
Marti, Gerald E.
Fuller, Stephen
Lyttelton, Matthew
Kipps, Thomas J.
Keating, Michael J.
Call, Timothy G.
Catovsky, Daniel
Caporaso, Neil
Houlston, Richard S.
First Published: 8-Aug-2007
Publisher: American Society of Hematology
Citation: Blood, 2007, 110 (9), pp. 3326-3333.
Abstract: 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.
DOI Link: 10.1182/blood-2007-05-091561
ISSN: 0006-4971
Type: Article
Rights: This is the author's final draft of the paper published as Blood, 2007, 110 (9), pp. 3326-3333. Copyright © 2007 American Society of Hematology. This material is posted here with permission of the American Society of Hematology. The final version is available from Doi: 10.1182/blood-2007-05-091561
Appears in Collections:Published Articles, MRC Toxicology Unit

Files in This Item:
File Description SizeFormat 
SNPs in CLL.pdf347.74 kBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.