A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci.


Sellick, GS; Webb, EL; Allinson, R; Matutes, E; Dyer, MJ; Jonsson, V; Langerak, AW; Mauro, FR; Fuller, S; Wiley, J; Lyttelton, M; Callea, V; Yuille, M; Catovsky, D; Houlston, RS; (2005) A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci. American journal of human genetics, 77 (3). pp. 420-9. ISSN 0002-9297 DOI: https://doi.org/10.1086/444472

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Abstract

Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) show clear evidence of familial aggregation, but the inherited basis is largely unknown. To identify a susceptibility gene for CLL, we conducted a genomewide linkage analysis of 115 pedigrees, using a high-density single-nucleotide polymorphism (SNP) array containing 11,560 markers. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. Our results confirm that the presence of high linkage disequilibrium (LD) between SNP markers can lead to inflated nonparametric linkage (NPL) and LOD scores. After the removal of high-LD SNPs, we obtained a maximum NPL of 3.14 (P=.0008) on chromosome 11p11. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under both dominant (HLOD 1.95) and recessive (HLOD 2.78) models. In addition, four other chromosomal positions (5q22-23, 6p22, 10q25, and 14q32) displayed HLOD scores >1.15 (which corresponds to a nominal P value <.01). None of the regions coincided with areas of common chromosomal abnormalities frequently observed for CLL. These findings strengthen the argument for an inherited predisposition to CLL and related B-cell LPDs.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 16080117
Web of Science ID: 231314100008
URI: http://researchonline.lshtm.ac.uk/id/eprint/2421

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