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

Gabrielle S. Sellick, Emily L. Webb, Ruth Allinson, Estella Matutes, Martin J S Dyer, Viggo Jønsson, Anton W. Langerak, Francesca R. Mauro, Stephen Fuller, James Wiley, Matthew Lyttelton, Vincenzo Callea, Martin Yuille, Daniel Catovsky, Richard S. Houlston

    Research output: Contribution to journalArticlepeer-review

    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
    Original languageEnglish
    Pages (from-to)420-429
    Number of pages9
    JournalAmerican Journal of Human Genetics
    Volume77
    Issue number3
    DOIs
    Publication statusPublished - Sept 2005

    Keywords

    • epidemiology
    • Europe
    • Genetic Predisposition to Disease
    • genetics
    • Genome,Human
    • Humans
    • Leukemia,Lymphocytic,Chronic,B-Cell
    • Linkage (Genetics)
    • Lod Score
    • Lymphoproliferative Disorders
    • methods
    • Models,Genetic
    • Pedigree
    • Polymorphism,Single Nucleotide

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