title: Fine-scale mapping of the 6p25.3 chronic lymphocytic leukaemia susceptibility locus.
abstract: A recent genome-wide association study of chronic lymphocytic leukaemia (CLL) has identified a susceptibility locus on 6p25.3 associated with a modest but highly significant increase in CLL risk. Using a set of single nucleotide polymorphism (SNP) markers, we generated a fine-scale map and narrowed the association signal to a 18 kb DNA segment within the 3'-untranslated region (UTR) of the IRF4 (interferon regulatory factor 4) gene. Resequencing this segment in European subjects identified 55 common polymorphisms, including 13 highly correlated candidate causal variants. In a large case-control study, it was shown that all but four variants could be excluded with 95% confidence. These four SNPs map to a 3 kb region of the 3'-UTR of IRF4, consistent with the causal basis of the association being mediated through differential IRF4 expression.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Dalemari
authors.initials: D
authors.lastname: Crowther-Swanepoel
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Yussanne
authors.initials: Y
authors.lastname: Ma
authors.forename: Lindsay
authors.initials: L
authors.lastname: Robertson
authors.forename: Alan M
authors.initials: AM
authors.lastname: Pittman
authors.forename: Amy
authors.initials: A
authors.lastname: Price
authors.forename: Philip
authors.initials: P
authors.lastname: Twiss
authors.forename: Jayaram
authors.initials: J
authors.lastname: Vijayakrishnan
authors.forename: Mobshra
authors.initials: M
authors.lastname: Qureshi
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Claire
authors.initials: C
authors.lastname: Dearden
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D014589:Utah; D044465:White People / Q000235:genetics; D000099218:Interferon Regulatory Factor-4
chemical_list: D020413:3' Untranslated Regions; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4