title: Analysis of a large multi-generational family provides insight into the genetics of chronic lymphocytic leukemia.
abstract: We report the genetic analysis of a large multi-generational family composed of 144 individuals in which 11 members have been diagnosed with chronic lymphocytic leukaemia (CLL). The observation of a significant over-representation of monoclonal B-cell lymphocytosis (MBL) in unaffected family members strongly supports MBL being a surrogate marker of carrier status. A genome-wide linkage scan of the family using high-density 10K single nucleotide polymorphisms provided no significant evidence for a single gene model of disease susceptibility, inviting speculation that susceptibility to CLL has a more complex basis. The absence of a correlation in IGHV usage between affected family members does however argue strongly against exposure to a single super-antigen in disease development.
authors.affiliation: Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia. sfuller@med.usyd.edu.au
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fuller
authors.forename: Elli
authors.initials: E
authors.lastname: Papaemmanuil
authors.forename: Leah
authors.initials: L
authors.lastname: McKinnon
authors.forename: Emily
authors.initials: E
authors.lastname: Webb
authors.forename: Gabrielle S
authors.initials: GS
authors.lastname: Sellick
authors.forename: Lan-Phuong
authors.initials: LP
authors.lastname: Dao-Ung
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Skarratt
authors.forename: Dalemari
authors.initials: D
authors.lastname: Crowther
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis / Q000379:methods; D005190:Family; D005434:Flow Cytometry; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology; D008218:Lymphocytosis / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D007143:Immunoglobulin Heavy Chains