Analysis of a large multi-generational family provides insight into the genetics of chronic lymphocytic leukemia.
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.
Fuller
Stephen J
SJ
Department of Medicine, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia. sfuller@med.usyd.edu.au
Papaemmanuil
Elli
E
McKinnon
Leah
L
Webb
Emily
E
Sellick
Gabrielle S
GS
Dao-Ung
Lan-Phuong
LP
Skarratt
Kristen K
KK
Crowther
Dalemari
D
Houlston
Richard S
RS
Wiley
James S
JS
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
D007143:Immunoglobulin Heavy Chains