A genome scan of 18 families with chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) accounts for about 30% of all leukaemias and is most prevalent in older individuals. Significant familial aggregation has been demonstrated but the mode of inheritance is unknown. Recurrent cytogenetic abnormalities are frequently found in CLL tumour cells but no susceptibility genes have been confirmed. We have collected clinical data and biospecimens on families ascertained for having at least two living patients with CLL. The current study included DNA samples from 94 individuals (38 affected patients) in 18 families. We have carried out a genome scan using the ABI 28-panel medium density linkage mapping set (average spacing of 10 cM and average heterozygosity of 80%). Genotypes for 359 markers were scored. Multipoint limit of detection (lod) scores were calculated, assuming both dominant and recessive inheritance and allowing for increased penetrance with age and genetic heterogeneity. Non-parametric linkage scores were also calculated. Lod scores of 1.0 or greater were found on regions of chromosomes 1, 3, 6, 12, 13 and 17, but none of these loci achieved statistical significance. Four of these six regions (6q, 13q, 12 and 17p) coincide with areas where cytogenetic abnormalities are frequently observed in CLL tumour cells and are, therefore, strong candidate regions for containing germ line changes.
Goldin
Lynn R
LR
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH, 6120 Executive Boulevard, Room 7008, MSC 7236, Bethesda, MD 20892-7236, USA. goldinl@mail.nih.gov
Ishibe
Naoko
N
Sgambati
Maria
M
Marti
Gerald E
GE
Fontaine
Laura
L
Lee
Maxwell P
MP
Kelley
Jenny M
JM
Scherpbier
Titia
T
Buetow
Kenneth H
KH
Caporaso
Neil E
NE
D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree