A genome scan of 18 families with chronic lymphocytic leukaemia
- 3 June 2003
- journal article
- research article
- Published by Wiley in British Journal of Haematology
- Vol. 121 (6), 866-873
- https://doi.org/10.1046/j.1365-2141.2003.04372.x
Abstract
Summary. 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.Keywords
This publication has 22 references indexed in Scilit:
- ATM mutations and protein expression are not associated with familial B-CLL casesLeukemia Research, 2003
- Clinical Characteristics of Familial B-CLL in the National Cancer Institute Familial RegistryLeukemia & Lymphoma, 2001
- Genomic Aberrations and Survival in Chronic Lymphocytic LeukemiaNew England Journal of Medicine, 2000
- Increased risk of lymphoproliferative disorders in relatives of patients withB‐cell chronic lymphocytic leukemia: relevance of the degree of familial linkageEuropean Journal of Haematology, 2000
- Linkage analysis for ATM in familial B cell chronic lymphocytic leukaemiaLeukemia, 1999
- Direct Power Comparisons between Simple LOD Scores and NPL Scores for Linkage Analysis in Complex DiseasesAmerican Journal of Human Genetics, 1999
- Anticipation in Familial Chronic Lymphocytic LeukemiaAmerican Journal of Human Genetics, 1999
- Allele-Sharing Models: LOD Scores and Accurate Linkage TestsAmerican Journal of Human Genetics, 1997
- Genetic dissection of complex traits: guidelines for interpreting and reporting linkage resultsNature Genetics, 1995
- Chronic lymphocytic leukaemia: case control epidemiological study in YorkshireBritish Journal of Cancer, 1987