A High-Density SNP Genomewide Linkage Scan for Chronic Lymphocytic Leukemia–Susceptibility Loci

Sellick, Gabrielle S.; Webb, Emily L.; Allinson, Ruth; Matutes, Estella; Dyer, Martin J. S.; Jønsson, Viggo; Langerak, Anton W.; Mauro, Francesca Romana; Fuller, Stephen J.; Wiley, James S.; Lyttelton, Matthew; Callea, Vincenzo; Yuille, Martin; Catovsky, Daniel; Houlston, Richard S.

doi:10.1086/444472

Cited by 62 publications

(59 citation statements)

References 32 publications

(38 reference statements)

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“…65 We observed 18 chromosomal regions attaining an NPL score X2.0 when LD was ignored, and 16 of these regions resulted in NPL scores X2.0 when LD was considered. We found that our methodology for eliminating high-LD SNPs was consistent and actually more conservative than that used by Sellick et al, 64 who also used a 10K SNP panel for study of a complex disease. We observed a median intermarker distance of 0.344 Mb (25th and 75th percentile 0.156-0.709 Mb) after elimination of high-LD SNPs, and Sellick et al 64 observed a median intermarker distance of 0.17 Mb (25th-75th percentile 0.06-0.38) after removal of high-LD SNPs by selecting a single SNP from clusters of SNPs with an r 2 > 0.4.…”

Section: Discussionmentioning

confidence: 54%

“…We found that our methodology for eliminating high-LD SNPs was consistent and actually more conservative than that used by Sellick et al, 64 who also used a 10K SNP panel for study of a complex disease. We observed a median intermarker distance of 0.344 Mb (25th and 75th percentile 0.156-0.709 Mb) after elimination of high-LD SNPs, and Sellick et al 64 observed a median intermarker distance of 0.17 Mb (25th-75th percentile 0.06-0.38) after removal of high-LD SNPs by selecting a single SNP from clusters of SNPs with an r 2 > 0.4. It is possible that LD may still have influenced our results, and it is also possible that we may have missed other potentially interesting regions by not assessing LD on the complete genome.…”

Section: Discussionmentioning

confidence: 54%

“…The majority of previous studies that have examined the effect of LD on linkage analyses have found an inflation of both NPL and LOD scores, 46,63,64 although a single study observed a slight decrease in NPL scores in the presence of LD. 65 We observed 18 chromosomal regions attaining an NPL score X2.0 when LD was ignored, and 16 of these regions resulted in NPL scores X2.0 when LD was considered.…”

Section: Discussionmentioning

confidence: 98%

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A high-density SNP genome-wide linkage scan in a large autism extended pedigree

et al. 2008

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We performed a high-density, single nucleotide polymorphism (SNP), genome-wide scan on a six-generation pedigree from Utah with seven affected males, diagnosed with autism spectrum disorder. Using a two-stage linkage design, we first performed a nonparametric analysis on the entire genome using a 10K SNP chip to identify potential regions of interest. To confirm potentially interesting regions, we eliminated SNPs in high linkage disequilibrium (LD) using a principal components analysis (PCA) method and repeated the linkage results. Three regions met genome-wide significance criteria after controlling for LD: 3q13.2-q13.31 (nonparametric linkage (NPL), 5.58), 3q26.31-q27.3 (NPL, 4.85) and 20q11.21-q13.12 (NPL, 5.56). Two regions met suggestive criteria for significance 7p14.1-p11.22 (NPL, 3.18) and 9p24.3 (NPL, 3.44). All five chromosomal regions are consistent with other published findings. Haplotype sharing results showed that five of the affected subjects shared more than a single chromosomal region of interest with other affected subjects. Although no common autism susceptibility genes were found for all seven autism cases, these results suggest that multiple genetic loci within these regions may contribute to the autism phenotype in this family, and further followup of these chromosomal regions is warranted.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 98%

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A high-density SNP genome-wide linkage scan in a large autism extended pedigree

et al. 2008

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“…Intriguingly, a recent SNP linkage analysis of familial chronic lymphocytic leukemia (CLL) provides evidence for linkage at 11p12, overlapping with the linkage peak reported here for RA. 54 Perhaps this indicates the involvement of common B cell genes in these disorders. Notably, CLL is often accompanied by the presence of autoantibodies, and current views of B-CLL pathogenesis invoke B cell autoreactivity as contributing to tumor development.…”

Section: Discussionmentioning

confidence: 97%

High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33

et al. 2006

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We have completed a genome wide linkage scan using 45700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD416), regions with LOD42.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.

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“…In the case of lymphomas, a family history of any hematopoietic malignancy was found to be associated with 2-3 fold increased risk of NHL [6,7]. Genome-wide linkage scans of CLL families revealed a number of chromosome bands with potential candidate genes, for example, 11p11 [8] and 13q22.1 [9]. The role and function of these candidate regions are under investigation now.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in xenobiotic‐metabolizing genes and the risk of chronic lymphocytic leukemia and non‐Hodgkin's lymphoma in adult Russian patients

et al. 2007

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Polymorphisms in genes coding xenobiotic-metabolizing enzymes are considered as risk factors modifying susceptibility to cancer. We developed a biochip for the analysis of 18 mutations in 10 genes of metabolizing system: CYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19, and NAT2. Using allele-specific hybridization on the biochip 76 T-cell non-Hodgkin's lymphoma (NHL) patients, 83 B-cell chronic lymphocytic leukemia (B-CLL) patients, and 177 healthy donors were tested. Polymorphic CYP1A1 alleles were more frequent in B-CLL patients relative to normal controls, for example, a combination of polymorphic variants 4887C > A, 4889A > G, and 6235T > C (OR 5 1.76, 95% CI 5 1.0-3.1). The GSTM1 null genotype was more frequent in NHL patients relative to controls (OR 5 1.82, 95% CI 5 1.1-3.1). The combination of unfavorable polymorphic CYP1A1 variants and GSTM1 null genotype was found more frequently in B-CLL patients relative to controls (OR 5 2.52, 95% CI 5 1.3-4.9). In addition, male B-CLL patients demonstrated a significantly increased occurrence of heterozygous and homozygous allele *2 of CYP2C9 gene (OR 5 2.38, 95% CI 5 1.1-5.2) as well as a combination of alleles *2 and *3 of the gene (OR 5 2.09, 95% CI 5 1.1-3.9). Thus, our findings show the association between polymorphic alleles of CYP1A1, GSTM1, and CYP2C9 genes and the risk to develop NHL or B-CLL. The developed biochip can be considered as a convenient analytical tool for research studies and predictive analysis in oncohematology. Am. J. Hematol. 83:279-287, 2008. V

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A High-Density SNP Genomewide Linkage Scan for Chronic Lymphocytic Leukemia–Susceptibility Loci

Cited by 62 publications

References 32 publications

A high-density SNP genome-wide linkage scan in a large autism extended pedigree

A high-density SNP genome-wide linkage scan in a large autism extended pedigree

High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33

Polymorphisms in xenobiotic‐metabolizing genes and the risk of chronic lymphocytic leukemia and non‐Hodgkin's lymphoma in adult Russian patients

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