A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci

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

doi:10.1086/444472

A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci

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

Research output: Contribution to journal › Article › peer-review

Abstract

Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) show clear evidence of familial aggregation, but the inherited basis is largely unknown. To identify a susceptibility gene for CLL, we conducted a genomewide linkage analysis of 115 pedigrees, using a high-density single-nucleotide polymorphism (SNP) array containing 11,560 markers. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. Our results confirm that the presence of high linkage disequilibrium (LD) between SNP markers can lead to inflated nonparametric linkage (NPL) and LOD scores. After the removal of high-LD SNPs, we obtained a maximum NPL of 3.14 (P = .0008) on chromosome 11p11. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under both dominant (HLOD 1.95) and recessive (HLOD 2.78) models. In addition, four other chromosomal positions (5q22-23, 6p22, 10q25, and 14q32) displayed HLOD scores >1.15 (which corresponds to a nominal P value

Original language	English
Pages (from-to)	420-429
Number of pages	9
Journal	American Journal of Human Genetics
Volume	77
Issue number	3
DOIs	https://doi.org/10.1086/444472
Publication status	Published - Sept 2005

Keywords

epidemiology
Europe
Genetic Predisposition to Disease
genetics
Genome,Human
Humans
Leukemia,Lymphocytic,Chronic,B-Cell
Linkage (Genetics)
Lod Score
Lymphoproliferative Disorders
methods
Models,Genetic
Pedigree
Polymorphism,Single Nucleotide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/444472

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Sellick, G. S., Webb, E. L., Allinson, R., Matutes, E., Dyer, M. J. S., Jønsson, V., Langerak, A. W., Mauro, F. R., Fuller, S., Wiley, J., Lyttelton, M., Callea, V., Yuille, M., Catovsky, D., & Houlston, R. S. (2005). A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci. American Journal of Human Genetics, 77(3), 420-429. https://doi.org/10.1086/444472

@article{f6a9e83fe6c3453a8ff491198978d75d,

title = "A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci",

abstract = "Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) show clear evidence of familial aggregation, but the inherited basis is largely unknown. To identify a susceptibility gene for CLL, we conducted a genomewide linkage analysis of 115 pedigrees, using a high-density single-nucleotide polymorphism (SNP) array containing 11,560 markers. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. Our results confirm that the presence of high linkage disequilibrium (LD) between SNP markers can lead to inflated nonparametric linkage (NPL) and LOD scores. After the removal of high-LD SNPs, we obtained a maximum NPL of 3.14 (P = .0008) on chromosome 11p11. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under both dominant (HLOD 1.95) and recessive (HLOD 2.78) models. In addition, four other chromosomal positions (5q22-23, 6p22, 10q25, and 14q32) displayed HLOD scores >1.15 (which corresponds to a nominal P value",

keywords = "epidemiology, Europe, Genetic Predisposition to Disease, genetics, Genome,Human, Humans, Leukemia,Lymphocytic,Chronic,B-Cell, Linkage (Genetics), Lod Score, Lymphoproliferative Disorders, methods, Models,Genetic, Pedigree, Polymorphism,Single Nucleotide",

author = "Sellick, {Gabrielle S.} and Webb, {Emily L.} and Ruth Allinson and Estella Matutes and Dyer, {Martin J S} and Viggo J{\o}nsson and Langerak, {Anton W.} and Mauro, {Francesca R.} and Stephen Fuller and James Wiley and Matthew Lyttelton and Vincenzo Callea and Martin Yuille and Daniel Catovsky and Houlston, {Richard S.}",

note = "DA - 20050804IS - 0002-9297 (Print)LA - engPT - Comparative StudyPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tSB - IM",

year = "2005",

month = sep,

doi = "10.1086/444472",

language = "English",

volume = "77",

pages = "420--429",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

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Sellick, GS, Webb, EL, Allinson, R, Matutes, E, Dyer, MJS, Jønsson, V, Langerak, AW, Mauro, FR, Fuller, S, Wiley, J, Lyttelton, M, Callea, V, Yuille, M, Catovsky, D & Houlston, RS 2005, 'A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci', American Journal of Human Genetics, vol. 77, no. 3, pp. 420-429. https://doi.org/10.1086/444472

TY - JOUR

T1 - A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci

AU - Sellick, Gabrielle S.

AU - Webb, Emily L.

AU - Allinson, Ruth

AU - Matutes, Estella

AU - Dyer, Martin J S

AU - Jønsson, Viggo

AU - Langerak, Anton W.

AU - Mauro, Francesca R.

AU - Fuller, Stephen

AU - Wiley, James

AU - Lyttelton, Matthew

AU - Callea, Vincenzo

AU - Yuille, Martin

AU - Catovsky, Daniel

AU - Houlston, Richard S.

N1 - DA - 20050804IS - 0002-9297 (Print)LA - engPT - Comparative StudyPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tSB - IM

PY - 2005/9

Y1 - 2005/9

N2 - Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) show clear evidence of familial aggregation, but the inherited basis is largely unknown. To identify a susceptibility gene for CLL, we conducted a genomewide linkage analysis of 115 pedigrees, using a high-density single-nucleotide polymorphism (SNP) array containing 11,560 markers. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. Our results confirm that the presence of high linkage disequilibrium (LD) between SNP markers can lead to inflated nonparametric linkage (NPL) and LOD scores. After the removal of high-LD SNPs, we obtained a maximum NPL of 3.14 (P = .0008) on chromosome 11p11. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under both dominant (HLOD 1.95) and recessive (HLOD 2.78) models. In addition, four other chromosomal positions (5q22-23, 6p22, 10q25, and 14q32) displayed HLOD scores >1.15 (which corresponds to a nominal P value

AB - Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) show clear evidence of familial aggregation, but the inherited basis is largely unknown. To identify a susceptibility gene for CLL, we conducted a genomewide linkage analysis of 115 pedigrees, using a high-density single-nucleotide polymorphism (SNP) array containing 11,560 markers. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. Our results confirm that the presence of high linkage disequilibrium (LD) between SNP markers can lead to inflated nonparametric linkage (NPL) and LOD scores. After the removal of high-LD SNPs, we obtained a maximum NPL of 3.14 (P = .0008) on chromosome 11p11. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under both dominant (HLOD 1.95) and recessive (HLOD 2.78) models. In addition, four other chromosomal positions (5q22-23, 6p22, 10q25, and 14q32) displayed HLOD scores >1.15 (which corresponds to a nominal P value

KW - epidemiology

KW - Europe

KW - Genetic Predisposition to Disease

KW - genetics

KW - Genome,Human

KW - Humans

KW - Leukemia,Lymphocytic,Chronic,B-Cell

KW - Linkage (Genetics)

KW - Lod Score

KW - Lymphoproliferative Disorders

KW - methods

KW - Models,Genetic

KW - Pedigree

KW - Polymorphism,Single Nucleotide

U2 - 10.1086/444472

DO - 10.1086/444472

M3 - Article

SN - 0002-9297

VL - 77

SP - 420

EP - 429

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 3

ER -

A high-density SNP genomewide linkage scan for chronic lymphocytic leukemia-susceptibility loci

Abstract

Keywords

UN SDGs

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