Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus

Robert R. Graham; Carl D. Langefeld; Patrick M. Gaffney; Ward A. Ortmann; Scott A. Selby; Emily C. Baechler; Katherine B. Shark; Theresa C. Ockenden; Kristine E. Rohlf; Kathleen L. Moser; William M. Brown; Sherine E. Gabriel; Ronald P. Messner; Richard A. King; Pavel Horak; James T. Elder; Philip E. Stuart; Steven S. Rich; Timothy W. Behrens

doi:10.1186/ar319

Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus

Robert R. Graham, Carl D. Langefeld, Patrick M. Gaffney, Ward A. Ortmann, Scott A. Selby, Emily C. Baechler, Katherine B. Shark, Theresa C. Ockenden, Kristine E. Rohlf, Kathleen L. Moser, William M. Brown, Sherine E. Gabriel, Ronald P. Messner, Richard A. King, Pavel Horak, James T. Elder, Philip E. Stuart, Steven S. Rich, Timothy W. Behrens

Quantitative Health Sciences

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

39 Scopus citations

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.

Original language	English (US)
Pages (from-to)	299-305
Number of pages	7
Journal	Arthritis Research
Volume	3
Issue number	5
DOIs	https://doi.org/10.1186/ar319
State	Published - 2001

Keywords

1q41
Autoimmunity
Linkage
Systemic lupus erythematosus
Transmission disequilibrium

ASJC Scopus subject areas

Rheumatology

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10.1186/ar319

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Graham, R. R., Langefeld, C. D., Gaffney, P. M., Ortmann, W. A., Selby, S. A., Baechler, E. C., Shark, K. B., Ockenden, T. C., Rohlf, K. E., Moser, K. L., Brown, W. M., Gabriel, S. E., Messner, R. P., King, R. A., Horak, P., Elder, J. T., Stuart, P. E., Rich, S. S., & Behrens, T. W. (2001). Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus. Arthritis Research, 3(5), 299-305. https://doi.org/10.1186/ar319

Graham, RR, Langefeld, CD, Gaffney, PM, Ortmann, WA, Selby, SA, Baechler, EC, Shark, KB, Ockenden, TC, Rohlf, KE, Moser, KL, Brown, WM, Gabriel, SE, Messner, RP, King, RA, Horak, P, Elder, JT, Stuart, PE, Rich, SS & Behrens, TW 2001, 'Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus', Arthritis Research, vol. 3, no. 5, pp. 299-305. https://doi.org/10.1186/ar319

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title = "Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus",

abstract = "Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.",

keywords = "1q41, Autoimmunity, Linkage, Systemic lupus erythematosus, Transmission disequilibrium",

author = "Graham, {Robert R.} and Langefeld, {Carl D.} and Gaffney, {Patrick M.} and Ortmann, {Ward A.} and Selby, {Scott A.} and Baechler, {Emily C.} and Shark, {Katherine B.} and Ockenden, {Theresa C.} and Rohlf, {Kristine E.} and Moser, {Kathleen L.} and Brown, {William M.} and Gabriel, {Sherine E.} and Messner, {Ronald P.} and King, {Richard A.} and Pavel Horak and Elder, {James T.} and Stuart, {Philip E.} and Rich, {Steven S.} and Behrens, {Timothy W.}",

year = "2001",

doi = "10.1186/ar319",

language = "English (US)",

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T1 - Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus

AU - Graham, Robert R.

AU - Langefeld, Carl D.

AU - Gaffney, Patrick M.

AU - Ortmann, Ward A.

AU - Selby, Scott A.

AU - Baechler, Emily C.

AU - Shark, Katherine B.

AU - Ockenden, Theresa C.

AU - Rohlf, Kristine E.

AU - Moser, Kathleen L.

AU - Brown, William M.

AU - Gabriel, Sherine E.

AU - Messner, Ronald P.

AU - King, Richard A.

AU - Horak, Pavel

AU - Elder, James T.

AU - Stuart, Philip E.

AU - Rich, Steven S.

AU - Behrens, Timothy W.

PY - 2001

Y1 - 2001

N2 - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.

AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.

KW - 1q41

KW - Autoimmunity

KW - Linkage

KW - Systemic lupus erythematosus

KW - Transmission disequilibrium

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JO - Arthritis Research

JF - Arthritis Research

IS - 5

ER -

Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus

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