Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus

Robert R. Graham; Ward A. Ortmann; Carl D. Langefeld; Damini Jawaheer; Scott A. Selby; Peter R. Rodine; Emily Baechler Gillespie; Kristine E. Rohlf; Katherine B. Shark; Karl J. Espe; Linda E. Green; Rajan P. Nair; Philip E. Stuart; James T. Elder; Richard A. King; Kathy L. Moser; Patrick M. Gaffney; Teodorica L. Bugawan; Henry A. Erlich; Stephen S. Rich; Peter K. Gregersen; Timothy W. Behrens

doi:10.1086/342290

Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus

Robert R. Graham, Ward A. Ortmann, Carl D. Langefeld, Damini Jawaheer, Scott A. Selby, Peter R. Rodine, Emily Baechler Gillespie, Kristine E. Rohlf, Katherine B. Shark, Karl J. Espe, Linda E. Green, Rajan P. Nair, Philip E. Stuart, James T. Elder, Richard A. King, Kathy L. Moser, Patrick M. Gaffney, Teodorica L. Bugawan, Henry A. Erlich, Stephen S. RichPeter K. Gregersen, Timothy W. Behrens

Medicine - Rheumatic and Autoimmune

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Abstract

Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB1*1501/DQB1*0602, DRB1*0801/DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an-500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.

Original language	English (US)
Pages (from-to)	543-553
Number of pages	11
Journal	American Journal of Human Genetics
Volume	71
Issue number	3
DOIs	https://doi.org/10.1086/342290
State	Published - 2002

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Graham, R. R., Ortmann, W. A., Langefeld, C. D., Jawaheer, D., Selby, S. A., Rodine, P. R., Baechler Gillespie, E., Rohlf, K. E., Shark, K. B., Espe, K. J., Green, L. E., Nair, R. P., Stuart, P. E., Elder, J. T., King, R. A., Moser, K. L., Gaffney, P. M., Bugawan, T. L., Erlich, H. A., ... Behrens, T. W. (2002). Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus. American Journal of Human Genetics, 71(3), 543-553. https://doi.org/10.1086/342290

Graham, RR, Ortmann, WA, Langefeld, CD, Jawaheer, D, Selby, SA, Rodine, PR, Baechler Gillespie, E, Rohlf, KE, Shark, KB, Espe, KJ, Green, LE, Nair, RP, Stuart, PE, Elder, JT, King, RA, Moser, KL, Gaffney, PM, Bugawan, TL, Erlich, HA, Rich, SS, Gregersen, PK & Behrens, TW 2002, 'Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus', American Journal of Human Genetics, vol. 71, no. 3, pp. 543-553. https://doi.org/10.1086/342290

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title = "Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus",

abstract = "Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB1*1501/DQB1*0602, DRB1*0801/DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an-500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.",

author = "Graham, {Robert R.} and Ortmann, {Ward A.} and Langefeld, {Carl D.} and Damini Jawaheer and Selby, {Scott A.} and Rodine, {Peter R.} and {Baechler Gillespie}, Emily and Rohlf, {Kristine E.} and Shark, {Katherine B.} and Espe, {Karl J.} and Green, {Linda E.} and Nair, {Rajan P.} and Stuart, {Philip E.} and Elder, {James T.} and King, {Richard A.} and Moser, {Kathy L.} and Gaffney, {Patrick M.} and Bugawan, {Teodorica L.} and Erlich, {Henry A.} and Rich, {Stephen S.} and Gregersen, {Peter K.} and Behrens, {Timothy W.}",

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AU - Jawaheer, Damini

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AU - Rodine, Peter R.

AU - Baechler Gillespie, Emily

AU - Rohlf, Kristine E.

AU - Shark, Katherine B.

AU - Espe, Karl J.

AU - Green, Linda E.

AU - Nair, Rajan P.

AU - Stuart, Philip E.

AU - Elder, James T.

AU - King, Richard A.

AU - Moser, Kathy L.

AU - Gaffney, Patrick M.

AU - Bugawan, Teodorica L.

AU - Erlich, Henry A.

AU - Rich, Stephen S.

AU - Gregersen, Peter K.

AU - Behrens, Timothy W.

PY - 2002

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N2 - Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB1*1501/DQB1*0602, DRB1*0801/DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an-500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.

AB - Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB1*1501/DQB1*0602, DRB1*0801/DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an-500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.

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Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus

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