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Mapping Susceptibility Gene in Systemic Lupus Erythematosus

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Autoimmunity

Part of the book series: Methods in Molecular Biology ((MIMB,volume 900))

Abstract

Genome-wide association studies have identified many dozen genetic intervals that harbor single-nucleotide polymorphisms (SNPs) showing statistical association with systemic lupus erythematosus. Despite the wealth of data produced, there are limitations of these studies. The causal alleles at a given locus are not identified; only SNP is strong linkage disequilibrium with the putative causative alleles. In order to address identification of the causative SNPs for lupus susceptibility genes, we have initiated a candidate gene study for which more than 40 investigators have contributed patient and control samples. In addition, these investigators have designated SNPs to be placed on a custom array. In this way fine mapping of genetic association findings can occur in order to identify causal alleles. These efforts have thus far benefitted greatly from comparisons of different ethnicities. Work on about ten previously identified associations has been published using this resource. Genome-wide association studies cannot identify rare SNPs or mutations, which may impart greater relative risks than common variants. Much of the genetics of lupus may be from rare variants or mutations. In order to approach this aspect of lupus genetics, next-generation sequencing has begun in which all exons will be sequenced in controls and patients. This effort can also be used to identify causal alleles from association intervals not yet otherwise identified.

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Authors and Affiliations

  1. Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

    R. Hal Scofield & Kenneth M. Kaufman

  2. Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    R. Hal Scofield & Kenneth M. Kaufman

  3. Department of Veterans Affairs Medical Center, Oklahoma City, OK, USA

    R. Hal Scofield & Kenneth M. Kaufman

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  1. R. Hal Scofield
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  2. Kenneth M. Kaufman
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Correspondence to R. Hal Scofield .

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Editors and Affiliations

  1. College of Medicine, Division of Rheumatology, State University of New York, UMU, East Adams St. 750, Syracuse, 13210, New York, USA

    Andras Perl

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Scofield, R.H., Kaufman, K.M. (2012). Mapping Susceptibility Gene in Systemic Lupus Erythematosus. In: Perl, A. (eds) Autoimmunity. Methods in Molecular Biology, vol 900. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-720-4_2

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  • DOI: https://doi.org/10.1007/978-1-60761-720-4_2

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  • Publisher Name: Humana Press, Totowa, NJ

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