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In recent years, technology to investigate association of genetic variants with common phenotypes has advanced at an impressive rate. A decade ago, a typical screen of the human genome for predisposing variations consisted of interrogation of a few hundred markers, followed by a search for weak linkage statistics. Thanks to the discovery of millions of single nucleotide polymorphisms (SNPs) and technological advances facilitating the testing of hundreds of thousands or millions of SNPs in parallel, scientists have been blessed with a wave of data under which many are drowning.
While technological advances have resulted in the identification of many susceptibility loci, many unforeseen and under-appreciated problems have taken center stage. For example, it is now common knowledge that segments of DNA tend to be transmitted in conserved blocks and that these blocks differ somewhat between races. This genomic structure can be both confounding and helpful. Also, many common phenotypes exhibit considerable genetic heterogeneity, further blurring an already fuzzy picture. Finally, interaction effects between loci can confer considerable risk, even when the participating variants have little or no influence over phenotypic state by themselves.
I am developing novel methods to better understand and detect associations between genetic variants and phenotypes. Of particular interest to me is the problem of epistatic interaction. My hope is to make use of other sources of information such as gene interaction networks to formulate association hypotheses in a semi-supervised framework. Such a reduced search space consisting of only biologically derived associations to test will facilitate the discovery of new effects by reducing computational complexity and preserving statistical significance typically lost through multiple testing.
Kilpatrick JR, Nakhleh LK. Classifying and evaluating methods for detecting multi-locus genotype-phenotype association. Submitted.
Kilpatrick JR, Nakhleh. SimGE: a tool to simulate genotypes in epistasis. In Preparation.
Chamberlain SA, Kilpatrick JR, Holland JN. Do extrafloral nectar resources, species abundances, and body sizes contribute to the structure of ant-plant mutualistic networks? To appear in Oecologia.
Harley ITW, Niewold TB, Stormont RM, Kaufman KM, Glenn SB, Franek BS, Kelly JA, Kilpatrick JR, Hutchings D, Divers J, Bruner GR, Edberg JC, McGwin G, Petri M, Ramsey-Goldman R, Reveille JD, Vila L, Merrill JT, Gilkeson GS, Vyse TJ, Alarcón-Riquelme ME, Jacob CO, Alarcón GS, Moser KL, Gaffney PM, Kimberly RP, Bae S-C, Langefeld CD, Harley JB, Guthridge JM, James JA. The role of genetic variation near interferon-κ in systemic lupus erythematosus. To appear in Journal of Biomedicine and Biotechnology.
Gu Y, Harley ITW, Henderson LB, Aronow BJ, Vietor I, Huber LA, Harley JB, Kilpatrick JR, Langefeld CD, Williams AH, Jegga AG, Chen J, Wills-Karp M, Arshad SH, Ewart SL, Thio CL, Flick LM, Filippi M, Grimes HL, Drumm ML, Cutting GR, Knowles MR, Karp CL. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature 2009 Apr 458 (7241): 1039-42.
Kelly JA, Kelley JM, Kaufman KM, Kilpatrick JR, et al. Interferon Regulatory Factor 5 (IRF5) is Genetically Associated with Systemic Lupus Erythematosus in African-Americans. Genes Immun. 2008 Apr 9; 9(3).
Sawalha A, Kaufman K, Kelly J, Adler A, Aberle T, Kilpatrick J, et al. Genetic association of IL-21 polymorphisms with systemic lupus erythematosus. Ann Rheum Dis. 2008 Apr; 67(4).
Namjou B, Kilpatrick J, Harley, J. Genetics of clinical expression of SLE. Autoimmunity. 2007 Dec; 40(8).
Namjou B, Kelly JA, Kilpatrick J, et al. Linkage at 5q14.3-15 in multiplex systemic lupus erythematosus pedigrees stratified by autoimmune thyroid disease. Arthritis Rheum. 2005 Aug; 52(11).
Nath SK, Kilpatrick J, Harley JB. Genetics of human systemic lupus erythematosus: the emerging picture. Curr Opin Immunol. 2004 Dec; 16(6). Review.
Nath SK, Namjou B. Garriott CP, Frank S, Joslin PA, Kilpatrick J, et al. Linkage analysis of SLE susceptibility: confirmation of SLER1 at 5p15.3. Genes Immun. 2004 May 5(3).
Namjou B, Kaufman KM, Kilpatrick J, et al. Genetic linkage and association at 1q23 in SLE: from animal models to human genetics: research on the induction and pathogenicity of autoantibodies. Report on the 7th Dresden Symposium on Autoantibodies. 2004.
Nath SK, Quintero-Del-Rio AI, Kilpatrick J, et al. Linkage at 12q24 with systemic lupus erythematosus (SLE) is established and confirmed in Hispanic and European American families. Am J Hum Genet. 2004 Jan;74(1).
Nath SK, Namjou B, Kilpatrick J, et al. A candidate region on 11p13 for systemic lupus erythematosus: a linkage identified in African-American families. J Investig Dermatol Symp Proc. 2004 Jan;9(1).
Scofield RH, Bruner GR, Kelly JA, Kilpatrick J, et al. Thrombocytopenia identifies a severe familial phenotype of systemic lupus erythematosus and reveals genetic linkages at 1q22 and 11p13. Blood. 2003 Feb 1;101(3).
Namjou B, Nath SK, Kilpatrick J, et al. Stratification of pedigrees multiplex for systemic lupus erythematosus and for self-reported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p15.3. Arthritis Rheum. 2002 Nov;46(11).
Quintero-Del-Rio AI, Kelly JA, Kilpatrick J, et al. The genetics of systemic lupus erythematosus stratified by renal disease: linkage at 10q22.3 (SLEN1), 2q34-35 (SLEN2), and 11p15.6 (SLEN3). Genes Immun. 2002 Oct;3 Suppl 1.
Namjou B, Nath SK, Kilpatrick J, et al. Genome scan stratified by the presence of anti- double-stranded DNA (dsDNA) autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE) establishes linkages at 19p13.2 (SLED1) and 18q21.1 (SLED2). Genes Immun. 2002 Oct;3 Suppl 1.
Sawalha AH, Namjou B, Nath SK, Kilpatrick J, et al. Genetic linkage of systemic lupus erythematosus with chromosome 11q14 (SLEH1) in African- American families stratified by a nucleolar antinuclear antibody pattern. Genes Immun. 2002 Oct;3 Suppl 1.
Kelly JA, Thompson K, Kilpatrick J, et al. Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemia. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18).
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