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Investigation of the HIN200 Locus in UK SLE Families Identifies Novel Copy Number Variants
Author(s) -
Fernando Michelle M. A.,
de Smith Adam J.,
Coin Lachlan,
Morris David L.,
Froguel Philippe,
Mangion Jonathan,
Blakemore Alexandra I. F.,
Graham Robert R.,
Behrens Timothy W.,
Vyse Timothy J.
Publication year - 2011
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2011.00641.x
Subject(s) - locus (genetics) , single nucleotide polymorphism , genetics , biology , copy number variation , international hapmap project , genome wide association study , candidate gene , snp , genetic association , disease , gene , genotype , medicine , genome
Summary We undertook a candidate locus study of the HIN200 gene cluster on 1q21‐23 in UK systemic lupus erythematosus (SLE) families. To date, despite mounting evidence demonstrating the importance of these proteins in autoimmune disease, cancer, apoptosis, inflammation, and cell cycle arrest, there has been a dearth of data with respect to the genetic characterisation of the HIN200 locus in SLE or any other disease. We typed 83 single nucleotide polymorphisms (SNPs) across 317 kb of the HIN200 cluster in 428 UK SLE families and sought replication from a European‐American lupus cohort. We do not find strong evidence of SNP association in either cohort. Interestingly, we do observe a trend for association with certain HIN200 SNPs and serologic subphenotypes in UK SLE that parallels the association of lupus antibodies with the orthologous murine locus. Furthermore, we find the HIN200 locus to be unexpectedly complex in terms of genetic structural organisation. We have identified a number of copy number variants (CNVs) in this region in healthy French males, HapMap samples, and UK SLE families. In summary, candidate interferon signalling genes show evidence of common CNV in human SLE and healthy subjects. The impact of these CNVs in health and disease remains to be determined.