title: Investigation of the HIN200 locus in UK SLE families identifies novel copy number variants.
abstract: 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.
authors.affiliation: Division of Genetics and Molecular Medicine and Division of Immunology, Infection and Inflammatory Disease, King's College London, UK.
authors.forename: Michelle M A
authors.initials: MM
authors.lastname: Fernando
authors.forename: Adam J
authors.initials: AJ
authors.lastname: de Smith
authors.forename: Lachlan
authors.initials: L
authors.lastname: Coin
authors.forename: David L
authors.initials: DL
authors.lastname: Morris
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mangion
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Robert R
authors.initials: RR
authors.lastname: Graham
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
mesh_terms: D002878:Chromosomes, Human, Pair 1; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom
chemical_list: C101635:HIN-200 protein, human; D009687:Nuclear Proteins