title: Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.
abstract: BACKGROUND
  One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3 (orthologous to Vav3 in Idd18).
  
  
  RESULTS
  Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls.
  
  
  CONCLUSIONS
  None of the candidate regions showed evidence of association with type 1 diabetes (P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, UK. lisa.maier@cimr.cam.ac.uk
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Maier
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Felicity
authors.initials: F
authors.lastname: Payne
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pask
authors.forename: Christopher
authors.initials: C
authors.lastname: Lowe
authors.forename: John
authors.initials: J
authors.lastname: Hulme
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Smink
authors.forename: Heather
authors.initials: H
authors.lastname: Fraser
authors.forename: Carolyn
authors.initials: C
authors.lastname: Moule
authors.forename: Kara M
authors.initials: KM
authors.lastname: Hunter
authors.forename: Giselle
authors.initials: G
authors.lastname: Chamberlain
authors.forename: Neil
authors.initials: N
authors.lastname: Walker
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
authors.forename: Kjersti S
authors.initials: KS
authors.lastname: Rønningen
authors.forename: Cristian
authors.initials: C
authors.lastname: Guja
authors.forename: Constantin
authors.initials: C
authors.lastname: Ionescu-Tîrgoviste
authors.forename: David A
authors.initials: DA
authors.lastname: Savage
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Laurence B
authors.initials: LB
authors.lastname: Peterson
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wicker
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Twells
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005192:Family Health; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D020506:Untranslated Regions / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D020506:Untranslated Regions
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D544-9
references.pmid: 15608258
references.citation: J Med Genet. 1999 Apr;36(4):295-9
references.pmid: 10227396
references.citation: J Med Genet. 2000 Feb;37(2):150-2
references.pmid: 10712108
references.citation: Genome Res. 2000 Apr;10(4):446-53
references.pmid: 10779485
references.citation: Arthritis Rheum. 2000 Jun;43(6):1397-404
references.pmid: 10857800
references.citation: Immunity. 2000 Jul;13(1):107-15
references.pmid: 10933399
references.citation: Genome Res. 2001 Jul;11(7):1262-8
references.pmid: 11435409
references.citation: Am J Hum Genet. 2001 Oct;69(4):820-30
references.pmid: 11507694
references.citation: Curr Dir Autoimmun. 2001;4:31-67
references.pmid: 11569409
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11533-8
references.pmid: 11572996
references.citation: Nat Genet. 2001 Oct;29(2):233-7
references.pmid: 11586306
references.citation: Diabetes. 2001 Nov;50(11):2633-7
references.pmid: 11679445
references.citation: Nucleic Acids Res. 2002 Jun 15;30(12):e53
references.pmid: 12060691
references.citation: Genome Res. 2002 Jul;12(7):1029-39
references.pmid: 12097339
references.citation: Nat Genet. 2002 Aug;31(4):391-4
references.pmid: 12118252
references.citation: Diabetes. 2003 Jun;52(6):1551-6
references.pmid: 12765969
references.citation: Nature. 2003 May 29;423(6939):506-11
references.pmid: 12724780
references.citation: Hum Hered. 2003;56(1-3):18-31
references.pmid: 14614235
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Diabetes. 2004 Apr;53(4):1158-61
references.pmid: 15047635
references.citation: Genes Immun. 2004 Jun;5(4):301-5
references.pmid: 15029236
references.citation: J Immunol. 2004 Jul 1;173(1):164-73
references.pmid: 15210771
references.citation: Science. 2004 Aug 6;305(5685):869-72
references.pmid: 15297675
references.citation: J Exp Med. 1981 Oct 1;154(4):1237-42
references.pmid: 7026724
references.citation: Nature. 1987 Oct 15-21;329(6140):599-604
references.pmid: 3309680
references.citation: Nat Genet. 1992 Sep;2(1):56-60
references.pmid: 1303251
references.citation: Am J Hum Genet. 1993 Sep;53(3):702-14
references.pmid: 8352278
references.citation: Annu Rev Immunol. 1995;13:179-200
references.pmid: 7612220
references.citation: J Immunol. 1998 Feb 1;160(3):1472-8
references.pmid: 9570569
references.citation: Diabetes. 1998 Nov;47(11):1797-9
references.pmid: 9792551
references.citation: Hum Genomics. 2004 Jan;1(2):98-109
references.pmid: 15601538