title: Linkage and association with type 1 diabetes on chromosome 1q42.
abstract: Type 1 diabetes is a complex disorder with multiple genetic loci and environmental factors contributing to disease etiology. In the current study, a human type 1 diabetes candidate region on chromosome 1q42 was mapped at high marker density in a panel of 616 multiplex type 1 diabetic families. To facilitate the identification and evaluation of candidate genes, a physical map of the 7-cM region surrounding the maximum logarithm of odds (LOD) score (2.46, P = 0.0004) was constructed. Genes were identified in the 500-kb region surrounding the marker yielding the peak LOD score and evaluated for polymorphism by resequencing. Single-nucleotide polymorphisms (SNPs) identified in these genes as well as other anonymous markers were tested for allelic association with type 1 diabetes by both family-based and case-control methods. A haplotype formed by common alleles at three adjacent markers (D1S225, D1S2383, and D1S251) was preferentially transmitted to affected offspring in type 1 diabetic families (nominal P = 0.006). These findings extend the evidence supporting the existence of a type 1 diabetes susceptibility locus on chromosome 1q42 and identify a candidate region amenable to positional cloning efforts.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Ewens
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Johnson
authors.forename: Beth
authors.initials: B
authors.lastname: Wapelhorst
authors.forename: Kristin
authors.initials: K
authors.lastname: O'Brien
authors.forename: Sarah
authors.initials: S
authors.lastname: Gutin
authors.forename: V Anne
authors.initials: VA
authors.lastname: Morrison
authors.forename: Craig
authors.initials: C
authors.lastname: Street
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.forename: Richard S
authors.initials: RS
authors.lastname: Spielman
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
mesh_terms: D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004798:Enzymes / Q000235:genetics; D005190:Family; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D011506:Proteins / Q000235:genetics
chemical_list: D004798:Enzymes; D005819:Genetic Markers; D011506:Proteins