title: Linkage-disequilibrium mapping without genotyping.
abstract: Genomic mismatch scanning (GMS) is a technique that enriches for regions of identity by descent (IBD) between two individuals without the need for genotyping or sequencing. Regions of IBD selected by GMS are mapped by hybridization to a microarray containing ordered clones of genomic DNA from chromosomes of interest. Here we demonstrate the feasibility and efficacy of this form of linkage-mapping, using congenital hyperinsulinism (HI), an autosomal recessive disease, whose relatively high frequency in Ashkenazi Jews suggests a founder effect. The gene responsible (SUR1) encodes the sulfonylurea receptor, which maps to chromosome 11p15.1. We show that the combination of GMS and hybridization of IBD products to a chromosome-11 microarray correctly maps the HI gene to a 2-Mb region, thereby demonstrating linkage-disequilibrium mapping without genotyping.
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA. vcheung@mail.med.upenn.edu
authors.forename: V G
authors.initials: VG
authors.lastname: Cheung
authors.forename: J P
authors.initials: JP
authors.lastname: Gregg
authors.forename: K J
authors.initials: KJ
authors.lastname: Gogolin-Ewens
authors.forename: J
authors.initials: J
authors.lastname: Bandong
authors.forename: C A
authors.initials: CA
authors.lastname: Stanley
authors.forename: L
authors.initials: L
authors.lastname: Baker
authors.forename: M J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: N J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: T B
authors.initials: TB
authors.lastname: Shows
authors.forename: W J
authors.initials: WJ
authors.lastname: Ewens
authors.forename: S F
authors.initials: SF
authors.lastname: Nelson
authors.forename: R S
authors.initials: RS
authors.lastname: Spielman
mesh_terms: D018528:ATP-Binding Cassette Transporters; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D002880:Chromosomes, Human, Pair 11; D018703:Founder Effect; D005821:Genetic Techniques; D006801:Humans; D006946:Hyperinsulinism / Q000208:ethnology / Q000235:genetics*; D017403:In Situ Hybridization / Q000379:methods; D015810:Linkage Disequilibrium; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors
chemical_list: C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors