title: Generation of a 3-Mb PAC contig spanning the Miyoshi myopathy/limb-girdle muscular dystrophy (MM/LGMD2B) locus on chromosome 2p13.
abstract: Miyoshi myopathy (MM) and limb-girdle muscular dystrophy subtype 2B (LGMD2B) map to the same region on chromosome 2p13. To facilitate the cloning of the defective gene causing these two diseases, we used a combination of chromosome walking and expressed sequence tag (EST) screening and identified 864 P1-derived artificial chromosomes (PACs) whose inserts map to the MM/LGMD2B candidate region and surrounding areas. Among them, 139 are from a chromosome 2-specific PAC library and 725 are from a total genomic PAC library. A 3-Mb contig spanning the candidate region for MM/LGMD2B was assembled. This contig contains 200 PACs, 10 known genetic markers, 5 new polymorphic markers, 57 sequence tagged sites (STSs) generated from PAC end fragments, and 4 random STSs. In addition, we mapped 24 ESTs to this contig and excluded 37 ESTs from the contig, thus eliminating them as candidate MM/LGMD2B genes. The high-resolution, sequence-ready PAC contig for the MM/LGMD2B region provides a backbone for the identification of the disease gene(s) and for clarification of the relationship between the two diseases.
authors.affiliation: Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Charlestown 02129, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Bossie
authors.forename: K
authors.initials: K
authors.lastname: Bejaoui
authors.forename: B A
authors.initials: BA
authors.lastname: Hosler
authors.forename: J C
authors.initials: JC
authors.lastname: Gingrich
authors.forename: M
authors.initials: M
authors.lastname: Ben Hamida
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.forename: E
authors.initials: E
authors.lastname: Schurr
authors.forename: P J
authors.initials: PJ
authors.lastname: de Jong
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D002889:Chromosomes, Human, Pair 2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009136:Muscular Dystrophies / Q000235:genetics*