title: Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig.
abstract: Cerebral cavernous malformations (CCM) are vascular lesions present in some 20 million people worldwide that are responsible for seizures, migraine, hemorrhage, and other neurologic problems. Familial cases ofCCM can be inherited as an autosomal dominant disorder with variable expression. A gene for CCM (CCM/)was recently mapped to a 33-cM segment of chromosome 7q in a large Hispanic family (Dubovsky et al.1995). Here, the collection of several new short tandem repeat polymorphisms (STRPs) within the region of interest on 7q and the refinement of the marker order in this region using both linkage analysis in CEPH families and especially YAC-based STS content mapping are described. Affected members of three Hispanic families share allele haplotypes indicating a common ancestral mutation within these families. Using the shared haplotype information along with analysis of crossovers in affected individuals from both the Hispanic and Caucasian families, the region likely to contain the CCMI gene has been reduced to a 4-cM segment of 7q between D7S2410 and D7S689. All markers within the refined chromosomal segment were located on a single YAC contig estimated to be approximately 2 Mb in size. Four potential candidate genes have been mapped to this region.
authors: Center for Medical Genetics, Marshfield Medical Research Foundation, Wisconsin 54449, USA. johnsone@mfldclin.edu
authors: E W
authors: EW
authors: Johnson
authors: L M
authors: LM
authors: Iyer
authors: S S
authors: SS
authors: Rich
authors: H T
authors: HT
authors: Orr
authors: A
authors: A
authors: Gil-Nagel
authors: J H
authors: JH
authors: Kurth
authors: J M
authors: JM
authors: Zabramski
authors: D A
authors: DA
authors: Marchuk
authors: J
authors: J
authors: Weissenbach
authors: C L
authors: CL
authors: Clericuzio
authors: L E
authors: LE
authors: Davis
authors: B L
authors: BL
authors: Hart
authors: J F
authors: JF
authors: Gusella
authors: B E
authors: BE
authors: Kosofsky
authors: D N
authors: DN
authors: Louis
authors: L A
authors: LA
authors: Morrison
authors: E D
authors: ED
authors: Green
authors: J L
authors: JL
authors: Weber
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D015698:Genomic Library; D006239:Haplotypes / Q000235:genetics; D006392:Hemangioma, Cavernous / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D017931:DNA Primers; D005819:Genetic Markers