title: Physical map of the chromosome 6q22 region containing the oculodentodigital dysplasia locus: analysis of thirteen candidate genes and identification of novel ESTs and DNA polymorphisms.
abstract: Oculodentodigital dysplasia (ODDD) is an autosomal dominant condition with congenital anomalies of the craniofacial and limb regions and neurodegeneration. Genetic anticipation for the dysmorphic and neurologic features has been inferred in a few families. Our previous linkage studies have refined the ODDD candidate region to chromosome 6q22-->q23. In an attempt to clone the ODDD gene, we created a yeast artificial chromosome contig with 31 redundant clones spanning the region and identified and ordered candidate genes and markers. Fluorescent IN SITU hybridization mapped two of these YAC clones to chromosome 6q22.2 telomeric to a known 6q21 fragile site, excluding it as a possible cause of the suggested anticipation. We performed mutation analysis on thirteen candidate genes - GRIK2, HDAC2, COL10A1, PTD013, KPNA5, PIST, ROS1, BRD7, PLN, HSF2, PKIB, FABP7, and HEY2. Although no mutations were found, we identified 44 polymorphisms, including 28 single nucleotide polymorphisms. Direct cDNA selection was performed and fifty-five clones were found to contain sequences that were not previously reported as known genes or ESTs. These clones and polymorphisms will assist in the further characterization of this region and identification of disease genes.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Boyadjiev
authors.forename: A B
authors.initials: AB
authors.lastname: Chowdry
authors.forename: R E
authors.initials: RE
authors.lastname: Shapiro
authors.forename: W A
authors.initials: WA
authors.lastname: Paznekas
authors.forename: A E
authors.initials: AE
authors.lastname: Wandstrat
authors.forename: J W
authors.initials: JW
authors.lastname: Choi
authors.forename: L
authors.initials: L
authors.lastname: Kasch
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Wollnik
authors.forename: C E
authors.initials: CE
authors.lastname: Burgess
authors.forename: M
authors.initials: M
authors.lastname: Schalling
authors.forename: M
authors.initials: M
authors.lastname: Lovett
authors.forename: E W
authors.initials: EW
authors.lastname: Jabs
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics; D002896:Chromosomes, Human, Pair 6; D004247:DNA / Q000235:genetics*; D017931:DNA Primers; D020224:Expressed Sequence Tags; D005124:Eye Abnormalities / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009410:Nerve Degeneration / Q000235:genetics; D018126:Odontodysplasia / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D011506:Proteins; D004247:DNA