title: Localization of the homolog of a mouse craniofacial mutant to human chromosome 18q11 and evaluation of linkage to human CLP and CPO.
abstract: The transgene-induced mutation 9257 and the spontaneous mutation twirler cause craniofacial and inner ear malformations and are located on mouse chromosome 18 near the ataxia locus ax. To map the human homolog of 9257, a probe from the transgene insertion site was used to screen a human genomic library. Analysis of a cross-hybridizing human clone identified a 3-kb conserved sequence block that does not appear to contain protein coding sequence. Analysis of somatic cell hybrid panels assigned the human locus to 18q11. The polymorphic microsatellite markers D18S1001 and D18S1002 were isolated from the human locus and mapped by linkage analysis using the CEPH pedigrees. The 9257 locus maps close to the centromeres of human chromosome 18q and mouse chromosome 18 at the proximal end of a conserved linkage group. To evaluate the role of this locus in human craniofacial disorders, linkage to D18S1002 was tested in 11 families with autosomal dominant nonsyndromic cleft lip and palate and 3 families with autosomal dominant cleft palate only. Obligatory recombinants were observed in 8 of the families, and negative lod scores from the other families indicated that these disorders are not linked to the chromosome 18 loci.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: D L
authors.initials: DL
authors.lastname: Burgess
authors.forename: D C
authors.initials: DC
authors.lastname: Kohrman
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Blaschak
authors.forename: S H
authors.initials: SH
authors.lastname: Blanton
authors.forename: M
authors.initials: M
authors.lastname: Boehnke
authors.forename: J T
authors.initials: JT
authors.lastname: Hecht
authors.forename: J
authors.initials: J
authors.lastname: Overhauser
authors.forename: M H
authors.initials: MH
authors.lastname: Meisler
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D017124:Conserved Sequence; D017931:DNA Primers; D004276:DNA, Satellite; D005145:Face / Q000002:abnormalities*; D005787:Gene Frequency; D015723:Gene Library; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012886:Skull / Q000002:abnormalities*
chemical_list: D017931:DNA Primers; D004276:DNA, Satellite; D005819:Genetic Markers