title: Physical map of a 1.5 mb region on 12p11.2 harbouring a synpolydactyly associated chromosomal breakpoint.
abstract: Synpolydactyly (SPD) is a rare malformation of the distal limbs known to be caused by mutations in HOXD13. We have previously described a complex form of SPD associated with synostoses in three members of a Belgian family, which co-segregates with a t(12;22)(p11.2;q13.3) chromosomal translocation. The chromosome 12 breakpoint of this translocation maps to 12p11.2 between markers D12S1034 and D12S1596. Here we show that a mutation in the HOXD13 gene is not responsible for the phenotype, and present a physical map of the region around the 12p11.2 breakpoint. Starting from D12S1034 and D12S1596, we have established a contig approximately 1.5 Mb in length, containing 13 YAC clones, 16 BAC clones, and 11 cosmid clones. FISH analysis shows that cosmid LL12NCO1-149H4 maps across the breakpoint, and Southern blot experiments using fragments of this cosmid as probes identify a rearranged BamHI fragment in the patients carrying the translocation. A search for expressed sequences within the contig have so far revealed one CpG island, seven anonymous ESTs and three previously characterised genes, DAD-R, KRAG and HT21, all of which were found not to be directly disrupted by the translocation. The gene represented by EST R72964 was found to be disrupted by the translocation. These findings lay the groundwork for further efforts to characterise a gene critical for normal distal limb development that is perturbed by this translocation.
authors.affiliation: Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Debeer
authors.forename: E F
authors.initials: EF
authors.lastname: Schoenmakers
authors.forename: R
authors.initials: R
authors.lastname: Thoelen
authors.forename: M
authors.initials: M
authors.lastname: Holvoet
authors.forename: T
authors.initials: T
authors.lastname: Kuittinen
authors.forename: G
authors.initials: G
authors.lastname: Fabry
authors.forename: J P
authors.initials: JP
authors.lastname: Fryns
authors.forename: F R
authors.initials: FR
authors.lastname: Goodman
authors.forename: W J
authors.initials: WJ
authors.lastname: Van de Ven
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins; D019457:Chromosome Breakage; D022202:Chromosomes, Artificial, Bacterial; D018244:Chromosomes, Artificial, Yeast; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D020451:Contig Mapping; D017931:DNA Primers / Q000737:chemistry; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D005820:Genetic Testing; D015698:Genomic Library; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins; D010375:Pedigree; D020161:Physical Chromosome Mapping; D017689:Polydactyly / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011544:Pseudogenes; D012097:Repressor Proteins / Q000235:genetics; D016324:Sequence Tagged Sites; D013576:Syndactyly / Q000235:genetics*; D013580:Synostosis / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; C409423:DAD1P1 protein, human; D017931:DNA Primers; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C109646:SSPN protein, human; C491632:Sspn protein, mouse; D014157:Transcription Factors