title: A preliminary gene map for the Van der Woude syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41.
abstract: Van der Woude syndrome (VWS) is a common form of syndromic cleft lip and palate and accounts for approximately 2% of all cleft lip and palate cases. Distinguishing characteristics include cleft lip with or without cleft palate, isolated cleft palate, bilateral lip pits, hypodontia, normal intelligence, and an autosomal-dominant mode of transmission with a high degree of penetrance. Previously, the VWS locus was mapped to a 1.6-cM region in 1q32-q41 between D1S491 and D1S205, and a 4.4-Mb contig of YAC clones of this region was constructed. In the current investigation, gene-based and anonymous STSs were developed from the existing physical map and were then used to construct a contig of sequence-ready bacterial clones across the entire VWS critical region. All STSs and BAC clones were shared with the Sanger Centre, which developed a contig of PAC clones over the same region. A subset of 11 clones from both contigs was selected for high-throughput sequence analysis across the approximately 1.1-Mb region; all but two of these clones have been sequenced completely. Over 900 kb of genomic sequence, including the 350-kb VWS critical region, were analyzed and revealed novel polymorphisms, including an 8-kb deletion/insertion, and revealed 4 known genes, 11 novel genes, 9 putative genes, and 3 psuedogenes. The positional candidates LAMB3, G0S2, HIRF6, and HSD11 were excluded as the VWS gene by mutation analysis. A preliminary gene map for the VWS critical region is as follows: [see text] 41-TEL. The data provided here will help lead to the identification of the VWS gene, and this study provides a model for how laboratories that have a regional interest in the human genome can contribute to the sequencing efforts of the entire human genome.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242 USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Schutte
authors.forename: B C
authors.initials: BC
authors.lastname: Bjork
authors.forename: K B
authors.initials: KB
authors.lastname: Coppage
authors.forename: M I
authors.initials: MI
authors.lastname: Malik
authors.forename: S G
authors.initials: SG
authors.lastname: Gregory
authors.forename: D J
authors.initials: DJ
authors.lastname: Scott
authors.forename: L M
authors.initials: LM
authors.lastname: Brentzell
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M J
authors.initials: MJ
authors.lastname: Dixon
authors.forename: J C
authors.initials: JC
authors.lastname: Murray
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics*; D020451:Contig Mapping; D003560:Cysts / Q000235:genetics*; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D006801:Humans; D008046:Lip; D051379:Mice; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic / Q000235:genetics*; D051381:Rats; D013577:Syndrome
chemical_list: D004269:DNA, Bacterial