Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb: sequencing does not identify the causative gene.
Tylosis (focal non-epidermolytic palmoplantar keratoderma) is associated with the early onset of squamous cell oesophageal cancer in three families. Linkage and haplotype analyses have previously mapped the tylosis with oesophageal cancer ( TOC) locus to a 500-kb region on chromosome 17q25 that has also been implicated in sporadically occurring squamous cell oesophageal cancer. In the current study, 17 additional putative microsatellite markers were identified within this 500-kb region by using sequence data and seven of these were shown to be polymorphic in the UK and US families. In addition, our complete sequence analysis of the non-repetitive parts of the TOC minimal region identified 53 novel and six known single nucleotide polymorphisms (SNPs) in one or both of these families. Further fine mapping of the TOC disease locus by haplotype analysis of the seven polymorphic markers and 21 of the 59 SNPs allowed the reduction of the minimal region to 42.5 kb. One known and two putative genes are located within this region but none of these genes shows tylosis-specific mutations within their protein-coding regions. Alternative mechanisms of disease gene action must therefore be considered.
Langan
Joanne E
JE
Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences, University of Liverpool, Edward's Building, Daulby Street, L69 3GN, Liverpool, UK.
Cole
Charlotte G
CG
Huckle
Elisabeth J
EJ
Byrne
Shaun
S
McRonald
Fiona E
FE
Rowbottom
Lynn
L
Ellis
Anthony
A
Shaw
Joan M
JM
Leigh
Irene M
IM
Kelsell
David P
DP
Dunham
Ian
I
Field
John K
JK
Risk
Janet M
JM
D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D004938:Esophageal Neoplasms / Q000150:complications / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015776:Keratoderma, Palmoplantar, Diffuse / Q000150:complications / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D006113:United Kingdom; D014481:United States
D017931:DNA Primers