Characterisation of mutations in the CBP-gene in Rubinstein-Taybi syndrome and tumors.
Department : Dept. of Human and Clinical Genetics
Project supervisor : Dr. D.J.M. Peters/ Dr. Jeroen H. Roelfsema
Address : Sylvius Laboratories, Wassenaarseweg 72, 2333 AL Leiden
Telephone number : 071-5276048
Fax number : 071-5276075
E-mail address : email@example.com
of research project :
syndrome (RTS) is characterised by mental retardation and specific skeletal
translocations and point mutations deleting or truncating one copy of CBP are
responsible for RTS in 30% of the patients we have examined. However, a
significant part of CBP has not yet been screened. A large number of binding
domains for interacting proteins, have been mapped accurately. Mutations in one
or more of these domains may account for a large number of as yet unidentified
mutations. One of the characteristics of Rubinstein-Taybi syndrome is a
predisposition for tumor development. This may be explained by mutation of both
copies of the CBP gene in the tumors. We would like to know whether
CBP has a role in tumor development or progression in tunors in RTS
patients and in sporadic tumors (keloids, breast cancer, cervix cancer).
We hypothesize that missense mutations in functional domains of CBP, which have not yet been screened, can be responsible for RTS in a subset of patients. We further hypothesize that tumors in RTS patients can be caused by the loss of the unaffected copy of the CBP gene.
description and experimental design
Intronic primers will be selected for the different
exons of CBP. For mutation analysis
fragments generated via the polymerase
chain reaction (PCR) will be analysed by electrophoresis on agarose-gels and on
polyacrylamide gels (Denaturing gradient gel electrophoresis, Single Strand
Conformation Polymorphism analysis). Mutations will be analysed using an
automatic sequencer. Whenever possible the mutation
will be confirmed by digesting the DNA with a restriction enzyme.
to be applied