Cowley, Catherine M.;
(1997)
Genetic analysis of the human desmosomal cadherin locus.
Doctoral thesis (Ph.D.), University College London (United Kingdom).
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Abstract
The desmosome type of cell-cell junction, which is characteristic of epithelial cells, but is also found in cardiac muscle, brain meninges and follicular dendritic cells, has two types of adhesive proteins, the desmocollins and the desmogleins, both members of the cadherin superfamily. Current evidence based on transfection and anti-sense experiments suggests that both types of desmosomal cadherin are necessary for strong cell-cell adhesion. Interestingly it has been found that all of the known desmocollin and desmoglein isoforms, which have differing tissue and developmental distributions, are coded by very closely linked genes at 18q12.1. I have isolated YAC clones which carry all three desmocollin genes (DSC1, 2 and 3) and all three desmoglein genes (DSG1, 2, and 3) as well as clones that join the DSC locus to the DSG locus, forming a complete contig for the region. Absence of chimaeric ends for some of the YACs was confirmed by isolating Vectorette PCR products for the YAC ends, and mapping the derived DNA sequences back to other YACs in the contig or to YACs from CEPH. The whole DSC/DSG gene complex occupies no more than about 650kb, and the genes are arranged in the order centromere-3'-DSC3-DSC2-DSC1-5'-5'--DSG1-DSG3-DSG3-3'- telomere, so that the two gene clusters are transcribed outwards from the interlocus region. A P1 clone carrying part of DSC2 and DSC3 confirmed the relative orientation of transcription of these two genes. I have found no evidence, using PCR, for any further DSC genes. The conservation of close genetic linkage may be of trivial importance related to the recent duplication of these genes or may be because there is a region within the locus which is involved in coordinating the expression of the desmoglein and desmocollin genes. Other work undertaken in this thesis includes the determination of the chromosomal location of the human PKP1 gene coding for the desmosomal plaque protein, plakophilin, using fluorescence in situ hybridisation.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D. |
| Title: | Genetic analysis of the human desmosomal cadherin locus |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | (UMI)AAI10042927; Biological sciences; Desmosomes |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10098958 |
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