Research on Skeletal Dysplasias
The objectives of ESDN-Research are to understand comprehensively the
molecular genetics and cell-matrix pathophysiology of skeletal dysplasias.
The extremely complex and heterogeneous presentation of these diseases
requires an integrated multidisciplinary research approach. In this
respect the overall methodology of this project consists of three integral
components:
- Patient ascertainment and comprehensive
clinical and radiographic diagnosis.
The ascertainment and correct diagnosis of individuals with skeletal
dysplasias is fundamental to the success of this project. Each of
the network partners has individual experience of this with particular
skills in their specific area of interest. The development of uniform
criteria for radiographic diagnosis will be provided by the expert
radiologists within the partnership.
- Molecular genetics and genetic heterogeneity.
The use of unique sources of novel human bone and cartilage cDNAs,
together with clinical material and mouse data, will generate a number
of positional and functional candidate genes for skeletal dysplasias.
In addition, genetic linkage analysis remains a very powerful technique
for rapidly identifying a sub-chromosomal location of a particular
disease gene and using suitable families, we intend to fully exploit
the recent technological advances in this approach.
- Molecular cell pathology and matrix structure/function
relationships.
Proteomics allows the identification and comparative analysis of proteins
expressed by cells or tissues. This approach is suited for identifying
groups of proteins associated with specific higher-molecular structures
or pathways, and how such patterns are perturbed as a result of pathological
changes. Furthermore, the development of biomolecular techniques now
makes it possible to study in high resolution the structural and functional
properties of proteins and investigate the effects of mutations. The
development of in vitro expression systems allows the production of
large quantities of biologically active recombinant protein that can
be engineered to contain disease mutations.
