|
|
Breakthrough for Retinitis Pigmentosa:
Isolating the genes
 Retinitis pigmentosa, a degenerative disease of the retina, is the leading heritable cause of blindness today. The condition is caused by mutations in genes responsible for a number of different retinal components. These genes and disease-causing mutations can be inherited. Modern genetic technologies allow for the location of these genes and mutations. Once found their effects can be studied, and the foundation laid down for the potential development of gene-based therapies.
A research team at the University of Cape Town, headed by Human Genetics professors Raj Ramesar, who also directs the Medical Research Council's Human Genetics Reseach Unit, and Jacquie Greenberg, working with Dr Chris Inglehearn in Leeds in the UK, have found the genetic defect which causes a form of retinitis pigmentosa. This form of the condition was prevalent in a very large family in South Africa, and with the co-operation of key members of the kindred, the UCT and UK researchers were able to track down the mutation responsible for their condition. The gene responsible was found on chromosome 17.
Many research teams around the world have made similar discoveries, but what sets this one apart is that the mutation is to a gene which has a universal function throughout the human body. Most other mutations discovered have been to genes which have a specific function within the retina alone.
There are a large number of different forms of retinitis pigmentosa, which themselves occur as part of a bigger spectrum of retinal degenerative disorders, which includes disorders like macular dystrophy. Specific clinical types of retinitis pigmentosa are due to the specific gene which carries a mutation, and many clinical sub-types exist within each of these based on where within the gene the mutation lies. The frequency of these mutations is most probably not any higher in SA than anywhere else in the world, but accurate statistical data to back this statement do not exist at present.
Professor Ramesar believes that quite a small percentage of retinitis pigmentosa cases will be caused by this exact mutation. Most of these will be within the family affected itself. The interesting thing however about this discovery is that it has uncovered a new gene mutation which causes retinitis pigmentosa, and that this mutation is within a gene which has a universal function within the body.
Technically, screening for the mutation is already possible, as it is for some forms of colorectal, breast and ovarian cancers, muscular dystrophies and neurodegenerative disorders. The unit does however insist that this type of testing be developed for this form of retinitis pigmentosa in conjunction with strong ethical review and input from members of the families to institute a protocol with requisite counselling that is internationally acceptable, to prepare individuals for test
results. It is important to note that the technical ability to now detect the mutation through routine molecular genetic techniques should not mean that any facility that is able to do this, ought to. The need to do genetic testing with the attendant clinical and counselling specialists according to international guidelines is imperative.
The finding of this defect in the gene sequence has been likened to finding a needle in a haystack. In order to find the gene, many affected individuals from a single family were required. Specific markers on their genomes needed to be chosen. Markers are distinctive sequences which can be tracked. During meiosis, which results in the formation of gametes, DNA is crossed over between parental chromosomes. If a marker and a gene are very closely linked they will be able to pass through 3-4-5 generations. Hence, by a process of screening the markers through many family members, the team was able to assess which ones were closest to the gene, and then predict the distance to the gene using a statistical method.
The mutated gene in this case turned out to be a medium sized gene. The rate at which mutations occur is reasonably constant. The larger the gene the more common genetic diseases of the gene are. Hence, more common conditions such as cystic fibrosis and muscular dystrophy are caused by mutations to very large genes.
The gene product itself is a component of the cellular machinery responsible for the splicing of RNA after its transcription from DNA. RNA is transcribed from DNA, then spliced and modified by proteins such as this one, and then translated into proteins based on its sequence of bases. Hence the protein itself performs a function similar to that of an editor, cutting out unnecessary bits and pieces so that the reader is able to understand the sentence correctly. Without this function, many cellular functions are likely to be impaired.
The research in this country was largely funded by the Retinal Preservation Foundation of South Africa. A certain amount was also contributed by THRIP and the Medical Research Council in more recent times.
Professor Ramesar is currently engaged in research into the genetics of both colorectal cancer and bipolar disorder. Screening of families with the genetic mutations linked to colorectal cancer has made it possible for individuals to receive predictive information about their risk for developing this potentially lethal disease. This different kind of medicine "predictive medicine", makes it possible for counselling and advanced care, which, if implemented and accepted, will prevent deaths from this disease.
Article prepared by Science in Africa
Pictures on this page courtesy of the DOE Human Genome Program Web-site
|
