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Chromosome ’Caps’ Predict Bone Marrow Disease


For the first time, Imperial College London researchers at the Hammersmith Hospital studying a rare bone marrow disease have found an association between ’telomere shortening’ - changes in the lengths of DNA repeats at the end of chromosomes - and the time of development and severity of disease symptoms in patients.

Reporting in Nature Genetics today (18 April 2004), the Hammersmith team, collaborating with scientists at the Washington University School of Medicine in the USA, is hoping that the findings could lead to better screening for this and other diseases, as well as suggest targets for new therapies.

Dyskeratosis congenita (DC) is a rare but serious inherited condition where the body is unable to make adequate numbers of blood cells. It can lead to bone marrow failure and a much higher risk of developing cancer. People with DC also have a mutation in an enzyme (telomerase) which repairs telomeres (sections of DNA repeats which ’cap’ the ends of chromosomes) and as a result, telomere length in their chromosomes is shorter.

In families with a history of a certain type of the disease, autosomal dominant DC, the disease becomes more severe in succeeding generations.

"We found when we looked at the DNA of families that suffer from the disease, the telomere length gave an indication of how soon and how severely patients were likely to get the disease," said Inderjeet Dokal, Professor of Haematology at Imperial College London and one of the authors of the study. "This ’disease anticipation’ was only thought to occur in specific neurological diseases until now."

The researchers propose that the shortening of the DNA repeats in
telomeres may be responsible for disease anticipation. They investigated the telomere lengths and disease status of 27 affected individuals from eight families with the autosomal dominant sub-type of DC and compared this to telomere length measurements in normal families. "The findings of this study provides a novel mechanism for disease anticipation in humans," explains Professor Doka.

Tony Stephenson | alfa
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