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Five new genes found which cause an extreme form of dwarfism.
March 2011
Five new genes have been found which cause an extreme form of dwarfism, known as primordial dwarfism, according to research carried out by Medical Research Council (MRC) scientists. The findings from two new research papers shed light on how human body size is determined, and for the first time make a direct link between the copying of DNA in cells and body growth. This discovery could open up new avenues of research into how growth disorders occur and offer people with severe growth disorders a chance of better and earlier diagnosis.
Primordial dwarfism is a group of incredibly rare growth disorders which significantly limit growth at every stage of life, from before birth to adulthood and includes the smallest people in the world. Many of those whose size is limited by these genes have small ears, no knee caps and an adult height can be as little as one metre. They may also have a reduced head size, in proportion to their body size, in contrast with other forms of dwarfism. Without a clear understanding of what causes the disorders, it can often be difficult for patients to get an accurate diagnosis and provide the best management of their condition.
The group of genes, collectively called the ‘pre-replication complex’, is known to play an important role in controlling the copying of DNA in our cells, but until now their formative link with primordial microcephalic dwarfism and developmental problems remained hidden.
The first study, led by Dr Mark O’Driscoll and Professor Penny Jeggo at the MRC Genome Damage and Stability Centre at the University of Sussex and Dr Andrew Jackson at the MRC Human Genetics Unit in Edinburgh, reveals that the gene ORC1, plays a key role in triggering the copying of our genetic material (DNA). This impacts upon the rate at which cells multiply and so lead to fewer cells being produced, thereby limiting growth. The researchers were able to substantiate this in zebrafish by removing ORC1 and observing how it impaired their growth.
The second study, by the team at the MRC Human Genetics Unit in conjunction with Dr Ernie Bongers and colleagues at Radboud University Nijmegen Medical Centre in the Netherlands, supports this finding and reveals that four further genes that are known to function in the pre-replication complex with ORC1 also cause this condition, suggesting that these genes and this complex are important for human growth.
Corresponding author, Dr Andrew Jackson at the MRC Human Genetics Unit in Edinburgh, says:
“This is the first time we’ve been able to find a link between genes controlling the basic process which copies our DNA in cells and an extreme form of dwarfism. We’re very excited that these discoveries not only help us understand what causes primordial dwarfism but could also offer us a general insight into how these genes may more widely influence human height and body size.”
Senior author on the first paper, Professor Penny Jeggo at the MRC Centre for Genome Damage and Stability at the University of Sussex, says:
“It’s exciting to discover that a protein complex that plays a key role in how cells copy their DNA has such a significant impact on development. This demonstrates that the investment in understanding basic mechanisms underlying cell growth and replication is critical for understanding development of organisms and disorders of human health.”
The two papers, together with a third led by researchers in Canada, are published online today in Nature Genetics.
Unit scientists share their expertise at Edinburgh Science Festival.
May 2011
Almost 1300 children took part in the Mini scientist activity in the MRC Lab at the City Arts Centre during the Edinburgh International Science Festival in April. They dressed-up in mini-lab-coats and safety specs, grabbed clip boards for their notes and peppered MRC scientists with their questions and ideas in response to the five activities on offer.
PhD and Masters students, research assistants and postdoctoral research scientists from the MRC Human Genetics Unit were among the 30 MRC volunteers who took time out of the lab to demonstrate the activities to visitors.
The MRC HGU activity DNA Sequencing Bracelets introduced the principles of DNA base pairs and of gene alleles: alternative forms of the same gene. Demonstrators showed visitors how to match-up beads representing base pairs to make a double stranded DNA bracelet that reflected their own hair and eye gene sequence.
Each activity in included in Mini Scientists is designed to be fun and to teach some basic principles about science and research. Scientists from all of the MRC units and centres in Scotland took the opportunity to take part as demonstrators and boost their science communication skills.
Adult audiences weren’t left out of the fun. This year, 87 people attended a talk titled ‘Why we have five fingers and toes’ delivered by HGU Professor Bob Hill, he described the evolutionary steps behind the development of human hands, feet and limbs with some interesting comparisons with other mammals.
Feedback from the parents and from the children who took part in MRC events at the festival was excellent and staff at HGU are already planning for 2012.