Disruption of chromosome loops can lead to Beckwith-Wiedemann Syndrome

Babraham Institute scientists have identified chromosome ‘loops’ which have implications for healthy growth of babies in the womb.

Disruption of these loops can lead to Beckwith-Wiedemann Syndrome (BWS) – over-large babies with various tumours – which affects 1 in 13,000 births. The risk of developing the syndrome is increased four-fold in babies born following IVF treatment.

Confirmation of the existence of the loops, described in an article published in Nature Genetics, was made by Dr Adele Murrell and colleagues, working with Dr Wolf Reik at the Babraham Institute. Scientists had previously speculated that these loops, or something similar, exist, but no-one had evidence to prove this was the case.

Dr Reik’s group studies imprinted genes, which are genes in mammals that are only expressed from one of the parental chromosomes. These genes have important roles in regulating the growth of the baby in the womb and its adaptations to life outside the womb. Many of them occur in clusters, and share elements by which their expression can be increased (enhancers) or decreased (silencers).

These elements of the chromosome may be thought of as beads on a necklace. They are distant from each other along the string (up to 10% of the length of the string), but it can be coiled to bring them into contact. The group has identified a looped area of a chromosome, which enables direct physical contact between two imprinted genes, allowing one or the other to be exclusively expressed.

This study confirms the existing theories of how these relatively remote elements are arranged in loops to allow their effects to be shared. Dr Reik comments “though the findings don't have a direct bearing on diagnosis, our work over the years has led to much better prediction as to which groups of children with BWS are at higher risk of developing certain symptoms”.