Wellcome Trust Senior Research Fellow Professor Philip Beales (Institute of Child Health) and colleagues have discovered that cilia – tiny hair-like structures on the surface of cells – may be involved in a range of fundamental developmental pathways. The researchers have identified several genes causing a rare genetic condition, Bardet–Biedl syndrome (BBS), and discovered that these can interact with each other to influence disease severity. Each appears to affect the function of cilia.

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BBS is an inherited complex disorder, causing obesity, vision defects, cognitive impairment, kidney failure and other problems. Several genes mutated in the condition have been discovered; one of the latest is BBS10, identified in studies of families from an isolated Lebanese village particularly affected by the condition.

In a separate study, Professor Beales and colleagues showed that a single nucleotide polymorphism in an interacting gene, MGC1203, does not itself cause BBS, but can have a novel effect on its severity. The MGC1203 protein was found at the base of cilia and interacts with most BBS proteins. Symptoms thus depend not only on which BBS gene is affected, but also on any other BBS gene alterations present, and on the effects exerted by mutations within other, non-disease (so-called 'modifier') genes, such as MGC1203.

The group also uncovered a connection with 'planar cell polarity', which controls aspects of cell function such as cell orientation and polarity. In mice, mutations in BBS genes disrupt cell polarity. Furthermore, BBS genes were shown to interact with cell polarity genes, suggesting a novel role for cilia in this process.

Other aspects of the syndrome, such as obesity and extra digits, cannot be readily explained by dysfunctional cilia but it is likely that further study of the BBS genes will eventually explain these links.

Image: Cross-section through cilia showing their distinctive microtubule rings; Dr David Furness

External links

• Ross AJ et al. Disruption of Bardet–Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet 2005;37(10):1135–40.
• Badano JL et al. Dissection of epistasis in oligogenic Bardet–Biedl syndrome. Nature 2006;439(7074):326–30.
• Stoetzel C et al. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet 2006;38(5):521–4.