Human Molecular Genetics, 2000, Vol. 9, No. 8 1201-1208
© 2000 Oxford University Press
Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage
Royal London and St Bartholomew’s School of Medicine and Dentistry, Department of Experimental Haematology, Turner Street, London E1 2AD, UK, 1Department of Medicine, Cardiac Molecular Biology Program, University of California San Diego, La Jolla, CA 92093-0613, USA, 2Service d’Haematologie Biologique, Hopital d’Enfants Armand Trousseau, 26 Avenue du Docteur Arnold Netter, 75571 Paris Cedex 12, France, 3Wellcome Centre of Human Genetics, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7BN, UK and 4Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK
Folate-sensitive fragile sites are associated with the expansion and hypermethylation of CCG-repeats. The fragile site in 11q23.3, FRA11B, has been shown to cause chromosome deletions in vivo, its expression being associated with Jacobsen (11q–) syndrome. However, the majority of Jacobsen deletions are distal to FRA11B and are not related to its expression. To test the hypothesis that other unidentified fragile sites might be located in 11q23.3–24 and may cause these deletions, we have identified and characterised CCG-trinucleotide repeats within a 40 Mb YAC contig spanning distal chromosome 11q. Only eight CCG-repeats were identified within the entire YAC contig (not including FRA11B), six of which map to the region of 11q23.3–24 that includes Jacobsen deletions. We have previously collated the deletion mapping data of 24 Jacobsen patients with the physical map of chromosome 11q, and accurately localised six breakpoints to short intervals corresponding to individual YAC clones. We now show that in each of these cases, YAC clones found to contain a deletion breakpoint also contain a CCG-repeat. The improved analysis of one of these deletions, together with those of several new Jacobsen cases, further strengthens this association by localising five breakpoints to individual PAC clones containing CCG-repeats. These data provide strong evidence for the non-random clustering of chromosome deletion breakpoints with CCG-repeats, and suggests that they may play an important role in a common mechanism of chromosome breakage.
+ To whom correspondence should be addressed. Tel: +44 207 377 7000 ext. 3152; Fax: +44 207 377 7629; Email: cjones2@hgmp.mrc.ac.uk
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