Deletion of part of chromosome 5 VideoChromosome 5 - Telomerase: Resetting the biological clock deletion of part of chromosome 5
Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.
Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of chromoeome WS4 patient presenting with a large deletion encompassing three of these enhancers.
Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies.
This opens up new routes to the molecular dissection of neural crest disorders. Waardenburg syndrome type 4 WS4also referred to as Shah—Waardenburg share marriate reserve or Waardenburg—Hirschsprung disease, is a neural crest disorder characterized by deletion of part of chromosome 5 association of Waardenburg syndrome features WS, depigmentation defects and deafness with the absence of enteric ganglia in the distal part of the intestine Hirschsprung disease, HD. Recent reports show that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies, particularly HD. Recently, sequence comparison analysis has led to the identification of several evolutionarily conserved regions with putative enhancer activity around the SOX10 locus.
The functional relevance of each of these elements was studied in different cell lines and in deletion of part of chromosome 5, chicken and mouse models. Most of them direct expression in several neural crest derivatives, the enteric nervous system, and melanocytes in particular. A total of 13 patients presenting with a classical form of WS4, and 9 patients with its neurological variant PCWH were screened in this study. DNA samples were obtained for genetic testing with informed consent, according to French law.
Genomic DNA was extracted from peripheral blood leucocytes using standard protocols. Copy number variations were considered significant if defined by three or more contiguous oligonucleotides. We identified a heterozygous deletion encompassing regulatory elements U1, 2, and 3 Figure 1asee regions indicated by black arrowheads in a patient presenting with a classical WS4 phenotype.
Segments analysed by the initial QMF-PCR are indicated by black arrowheads, whereas additional primers used to delineate the deleted regions are indicated by grey arrowheads see Supplementary Table 1 for primer sequences. Localisation of Alu1 and 2 sequences described in Figure 2 are indicated.]