Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls

Makrythanasis, P., Kapranov, P., Bartoloni, L., Reymond, A., Deutsch, S., Guigo, R., Denoeud, F., Drenkow, J., Rossier, C., Ariani, F., Capra, V., Excoffier, L., Renieri, A., Gingeras, T. R., Antonarakis, S. E. (September 2009) Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls. Human Mutation, 30 (9). E866-79. ISSN 1059-7794

URL: http://www.ncbi.nlm.nih.gov/pubmed/19562714
DOI: 10.1002/humu.21073

Abstract

The study of transcription using genomic tiling arrays has lead to the identification of numerous additional exons. One example is the MECP2 gene on the X chromosome; using 5'RACE and RT-PCR in human tissues and cell lines, we have found more than 70 novel exons (RACEfrags) connecting to at least one annotated exon.. We sequenced all MECP2-connected exons and flanking sequences in 3 groups: 46 patients with the Rett syndrome and without mutations in the currently annotated exons of the MECP2 and CDKL5 genes; 32 patients with the Rett syndrome and identified mutations in the MECP2 gene; 100 control individuals from the same geoethnic group. Approximately 13 kb were sequenced per sample, (2.4 Mb of DNA resequencing). A total of 75 individuals had novel rare variants (mostly private variants) but no statistically significant difference was found among the 3 groups. These results suggest that variants in the newly discovered exons may not contribute to Rett syndrome. Interestingly however, there are about twice more variants in the novel exons than in the flanking sequences (44 vs. 21 for approximately 1.3 Mb sequenced for each class of sequences, p=0.0025). Thus the evolutionary forces that shape these novel exons may be different than those of neighboring sequences.

Item Type: Paper
Uncontrolled Keywords: DNA Mutational Analysis Exons/*genetics Female *Genetic Variation Humans Male Methyl-CpG-Binding Protein 2/*genetics/metabolism Protein-Serine-Threonine Kinases Rett Syndrome/*genetics/metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: Matt Covey
Date: September 2009
Date Deposited: 21 Mar 2014 19:29
Last Modified: 21 Mar 2014 19:29
PMCID: PMC3708316
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29695

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