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

Periklis Makrythanasis, Philipp Kapranov, Lucia Bartoloni, Alexandre Reymond, Samuel Deutsch, Roderic Guigó, France Denoeud, Jorg Drenkow, Colette Rossier, Francesca Ariani, Valeria Capra, Laurent Excoffier, Alessandra Renieri, Thomas R. Gingeras, Stylianos E. Antonarakis

Research output: Contribution to journalArticle

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 13kb were sequenced per sample, (2.4Mb 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.

Original languageEnglish
JournalHuman Mutation
Volume30
Issue number9
DOIs
Publication statusPublished - Sep 2009

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Keywords

  • MECP2
  • Positive selection
  • RACEfrags
  • Rare variants
  • Rett syndrome
  • SNP

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Makrythanasis, P., Kapranov, P., Bartoloni, L., Reymond, A., Deutsch, S., Guigó, R., Denoeud, F., Drenkow, J., Rossier, C., Ariani, F., Capra, V., Excoffier, L., Renieri, A., Gingeras, T. R., & Antonarakis, S. E. (2009). Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls. Human Mutation, 30(9). https://doi.org/10.1002/humu.21073