title: Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls.
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.
authors: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
authors: Periklis
authors: P
authors: Makrythanasis
authors: Philipp
authors: P
authors: Kapranov
authors: Lucia
authors: L
authors: Bartoloni
authors: Alexandre
authors: A
authors: Reymond
authors: Samuel
authors: S
authors: Deutsch
authors: Roderic
authors: R
authors: Guigó
authors: France
authors: F
authors: Denoeud
authors: Jorg
authors: J
authors: Drenkow
authors: Colette
authors: C
authors: Rossier
authors: Francesca
authors: F
authors: Ariani
authors: Valeria
authors: V
authors: Capra
authors: Laurent
authors: L
authors: Excoffier
authors: Alessandra
authors: A
authors: Renieri
authors: Thomas R
authors: TR
authors: Gingeras
authors: Stylianos E
authors: SE
authors: Antonarakis
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human