" real-time PCR" . "2010-04-06+02:00"^^ . " phenylbutyrate" . "Molekul\u00E1rn\u00ED aspekty diagnostiky a terapie spin\u00E1ln\u00ED svalov\u00E9 atrofie" . "Spinal muscular atrophy is autosomal-recessive disease caused in ca. 95% of cases by homozygous deletion of the SMN1 gene. The SMN1 gene and its SMN2 copy localise to chromosome 5q13. Differences between SMN1 and SMN2 result in different splicing. Transcription and splicing of the SMN1 gene results in full-length mRNA in about 70%, while about the same fraction of SMN2 products shows deletion of the exon 7. Compounds affecting SMN mRNA splicing towards exon 7 inclusion could be used in therapy. The project expands SMA diagnostics by detection of point mutations (ca.5% of SMA cases are caused by SMN1 deletion at one chromosome and point mutation at the other), evaluation of copy no. of SMN2 and correlation of the copy no. and disease phenotype. The project goal is to analyse changes in SMN2 expression at the mRNA and protein level in lymphoblastoid cell lines derived from SMA patients, cultivated with or without phenylbutyrate, i.e., the compound affecting mRNA splicing."@en . "2005-08-01+02:00"^^ . . . " SMN2" . . "0"^^ . " SMN1" . . . . "3"^^ . . " lymphoblastoid cell lines" . "0"^^ . . "3"^^ . "2008-12-31+01:00"^^ . "1"^^ . . "spinal muscular atrophy" . . "http://www.isvav.cz/projectDetail.do?rowId=1A8608"^^ . "spinal muscular atrophy; SMA; SMN1; SMN2; phenylbutyrate; real-time PCR; lymphoblastoid cell lines; mRNA splicing"@en . "Molecular aspects of diagnostics and therapy of spinal muscular atrophy"@en . "Project solution resulted in establishment of complex molecular genetic diagnostics of spinal muscular atrophy (SMA) and in evaluation of the effect of histone deacetylase inhibitors on SMN2 gene expression and acetylation of H3 histone"@en . "Spin\u00E1ln\u00ED svalov\u00E1 atrofie je autosom\u00E1ln\u011B recesivn\u00ED onemocn\u011Bn\u00ED zp\u016Fsoben\u00E9 v cca 95% p\u0159\u00EDpad\u016F homozygotn\u00ED delec\u00ED genu SMN1. Gen SMN1 je se svou kopi\u00ED, genem SMN2, lokalizov\u00E1n na chromosomu 5q13. Rozd\u00EDly mezi genem SMN1 a SMN2 se projevuj\u00ED rozd\u00EDln\u00FDm sest\u0159ihem. Transkripc\u00ED a sest\u0159ihem genu SMN1 vznik\u00E1 v 70% mRNA o pln\u00E9 d\u00E9lce, transkripc\u00ED a sest\u0159ihem genu SMN2 v 70% mRNA s delec\u00ED exonu 7. L\u00E1tky modifikuj\u00EDc\u00ED sest\u0159ih mRNA genu SMN2 sm\u011Brem k za\u010Dlen\u011Bn\u00ED exonu 7 mohou m\u00EDt v p\u0159\u00EDpad\u011B SMA potenci\u00E1ln\u00ED terapeutick\u00FD efekt. \u00DAkolem projektu bude roz\u0161\u00ED\u0159en\u00ED diagnostiky SMA o detekci bodov\u00FDch mutac\u00ED (cca 5% p\u0159\u00EDpad\u016F SMA je zp\u016Fsobeno delec\u00ED genu SMN1 na jednom chromosomu a bodou mutac\u00ED na druh\u00E9m), d\u00E1le stanoven\u00ED po\u010Dtu kopi\u00ED genu SMN2 a korelace po\u010Det kopi\u00ED/fenotyp onemocn\u011Bn\u00ED. \u00DAkolem projektu bude sledov\u00E1n\u00ED zm\u011Bn exprese genu SMN2 na \u00FArovni mRNA a proteinu u lymfoblastoidn\u00EDch bun\u011B\u010Dn\u00FDch lini\u00ED odvozen\u00FDch od pacient\u016F s diagn\u00F3zou SMA a kultivovan\u00FDch v p\u0159\u00EDtomnosti fenylbutyr\u00E1tu, tj. l\u00E1tky modifikuj\u00EDc\u00ED sest\u0159ih mRNA." . . " SMA" . "V\u00FDsledkem projektu je zaveden\u00ED nov\u00E9 vy\u0161et\u0159ovac\u00ED metody a sice komplexn\u00ED genetick\u00E9 diagnostiky spin\u00E1ln\u00ED svalov\u00E9 atrofie (SMA) v\u010Detn\u011B zji\u0161t\u011Bn\u00ED vlivu inhibitor\u016F histonaacetyl\u00E1z na expresi genu SMN2 a acetylaci histonu H3."@cs . . . "2008-03-05+01:00"^^ . . . . . . . "1A8608" .