Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers
Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a "molecular signature" in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 109(2012), 40 vom: 02. Okt., Seite 16234-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rahimov, Fedik [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 31.12.2012 Date Revised 18.04.2024 published: Print-Electronic GEO: GSE3639 Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1209508109 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM221117326 |
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| 245 | 1 | 0 | |a Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a "molecular signature" in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids | ||
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| 700 | 1 | |a King, Oliver D |e verfasserin |4 aut | |
| 700 | 1 | |a Leung, Doris G |e verfasserin |4 aut | |
| 700 | 1 | |a Bibat, Genila M |e verfasserin |4 aut | |
| 700 | 1 | |a Emerson, Charles P |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Kunkel, Louis M |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Kathryn R |e verfasserin |4 aut | |
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