Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers
Wellstone Center for FSHD
Medical Subject Headings
Biological Markers; *Gene Expression Profiling; Humans; Logistic Models; Muscle, Skeletal; Muscular Dystrophy, Facioscapulohumeral; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Real-Time Polymerase Chain Reaction
Cell Biology | Developmental Biology | Molecular Biology | Molecular Genetics | Musculoskeletal Diseases | Nervous System Diseases
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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Citation: Rahimov F, King OD, Leung DG, Bibat GM, Emerson CP Jr, Kunkel LM, Wagner KR. Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16234-9. doi:10.1073/pnas.1209508109. Link to article on publisher's site
Rahimov, Fedik; King, Oliver D.; Leung, Doris G.; Bibat, Genila M.; Emerson, Charles P. Jr.; Kunkel, Louis M.; and Wagner, Kathryn R., "Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers" (2012). Wellstone Center for FSHD Publications and Presentations. 9.