Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease seve...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Jones, Ashley R. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2015transfer abstract |
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| Schlagwörter: |
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| Umfang: |
9 |
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| Übergeordnetes Werk: |
Enthalten in: Corrigendum to “Electrical and thermal transport properties of Fe–Ni based ternary alloys in the earth's inner core: An ab initio study” [Physics of the Earth and Planetary Interiors - Zidane, Mustapha ELSEVIER, 2021, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:36 ; year:2015 ; number:5 ; pages:20061-20069 ; extent:9 |
| Links: |
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| DOI / URN: |
10.1016/j.neurobiolaging.2015.02.017 |
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| 245 | 1 | 0 | |a Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes |
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| 520 | |a Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. | ||
| 520 | |a Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. | ||
| 650 | 7 | |a Spinal cord |2 Elsevier | |
| 650 | 7 | |a Amyotrophic lateral sclerosis |2 Elsevier | |
| 650 | 7 | |a Gene expression |2 Elsevier | |
| 650 | 7 | |a Disease spread |2 Elsevier | |
| 650 | 7 | |a RNA processing |2 Elsevier | |
| 650 | 7 | |a C9ORF72 |2 Elsevier | |
| 700 | 1 | |a Troakes, Claire |4 oth | |
| 700 | 1 | |a King, Andrew |4 oth | |
| 700 | 1 | |a Sahni, Vibhu |4 oth | |
| 700 | 1 | |a De Jong, Simone |4 oth | |
| 700 | 1 | |a Bossers, Koen |4 oth | |
| 700 | 1 | |a Papouli, Efterpi |4 oth | |
| 700 | 1 | |a Mirza, Muddassar |4 oth | |
| 700 | 1 | |a Al-Sarraj, Safa |4 oth | |
| 700 | 1 | |a Shaw, Christopher E. |4 oth | |
| 700 | 1 | |a Shaw, Pamela J. |4 oth | |
| 700 | 1 | |a Kirby, Janine |4 oth | |
| 700 | 1 | |a Veldink, Jan H. |4 oth | |
| 700 | 1 | |a Macklis, Jeffrey D. |4 oth | |
| 700 | 1 | |a Powell, John F. |4 oth | |
| 700 | 1 | |a Al-Chalabi, Ammar |4 oth | |
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10.1016/j.neurobiolaging.2015.02.017 doi GBVA2015008000022.pica (DE-627)ELV018411932 (ELSEVIER)S0197-4580(15)00117-7 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 520 VZ 38.70 bkl 39.53 bkl Jones, Ashley R. verfasserin aut Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes 2015transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Spinal cord Elsevier Amyotrophic lateral sclerosis Elsevier Gene expression Elsevier Disease spread Elsevier RNA processing Elsevier C9ORF72 Elsevier Troakes, Claire oth King, Andrew oth Sahni, Vibhu oth De Jong, Simone oth Bossers, Koen oth Papouli, Efterpi oth Mirza, Muddassar oth Al-Sarraj, Safa oth Shaw, Christopher E. oth Shaw, Pamela J. oth Kirby, Janine oth Veldink, Jan H. oth Macklis, Jeffrey D. oth Powell, John F. oth Al-Chalabi, Ammar oth Enthalten in Elsevier Science Zidane, Mustapha ELSEVIER Corrigendum to “Electrical and thermal transport properties of Fe–Ni based ternary alloys in the earth's inner core: An ab initio study” [Physics of the Earth and Planetary Interiors 2021 Amsterdam [u.a.] (DE-627)ELV005660645 volume:36 year:2015 number:5 pages:20061-20069 extent:9 https://doi.org/10.1016/j.neurobiolaging.2015.02.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-GGO SSG-OPC-GEO SSG-OPC-AST 38.70 Geophysik: Allgemeines VZ 39.53 Planeten VZ AR 36 2015 5 20061-20069 9 36.2015, 5, 2006.e1-, (9 S.) 045F 610 |
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10.1016/j.neurobiolaging.2015.02.017 doi GBVA2015008000022.pica (DE-627)ELV018411932 (ELSEVIER)S0197-4580(15)00117-7 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 520 VZ 38.70 bkl 39.53 bkl Jones, Ashley R. verfasserin aut Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes 2015transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Spinal cord Elsevier Amyotrophic lateral sclerosis Elsevier Gene expression Elsevier Disease spread Elsevier RNA processing Elsevier C9ORF72 Elsevier Troakes, Claire oth King, Andrew oth Sahni, Vibhu oth De Jong, Simone oth Bossers, Koen oth Papouli, Efterpi oth Mirza, Muddassar oth Al-Sarraj, Safa oth Shaw, Christopher E. oth Shaw, Pamela J. oth Kirby, Janine oth Veldink, Jan H. oth Macklis, Jeffrey D. oth Powell, John F. oth Al-Chalabi, Ammar oth Enthalten in Elsevier Science Zidane, Mustapha ELSEVIER Corrigendum to “Electrical and thermal transport properties of Fe–Ni based ternary alloys in the earth's inner core: An ab initio study” [Physics of the Earth and Planetary Interiors 2021 Amsterdam [u.a.] (DE-627)ELV005660645 volume:36 year:2015 number:5 pages:20061-20069 extent:9 https://doi.org/10.1016/j.neurobiolaging.2015.02.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-GGO SSG-OPC-GEO SSG-OPC-AST 38.70 Geophysik: Allgemeines VZ 39.53 Planeten VZ AR 36 2015 5 20061-20069 9 36.2015, 5, 2006.e1-, (9 S.) 045F 610 |
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10.1016/j.neurobiolaging.2015.02.017 doi GBVA2015008000022.pica (DE-627)ELV018411932 (ELSEVIER)S0197-4580(15)00117-7 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 520 VZ 38.70 bkl 39.53 bkl Jones, Ashley R. verfasserin aut Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes 2015transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Spinal cord Elsevier Amyotrophic lateral sclerosis Elsevier Gene expression Elsevier Disease spread Elsevier RNA processing Elsevier C9ORF72 Elsevier Troakes, Claire oth King, Andrew oth Sahni, Vibhu oth De Jong, Simone oth Bossers, Koen oth Papouli, Efterpi oth Mirza, Muddassar oth Al-Sarraj, Safa oth Shaw, Christopher E. oth Shaw, Pamela J. oth Kirby, Janine oth Veldink, Jan H. oth Macklis, Jeffrey D. oth Powell, John F. oth Al-Chalabi, Ammar oth Enthalten in Elsevier Science Zidane, Mustapha ELSEVIER Corrigendum to “Electrical and thermal transport properties of Fe–Ni based ternary alloys in the earth's inner core: An ab initio study” [Physics of the Earth and Planetary Interiors 2021 Amsterdam [u.a.] (DE-627)ELV005660645 volume:36 year:2015 number:5 pages:20061-20069 extent:9 https://doi.org/10.1016/j.neurobiolaging.2015.02.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-GGO SSG-OPC-GEO SSG-OPC-AST 38.70 Geophysik: Allgemeines VZ 39.53 Planeten VZ AR 36 2015 5 20061-20069 9 36.2015, 5, 2006.e1-, (9 S.) 045F 610 |
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10.1016/j.neurobiolaging.2015.02.017 doi GBVA2015008000022.pica (DE-627)ELV018411932 (ELSEVIER)S0197-4580(15)00117-7 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 520 VZ 38.70 bkl 39.53 bkl Jones, Ashley R. verfasserin aut Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes 2015transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Spinal cord Elsevier Amyotrophic lateral sclerosis Elsevier Gene expression Elsevier Disease spread Elsevier RNA processing Elsevier C9ORF72 Elsevier Troakes, Claire oth King, Andrew oth Sahni, Vibhu oth De Jong, Simone oth Bossers, Koen oth Papouli, Efterpi oth Mirza, Muddassar oth Al-Sarraj, Safa oth Shaw, Christopher E. oth Shaw, Pamela J. oth Kirby, Janine oth Veldink, Jan H. oth Macklis, Jeffrey D. oth Powell, John F. oth Al-Chalabi, Ammar oth Enthalten in Elsevier Science Zidane, Mustapha ELSEVIER Corrigendum to “Electrical and thermal transport properties of Fe–Ni based ternary alloys in the earth's inner core: An ab initio study” [Physics of the Earth and Planetary Interiors 2021 Amsterdam [u.a.] (DE-627)ELV005660645 volume:36 year:2015 number:5 pages:20061-20069 extent:9 https://doi.org/10.1016/j.neurobiolaging.2015.02.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-GGO SSG-OPC-GEO SSG-OPC-AST 38.70 Geophysik: Allgemeines VZ 39.53 Planeten VZ AR 36 2015 5 20061-20069 9 36.2015, 5, 2006.e1-, (9 S.) 045F 610 |
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10.1016/j.neurobiolaging.2015.02.017 doi GBVA2015008000022.pica (DE-627)ELV018411932 (ELSEVIER)S0197-4580(15)00117-7 DE-627 ger DE-627 rakwb eng 610 610 DE-600 550 520 VZ 38.70 bkl 39.53 bkl Jones, Ashley R. verfasserin aut Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes 2015transfer abstract 9 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. Spinal cord Elsevier Amyotrophic lateral sclerosis Elsevier Gene expression Elsevier Disease spread Elsevier RNA processing Elsevier C9ORF72 Elsevier Troakes, Claire oth King, Andrew oth Sahni, Vibhu oth De Jong, Simone oth Bossers, Koen oth Papouli, Efterpi oth Mirza, Muddassar oth Al-Sarraj, Safa oth Shaw, Christopher E. oth Shaw, Pamela J. oth Kirby, Janine oth Veldink, Jan H. oth Macklis, Jeffrey D. oth Powell, John F. oth Al-Chalabi, Ammar oth Enthalten in Elsevier Science Zidane, Mustapha ELSEVIER Corrigendum to “Electrical and thermal transport properties of Fe–Ni based ternary alloys in the earth's inner core: An ab initio study” [Physics of the Earth and Planetary Interiors 2021 Amsterdam [u.a.] (DE-627)ELV005660645 volume:36 year:2015 number:5 pages:20061-20069 extent:9 https://doi.org/10.1016/j.neurobiolaging.2015.02.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-GGO SSG-OPC-GEO SSG-OPC-AST 38.70 Geophysik: Allgemeines VZ 39.53 Planeten VZ AR 36 2015 5 20061-20069 9 36.2015, 5, 2006.e1-, (9 S.) 045F 610 |
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Stratified gene expression analysis identifies major amyotrophic lateral sclerosis genes |
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. |
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. |
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis. Gene expression studies of ALS only rarely identify the same gene pathways as gene association studies. We hypothesized that analyzing tissues by matching on degree of disease severity would identify different patterns of gene expression from a traditional case-control comparison. We analyzed gene expression changes in 4 postmortem central nervous system regions, stratified by severity of motor neuron loss. An overall comparison of cases (n = 6) and controls (n = 3) identified known ALS gene, SOX5, as showing differential expression (log2 fold change = 0.09, p = 5.5 × 10−5). Analyses stratified by disease severity identified expression changes in C9orf72 (p = 2.77 × 10−3), MATR3 (p = 3.46 × 10−3), and VEGFA (p = 8.21 × 10−4), all implicated in ALS through genetic studies, and changes in other genes in pathways involving RNA processing and immune response. These findings suggest that analysis of gene expression stratified by disease severity can identify major ALS genes and may be more efficient than traditional case-control comparison. |
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