Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease
Cytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including Huntington’s disease (HD), six different spinocerebellar ataxias (SCA...
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doaj-82a38fdd6d4e4c7fa181c03435522c842020-11-25T00:49:20ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-11-011010.3389/fnmol.2017.00399302189Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s DiseaseArlin Keo0Arlin Keo1N. Ahmad Aziz2Oleh Dzyubachyk3Jeroen van der Grond4Willeke M. C. van Roon-Mom5Boudewijn P. F. Lelieveldt6Boudewijn P. F. Lelieveldt7Boudewijn P. F. Lelieveldt8Marcel J. T. Reinders9Marcel J. T. Reinders10Ahmed Mahfouz11Ahmed Mahfouz12Computational Biology Center, Leiden University Medical Center, Leiden, NetherlandsDelft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, Delft, NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, NetherlandsComputational Biology Center, Leiden University Medical Center, Leiden, NetherlandsDelft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, Delft, NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, NetherlandsComputational Biology Center, Leiden University Medical Center, Leiden, NetherlandsDelft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, Delft, NetherlandsComputational Biology Center, Leiden University Medical Center, Leiden, NetherlandsDelft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, Delft, NetherlandsCytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including Huntington’s disease (HD), six different spinocerebellar ataxias (SCAs), dentatorubral-pallidoluysian atrophy, and spinobulbar muscular atrophy. The expanded CAG repeat length in the causative gene is negatively related to the age-at-onset (AAO) of clinical symptoms. In addition to the expanded CAG repeat length in the causative gene, the normal CAG repeats in the other polyQ genes can affect the AAO, suggesting functional interactions between the polyQ genes. However, there is no detailed assessment of the relationships among polyQ genes in pathologically relevant brain regions. We used gene co-expression analysis to study the functional relationships among polyQ genes in different brain regions using the Allen Human Brain Atlas (AHBA), a spatial map of gene expression in the healthy brain. We constructed co-expression networks for seven anatomical brain structures, as well as a region showing a specific pattern of atrophy in HD patients detected by magnetic resonance imaging (MRI) of the brain. In this HD-associated region, we found that ATN1 and ATXN2 were co-expressed and shared co-expression partners which were enriched for DNA repair genes. We observed a similar co-expression pattern in the frontal lobe, parietal lobe, and striatum in which this relation was most pronounced. Given that the co-expression patterns for these anatomical structures were similar to those for the HD-associated region, our results suggest that their disruption is likely involved in HD pathology. Moreover, ATN1 and ATXN2 also shared many co-expressed genes with HTT, the causative gene of HD, across the brain. Although this triangular relationship among these three polyQ genes may also be dysregulated in other polyQ diseases, stronger co-expression patterns between ATN1 and ATXN2 observed in the HD-associated region, especially in the striatum, may be more specific to HD.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00399/fullgene co-expressionpolyglutamine diseaseshuman brainHuntington’s diseaseneurodegenerationMRI |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arlin Keo Arlin Keo N. Ahmad Aziz Oleh Dzyubachyk Jeroen van der Grond Willeke M. C. van Roon-Mom Boudewijn P. F. Lelieveldt Boudewijn P. F. Lelieveldt Boudewijn P. F. Lelieveldt Marcel J. T. Reinders Marcel J. T. Reinders Ahmed Mahfouz Ahmed Mahfouz |
spellingShingle |
Arlin Keo Arlin Keo N. Ahmad Aziz Oleh Dzyubachyk Jeroen van der Grond Willeke M. C. van Roon-Mom Boudewijn P. F. Lelieveldt Boudewijn P. F. Lelieveldt Boudewijn P. F. Lelieveldt Marcel J. T. Reinders Marcel J. T. Reinders Ahmed Mahfouz Ahmed Mahfouz Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease Frontiers in Molecular Neuroscience gene co-expression polyglutamine diseases human brain Huntington’s disease neurodegeneration MRI |
author_facet |
Arlin Keo Arlin Keo N. Ahmad Aziz Oleh Dzyubachyk Jeroen van der Grond Willeke M. C. van Roon-Mom Boudewijn P. F. Lelieveldt Boudewijn P. F. Lelieveldt Boudewijn P. F. Lelieveldt Marcel J. T. Reinders Marcel J. T. Reinders Ahmed Mahfouz Ahmed Mahfouz |
author_sort |
Arlin Keo |
title |
Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease |
title_short |
Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease |
title_full |
Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease |
title_fullStr |
Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease |
title_full_unstemmed |
Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease |
title_sort |
co-expression patterns between atn1 and atxn2 coincide with brain regions affected in huntington’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2017-11-01 |
description |
Cytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including Huntington’s disease (HD), six different spinocerebellar ataxias (SCAs), dentatorubral-pallidoluysian atrophy, and spinobulbar muscular atrophy. The expanded CAG repeat length in the causative gene is negatively related to the age-at-onset (AAO) of clinical symptoms. In addition to the expanded CAG repeat length in the causative gene, the normal CAG repeats in the other polyQ genes can affect the AAO, suggesting functional interactions between the polyQ genes. However, there is no detailed assessment of the relationships among polyQ genes in pathologically relevant brain regions. We used gene co-expression analysis to study the functional relationships among polyQ genes in different brain regions using the Allen Human Brain Atlas (AHBA), a spatial map of gene expression in the healthy brain. We constructed co-expression networks for seven anatomical brain structures, as well as a region showing a specific pattern of atrophy in HD patients detected by magnetic resonance imaging (MRI) of the brain. In this HD-associated region, we found that ATN1 and ATXN2 were co-expressed and shared co-expression partners which were enriched for DNA repair genes. We observed a similar co-expression pattern in the frontal lobe, parietal lobe, and striatum in which this relation was most pronounced. Given that the co-expression patterns for these anatomical structures were similar to those for the HD-associated region, our results suggest that their disruption is likely involved in HD pathology. Moreover, ATN1 and ATXN2 also shared many co-expressed genes with HTT, the causative gene of HD, across the brain. Although this triangular relationship among these three polyQ genes may also be dysregulated in other polyQ diseases, stronger co-expression patterns between ATN1 and ATXN2 observed in the HD-associated region, especially in the striatum, may be more specific to HD. |
topic |
gene co-expression polyglutamine diseases human brain Huntington’s disease neurodegeneration MRI |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00399/full |
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