Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2

Human Molecular Genetics
Lance T PfliegerStefan M Pulst

Abstract

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice versus wild-type (WT) littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes. Our analysis revealed previously uncharacterized early and progressive abnormal patterning of cerebellar gene expression. Weighted Gene Coexpression Network Analysis revealed four gene modules that were significantly correlated with disease status, composed primarily of genes associated with GTPase signaling, calcium signaling and cell death. Of these genes, few overlapped with differentially expressed cerebellar genes that we identified in Atxn2-/- knockout mice versus WT littermates, suggesting that loss-of-function is not a significant component of disease pathology. We conclude that SCA2 is a disease c...Continue Reading

References

Oct 25, 2003·Journal of Neuropathology and Experimental Neurology·Bernd O EvertUllrich Wüllner
Dec 17, 2003·Archives of Neurology·Ichiro YabeKunio Tashiro
Mar 19, 2004·BMC Bioinformatics·Zhenjun HuCharles DeLisi
Dec 8, 2004·Brain Research. Molecular Brain Research·Yongqi RongJames I Morgan
Nov 19, 2005·Biochemical and Biophysical Research Communications·Tim-Rasmus KiehlStefan-M Pulst
Dec 24, 2005·RNA·Praveen SethupathyArtemis G Hatzigeorgiou
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Bin Zhang, Steve Horvath
Jun 26, 2007·PLoS Genetics·Joyce van de LeemputAndrew B Singleton
Nov 23, 2007·BMC Systems Biology·Peter Langfelder, Steve Horvath
Feb 6, 2008·Human Molecular Genetics·Isabel Lastres-BeckerGeorg Auburger
Aug 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kei WataseHuda Y Zoghbi
Oct 29, 2008·Genome Research·Robin C FriedmanDavid P Bartel
Nov 28, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xi ChenIlya Bezprozvanny
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jul 21, 2009·PloS One·Duong P HuynhStefan M Pulst
Jul 25, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jing LiuIlya Bezprozvanny
Apr 27, 2012·Journal of Biomedicine & Biotechnology·Mykol LarvieKazue Takahashi
Oct 23, 2012·Human Molecular Genetics·Stephen T HansenStefan M Pulst
Feb 5, 2013·Neurobiology of Disease·Edgardo Rodriguez-LebronBeverly L Davidson
Apr 25, 2013·PloS One·Peter LangfelderSteve Horvath
May 28, 2013·Genome Medicine·Jeremy A MillerDaniel H Geschwind
Jan 7, 2014·Frontiers in Cellular Neuroscience·Simona MaciottaYvan Torrente
Mar 5, 2014·Systems and Synthetic Biology·Pramod Rajaram Somvanshi, K V Venkatesh
Oct 16, 2014·Neurobiology of Disease·Aikaterini S PapadopoulouBart De Strooper
Jan 23, 2015·Frontiers in Cellular Neuroscience·Elizabeth K LucasRita M Cowell
Apr 23, 2015·PLoS Genetics·Warunee DansithongStefan M Pulst
Jun 11, 2015·BioMed Research International·Grigory A StepanovDmitry V Semenov
Aug 13, 2015·ELife·Vikram AgarwalDavid P Bartel
Dec 29, 2015·Neurobiology of Disease·Conceição BettencourtHenry Houlden
Apr 29, 2016·Molecular Medicine Reports·Jinqian LiangShugang Li
May 21, 2016·The Journal of Physiology·Pratap MeeraThomas S Otis

❮ Previous
Next ❯

Citations

Oct 11, 2017·Human Molecular Genetics·James M Dell'OrcoVikram G Shakkottai
Sep 1, 2017·Nature Reviews. Neuroscience·Henry L PaulsonHarry T Orr
Jan 2, 2020·International Journal of Molecular Sciences·Francesca PrestoriEgidio D'Angelo
Aug 23, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Polina A Egorova, Ilya B Bezprozvanny
Sep 17, 2020·International Journal of Molecular Sciences·Aleksandar ArsovićGeorg Auburger
Jun 26, 2020·Frontiers in Neuroscience·Anna Niewiadomska-CimickaYvon Trottier
Sep 27, 2018·Acta Neuropathologica Communications·Maggie M K WongEsther B E Becker
May 26, 2021·Stem Cell Reviews and Reports·Marina P HommersomHans van Bokhoven

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.