Allele-specific expression of Parkinson’s disease susceptibility genes in human brain

Abstract Genome-wide association studies have identified genetic variation in genomic loci associated with susceptibility to Parkinson’s disease (PD), the most common neurodegenerative movement disorder worldwide. We used allelic expression profiling of genes located within PD-associated loci to ide...

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Autores principales:	Margrete Langmyhr, Sandra Pilar Henriksen, Chiara Cappelletti, Wilma D. J. van de Berg, Lasse Pihlstrøm, Mathias Toft
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/911000b21a6c43fa84edbe5866d2fd5f
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spelling	oai:doaj.org-article:911000b21a6c43fa84edbe5866d2fd5f2021-12-02T14:01:38ZAllele-specific expression of Parkinson’s disease susceptibility genes in human brain10.1038/s41598-020-79990-92045-2322https://doaj.org/article/911000b21a6c43fa84edbe5866d2fd5f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79990-9https://doaj.org/toc/2045-2322Abstract Genome-wide association studies have identified genetic variation in genomic loci associated with susceptibility to Parkinson’s disease (PD), the most common neurodegenerative movement disorder worldwide. We used allelic expression profiling of genes located within PD-associated loci to identify cis-regulatory variation affecting gene expression. DNA and RNA were extracted from post-mortem superior frontal gyrus tissue and whole blood samples from PD patients and controls. The relative allelic expression of transcribed SNPs in 12 GWAS risk genes was analysed by real-time qPCR. Allele-specific expression was identified for 9 out of 12 genes tested (GBA, TMEM175, RAB7L1, NUCKS1, MCCC1, BCKDK, ZNF646, LZTS3, and WDHD1) in brain tissue samples. Three genes (GPNMB, STK39 and SIPA1L2) did not show significant allele-specific effects. Allele-specific effects were confirmed in whole blood for three genes (BCKDK, LZTS3 and MCCC1), whereas two genes (RAB7L1 and NUCKS1) showed brain-specific allelic expression. Our study supports the hypothesis that changes to the cis-regulation of gene expression is a major mechanism behind a large proportion of genetic associations in PD. Interestingly, allele-specific expression was also observed for coding variants believed to be causal variants (GBA and TMEM175), indicating that splicing and other regulatory mechanisms may be involved in disease development.Margrete LangmyhrSandra Pilar HenriksenChiara CappellettiWilma D. J. van de BergLasse PihlstrømMathias ToftNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Margrete Langmyhr Sandra Pilar Henriksen Chiara Cappelletti Wilma D. J. van de Berg Lasse Pihlstrøm Mathias Toft Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
description	Abstract Genome-wide association studies have identified genetic variation in genomic loci associated with susceptibility to Parkinson’s disease (PD), the most common neurodegenerative movement disorder worldwide. We used allelic expression profiling of genes located within PD-associated loci to identify cis-regulatory variation affecting gene expression. DNA and RNA were extracted from post-mortem superior frontal gyrus tissue and whole blood samples from PD patients and controls. The relative allelic expression of transcribed SNPs in 12 GWAS risk genes was analysed by real-time qPCR. Allele-specific expression was identified for 9 out of 12 genes tested (GBA, TMEM175, RAB7L1, NUCKS1, MCCC1, BCKDK, ZNF646, LZTS3, and WDHD1) in brain tissue samples. Three genes (GPNMB, STK39 and SIPA1L2) did not show significant allele-specific effects. Allele-specific effects were confirmed in whole blood for three genes (BCKDK, LZTS3 and MCCC1), whereas two genes (RAB7L1 and NUCKS1) showed brain-specific allelic expression. Our study supports the hypothesis that changes to the cis-regulation of gene expression is a major mechanism behind a large proportion of genetic associations in PD. Interestingly, allele-specific expression was also observed for coding variants believed to be causal variants (GBA and TMEM175), indicating that splicing and other regulatory mechanisms may be involved in disease development.
format	article
author	Margrete Langmyhr Sandra Pilar Henriksen Chiara Cappelletti Wilma D. J. van de Berg Lasse Pihlstrøm Mathias Toft
author_facet	Margrete Langmyhr Sandra Pilar Henriksen Chiara Cappelletti Wilma D. J. van de Berg Lasse Pihlstrøm Mathias Toft
author_sort	Margrete Langmyhr
title	Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
title_short	Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
title_full	Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
title_fullStr	Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
title_full_unstemmed	Allele-specific expression of Parkinson’s disease susceptibility genes in human brain
title_sort	allele-specific expression of parkinson’s disease susceptibility genes in human brain
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/911000b21a6c43fa84edbe5866d2fd5f
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Allele-specific expression of Parkinson’s disease susceptibility genes in human brain

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