Deciphering the role of a SINE-VNTR-Alu retrotransposon polymorphism as a biomarker of Parkinson's disease progression.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 05 2024
13 05 2024
Historique:
received:
27
04
2023
accepted:
09
05
2024
medline:
14
5
2024
pubmed:
14
5
2024
entrez:
13
5
2024
Statut:
epublish
Résumé
SINE-VNTR-Alu (SVA) retrotransposons are transposable elements which represent a source of genetic variation. We previously demonstrated that the presence/absence of a human-specific SVA, termed SVA_67, correlated with the progression of Parkinson's disease (PD). In the present study, we demonstrate that SVA_67 acts as expression quantitative trait loci, thereby exhibiting a strong regulatory effect across the genome using whole genome and transcriptomic data from the Parkinson's progression markers initiative cohort. We further show that SVA_67 is polymorphic for its variable number tandem repeat domain which correlates with both regulatory properties in a luciferase reporter gene assay in vitro and differential expression of multiple genes in vivo. Additionally, this variation's utility as a biomarker is reflected in a correlation with a number of PD progression markers. These experiments highlight the plethora of transcriptomic and phenotypic changes associated with SVA_67 polymorphism which should be considered when investigating the missing heritability of neurodegenerative diseases.
Identifiants
pubmed: 38740892
doi: 10.1038/s41598-024-61753-5
pii: 10.1038/s41598-024-61753-5
doi:
Substances chimiques
Retroelements
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10932Subventions
Organisme : Motor Neurone Disease Association
ID : ref Quinn/Apr20/875-791
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
Références
Wang, H. et al. SVA elements: A hominid-specific retroposon family. J. Mol. Biol. 354, 994–1007 (2005).
pubmed: 16288912
doi: 10.1016/j.jmb.2005.09.085
Hancks, D. C. & Kazazian, H. H. Active human retrotransposons: Variation and disease. Curr. Opin. Genet. Dev. 22, 191–203 (2012).
pubmed: 22406018
pmcid: 3376660
doi: 10.1016/j.gde.2012.02.006
McClintock, B. The origin and behavior of mutable loci in maize. Proc. Natl. Acad. Sci. U. S. A. 36, 344–355 (1950).
pubmed: 15430309
pmcid: 1063197
doi: 10.1073/pnas.36.6.344
Beck, C. R., Garcia-Perez, J. L., Badge, R. M. & Moran, J. V. LINE-1 elements in structural variation and disease. Annu. Rev. Genom. Hum. Genet. 12, 187–215 (2011).
doi: 10.1146/annurev-genom-082509-141802
Gianfrancesco, O. et al. The role of SINE-VNTR-Alu (SVA) retrotransposons in shaping the human genome. IJMS 20, 5977 (2019).
pubmed: 31783611
pmcid: 6928650
doi: 10.3390/ijms20235977
Payer, L. M. & Burns, K. H. Transposable elements in human genetic disease. Nat. Rev. Genet. 20, 760–772 (2019).
pubmed: 31515540
doi: 10.1038/s41576-019-0165-8
Soreq, L. et al. Long non-coding RNA and alternative splicing modulations in Parkinson’s leukocytes identified by RNA sequencing. PLoS Comput. Biol. 10, e1003517 (2014).
pubmed: 24651478
pmcid: 3961179
doi: 10.1371/journal.pcbi.1003517
Elbarbary, R. A., Lucas, B. A. & Maquat, L. E. Retrotransposons as regulators of gene expression. Science 351, aac7247 (2016).
pubmed: 26912865
pmcid: 4788378
doi: 10.1126/science.aac7247
Quinn, J. P. & Bubb, V. J. SVA retrotransposons as modulators of gene expression. Mobile Genet. Elements 4, e32102 (2014).
doi: 10.4161/mge.32102
Gianfrancesco, O., Bubb, V. J. & Quinn, J. P. SVA retrotransposons as potential modulators of neuropeptide gene expression. Neuropeptides 64, 3–7 (2017).
pubmed: 27743609
pmcid: 5529292
doi: 10.1016/j.npep.2016.09.006
Savage, A. L., Bubb, V. J., Breen, G. & Quinn, J. P. Characterisation of the potential function of SVA retrotransposons to modulate gene expression patterns. BMC Evol. Biol. 13, 101 (2013).
pubmed: 23692647
pmcid: 3667099
doi: 10.1186/1471-2148-13-101
Savage, A. L. et al. An evaluation of a SVA retrotransposon in the FUS promoter as a transcriptional regulator and its association to ALS. PLoS One 9, e90833 (2014).
pubmed: 24608899
pmcid: 3946630
doi: 10.1371/journal.pone.0090833
Hancks, D. C. & Kazazian, H. H. Roles for retrotransposon insertions in human disease. Mobile DNA 7, 9 (2016).
pubmed: 27158268
pmcid: 4859970
doi: 10.1186/s13100-016-0065-9
Pugacheva, E. M. et al. CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention. Proc. Natl. Acad. Sci. U. S. A. 117, 2020–2031 (2020).
pubmed: 31937660
pmcid: 6995019
doi: 10.1073/pnas.1911708117
Pugacheva, E. M. et al. The cancer-associated CTCFL/BORIS protein targets multiple classes of genomic repeats, with a distinct binding and functional preference for humanoid-specific SVA transposable elements. Epigenet. Chromatin 9, 35 (2016).
doi: 10.1186/s13072-016-0084-2
Colonna Romano, N. & Fanti, L. Transposable elements: Major players in shaping genomic and evolutionary patterns. Cells 11, 1048 (2022).
pubmed: 35326499
pmcid: 8947103
doi: 10.3390/cells11061048
Diehl, A. G., Ouyang, N. & Boyle, A. P. Transposable elements contribute to cell and species-specific chromatin looping and gene regulation in mammalian genomes. Nat. Commun. 11, 1796 (2020).
pubmed: 32286261
pmcid: 7156512
doi: 10.1038/s41467-020-15520-5
Kentepozidou, E. et al. Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains. Genome Biol. 21, 5 (2020).
pubmed: 31910870
pmcid: 6945661
doi: 10.1186/s13059-019-1894-x
Wang, J. et al. dbRIP: A highly integrated database of retrotransposon insertion polymorphisms in humans. Hum. Mutat. 27, 323–329 (2006).
pubmed: 16511833
pmcid: 1855216
doi: 10.1002/humu.20307
Makino, S. et al. Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-Parkinsonism. Am. J. Hum. Genet. 80, 393–406 (2007).
pubmed: 17273961
pmcid: 1821114
doi: 10.1086/512129
Bragg, D. C. et al. Disease onset in X-linked dystonia-parkinsonism correlates with expansion of a hexameric repeat within an SVA retrotransposon in TAF1. Proc. Natl. Acad. Sci. U. S. A. https://doi.org/10.1073/pnas.1712526114 (2017).
doi: 10.1073/pnas.1712526114
pubmed: 29229810
pmcid: 5754783
Aneichyk, T. et al. Dissecting the causal mechanism of X-linked dystonia-Parkinsonism by integrating genome and transcriptome assembly. Cell 172, 897-909.e21 (2018).
pubmed: 29474918
pmcid: 5831509
doi: 10.1016/j.cell.2018.02.011
Bychkov, I. et al. Complex transposon insertion as a novel cause of pompe disease. IJMS 22, 10887 (2021).
pubmed: 34639227
pmcid: 8509548
doi: 10.3390/ijms221910887
Pfaff, A. L., Singleton, L. M. & Kõks, S. Mechanisms of disease-associated SINE-VNTR-Alus. Exp. Biol. Med. (Maywood) 247, 756–764 (2022).
pubmed: 35387528
pmcid: 9134764
doi: 10.1177/15353702221082612
Zody, M. C. et al. Evolutionary toggling of the MAPT 17q21.31 inversion region. Nat. Genet. 40, 1076–1083 (2008).
pubmed: 19165922
pmcid: 2684794
doi: 10.1038/ng.193
Donnelly, M. P. et al. The distribution and most recent common ancestor of the 17q21 inversion in humans. Am. J. Hum. Genet. 86, 161–171 (2010).
pubmed: 20116045
pmcid: 2820164
doi: 10.1016/j.ajhg.2010.01.007
Wider, C. et al. Association of the MAPT locus with Parkinson’s disease: MAPT H1 in Parkinson’s disease. Eur. J. Neurol. 17, 483–486 (2010).
pubmed: 19912324
doi: 10.1111/j.1468-1331.2009.02847.x
Sánchez-Juan, P. et al. The MAPT H1 haplotype is a risk factor for Alzheimer’s disease in APOE ε4 non-carriers. Front. Aging Neurosci. 11, 327 (2019).
pubmed: 31866851
pmcid: 6905227
doi: 10.3389/fnagi.2019.00327
Verpillat, P. et al. Association between the extended tau haplotype and frontotemporal dementia. Arch. Neurol. 59, 935 (2002).
pubmed: 12056929
doi: 10.1001/archneur.59.6.935
Higgins, J. J. et al. An extended 5′- tau susceptibility haplotype in progressive supranuclear palsy. Neurology 55, 1364–1367 (2000).
pubmed: 11087782
doi: 10.1212/WNL.55.9.1364
Martin, E. R. Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease. JAMA 286, 2245 (2001).
pubmed: 11710889
pmcid: 3973175
doi: 10.1001/jama.286.18.2245
Simón-Sánchez, J. et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat. Genet. 41, 1308–1312 (2009).
pubmed: 19915575
pmcid: 2787725
doi: 10.1038/ng.487
Bandrés-Ciga, S. et al. Genome-wide assessment of Parkinson’s disease in a Southern Spanish population. Neurobiol. Aging 45(213), e3-213.e9 (2016).
Desikan, R. S. et al. Genetic overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus. Mol. Psychiatry 20, 1588–1595 (2015).
pubmed: 25687773
pmcid: 4539304
doi: 10.1038/mp.2015.6
Nalls, M. A. et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: A meta-analysis of genome-wide association studies. Lancet Neurol. 18, 1091–1102 (2019).
pubmed: 31701892
pmcid: 8422160
doi: 10.1016/S1474-4422(19)30320-5
Nalls, M. A. et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat. Genet. 46, 989–993 (2014).
pubmed: 25064009
pmcid: 4146673
doi: 10.1038/ng.3043
Pfaff, A. L., Bubb, V. J., Quinn, J. P. & Koks, S. Reference SVA insertion polymorphisms are associated with Parkinson’s disease progression and differential gene expression. NPJ Parkinsons Dis. 7, 44 (2021).
pubmed: 34035310
pmcid: 8149882
doi: 10.1038/s41531-021-00189-4
Fröhlich, A., Pfaff, A. L., Bubb, V. J., Koks, S. & Quinn, J. P. Characterisation of the function of a SINE-VNTR-Alu retrotransposon to modulate isoform expression at the MAPT locus. Front. Mol. Neurosci. 15, 815695 (2022).
pubmed: 35370538
pmcid: 8965460
doi: 10.3389/fnmol.2022.815695
O’Brien, H. E. et al. Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders. Genome Biol. 19, 194 (2018).
pubmed: 30419947
pmcid: 6231252
doi: 10.1186/s13059-018-1567-1
Simuni, T. et al. Longitudinal change of clinical and biological measures in early Parkinson’s disease: Parkinson’s progression markers initiative cohort: Early PD and MDS-UPDRS and dat binding change. Mov. Disord. 33, 771–782 (2018).
pubmed: 29572948
pmcid: 6001458
doi: 10.1002/mds.27361
Ikeda, K., Ebina, J., Kawabe, K. & Iwasaki, Y. Dopamine transporter imaging in Parkinson disease: Progressive changes and therapeutic modification after anti-Parkinsonian medications. Intern. Med. 58, 1665–1672 (2019).
pubmed: 30799370
pmcid: 6630131
doi: 10.2169/internalmedicine.2489-18
Wang, L., Rishishwar, L., Mariño-Ramírez, L. & Jordan, I. K. Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements. Nucleic Acids Res. https://doi.org/10.1093/nar/gkw1286 (2016).
doi: 10.1093/nar/gkw1286
pubmed: 28053168
pmcid: 5389537
Li, T. et al. Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with Koolen-de Vries syndrome in mice. Nat. Commun. 13, 931 (2022).
pubmed: 35177641
pmcid: 8854428
doi: 10.1038/s41467-022-28613-0
Guo, F., Liu, X., Cai, H. & Le, W. Autophagy in neurodegenerative diseases: Pathogenesis and therapy. Brain Pathol. 28, 3–13 (2018).
pubmed: 28703923
doi: 10.1111/bpa.12545
Linda, K. et al. Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders. Autophagy 18, 423–442 (2022).
pubmed: 34286667
doi: 10.1080/15548627.2021.1936777
Soutar, M. P. M. et al. Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci. Brain 145, 4349–4367 (2022).
pubmed: 36074904
pmcid: 9762952
doi: 10.1093/brain/awac325
Plotegher, N. & Duchen, M. R. Crosstalk between lysosomes and mitochondria in Parkinson’s disease. Front. Cell Dev. Biol. 5, 110 (2017).
pubmed: 29312935
pmcid: 5732996
doi: 10.3389/fcell.2017.00110
Bowles, K. R. et al. 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes. Mol. Neurodegen. 17, 48 (2022).
doi: 10.1186/s13024-022-00551-x
Marshall, J. N. et al. Variable number tandem repeats—Their emerging role in sickness and health. Exp. Biol. Med. (Maywood) 246, 1368–1376 (2021).
pubmed: 33794697
doi: 10.1177/15353702211003511
Marshall, J. N. G. et al. A polymorphic transcriptional regulatory domain in the amyotrophic lateral sclerosis risk gene CFAP410 correlates with differential isoform expression. Front. Mol. Neurosci. 15, 954928 (2022).
pubmed: 36131690
pmcid: 9484465
doi: 10.3389/fnmol.2022.954928
Fröhlich, A. et al. CRISPR deletion of a SINE-VNTR-Alu (SVA_67) retrotransposon demonstrates its ability to differentially modulate gene expression at the MAPT locus. Front. Neurol. 14, 1273036 (2023).
pubmed: 37840928
pmcid: 10570551
doi: 10.3389/fneur.2023.1273036
Hill, E. J. et al. Genome sequencing in the Parkinson disease clinic. Neurol. Genet. 8, e200002 (2022).
pubmed: 35747619
pmcid: 9210549
doi: 10.1212/NXG.0000000000200002
Kovanda, A. et al. A multicenter study of genetic testing for Parkinson’s disease in the clinical setting. NPJ Parkinsons Dis. 8, 149 (2022).
pubmed: 36333361
pmcid: 9636217
doi: 10.1038/s41531-022-00408-6
Yeow, D., Rudaks, L. I., Siow, S.-F., Davis, R. L. & Kumar, K. R. Genetic testing of movements disorders: A review of clinical utility. Tremor Hyperkinet. Mov. 14, 2 (2024).
doi: 10.5334/tohm.835
Shabalin, A. A. Matrix eQTL: Ultra fast eQTL analysis via large matrix operations. Bioinformatics 28, 1353–1358 (2012).
pubmed: 22492648
pmcid: 3348564
doi: 10.1093/bioinformatics/bts163
Purcell, S. et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
pubmed: 17701901
pmcid: 1950838
doi: 10.1086/519795
Soneson, C., Love, M. I. & Robinson, M. D. Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences. F1000Research 4, 1521 (2016).
pmcid: 4712774
doi: 10.12688/f1000research.7563.2
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8