Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls

Infante, Jon; Prieto, Carlos; Sierra, María; Sánchez‐Juan, Pascual; González‐Aramburu, Isabel; Sánchez-Quintana, Coro; Berciano, José; Combarros, Onofre; Sainz, Jesús

doi:10.1016/j.neurobiolaging.2014.10.039

Cited by 38 publications

(45 citation statements)

References 34 publications

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“…For the 26 original studies on blood, the majority (10 studies) were performed on venous whole blood (Scherzer et al., ; Aguiar & Severino, ; Shehadeh et al., ; Potashkin et al., ; Karlsson et al., ; Alieva et al., ; Calligaris et al., ; Infante et al., , ; Pinho et al., ). In the remaining studies, five studies were on peripheral blood mononuclear cells (Kedmi et al., ; Martins et al., ; Mutez et al., , ; Nkiliza et al., ), five studies on white blood cells (Soreq et al., , ,b; Soreq et al., ; Kobo et al., ), four on serum (Botta‐Orfila et al., ; Vallelunga et al., ; Ding et al., ; Dong et al., ) and two on plasma (Table ; Table S1; Khoo et al., ; Cardo et al., ).…”

Section: Description Of Samples Used Across the 63 Original Studiesmentioning

confidence: 99%

“…The mean number of controls was 30, with a median of 20. All 26 studies on blood stated that the controls were matched for age and 21 studies were matched for sex, whereas only seven studies matched cases and controls on ethnicity (Kedmi et al., ; Alieva et al., ; Vallelunga et al., ; Calligaris et al., ; Infante et al., , ; Kobo et al., ). Another criterion for suitable control selection mentioned in 13 of the 26 studies was the absence of any personal or family history of neurological disease.…”

Section: Description Of Samples Used Across the 63 Original Studiesmentioning

confidence: 99%

“…A few of the studies used Agilent (Mutez et al., , ; Nkiliza et al., ) or Illumina microarrays (Karlsson et al., ; Alieva et al., ). To date, only three of the 26 original blood studies used the RNA‐Seq technique, two of which were performed using the Illumina TruSeq SBS (Infante et al., , ) and one used the SOLiD Total RNA‐seq (Soreq et al., ). Eight studies were performed using miRNA arrays or small RNA sequencing approaches (Table ; Martins et al., ; Khoo et al., ; Cardo et al., ; Soreq et al., ; Botta‐Orfila et al., ; Vallelunga et al., ; Ding et al., ; Dong et al., ).…”

Section: Transcriptomic Platforms Usedmentioning

confidence: 99%

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A review of genome‐wide transcriptomics studies in Parkinson's disease

Borrageiro

Haylett

Seedat

et al. 2017

Eur J of Neuroscience

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Parkinson's disease (PD) is a progressive and incurable neurodegenerative disorder. Although numerous genetic and environmental factors have been linked to the aetiology of PD the underlying pathobiology remains poorly understood, hampering the development of improved therapies. Transcriptomics has the potential to reveal significant insights into disease processes. In this review, we focused on published transcriptomics studies on PD with the aim of summarizing studies and identifying common biological pathways. A total of 96 articles were identified as follows: 12 meta-analyses, 21 re-analyses of existing data and 63 original studies. Of the 63 original studies, 33 were performed on brain tissue, 26 on blood, three on cerebrospinal fluid and one on skin. In the brain studies, altered pathways identified included those involved in dopamine metabolism, mitochondrial function, oxidative stress, protein degradation, neuroinflammation, vesicular transport and synaptic transmission. Studies on blood samples revealed alterations in pathways involved in immune function, inflammation, RNA processing, protein chaperones, mitochondrial function and programmed cell death. Limitations of these studies include small sample sizes (generally <40 cases/40 controls) and the application of widely varying statistical analysis and parameters. Only eight studies used the RNA-Seq technique. This review highlights the need for harmonization of transcriptomic approaches and the statistical analyses, and for the data to be deposited into publicly available databases in a standardized format for meta-analyses. Notably, the concordance of several pathways such as mitochondrial function, protein degradation and inflammation, identified in both blood and brain tissues, suggests that the disease process is systemic and not restricted to neurological tissues.

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Section: Description Of Samples Used Across the 63 Original Studiesmentioning

confidence: 99%

Section: Description Of Samples Used Across the 63 Original Studiesmentioning

confidence: 99%

Section: Transcriptomic Platforms Usedmentioning

confidence: 99%

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A review of genome‐wide transcriptomics studies in Parkinson's disease

Borrageiro

Haylett

Seedat

et al. 2017

Eur J of Neuroscience

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“…Like NRXN1 , also CNTNAP2 belongs to neurexin superfamily and encodes a neuronal transmembrane protein involved in neural-glia interactions and clustering of potassium channels in myelinated axons. Variations in this gene have been involved in susceptibility to neurodevelopmental disorders and language impairment (Infante et al 2015). Moreover, downregulation of CNTNAP2 has been associated with AD and PD conditions (Infante et al 2015; van Abel et al 2012).…”

Section: A Systems Biology Approach For Rare and Singleton Cnvsmentioning

confidence: 99%

“…Variations in this gene have been involved in susceptibility to neurodevelopmental disorders and language impairment (Infante et al 2015). Moreover, downregulation of CNTNAP2 has been associated with AD and PD conditions (Infante et al 2015; van Abel et al 2012). It has been suggested that neurexins–neuroligins level fluctuations sway the balance between excitatory and inhibitory neurotransmission, leading to damage of synapses and dendrites and maybe triggering protein aggregates in neurodegenerative conditions (Sindi et al 2014).…”

Section: A Systems Biology Approach For Rare and Singleton Cnvsmentioning

confidence: 99%

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

et al. 2016

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Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder of aging, was long believed to be a non-genetic sporadic origin syndrome. The proof that several genetic loci are responsible for rare Mendelian forms has represented a revolutionary breakthrough, enabling to reveal molecular mechanisms underlying this debilitating still incurable condition. While single nucleotide polymorphisms (SNPs) and small indels constitute the most commonly investigated DNA variations accounting for only a limited number of PD cases, larger genomic molecular rearrangements have emerged as significant PD-causing mutations, including submicroscopic Copy Number Variations (CNVs). CNVs constitute a prevalent source of genomic variations and substantially participate in each individual’s genomic makeup and phenotypic outcome. However, the majority of genetic studies have focused their attention on single candidate-gene mutations or on common variants reaching a significant statistical level of acceptance. This gene-centric approach is insufficient to uncover the genetic background of polygenic multifactorial disorders like PD, and potentially masks rare individual CNVs that all together might contribute to disease development or progression. In this review, we will discuss literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will analyze the most frequent copy number changes in familiar PD genes and provide a “systems biology” overview of rare individual rearrangements that could functionally act on commonly deregulated molecular pathways. Assessing the global genome-wide burden of CNVs in PD patients may reveal new disease-related molecular mechanisms, and open the window to a new possible genetic scenario in the unsolved PD puzzle.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1749-4) contains supplementary material, which is available to authorized users.

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Detection of a Parkinson's Disease–Specific MicroRNA Signature in Nasal and Oral Swabs

Schließer,

Struebing,

Northoff

et al. 2023

Movement Disorders

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BackgroundBiomaterials from oral and nasal swabs provide, in theory, a potential resource for biomarker development. However, their diagnostic value has not yet been investigated in the context of Parkinson's disease (PD) and associated conditions.ObjectiveWe have previously identified a PD‐specific microRNA (miRNA) signature in gut biopsies. In this work, we aimed to investigate the expression of miRNAs in routine buccal (oral) and nasal swabs obtained from cases with idiopathic PD and isolated rapid eye movement sleep behavior disorder (iRBD), a prodromal symptom that often precedes α‐synucleinopathies. We aimed to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression.MethodsHealthy control cases (n = 28), cases with PD (n = 29), and cases with iRBD (n = 8) were prospectively recruited to undergo routine buccal and nasal swabs. Total RNA was extracted from the swab material, and the expression of a predefined set of miRNAs was quantified by quantitative real‐time polymerase chain reaction.ResultsStatistical analysis revealed a significantly increased expression of hsa‐miR‐1260a in cases who had PD. Interestingly, hsa‐miR‐1260a expression levels correlated with diseases severity, as well as olfactory function, in the PD and iRBD cohorts. Mechanistically, hsa‐miR‐1260a segregated to Golgi‐associated cellular processes with a potential role in mucosal plasma cells. Predicted hsa‐miR‐1260a target gene expression was reduced in iRBD and PD groups.ConclusionsOur work demonstrates oral and nasal swabs as a valuable biomarker pool in PD and associated neurodegenerative conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls

Cited by 38 publications

References 34 publications

A review of genome‐wide transcriptomics studies in Parkinson's disease

A review of genome‐wide transcriptomics studies in Parkinson's disease

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

Detection of a Parkinson's Disease–Specific MicroRNA Signature in Nasal and Oral Swabs

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