NDLI: Rare variants in LRRK1 and Parkinson's disease

Content Provider	Springer Nature Link
Author	Schulte, Eva C. Ellwanger, Daniel C. Dihanich, Sybille Manzoni, Claudia Stangl, Katrin Schormair, Barbara Graf, Elisabeth Eck, Sebastian Mollenhauer, Brit Haubenberger, Dietrich Pirker, Walter Zimprich, Alexander Brücke, Thomas Lichtner, Peter Peters, Annette Gieger, Christian Trenkwalder, Claudia Mewes, Hans Werner Meitinger, Thomas Lewis, Patrick A. Klünemann, Hans H. Winkelmann, Juliane
Copyright Year	2013
Abstract	Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow-up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance.
Starting Page	49
Ending Page	57
Page Count	9
File Format	PDF
ISSN	13646745
Journal	Neurogenetics
Volume Number	15
Issue Number	1
e-ISSN	13646753
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2013-11-16
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Parkinson's disease LRRK1 EEF1D Exome sequencing Neurosciences Human Genetics Molecular Medicine
Content Type	Text
Resource Type	Article
Subject	Genetics Cellular and Molecular Neuroscience Genetics (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Rare variants in LRRK1 and Parkinson's disease

Rare variants in LRRK1 and Parkinson's disease

Variants in eukaryotic translation initiation factor 4G1 in sporadic Parkinson’s disease

Lrrk2 pathogenic substitutions in Parkinson's disease

An exome study of Parkinson’s disease in Sardinia, a Mediterranean genetic isolate

Novel recessive myotilin mutation causes severe myofibrillar myopathy

Leucine-rich repeat kinase 1: a paralog of LRRK2 and a candidate gene for Parkinson’s disease

Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia

Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld–Rieger syndrome

Rare variants in LRRK1 and Parkinson's disease

Similar Documents

Rare variants in LRRK1 and Parkinson's disease

Rare variants in LRRK1 and Parkinson's disease

Variants in eukaryotic translation initiation factor 4G1 in sporadic Parkinson’s disease

Lrrk2 pathogenic substitutions in Parkinson's disease

An exome study of Parkinson’s disease in Sardinia, a Mediterranean genetic isolate

Novel recessive myotilin mutation causes severe myofibrillar myopathy

Leucine-rich repeat kinase 1: a paralog of LRRK2 and a candidate gene for Parkinson’s disease

Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia

Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld–Rieger syndrome

Rare variants in LRRK1 and Parkinson's disease