Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database

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dc.authorid0000-0001-6032-0856
dc.authorid0000-0002-5792-2888
dc.authorid0000-0002-4467-1610
dc.authorid0000-0001-7058-5372
dc.authorid0000-0002-7720-455X
dc.authorid0000-0001-6344-503X
dc.authorid0000-0002-1598-5944
dc.authorscopusid57190379553
dc.authorscopusid36464272400
dc.authorscopusid57200644602
dc.authorscopusid57200649133
dc.authorscopusid57217388208
dc.authorscopusid57211855095
dc.authorscopusid57206483695
dc.authorwosidERTAS, MUSTAFA/ABE-3383-2020
dc.authorwosidBilgic, Basar/E-4821-2012
dc.authorwosidSahin, Erdi/A-4787-2018
dc.authorwosidSoysal, Aysun/AAX-7696-2021
dc.authorwosidOlgun, Gulden/AAB-1165-2020
dc.authorwosidBOZ, Cavit/V-5127-2017
dc.authorwosidKoc, Filiz/A-9125-2017
dc.contributor.authorTunca, Ceren
dc.contributor.authorŞeker, Tuncay
dc.contributor.authorAkçimen, Fulya
dc.contributor.authorCoşkun, Cemre
dc.contributor.authorBayraktar, Elif
dc.contributor.authorPalvadeau, Robin
dc.contributor.authorBaşak, A. Nazlı
dc.contributor.authorTurgut, Nilda
dc.date.accessioned2022-05-11T14:40:18Z
dc.date.available2022-05-11T14:40:18Z
dc.date.issued2020
dc.departmentFakülteler, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Nöroloji Ana Bilim Dalı
dc.description.abstractThe last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with similar to 70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlightsDECR1, ATL1, HDAC2, GEMIN4, andHNRNPA3as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).
dc.description.sponsorshipTUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S075]; Bogazici University Research FundsBogazici University [15B01P1]; Suna and Inan Kirac Foundation [2005-2020]
dc.description.sponsorshipTUBITAK, Grant/Award Number: 109S075; Bogazici University Research Funds, Grant/Award Number: 15B01P1; Suna and Inan Kirac Foundation, Grant/Award Number: 2005-2020
dc.identifier.doi10.1002/humu.24055
dc.identifier.endpageE45
dc.identifier.issn1059-7794
dc.identifier.issn1098-1004
dc.identifier.issue8en_US
dc.identifier.pmid32579787
dc.identifier.scopus2-s2.0-85087143307
dc.identifier.scopusqualityQ1
dc.identifier.startpageE7
dc.identifier.urihttps://doi.org/10.1002/humu.24055
dc.identifier.urihttps://hdl.handle.net/20.500.11776/8931
dc.identifier.volume41
dc.identifier.wosWOS:000542467300001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorTurgut, Nilda
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofHuman Mutation
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectALS
dc.subjectALS variant database
dc.subjectgenetics
dc.subjectclinical exome sequencing
dc.subjectcoexpression network analysis
dc.subjectgenetics
dc.subjectgenome-wide association study
dc.subjectmotor neuron disease
dc.subjectnext generation sequencing
dc.subjectTurkish peninsula
dc.subjectAmyotrophic-Lateral-Sclerosis
dc.subjectMotor-Neuron Disease
dc.subjectSpinal Muscular-Atrophy
dc.subjectCell-Cycle Regulators
dc.subjectCoexpression Network
dc.subjectSequence Variation
dc.subjectAnalyses Identify
dc.subjectGene-Mutations
dc.subjectRisk
dc.subjectForm
dc.titleRevisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database
dc.typeArticle

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