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

buir.contributor.authorNorman, Utku
buir.contributor.authorKarakahya, Oğuzhan
buir.contributor.authorOlgun, Gülden
buir.contributor.authorÇiçek, A. Ercüment
dc.citation.epagee45en_US
dc.citation.issueNumber8en_US
dc.citation.spagee7en_US
dc.citation.volumeNumber41en_US
dc.contributor.authorTunca, C.en_US
dc.contributor.authorŞeker, T.en_US
dc.contributor.authorAkçimen, F.en_US
dc.contributor.authorCoşkun, C.en_US
dc.contributor.authorBayraktar, E.en_US
dc.contributor.authorPalvadeau, R.en_US
dc.contributor.authorZor, S.en_US
dc.contributor.authorKoçoğlu, C.en_US
dc.contributor.authorKartal, E.en_US
dc.contributor.authorŞen, N. E.en_US
dc.contributor.authorHamzeiy, H.en_US
dc.contributor.authorÖzoğuz-Erimiş, A.en_US
dc.contributor.authorNorman, Utkuen_US
dc.contributor.authorKarakahya, Oğuzhanen_US
dc.contributor.authorOlgun, Güldenen_US
dc.contributor.authorAkgün, T.en_US
dc.contributor.authorDurmuş, H.en_US
dc.contributor.authorŞahin, E.en_US
dc.contributor.authorÇakar, A.en_US
dc.contributor.authorBaşar-Gürsoy, E.en_US
dc.contributor.authorBabacan-Yıldız, G.en_US
dc.contributor.authorİşak, B.en_US
dc.contributor.authorUluç, K.en_US
dc.contributor.authorHanağası, H.en_US
dc.contributor.authorBilgiç, B.en_US
dc.contributor.authorTurgut, N.en_US
dc.contributor.authorAysal, F.en_US
dc.contributor.authorErtaş, M.en_US
dc.contributor.authorBoz, C.en_US
dc.contributor.authorKotan, D.en_US
dc.contributor.authorİdrisoğlu, H.en_US
dc.contributor.authorSoysal, A.en_US
dc.contributor.authorUzun-Adatepe, N.en_US
dc.contributor.authorAkalın, M. A.en_US
dc.contributor.authorKoç, F.en_US
dc.contributor.authorTan, E.en_US
dc.contributor.authorOflazer, P.en_US
dc.contributor.authorDeymeer, F.en_US
dc.contributor.authorTaştan, Ö.en_US
dc.contributor.authorÇiçek, A. Ercümenten_US
dc.contributor.authorKavak, E.en_US
dc.contributor.authorParman, Y.en_US
dc.contributor.authorBaşak, A. N.en_US
dc.date.accessioned2021-02-10T11:01:16Z
dc.date.available2021-02-10T11:01:16Z
dc.date.issued2020
dc.departmentDepartment of Computer Engineeringen_US
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 ~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 highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as 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).en_US
dc.description.provenanceSubmitted by Onur Emek (onur.emek@bilkent.edu.tr) on 2021-02-10T11:01:16Z No. of bitstreams: 1 Revisiting_the_complex_architecture_of_ALS_in_Turkey_Expanding_genotypes,_shared_phenotypes,_molecularnetworks,_and_a_public_variant_database.pdf: 3299271 bytes, checksum: e4cbfb1527c14a828f669082cc7f7e76 (MD5)en
dc.description.provenanceMade available in DSpace on 2021-02-10T11:01:16Z (GMT). No. of bitstreams: 1 Revisiting_the_complex_architecture_of_ALS_in_Turkey_Expanding_genotypes,_shared_phenotypes,_molecularnetworks,_and_a_public_variant_database.pdf: 3299271 bytes, checksum: e4cbfb1527c14a828f669082cc7f7e76 (MD5) Previous issue date: 2020en
dc.description.sponsorshipTÜBITAK, Grant/Award Number: 109S075;Bogaziçi University Research Funds,Grant/Award Number: 15B01P1; Suna andİnan Kıraç Foundation, Grant/Award Number:2005–2020en_US
dc.embargo.release2021-08-01
dc.identifier.doi10.1002/humu.24055en_US
dc.identifier.issn1059-7794en_US
dc.identifier.urihttp://hdl.handle.net/11693/55039en_US
dc.language.isoEnglishen_US
dc.publisherJohn Wiley and Sonsen_US
dc.relation.isversionofhttps://dx.doi.org/10.1002/humu.24055en_US
dc.source.titleHuman Mutationen_US
dc.subjectALSen_US
dc.subjectALS variant databaseen_US
dc.subjectGeneticsen_US
dc.subjectClinical exome sequencingen_US
dc.subjectCoexpression network analysisen_US
dc.subjectGenome-wide association studyen_US
dc.subjectMotor neuron diseaseen_US
dc.subjectNext generation sequencingen_US
dc.subjectTurkish peninsulaen_US
dc.titleRevisiting the complex architecture of ALS in Turkey: expanding genotypes, shared phenotypes, molecular networks, and a public variant databaseen_US
dc.typeArticleen_US

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