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

Tunca, Ceren and Şeker, Tuncay and Akçimen, Fulya and Coşkun, Cemre and Bayraktar, Elif and Palvadeau, Robin and Zor, Seyit and Koçoğlu, Cemile and Kartal, Ece and Şen, Nesli Ece and Hamzeiy, Hamid and Özoğuz Erimiş, Aslıhan and Norman, Utku and Karakahya, Oğuzhan and Olgun, Gülden and Akgün, Tahsin and Durmuş, Hacer and Şahin, Erdi and Çakar, Arman and Başar Gürsoy, Esra and Babacan Yıldız, Gülsen and İşak, Barış and Uluç, Kayıhan and Hanağası, Haşmet and Bilgiç, Başar and Turgut, Nilda and Aysal, Fikret and Ertaş, Mustafa and Boz, Cavit and Kotan, Dilcan and İdrisoğlu, Halil and Soysal, Aysun and Uzun Adatepe, Nurten and Akalın, Mehmet Ali and Koç, Filiz and Tan, Ersin and Oflazer, Piraye and Deymeer, Feza and Taştan, Öznur and Çiçek, A. Ercüment and Kavak, Erşen and Parman, Yeşim and Başak, A. Nazlı (2020) Revisiting the complex architecture of ALS in Turkey: expanding genotypes, shared phenotypes, molecular networks, and a public variant database. Human Mutation, 41 (8). e7-e45. ISSN 1059-7794 (Print) 1098-1004 (Online)

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The 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 (
Item Type: Article
Additional Information: Scopus'da "Data Paper" olarak geçiyor.
Uncontrolled Keywords: ALS; ALS variant database; clinical exome sequencing; coexpression network analysis; genetics; genome-wide association study; motor neuron disease; next generation sequencing; Turkish peninsula
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Computer Science & Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Öznur Taştan
Date Deposited: 01 Aug 2023 23:18
Last Modified: 01 Aug 2023 23:18

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