Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database
Tunca, Ceren; Seker, Tuncay; Akcimen, Fulya; Coskun, Cemre; Bayraktar, Elif; Palvadeau, Robin; Zor, Seyit; Kocoglu, Cemile; Kartal, Ece; Sen, Nesli Ece; Hamzeiy, Hamid; Erimis, Aslihan Ozoguz; Norman, Utku; Karakahya, Oguzhan; Olgun, Gulden; Akgun, Tahsin; Durmus, Hacer; Sahin, Erdi; Cakar, Arman; Gursoy, Esra Baar; Yildiz, Gulsen Babacan; Isak, Baris; Uluc, Kayihan; Hanagasi, Hasmet; Bilgic, Basar; Turgut, Nilda; Aysal, Fikret; Ertas, Mustafa; Boz, Cavit; Kotan, Dilcan; Idrisoglu, Halil; Soysal, Aysun; Adatepe, Nurten Uzun; Akalin, Mehmet Ali; Koc, Filiz; Tan, Ersin; Oflazer, Piraye; Deymeer, Feza; Tastan, Oznur; Cicek, A. Ercument; Kavak, Ersen; Parman, Yesim; Basak, A. Nazli
Date:
2020
Abstract:
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 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).
Description:
Bu yayın 06.11.1981 tarihli ve 17506 sayılı Resmî Gazete’de yayımlanan 2547 sayılı Yükseköğretim Kanunu’nun 4/c, 12/c, 42/c ve 42/d maddelerine dayalı 12/12/2019 tarih, 543 sayılı ve 05 numaralı Üniversite Senato Kararı ile hazırlanan Sakarya Üniversitesi Açık Bilim ve Açık Akademik Arşiv Yönergesi gereğince açık akademik arşiv sistemine açık erişim olarak yüklenmiştir.
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