Avtor/Urednik		Mitropoulos, Konstantinos; Merkouri Papadima, Eleni; Xiromerisiou, Georgia; Balasopoulou, Angeliki; Charalampidou, Kyriaki; Galani, Vasiliki; Zafeiri, Krystallia-Vassiliki; Dardiotis, Efthymios; Ralli, Styliani; Tsermpini, Evangelia Erini
Naslov		Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients
Tip		članek
Vol. in št.		Letnik 11, št. 1
Leto izdaje		2017
Obseg		str. 1-10
ISSN		1479-7364 - Human genomics
Jezik		eng
Abstrakt		Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). Results: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific disease-associated haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic variants in question. Conclusions: To our knowledge, this is the first study to present a possible association between FTO gene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance.
Proste vsebinske oznake		FTO gene genomic variants sporadic amyotrophic lateral sclerosis gen FTO genomske različice sporadična amiotrofična lateralna skleroza