TY - JOUR
T1 - Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients
AU - Mitropoulos, Konstantinos
AU - Papadima, Eleni Merkouri
AU - Xiromerisiou, Georgia
AU - Balasopoulou, Angeliki
AU - Charalampidou, Kyriaki
AU - Galani, Vasiliki
AU - Zafeiri, Krystallia Vassiliki
AU - Dardiotis, Efthymios
AU - Ralli, Styliani
AU - Deretzi, Georgia
AU - John, Anne
AU - Kydonopoulou, Kyriaki
AU - Papadopoulou, Elpida
AU - Di Pardo, Alba
AU - Akcimen, Fulya
AU - Loizedda, Annalisa
AU - Dobriĉić, Valerija
AU - Novaković, Ivana
AU - Kostic, Vladimir S.
AU - Mizzi, Clint
AU - Peters, Brock A.
AU - Basak, Nazli
AU - Orrù, Sandro
AU - Kiskinis, Evangelos
AU - Cooper, David N.
AU - Gerou, Spyridon
AU - Drmanac, Radoje
AU - Bartsakoulia, Marina
AU - Tsermpini, Evangelia Eirini
AU - Hadjigeorgiou, Georgios M.
AU - Ali, Bassam R.
AU - Katsila, Theodora
AU - Patrinos, George P.
N1 - Publisher Copyright:
© The Author(s).
PY - 2017/3/4
Y1 - 2017/3/4
N2 - 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 diseaseassociated 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.
AB - 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 diseaseassociated 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.
UR - http://www.scopus.com/inward/record.url?scp=85045543468&partnerID=8YFLogxK
U2 - 10.1186/s40246-017-0126-2
DO - 10.1186/s40246-017-0126-2
M3 - Journal articles
C2 - 29216901
AN - SCOPUS:85045543468
SN - 1473-9542
VL - 11
JO - Human Genomics
JF - Human Genomics
IS - 1
M1 - 30
ER -