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Hum Genomics. 2017 Dec 8;11(1):30. doi: 10.1186/s40246-017-0126-2.

Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients.

Author information

1
National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
2
Department of Pharmacy, University of Patras School of Health Sciences, Campus, Rion, GR-26504, Patras, Greece.
3
School of Medicine, University of Thessaly, Larisa, Greece.
4
Papageorgiou hospital, Thessaloniki, Greece.
5
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, UAE.
6
ANALYSI Diagnostic Laboratories S.A, Thessaloniki, Greece.
7
Departments of Neurology and Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
8
Suna and Inan Kirac Foundation, NDAL, Bogazici University, Istanbul, Turkey.
9
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
10
CNR IRGB, Cagliari, Italy.
11
Institute of Neurology CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
12
Faculty of Medicine, Institute of Human Genetics, University of Belgrade, Belgrade, Serbia.
13
Complete Genomics Inc., Mountain View, CA, USA.
14
BGI Shenzhen, Shenzhen, People's Republic of China.
15
Institute of Medical Genetics, Cardiff University, Cardiff, UK.
16
Department of Pharmacy, University of Patras School of Health Sciences, Campus, Rion, GR-26504, Patras, Greece. gpatrinos@upatras.gr.
17
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, UAE. gpatrinos@upatras.gr.

Abstract

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.

KEYWORDS:

FTO gene; Founder population; Genomic variants; Sporadic amyotrophic lateral sclerosis; Whole-genome sequencing

PMID:
29216901
PMCID:
PMC5721583
DOI:
10.1186/s40246-017-0126-2
[Indexed for MEDLINE]
Free PMC Article

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