Genetic variants of Complex I in multiple sclerosis
Related Experiment Video
Updated: Aug 20, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Tamara Vyshkina1, Ileana Banisor, Yin Yao Shugart
1Department of Neurology, SLRHC, Columbia University, 432W 58th Street, New York, NY 10019, USA.
Hypothesis:
A mitochondrial mechanism contributes to neurodegeneration in multiple sclerosis (MS). Genetic variants of Complex I genes may influence the nature of tissue response to inflammation in the central nervous system (CNS).
Background:
Complex I is encoded by seven mitochondrial and 38 nuclear genes. Many of the nuclear genes colocalize with regions where full genome scans detected linkage in MS. Previous studies revealed an association between variants of mitochondrial (mt)DNA encoded subunits of Complex I and MS. Biochemical studies suggested a functional involvement of Complex I in the degenerative processes downstream to inflammatory injury in the CNS.
Methods:
Patients with all MS phenotypes were included. DNA specimens of affected sib pair, trio and multiplex families were studied. Single nucleotide polymorphisms (SNP) were determined by using the Taqman assay. The association of MS with nuclear DNA encoded alleles and haplotypes of Complex I was tested by the pedigree disequilibrium test (PDT) and by the transmit program in the families. Haplotypes were further investigated by using ldmax (GOLD). The association of mtDNA encoded variants with MS was tested by the Fisher's Exact Test.
Results:
The previously identified MS-associated mtDNA variants and haplotypes were not increased in mothers as compared to fathers in these families. However, an association of all clinical phenotypes with haplotypes within NDUFS5 (1p34.2-p33), NDUFS7 (19p13) and NDUFA7 (19p13) was detected. The inclusion of families with primary progressive (PP)-MS phenotype did not modify the outcome and, as a subgroup alone, did not have a sufficient size to draw conclusion regarding phenotype specific associations.
Conclusions:
SNP haplotypes within Complex I genes are associated with MS. Further studies are needed to refine the identification of disease relevant variants nearby or within these haplotypes. Molecular and functional properties of Complex I subunits may offer novel explanations to better understand the relationship between inflammation and neurodegeneration.
More Related Videos
Related Concept Videos
Multiple Sclerosis l: Introduction
Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Single Nucleotide Polymorphisms-SNPs
ATP Synthase: Mechanism
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Protein Complexes with Interchangeable Parts
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...

