Review Article
From genetic associations to functional studies in multiple sclerosis
S. D. Bos,
T. Berge,
E. G. Celius,
H. F. Harbo,
Corresponding Author
S. D. Bos
Institute of Clinical Medicine, University of Oslo, Oslo
Department of Neurology, Oslo University Hospital, Oslo
Correspondence: S. D. Bos, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway (tel.: +47 9601 6326; fax: +47 2302 7455; e-mail: [email protected]).Search for more papers by this authorT. Berge
Institute of Clinical Medicine, University of Oslo, Oslo
Department of Neurology, Oslo University Hospital, Oslo
Search for more papers by this authorE. G. Celius
Department of Neurology, Oslo University Hospital, Oslo
Institute of Health and Society, University of Oslo, Oslo, Norway
Search for more papers by this authorH. F. Harbo
Institute of Clinical Medicine, University of Oslo, Oslo
Department of Neurology, Oslo University Hospital, Oslo
Search for more papers by this authorS. D. Bos,
T. Berge,
E. G. Celius,
H. F. Harbo,
Corresponding Author
S. D. Bos
Institute of Clinical Medicine, University of Oslo, Oslo
Department of Neurology, Oslo University Hospital, Oslo
Correspondence: S. D. Bos, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway (tel.: +47 9601 6326; fax: +47 2302 7455; e-mail: [email protected]).Search for more papers by this authorT. Berge
Institute of Clinical Medicine, University of Oslo, Oslo
Department of Neurology, Oslo University Hospital, Oslo
Search for more papers by this authorE. G. Celius
Department of Neurology, Oslo University Hospital, Oslo
Institute of Health and Society, University of Oslo, Oslo, Norway
Search for more papers by this authorH. F. Harbo
Institute of Clinical Medicine, University of Oslo, Oslo
Department of Neurology, Oslo University Hospital, Oslo
Search for more papers by this authorThis paper was submitted to the Journal for peer review after presentation at the 2015 Norwegian Neurological Association meeting.
Abstract
Genetic screens steadily reveal more loci that show robust associations to complex human diseases, including multiple sclerosis (MS). Although some of the identified genetic variants are easily interpreted into a biological function, most of the genetic associations are frequently challenging to interpret. Underlying these difficulties is the fact that chip-based assays typically detect single nucleotide polymorphisms (SNPs) representative of a stretch of DNA containing many genomic variants in linkage disequilibrium. Furthermore, a large proportion of the SNPs with strongest association to MS are located in regions of the DNA that do not directly code for proteins. Here we discuss challenges faced by MS researchers to follow up the large-scale genetic screens that have been published over the past years in search of functional consequences of the identified MS-associated SNPs. We discuss experimental design, tools and methods that may provide the much-needed biological insights in both disease etiology and disease manifestations.
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