Next-generation Sequencing in Understanding Complex Neurological Disease

Overview

Journal Expert Rev Neurother

Specialties Neurology
Pharmacology

Date 2013 Feb 2

PMID 23368808

Citations 10

Authors

Adam E Handel

Giulio Disanto

Sreeram V Ramagopalan

Affiliations

Soon will be listed here.

Abstract

Next-generation sequencing techniques have made vast quantities of data on human genomes and transcriptomes available to researchers. Huge progress has been made towards understanding the basis of many Mendelian neurological conditions, but progress has been considerably slower in complex neurological diseases (multiple sclerosis, migraine, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and so on). The authors review current next-generation sequencing methodologies and present selected studies illustrating how these have been used to cast light on the genetic etiology of complex neurological diseases with specific focus on multiple sclerosis. The authors highlight particular pitfalls in next-generation sequencing experiments and speculate on both clinical and research applications of these sequencing platforms for complex neurological disorders in the future.

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References

Wang Z, Gerstein M, Snyder M . RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2008; 10(1):57-63. PMC: 2949280. DOI: 10.1038/nrg2484. View

Wrensch M, Jenkins R, Chang J, Yeh R, Xiao Y, Decker P . Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009; 41(8):905-8. PMC: 2923561. DOI: 10.1038/ng.408. View

Rosewich H, Thiele H, Ohlenbusch A, Maschke U, Altmuller J, Frommolt P . Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. Lancet Neurol. 2012; 11(9):764-73. DOI: 10.1016/S1474-4422(12)70182-5. View

Saitsu H, Kato M, Osaka H, Moriyama N, Horita H, Nishiyama K . CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia. Epilepsia. 2012; 53(8):1441-9. DOI: 10.1111/j.1528-1167.2012.03548.x. View

Herdewyn S, Zhao H, Moisse M, Race V, Matthijs G, Reumers J . Whole-genome sequencing reveals a coding non-pathogenic variant tagging a non-coding pathogenic hexanucleotide repeat expansion in C9orf72 as cause of amyotrophic lateral sclerosis. Hum Mol Genet. 2012; 21(11):2412-9. PMC: 3349421. DOI: 10.1093/hmg/dds055. View

Dering C, Hemmelmann C, Pugh E, Ziegler A . Statistical analysis of rare sequence variants: an overview of collapsing methods. Genet Epidemiol. 2011; 35 Suppl 1:S12-7. PMC: 3277891. DOI: 10.1002/gepi.20643. View

Wu J, Shen E, Shi D, Sun Z, Cai T . Identification of a novel Cys146X mutation of SOD1 in familial amyotrophic lateral sclerosis by whole-exome sequencing. Genet Med. 2012; 14(9):823-6. DOI: 10.1038/gim.2012.50. View

Naj A, Jun G, Beecham G, Wang L, Vardarajan B, Buros J . Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet. 2011; 43(5):436-41. PMC: 3090745. DOI: 10.1038/ng.801. View

Blumkin L, Kivity S, Lev D, Cohen S, Shomrat R, Lerman-Sagie T . A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome. J Neurol. 2012; 259(12):2590-8. DOI: 10.1007/s00415-012-6545-z. View

10.

Neale B, Kou Y, Liu L, Maayan A, Samocha K, Sabo A . Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. 2012; 485(7397):242-5. PMC: 3613847. DOI: 10.1038/nature11011. View

11.

Chahrour M, Yu T, Lim E, Ataman B, Coulter M, Hill R . Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism. PLoS Genet. 2012; 8(4):e1002635. PMC: 3325173. DOI: 10.1371/journal.pgen.1002635. View

12.

Grundberg E, Small K, Hedman A, Nica A, Buil A, Keildson S . Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat Genet. 2012; 44(10):1084-9. PMC: 3784328. DOI: 10.1038/ng.2394. View

13.

. Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet. 2009; 41(7):824-8. DOI: 10.1038/ng.396. View

14.

Kang H, Kawasawa Y, Cheng F, Zhu Y, Xu X, Li M . Spatio-temporal transcriptome of the human brain. Nature. 2011; 478(7370):483-9. PMC: 3566780. DOI: 10.1038/nature10523. View

15.

Forman O, De Risio L, Stewart J, Mellersh C, Beltran E . Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genet. 2012; 13:55. PMC: 3413603. DOI: 10.1186/1471-2156-13-55. View

16.

Miyagawa T, Kawashima M, Nishida N, Ohashi J, Kimura R, Fujimoto A . Variant between CPT1B and CHKB associated with susceptibility to narcolepsy. Nat Genet. 2008; 40(11):1324-8. DOI: 10.1038/ng.231. View

17.

Anttila V, Stefansson H, Kallela M, Todt U, Terwindt G, Calafato M . Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet. 2010; 42(10):869-73. PMC: 2948563. DOI: 10.1038/ng.652. View

18.

Ng P, Henikoff S . SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003; 31(13):3812-4. PMC: 168916. DOI: 10.1093/nar/gkg509. View

19.

Hamza T, Zabetian C, Tenesa A, Laederach A, Montimurro J, Yearout D . Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nat Genet. 2010; 42(9):781-5. PMC: 2930111. DOI: 10.1038/ng.642. View

20.

Berger I, Dor T, Halvardson J, Edvardson S, Shaag A, Feuk L . Intractable epilepsy of infancy due to homozygous mutation in the EFHC1 gene. Epilepsia. 2012; 53(8):1436-40. DOI: 10.1111/j.1528-1167.2012.03536.x. View