Next-generation sequencing in understanding complex neurological disease

Expert Review of Neurotherapeutics

Volumn 13, Issue 2, 2013, Pages 215-227

  Handel, Adam E ^a,b   Disanto, Giulio ^a,b   Ramagopalan, Sreeram V ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Complex disease; Functional genomics; Neurological disease; Next generation sequencing; Transcriptomics

Indexed keywords

ALPHA SYNUCLEIN; GENOMIC DNA; MESSENGER RNA; VITAMIN D RECEPTOR;

ACCURACY; ALLELIC IMBALANCE; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BIOINFORMATICS; CHROMATIN IMMUNOPRECIPITATION; COPY NUMBER VARIATION; COST EFFECTIVENESS ANALYSIS; DISEASE PREDISPOSITION; DNA FRAGMENTATION; DNA METHYLATION; EPIGENETICS; EXOME; FALSE POSITIVE RESULT; GENE EXPRESSION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HISTONE ACETYLATION; HISTONE METHYLATION; HUMAN; HYDROXYLATION; MIGRAINE; MULTIPLE SCLEROSIS; NEXT GENERATION SEQUENCING; NONHUMAN; NUCLEOTIDE REPEAT; PARKINSON DISEASE; PHENOTYPE; REVIEW; SENSITIVITY AND SPECIFICITY; SINGLE NUCLEOTIDE POLYMORPHISM; STATISTICAL SIGNIFICANCE; TRANSCRIPTOMICS; VITAMIN D DEFICIENCY;

CHROMATIN IMMUNOPRECIPITATION; DATABASES, GENETIC; EPIGENOMICS; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; HUMANS; NERVOUS SYSTEM DISEASES; SEQUENCE ANALYSIS, DNA;

EID: 84873158451     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/ern.12.165     Document Type: Review

References (171)

1. Schmutz J, Wheeler J, Grimwood J et al. Quality assessment of the human genome sequence. Nature 429(6990), 365-368 (2004). (Pubitemid 38715122)
2. [No authors listed]. The human genome at ten. Nature 464(7289), 649-650 (2010).
3. Mardis ER. A decade's perspective on DNA sequencing technology. Nature 470(7333), 198-203 (2011).
4. Cirulli ET, Goldstein DB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat. Rev. Genet. 11(6), 415-425 (2010).
5. Bailey-Wilson JE, Wilson AF. Linkage analysis in the next-generation sequencing era. Hum. Hered. 72(4), 228-236 (2011).
6. Hindorff LA, Sethupathy P, Junkins HA et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl Acad. Sci. USA 106(23), 9362-9367 (2009).
7. Handel AE, Handunnetthi L, Berlanga AJ, Watson CT, Morahan JM, Ramagopalan SV. The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression. PLoS ONE 5(4), e10142 (2010).
8. Boyle AP, Hong EL, Hariharan M et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22(9), 1790-1797 (2012).
9. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB. Rare variants create synthetic genome-wide associations. PLoS Biol. 8(1), e1000294 (2010).
10. Nejentsev S, Walker N, Riches D, Egholm M, Todd JA. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324(5925), 387-389 (2009).
11. Anderson CA, Soranzo N, Zeggini E, Barrett JC. Synthetic associations are unlikely to account for many common disease genome-wide association signals. PLoS Biol. 9(1), e1000580 (2011).
12. Foo JN, Liu JJ, Tan EK. Whole-genome and whole-exome sequencing in neurological diseases. Nat. Rev. Neurol. 8(9), 508-517 (2012).
13. Vernot B, Stergachis AB, Maurano MT et al. Personal and population genomics of human regulatory variation. Genome Res. 22(9), 1689-1697 (2012).
14. Hooli BV, Mohapatra G, Mattheisen M et al. Role of common and rare APP DNA sequence variants in Alzheimer disease. Neurology 78(16), 1250-1257 (2012).
15. Pankratz N, Dumitriu A, Hetrick KN et al.; PSG-PROGENI and GenePD Investigators, Coordinators and Molecular Genetic Laboratories. Copy number variation in familial Parkinson disease. PLoS ONE 6(8), e20988 (2011).
16. Surolia I, Pirnie SP, Chellappa V et al. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 466(7303), 243-247 (2010).
17. Ramagopalan SV, Dyment DA, Cader MZ et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann. Neurol. 70(6), 881-886 (2011).
18. Dyment DA, Cader MZ, Chao MJ et al. Exome sequencing identifies a novel multiple sclerosis susceptibility variant in the TYK2 gene. Neurology 79(5), 406-411 (2012).
19. Cortes A, Brown MA. Promise and pitfalls of the Immunochip. Arthritis Res. Ther. 13(1), 101 (2011).
20. Hunt KA, Smyth DJ, Balschun T et al.; Type 1 Diabetes Genetics Consortium; UK Inflammatory Bowel Disease (IBD) Genetics Consortium; Wellcome Trust Case Control Consortium. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry. Nat. Genet. 44(1), 3-5 (2012).
21. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxy vitamin D levels and risk of multiple sclerosis. JAMA 296(23), 2832-2838 (2006). (Pubitemid 44969183)
22. Baranzini SE, Mudge J, van Velkinburgh JC et al. Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature 464(7293), 1351-1356 (2010).
23. Handunnetthi L, Handel AE, Ramagopalan SV. Contribution of genetic, epigenetic and transcriptomic differences to twin discordance in multiple sclerosis. Expert Rev. Neurother. 10(9), 1379-1381 (2010).
24. Reumers J, De Rijk P, Zhao H et al. Optimized filtering reduces the error rate in detecting genomic variants by short-read sequencing. Nat. Biotechnol. 30(1), 61-68 (2012).
25. Heinzen EL, Depondt C, Cavalleri GL et al. Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy. Am. J. Hum. Genet. 91(2), 293-302 (2012).
26. Sidransky E, Nalls MA, Aasly JO et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N. Engl. J. Med. 361(17), 1651-1661 (2009).
27. Dering C, Hemmelmann C, Pugh E, Ziegler A. Statistical analysis of rare sequence variants: an overview of collapsing methods. Genet. Epidemiol. 35(Suppl. 1), S12-S17 (2011).
28. Adzhubei IA, Schmidt S, Peshkin L et al. A method and server for predicting damaging missense mutations. Nat. Methods 7(4), 248-249 (2010).
29. Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 31(13), 3812-3814 (2003). (Pubitemid 37442253)
30. González-Pérez A, López-Bigas N. Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. Am. J. Hum. Genet. 88(4), 440-449 (2011).
31. Schwarz JM, Rödelsperger C, Schuelke M, Seelow D. MutationTaster evaluates disease-causing potential of sequence alterations. Nat. Methods 7(8), 575-576 (2010).
32. Tchernitchko D, Goossens M, Wajcman H. In silico prediction of the deleterious effect of a mutation: proceed with caution in clinical genetics. Clin. Chem. 50(11), 1974-1978 (2004). (Pubitemid 39425832)
33. Healy DG, Falchi M, O'Sullivan SS et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol. 7(7), 583-590 (2008).
34. Kumari U, Tan EK. LRRK2 in Parkinson's disease: genetic and clinical studies from patients. FEBS J. 276(22), 6455-6463 (2009).
35. Schaub MA, Boyle AP, Kundaje A, Batzoglou S, Snyder M. Linking disease associations with regulatory information in the human genome. Genome Res. 22(9), 1748-1759 (2012).
36. Ramagopalan SV, Heger A, Berlanga AJ et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 20(10), 1352-1360 (2010).
37. Sugaya Y, Akazawa Y, Saito A, Kamitsuji S. NDesign: software for study design for the detection of rare variants from next- generation sequencing data. J. Hum. Genet. 57(10), 676-678 (2012).
38. Liu DJ, Leal SM. Replication strategies for rare variant complex trait association studies via next-generation sequencing. Am. J. Hum. Genet. 87(6), 790-801 (2010).
39. Wang Z, Gerstein M, Snyder M. RNASeq: a revolutionary tool for transcriptomics. Nat. Rev. Genet. 10(1), 57-63 (2009).
40. Fairfax BP, Makino S, Radhakrishnan J et al. Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles. Nat. Genet. 44(5), 502-510 (2012).
41. Grundberg E, Small KS, Hedman ÅK et al.; Multiple Tissue Human Expression Resource (MuTHER) Consortium. Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat. Genet. 44(10), 1084-1089 (2012).
42. Eran A, Li JB, Vatalaro K et al. Comparative RNA editing in autistic and neurotypical cerebella. Mol. Psychiatry doi:10.1038/ mp.2012.118 (2012) (Epub ahead of print).
43. Gandhi KS, McKay FC, Cox M et al.; ANZgene Multiple Sclerosis Genetics Consortium. The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum. Mol. Genet. 19(11), 2134-2143 (2010).
44. Kang HJ, Kawasawa YI, Cheng F et al. Spatio-temporal transcriptome of the human brain. Nature 478(7370), 483-489 (2011).
45. Koppelkamm A, Vennemann B, Lutz- Bonengel S, Fracasso T, Vennemann M. RNA integrity in post-mortem samples: influencing parameters and implications on RT-qPCR assays. Int. J. Legal Med. 125(4), 573-580 (2011).
46. Pickrell JK, Gilad Y, Pritchard JK. Comment on 'Widespread RNA and DNA sequence differences in the human transcriptome'. Science 335(6074), 1302; author reply 1302 (2012).
47. Barski A, Zhao K. Genomic location analysis by ChIP-Seq. J. Cell. Biochem. 107(1), 11-18 (2009).
48. Denes A, Thornton P, Rothwell NJ, Allan SM. Inflammation and brain injury: acute cerebral ischaemia, peripheral and central inflammation. Brain Behav. Immun. 24(5), 708-723 (2010).
49. Hamed SA. The vascular risk associations with migraine: relation to migraine susceptibility and progression. Atherosclerosis 205(1), 15-22 (2009).
50. Martins M, Rosa A, Guedes LC et al. Convergence of miRNA expression profiling, a-synuclein interaction and GWAS in Parkinson's disease. PLoS ONE 6(10), e25443 (2011).
51. Handel AE, Ebers GC, Ramagopalan SV. Epigenetics: molecular mechanisms and implications for disease. Trends Mol. Med. 16(1), 7-16 (2010).
52. Ku CS, Naidoo N, Wu M, Soong R. Studying the epigenome using next generation sequencing. J. Med. Genet. 48(11), 721-730 (2011).
53. Gordon L, Joo JE, Powell JE et al. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissuespecific influence. Genome Res. 22(8), 1395-1406 (2012).
54. Walker RH, Schulz VP, Tikhonova IR et al. Genetic diagnosis of neuroacanthocytosis disorders using exome sequencing. Mov. Disord. 27(4), 539-543 (2012).
55. Pierson TM, Adams DA, Markello T et al.; NISC Comparative Sequencing Program. Exome sequencing as a diagnostic tool in a case of undiagnosed juvenile-onset GM1-gangliosidosis. Neurology 79(2), 123-126 (2012).
56. Montenegro G, Powell E, Huang J et al. Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Ann. Neurol. 69(3), 464-470 (2011).
57. Johnson JO, Gibbs JR, Megarbane A et al. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. Brain 135(Pt 9), 2875-2882 (2012).
58. Need AC, Shashi V, Hitomi Y et al. Clinical application of exome sequencing in undiagnosed genetic conditions. J. Med. Genet. 49(6), 353-361 (2012).
59. Samuel GN, Jordens CF, Kerridge I. Direct-to-consumer personal genome testing: ethical and regulatory issues that arise from wanting to 'know' your DNA. Intern. Med. J. 40(3), 220-224 (2010).
60. Maman S, King E. Changes in HIV testing policies and the implications for women. J. Midwifery Womens Health 53(3), 195-201 (2008). (Pubitemid 351597907)
61. Burke RC, Sepkowitz KA, Bernstein KT et al. Why don't physicians test for HIV? A review of the US literature. AIDS 21(12), 1617-1624 (2007). (Pubitemid 47075483)
62. Altman RB, Kroemer HK, McCarty CA, Ratain MJ, Roden D. Pharmacogenomics: will the promise be fulfilled? Nat. Rev. Genet. 12(1), 69-73 (2011).
63. Seshadri S, Fitzpatrick AL, Ikram MA et al.; CHARGE Consortium; GERAD1 Consortium; EADI1 Consortium. Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303(18), 1832-1840 (2010).
64. Hollingworth P, Harold D, Sims R et al.; Alzheimer's Disease Neuroimaging Initiative; CHARGE consortium; EADI1 consortium. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat. Genet. 43(5), 429-435 (2011).
65. Lambert JC, Grenier-Boley B, Harold D et al. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Mol. Psychiatry (2012) doi:10.1038/mp.2012.75 (Epub ahead of print).
66. Harold D, Abraham R, Hollingworth P et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat. Genet. 41(10), 1088-1093 (2009).
67. Kamboh MI, Barmada MM, Demirci FY et al.; The Alzheimer's Disease Neuroimaging Initiative. Genome-wide association analysis of age-at-onset in Alzheimer's disease. Mol. Psychiatry 17(12), 1340-1346 (2012).
68. Naj AC, Beecham GW, Martin ER et al. Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities. PLoS Genet. 6(9), e1001130 (2010).
69. Naj AC, Jun G, Beecham GW et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat. Genet. 43(5), 436-441 (2011).
70. Reiman EM, Webster JA, Myers AJ et al. GAB2 alleles modify Alzheimer's risk in APOE ε4 carriers. Neuron 54(5), 713-720 (2007). (Pubitemid 46843528)
71. van Es MA, Veldink JH, Saris CG et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat. Genet. 41(10), 1083-1087 (2009).
72. Shatunov A, Mok K, Newhouse S et al. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol. 9(10), 986-994 (2010).
73. Laaksovirta H, Peuralinna T, Schymick JC et al. Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study. Lancet Neurol. 9(10), 978-985 (2010).
74. Landers JE, Melki J, Meininger V et al. Reduced expression of the kinesin-associated protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis. Proc. Natl Acad. Sci. USA 106(22), 9004-9009 (2009).
75. van Es MA, van Vught PW, Blauw HM et al. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nat. Genet. 40(1), 29-31 (2008).
76. Wang K, Zhang H, Ma D et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 459(7246), 528-533 (2009).
77. Anney R, Klei L, Pinto D et al. A genome-wide scan for common alleles affecting risk for autism. Hum. Mol. Genet. 19(20), 4072-4082 (2010).
78. Mead S, Poulter M, Uphill J et al. Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol. 8(1), 57-66 (2009).
79. Sanchez-Juan P, Bishop MT, Aulchenko YS et al. Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk. Neurobiol. Aging 33(7), 1487.e21-1487.e28 (2012).
80. Guo Y, Baum LW, Sham PC et al. Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese. Hum. Mol. Genet. 21(5), 1184-1189 (2012).
81. Stefansson H, Steinberg S, Petursson H et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat. Genet. 41(3), 277-279 (2009).
82. Thier S, Lorenz D, Nothnagel M et al. Polymorphisms in the glial glutamate transporter SLC1A2 are associated with essential tremor. Neurology 79(3), 243-248 (2012).
83. Sanson M, Hosking FJ, Shete S et al. Chromosome 7p11.2 (EGFR) variation influences glioma risk. Hum. Mol. Genet. 20(14), 2897-2904 (2011).
84. Shete S, Hosking FJ, Robertson LB et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat. Genet. 41(8), 899-904 (2009).
85. Wrensch M, Jenkins RB, Chang JS et al. Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat. Genet. 41(8), 905-908 (2009).
86. Dobbins SE, Broderick P, Melin B et al. Common variation at 10p12.31 near MLLT10 influences meningioma risk. Nat. Genet. 43(9), 825-827 (2011).
87. Freilinger T, Anttila V, de Vries B et al.; International Headache Genetics Consortium. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat. Genet. 44(7), 777-782 (2012).
88. Anttila V, Stefansson H, Kallela M et al.; International Headache Genetics Consortium. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat. Genet. 42(10), 869-873 (2010).
89. Chasman DI, Schürks M, Anttila V et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat. Genet. 43(7), 695-698 (2011).
90. De Jager PL, Jia X, Wang J et al.; International MS Genetics Consortium. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat. Genet. 41(7), 776-782 (2009).
91. Hafler DA, Compston A, Sawcer S et al. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med. 357(9), 851-862 (2007). (Pubitemid 47347319)
92. Sawcer S, Hellenthal G, Pirinen M et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476(7359), 214-219 (2011).
93. Nischwitz S, Cepok S, Kroner A et al. Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis. J. Neuroimmunol. 227(1-2), 162-166 (2010).
94. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat. Genet. 41(7), 824-828 (2009).
95. Sanna S, Pitzalis M, Zoledziewska M et al. Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis. Nat. Genet. 42(6), 495-497 (2010).
96. Aulchenko YS, Hoppenbrouwers IA, Ramagopalan SV et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat. Genet. 40(12), 1402-1403 (2008).
97. Jakkula E, Leppä V, Sulonen AM et al. Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene. Am. J. Hum. Genet. 86(2), 285-291 (2010).
98. Wang JH, Pappas D, De Jager PL et al.; Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data. Genome Med. 3(1), 3 (2011).
99. Matesanz F, González-Pérez A, Lucas M et al. Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1. PLoS ONE 7(5), e36140 (2012).
100. Patsopoulos NA, Esposito F, Reischl J et al.; Bayer Pharma MS Genetics Working Group; Steering Committees of Studies Evaluating IFNβ-1b and a CCR1-Antagonist; ANZgene Consortium; GeneMSA; International Multiple Sclerosis Genetics Consortium. Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann. Neurol. 70(6), 897-912 (2011).
101. Hallmayer J, Faraco J, Lin L et al. Narcolepsy is strongly associated with the T-cell receptor α locus. Nat. Genet. 41(6), 708-711 (2009).
102. Hor H, Kutalik Z, Dauvilliers Y et al. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nat. Genet. 42(9), 786-789 (2010).
103. Miyagawa T, Kawashima M, Nishida N et al. Variant between CPT1B and CHKB associated with susceptibility to narcolepsy. Nat. Genet. 40(11), 1324-1328 (2008).
104. Wang K, Diskin SJ, Zhang H et al. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature 469(7329), 216-220 (2011).
105. Capasso M, Devoto M, Hou C et al. Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat. Genet. 41(6), 718-723 (2009).
106. Lill CM, Roehr JT, McQueen MB et al.; 23andMe Genetic Epidemiology of Parkinson's Disease Consortium; International Parkinson's Disease Genomics Consortium; Parkinson's Disease GWAS Consortium; Wellcome Trust Case Control Consortium 2. Comprehensive research synopsis and systematic meta-analyses in Parkinson's idisease genetics: the PDGene database. PLoS Genet. 8(3), e1002548 (2012).
107. Do CB, Tung JY, Dorfman E et al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. PLoS Genet. 7(6), e1002141 (2011).
108. Pankratz N, Beecham GW, DeStefano AL et al.; PD GWAS Consortium. Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2. Ann. Neurol. 71(3), 370-384 (2012).
109. Nalls MA, Plagnol V, Hernandez DG et al. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genomewide association studies. Lancet 377(9766), 641-649 (2011).
110. Simón-Sánchez J, Schulte C, Bras JM et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet. 41(12), 1308-1312 (2009).
111. Satake W, Nakabayashi Y, Mizuta I et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat. Genet. 41(12), 1303-1307 (2009).
112. Hamza TH, Zabetian CP, Tenesa A et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nat. Genet. 42(9), 781-785 (2010).
113. Edwards TL, Scott WK, Almonte C et al. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann. Hum. Genet. 74(2), 97-109 (2010).
114. Höglinger GU, Melhem NM, Dickson DW et al.; PSP Genetics Study Group. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43(7), 699-705 (2011).
115. Winkelmann J, Czamara D, Schormair B et al. Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1. PLoS Genet. 7(7), e1002171 (2011).
116. Schormair B, Kemlink D, Roeske D et al. PTPRD (protein tyrosine phosphatase receptor type δ) is associated with restless legs syndrome. Nat. Genet. 40(8), 946-948 (2008).
117. Bellenguez C, Bevan S, Gschwendtner A et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat. Genet. 44(3), 328-333 (2012).
118. Ikram MA, Seshadri S, Bis JC et al. Genomewide association studies of stroke. N. Engl. J. Med. 360(17), 1718-1728 (2009).
119. Gretarsdottir S, Thorleifsson G, Manolescu A et al. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann. Neurol. 64(4), 402-409 (2008).
120. Blumkin L, Kivity S, Lev D et al. A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome. J. Neurol. 259(12), 2590-2598 (2012).
121. Xiao J, Uitti RJ, Zhao Y et al. Mutations in CIZ1 cause adult onset primary cervical dystonia. Ann. Neurol. 71(4), 458-469 (2012).
122. Rosewich H, Thiele H, Ohlenbusch A et al. Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. Lancet Neurol. 11(9), 764-773 (2012).
123. Heinzen EL, Swoboda KJ, Hitomi Y et al.; European Alternating Hemiplegia of Childhood (AHC) Genetics Consortium; Biobanca e Registro Clinico per l'Emiplegia Alternante (I.B.AHC) Consortium; European Network for Research on Alternating Hemiplegia (ENRAH) for Small and Medium-sized Enterprise (SMEs) Consortium. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat. Genet. 44(9), 1030-1034 (2012).
124. Iossifov I, Ronemus M, Levy D et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74(2), 285-299 (2012).
125. Neale BM, Kou Y, Liu L et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 485(7397), 242-245 (2012).
126. Chahrour MH, Yu TW, Lim ET et al.; ARRA Autism Sequencing Collaboration. Whole-exome sequencing and homozygosity analysis implicate depolarization- regulated neuronal genes in autism. PLoS Genet. 8(4), e1002635 (2012).
127. Bi C, Wu J, Jiang T et al. Mutations of ANK3 identified by exome sequencing are associated with autism susceptibility. Hum. Mutat. 33(12), 1635-1638 (2012).
128. Sanders SJ, Murtha MT, Gupta AR et al. De novo mutations revealed by wholeexome sequencing are strongly associated with autism. Nature 485(7397), 237-241 (2012).
129. Lee H, Graham JM Jr, Rimoin DL et al. Exome sequencing identifies PDE4D mutations in acrodysostosis. Am. J. Hum. Genet. 90(4), 746-751 (2012).
130. Winkelmann J, Lin L, Schormair B et al. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum. Mol. Genet. 21(10), 2205-2210 (2012).
131. Pottier C, Hannequin D, Coutant S et al.; PHRC GMAJ Collaborators. High frequency of potentially pathogenic SORL1 mutations in autosomal dominant early-onset Alzheimer disease. Mol. Psychiatry 17(9), 875-879 (2012).
132. Ishiura H, Sako W, Yoshida M et al. The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement. Am. J. Hum. Genet. 91(2), 320-329 (2012).
133. Harms MB, Sommerville RB, Allred P et al. Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Ann. Neurol. 71(3), 407-416 (2012).
134. Staropoli JF, Karaa A, Lim ET et al. A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system. Am. J. Hum. Genet. 91(1), 202-208 (2012).
135. Sailer A, Scholz SW, Gibbs JR et al. Exome sequencing in an SCA14 family demonstrates its utility in diagnosing heterogeneous diseases. Neurology 79(2), 127-131 (2012).
136. Li M, Pang S, Song Y, Kung M, Ho S-L, Sham P-C. Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family. Clin. Genet. doi:10.1111/j.1399-0004.2012.01895.x (2012) (Epub ahead of print).
137. Delmaghani S, Aghaie A, Michalski N, Bonnet C, Weil D, Petit C. Defect in the gene encoding the EAR/EPTP domaincontaining protein TSPEAR causes DFNB98 profound deafness. Hum. Mol. Genet. 21(17), 3835-3844 (2012).
138. Jimenez-Escrig A, Gobernado I, Garcia- Villanueva M, Sanchez-Herranz A. Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing. Muscle Nerve 45(4), 605-610 (2012).
139. Dündar H, Ozgül RK, Yalnizoglu D et al. Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing. Pediatr. Neurol. 46(3), 172-177 (2012).
140. Schossig A, Wolf NI, Fischer C et al. Mutations in ROGDI cause Kohlschütter- Tönz syndrome. Am. J. Hum. Genet. 90(4), 701-707 (2012).
141. Raja Rayan DL, Haworth A, Sud R et al. A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1. Neurology 78(24), 1953-1958 (2012).
142. Wan J, Yourshaw M, Mamsa H et al. Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat. Genet. 44(6), 704-708 (2012).
143. Zhou J, Tawk M, Tiziano FD et al. Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1. Am. J. Hum. Genet. 91(1), 5-14 (2012).
144. Choi BO, Koo SK, Park MH et al. Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth disease. Hum. Mutat. 33(11), 1610-1615 (2012).
145. Timal S, Hoischen A, Lehle L et al. Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing. Hum. Mol. Genet. 21(19), 4151-4161 (2012).
146. Beetz C, Pieber TR, Hertel N et al. Exome sequencing identifies a REEP1 mutation involved in distal hereditary motor neuropathy type V. Am. J. Hum. Genet. 91(1), 139-145 (2012).
147. Merner ND, Girard SL, Catoire H et al. Exome sequencing identifies FUS mutations as a cause of essential tremor. Am. J. Hum. Genet. 91(2), 313-319 (2012).
148. Wu CH, Fallini C, Ticozzi N et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488(7412), 499-503 (2012).
149. Herdewyn S, Zhao H, Moisse M et al. 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. 21(11), 2412-2419 (2012).
150. Williams KL, Warraich ST, Yang S et al. UBQLN2/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis. Neurobiol. Aging 33(10), 2527.e3-2527.10 (2012).
151. 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. 14(9), 823-826 (2012).
152. Elo JM, Yadavalli SS, Euro L et al. Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy. Hum. Mol. Genet. 21(20), 4521-4529 (2012).
153. Lee JH, Huynh M, Silhavy JL et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat. Genet. 44(8), 941-945 (2012).
154. Edvardson S, Cinnamon Y, Jalas C et al. Hereditary sensory autonomic neuropathy caused by a mutation in dystonin. Ann. Neurol. 71(4), 569-572 (2012).
155. Veeramah KR, O'Brien JE, Meisler MH et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am. J. Hum. Genet. 90(3), 502-510 (2012).
156. Berger I, Dor T, Halvardson J et al. Intractable epilepsy of infancy due to homozygous mutation in the EFHC1 gene. Epilepsia 53(8), 1436-1440 (2012).
157. Cole JW, Stine OC, Liu X et al. Rare variants in ischemic stroke: an exome pilot study. PLoS ONE 7(4), e35591 (2012).
158. Edvardson S, Cinnamon Y, Ta-Shma A et al. A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrinuncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLoS ONE 7(5), e36458 (2012).
159. Steenweg ME, Ghezzi D, Haack T et al. Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations. Brain 135(Pt 5), 1387-1394 (2012).
160. Horvath R, Holinski-Feder E, Neeve VC et al. A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy. Mov. Disord. 27(6), 789-793 (2012).
161. Bras J, Verloes A, Schneider SA, Mole SE, Guerreiro RJ. Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis. Hum. Mol. Genet. 21(12), 2646-2650 (2012).
162. Saitsu H, Kato M, Osaka H et al. CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia. Epilepsia 53(8), 1441-1449 (2012).
163. Andrade DM, Paton T, Turnbull J, Marshall CR, Scherer SW, Minassian BA. Mutation of the CLN6 gene in teenageonset progressive myoclonus epilepsy. Pediatr. Neurol. 47(3), 205-208 (2012).
164. Pyle A, Griffin H, Yu-Wai-Man P et al. Prominent sensorimotor neuropathy due to SACS mutations revealed by whole-exome sequencing. Arch. Neurol. 2, 1-4 (2012)
165. Twine NA, Janitz K, Wilkins MR, Janitz M. Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer's disease. PLoS ONE 6(1), e16266 (2011).
166. Hazelett DJ, Chang JC, Lakeland DL, Morton DB. Comparison of parallel high-throughput RNA sequencing between knockout of TDP-43 and its overexpression reveals primarily nonreciprocal and nonoverlapping gene expression changes in the central nervous system of Drosophila. G3 (Bethesda) 2(7), 789-802 (2012).
167. Fogel BL, Wexler E, Wahnich A et al. RBFOX1 regulates both splicing and transcriptional networks in human neuronal development. Hum. Mol. Genet. 21(19), 4171-4186 (2012).
168. Forman OP, De Risio L, Stewart J, Mellersh CS, 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. 13, 55 (2012).
169. Kriesel JD, Hobbs MR, Jones BB, Milash B, Nagra RM, Fischer KF. Deep sequencing for the detection of virus-like sequences in the brains of patients with multiple sclerosis: detection of GBV-C in human brain. PLoS ONE 7(3), e31886 (2012).
170. Heap GA, Yang JH, Downes K et al. Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing. Hum. Mol. Genet. 19(1), 122-134 (2010).
171. Lin M, Pedrosa E, Shah A et al. RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS ONE 6(9), e23356 (2011).