High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism

PLoS ONE

Volumn 7, Issue 4, 2012, Pages

  Kelleher III, Raymond J ^a,b   Geigenmüller, Ute ^c,e   Hovhannisyan, Hayk ^c   Trautman, Edwin ^c   Pinard, Robert ^c   Rathmell, Barbara ^d   Carpenter, Randall ^d   Margulies, David ^c  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c Harvard Medical School ^*  (United States)

^d Seaside Therapeutics   (United States)

^e BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

METABOTROPIC RECEPTOR; CARRIER PROTEIN; NERVE PROTEIN; PROTEIN HOMER; SHANK3 PROTEIN, HUMAN; TUBERIN; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; AUTISM; CONTROLLED STUDY; FEMALE; GENE DELETION; GENE IDENTIFICATION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HIGH THROUGHPUT SEQUENCING; HOMER1 GENE; HUMAN; MALE; MUTATOR GENE; PATHOGENESIS; SEQUENCE ANALYSIS; SHANK3 GENE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; TSC1 GENE; TSC2 GENE; CASE CONTROL STUDY; GENETICS; METABOLISM; RISK FACTOR;

AUTISTIC DISORDER; CARRIER PROTEINS; CASE-CONTROL STUDIES; FEMALE; GENETIC VARIATION; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MALE; NERVE TISSUE PROTEINS; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, METABOTROPIC GLUTAMATE; RISK FACTORS; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 84860446920     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0035003     Document Type: Article

References (53)

1. Abrahams BS, Geschwind DH, (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9: 341-355.
2. El-Fishawy P, State MW, (2010) The genetics of autism: key issues, recent findings, and clinical implications. Psychiatr Clin North Am 33: 83-105.
3. Toro R, Konyukh M, Delorme R, Leblond C, Chaste P, et al. (2010) Key role for gene dosage and synaptic homeostasis in autism spectrum disorders. Trends Genet 26: 363-372.
4. Kelleher RJ 3rd, Bear MF, (2008) The autistic neuron: troubled translation? Cell 135: 401-406.
5. Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, et al. (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet 39: 319-328.
6. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, et al. (2007) Strong association of de novo copy number mutations with autism. Science 316: 445-449.
7. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, et al. (2010) Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466: 368-372.
8. Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, et al. (2009) Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459: 569-573.
9. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, et al. (2008) Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 358: 667-675.
10. Krueger DD, Bear MF Toward Fulfilling the Promise of Molecular Medicine in Fragile X Syndrome. Annu Rev Med.
11. Ramocki MB, Zoghbi HY, (2008) Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature 455: 912-918.
12. Sudhof TC, (2008) Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455: 903-911.
13. Gilman SR, Iossifov I, Levy D, Ronemus M, Wigler M, et al. (2011) Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron 70: 898-907.
14. Gai X, Xie HM, Perin JC, Takahashi N, Murphy K, et al. (2011) Rare structural variation of synapse and neurotransmission genes in autism. Mol Psychiatry.
15. Bear MF, Huber KM, Warren ST, (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27: 370-377.
16. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, et al. (2007) Correction of fragile X syndrome in mice. Neuron 56: 955-962.
17. Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, et al. (2002) Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415: 526-530.
18. Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, et al. (2008) Reversal of learning deficits in a Tsc2(+/-) mouse model of tuberous sclerosis. Nat Med 14: 843-848.
19. Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, et al. (2010) The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 140: 704-716.
20. Geschwind DH, Sowinski J, Lord C, Iversen P, Shestack J, et al. (2001) The autism genetic resource exchange: a resource for the study of autism and related neuropsychiatric conditions. American journal of human genetics 69: 463-466.
21. Thusberg J, Olatubosun A, Vihinen M, (2011) Performance of mutation pathogenicity prediction methods on missense variants. Hum Mutat 32: 358-368.
22. Wiznitzer M, (2004) Autism and tuberous sclerosis. J Child Neurol 19: 675-679.
23. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, et al. (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39: 25-27.
24. Xiao B, Tu JC, Worley PF, (2000) Homer: a link between neural activity and glutamate receptor function. Curr Opin Neurobiol 10: 370-374.
25. Ronesi JA, Huber KM, (2008) Homer interactions are necessary for metabotropic glutamate receptor-induced long-term depression and translational activation. J Neurosci 28: 543-547.
26. Hayashi MK, Tang C, Verpelli C, Narayanan R, Stearns MH, et al. (2009) The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell 137: 159-171.
27. Sala C, Piech V, Wilson NR, Passafaro M, Liu G, et al. (2001) Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31: 115-130.
28. Chen JM, Ferec C, Cooper DN, (2006) A systematic analysis of disease-associated variants in the 3' regulatory regions of human protein-coding genes I: general principles and overview. Human genetics 120: 1-21.
29. Conne B, Stutz A, Vassalli JD, (2000) The 3' untranslated region of messenger RNA: A molecular 'hotspot' for pathology? Nature medicine 6: 637-641.
30. Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, et al. (2005) Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310: 317-320.
31. Sayed D, Abdellatif M, (2011) MicroRNAs in development and disease. Physiological reviews 91: 827-887.
32. John B, Enright AJ, Aravin A, Tuschl T, Sander C, et al. (2004) Human MicroRNA targets. PLoS Biol 2: e363.
33. Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ, (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36: D154-158.
34. Zhao X, Leotta A, Kustanovich V, Lajonchere C, Geschwind DH, et al. (2007) A unified genetic theory for sporadic and inherited autism. Proc Natl Acad Sci U S A 104: 12831-12836.
35. O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, et al. (2011) Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature genetics 43: 585-589.
36. Levy D, Ronemus M, Yamrom B, Lee YH, Leotta A, et al. (2011) Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron 70: 886-897.
37. Abankwa D, Hanzal-Bayer M, Ariotti N, Plowman SJ, Gorfe AA, et al. (2008) A novel switch region regulates H-ras membrane orientation and signal output. EMBO J 27: 727-735.
38. Nava C, Hanna N, Michot C, Pereira S, Pouvreau N, et al. (2007) Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome. J Med Genet 44: 763-771.
39. Aoki Y, Niihori T, Narumi Y, Kure S, Matsubara Y, (2008) The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders. Hum Mutat 29: 992-1006.
40. Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, et al. (2011) Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70: 863-885.
41. Schaaf CP, Sabo A, Sakai Y, Crosby J, Muzny D, et al. (2011) Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders. Human molecular genetics 20: 3366-3375.
42. Berkel S, Marshall CR, Weiss B, Howe J, Roeth R, et al. (2010) Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat Genet 42: 489-491.
43. Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, et al. (2003) Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34: 27-29.
44. Ronesi JA, Collins KA, Hays SA, Tsai NP, Guo W, et al. (2012) Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat Neurosci 15: 431-440.
45. Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, et al. (2009) Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. N Engl J Med 360: 599-605.
46. Rumbaugh G, Adams JP, Kim JH, Huganir RL, (2006) SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons. Proc Natl Acad Sci U S A 103: 4344-4351.
47. Gallagher SM, Daly CA, Bear MF, Huber KM, (2004) Extracellular signal-regulated protein kinase activation is required for metabotropic glutamate receptor-dependent long-term depression in hippocampal area CA1. J Neurosci 24: 4859-4864.
48. Kelleher RJ 3rd, Govindarajan A, Jung H-Y, Kang H, Tonegawa S, (2004) Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116: 467-469.
49. Sweatt JD, (2004) Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol 14: 311-317.
50. Ng PC, Henikoff S, (2001) Predicting deleterious amino acid substitutions. Genome Res 11: 863-874.
51. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, et al. (2010) A method and server for predicting damaging missense mutations. Nat Methods 7: 248-249.
52. Li B, Krishnan VG, Mort ME, Xin F, Kamati KK, et al. (2009) Automated inference of molecular mechanisms of disease from amino acid substitutions. Bioinformatics 25: 2744-2750.
53. Calabrese R, Capriotti E, Fariselli P, Martelli PL, Casadio R, (2009) Functional annotations improve the predictive score of human disease-related mutations in proteins. Hum Mutat 30: 1237-1244.