Top

Published in:

Open Access 01-12-2012 | Research

Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci

Authors: Dale J Hedges, Kara L Hamilton-Nelson, Stephanie J Sacharow, Laura Nations, Gary W Beecham, Zhanna M Kozhekbaeva, Brittany L Butler, Holly N Cukier, Patrice L Whitehead, Deqiong Ma, James M Jaworski, Lubov Nathanson, Joycelyn M Lee, Stephen L Hauser, Jorge R Oksenberg, Michael L Cuccaro, Jonathan L Haines, John R Gilbert, Margaret A Pericak-Vance

Published in: Molecular Autism | Issue 1/2012

Abstract

Background

Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism.

Methods

As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members.

Results

Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions.

Conclusions

These results provide additional support for the role of rare structural variation in ASD.

Available only for authorised users

Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M: Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995, 25: 63-77. 10.1017/S0033291700028099.CrossRefPubMed

Meyer-Lindenberg A, Kolachana B, Gold B, Olsh A, Nicodemus KK, Mattay V, Dean M, Weinberger DR: Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry. 2008, 14: 968-975.PubMedCentralCrossRefPubMed

Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA: Identifying autism loci and genes by tracing recent shared ancestry. Science. 2008, 321: 218-223. 10.1126/science.1157657.PubMedCentralCrossRefPubMed

Yan J, Noltner K, Feng J, Li W, Schroer R, Skinner C, Zeng W, Schwartz CE, Sommer SS: Neurexin 1alpha structural variants associated with autism. Neurosci Lett. 2008, 438: 368-370. 10.1016/j.neulet.2008.04.074.CrossRefPubMed

Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bolte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C: Functional impact of global rare copy number variation in autism spectrum disorders. Nature. 2010, 466: 368-372. 10.1038/nature09146.PubMedCentralCrossRefPubMed

Weiss LA, Arking DE, Gene Discovery Project of Johns Hopkins & the Autism Consortium, Daly MJ, Chakravarti A: A genome-wide linkage and association scan reveals novel loci for autism. Nature. 2009, 461: 802-808. 10.1038/nature08490.PubMedCentralCrossRefPubMed

Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A: Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009, 459: 528-533. 10.1038/nature07999.PubMedCentralCrossRefPubMed

Rudan I: New technologies provide insights into genetic basis of psychiatric disorders and explain their co-morbidity. Psychiatr Danub. 2010, 22: 190-192.PubMed

Fernandez BA, Roberts W, Chung B, Weksberg R, Meyn S, Szatmari P, Joseph-George AM, Mackay S, Whitten K, Noble B, Vardy C, Crosbie V, Luscombe S, Tucker E, Turner L, Marshall CR, Scherer SW: Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet. 2010, 47: 195-203. 10.1136/jmg.2009.069369.CrossRefPubMed

10.

Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, Sonnenblick LI, Alvarez Retuerto AI, Imielinski M, Hadley D, Bradfield JP, Kim C, Gidaya NB, Lindquist I, Hutman T, Sigman M, Kustanovich V, Lajonchere CM, Singleton A, Kim J, Wassink TH, McMahon WM, Owley T, Sweeney JA, Coon H, Nurnberger JI, Li M, Cantor RM, Minshew NJ, Sutcliffe JS, Cook EH: Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genet. 2009, 5: e1000536-10.1371/journal.pgen.1000536.PubMedCentralCrossRefPubMed

11.

Cho SC, Yim SH, Yoo HK, Kim MY, Jung GY, Shin GW, Kim BN, Hwang JW, Kang JJ, Kim TM, Chung YJ: Copy number variations associated with idiopathic autism identified by whole-genome microarray-based comparative genomic hybridization. Psychiatr Genet. 2009, 19: 177-185. 10.1097/YPG.0b013e32832bdafa.CrossRefPubMed

12.

Sykes NH, Toma C, Wilson N, Volpi EV, Sousa I, Pagnamenta AT, Tancredi R, Battaglia A, Maestrini E, Bailey AJ, Monaco AP, International Molecular Genetic Study of Autism Consortium (IMGSAC): Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection. Eur J Hum Genet. 2009, 17: 1347-1353. 10.1038/ejhg.2009.47.PubMedCentralCrossRefPubMed

13.

Christian SL, Brune CW, Sudi J, Kumar RA, Liu S, Karamohamed S, Badner JA, Matsui S, Conroy J, McQuaid D, Gergel J, Hatchwell E, Gilliam TC, Gershon ES, Nowak NJ, Dobyns WB, Cook EH: Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder. Biol Psychiatry. 2008, 63: 1111-1117. 10.1016/j.biopsych.2008.01.009.PubMedCentralCrossRefPubMed

14.

Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R: Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008, 82: 477-488. 10.1016/j.ajhg.2007.12.009.PubMedCentralCrossRefPubMed

15.

Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC: Strong association of de novo copy number mutations with autism. Science. 2007, 316: 445-449. 10.1126/science.1138659.PubMedCentralCrossRefPubMed

16.

Perry GH, Ben-Dor A, Tsalenko A, Sampas N, Rodriguez-Revenga L, Tran CW, Scheffer A, Steinfeld I, Tsang P, Yamada NA, Park HS, Kim JI, Seo JS, Yakhini Z, Laderman S, Bruhn L, Lee C: The fine-scale and complex architecture of human copy-number variation. Am J Hum Genet. 2008, 82: 685-695. 10.1016/j.ajhg.2007.12.010.PubMedCentralCrossRefPubMed

17.

Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R: GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev. 2007, 87: 1215-1284. 10.1152/physrev.00017.2006.CrossRefPubMed

18.

Takayama C, Inoue Y: GABAergic signaling in the developing cerebellum. Anat Sci Int. 2004, 79: 124-136. 10.1111/j.1447-073x.2004.00081.x.CrossRefPubMed

19.

Menold MM, Shao Y, Wolpert CM, Donnelly SL, Raiford KL, Martin ER, Ravan SA, Abramson RK, Wright HH, DeLong GR, Cuccaro ML, Pericak-Vance MA, Gilbert JR: Association analysis of chromosome 15 gabaa receptor subunit genes in autistic disorder. J Neurogenet. 2001, 15: 245-259. 10.3109/01677060109167380.CrossRefPubMed

20.

Bass MP, Menold MM, Wolpert CM, Donnelly SL, Ravan SA, Hauser ER, Maddox LO, Vance JM, Abramson RK, Wright HH, Gilbert JR, Cuccaro ML, DeLong GR, Pericak-Vance MA: Genetic studies in autistic disorder and chromosome 15. Neurogenetics. 2000, 2: 219-226. 10.1007/s100489900081.CrossRefPubMed

21.

Fatemi SH, Reutiman TJ, Folsom TD, Thuras PD: GABA(A) receptor downregulation in brains of subjects with autism. J Autism Dev Disord. 2009, 39: 223-230. 10.1007/s10803-008-0646-7.PubMedCentralCrossRefPubMed

22.

Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD: Expression of GABA(B) receptors is altered in brains of subjects with autism. Cerebellum. 2009, 8: 64-69. 10.1007/s12311-008-0075-3.PubMedCentralCrossRefPubMed

23.

Oblak AL, Gibbs TT, Blatt GJ: Decreased GABA(B) Receptors in the Cingulate Cortex and Fusiform Gyrus in Autism. J Neurochem. 2010, 114: 1414-1423.PubMedCentralPubMed

24.

Delahanty RJ, Kang JQ, Brune CW, Kistner EO, Courchesne E, Cox NJ, Cook EH, Macdonald RL, Sutcliffe JS: Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism. Mol Psychiatry. 2011, 16: 86-96. 10.1038/mp.2009.118.PubMedCentralCrossRefPubMed

25.

Rutter M, LeCouteur A, Lord C: Autism Diagnostic Interview, Revised (ADI-R). 2003, Los Angeles, CA: Western Psychological Services

26.

Lord C, Rutter M, DiLavore P, Risi S: Autism Diagnostic Observation Schedule-WPS. 1999, Los Angeles, CA: Western Psychological Services, WPSth {Version 1AU Query: please confirm the edition number} edition.

27.

Sparrow SS, Balla D, Cicchetti D: Vineland Adaptive Behavior Scales, Interview Edition. 1984, Circle Pines, MN: AGS Publishing

28.

Rutter M, Bailey A, Berument SK, LeCouteur A, Lord C, Pickles A: Social Communication Questionnaire (SCQ). 2003, Los Angeles, CA: Western Psychological Services

29.

Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D: Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006, 38: 904-909. 10.1038/ng1847.CrossRefPubMed

30.

Scherer SW, Lee C, Birney E, Altshuler DM, Eichler EE, Carter NP, Hurles ME, Feuk L: Challenges and standards in integrating surveys of structural variation. Nat Genet. 2007, 39: S7-S15. 10.1038/ng2093.PubMedCentralCrossRefPubMed

31.

Olshen AB, Venkatraman ES, Lucito R, Wigler M: Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 2004, 5: 557-572. 10.1093/biostatistics/kxh008.CrossRefPubMed

32.

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81: 559-575. 10.1086/519795.PubMedCentralCrossRefPubMed

33.

Liang K, Zeger SL: Longitudinal data analysis using generalized linear models. Biometrika. 1986, 73: 13-22. 10.1093/biomet/73.1.13.CrossRef

34.

Oxford Statistical Science Series, Diggle PJ, Heagerty P, Liang K, Zeger SL: Analysis of Longitudinal Data. 2002, Oxford Statistical Science Series

35.

Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C, Williams C, Stalker H, Hamid R, Hannig V, Abdel-Hamid H, Bader P, McCracken E, Niyazov D, Leppig K, Thiese H, Hummel M, Alexander N, Gorski J, Kussmann J, Shashi V, Johnson K, Rehder C, Ballif BC, Shaffer LG, Eichler EE: A copy number variation morbidity map of developmental delay. Nat Genet. 2011, 43: 838-846. 10.1038/ng.909.PubMedCentralCrossRefPubMed

36.

Couve A, Restituito S, Brandon JM, Charles KJ, Bawagan H, Freeman KB, Pangalos MN, Calver AR, Moss SJ: Marlin-1, a novel RNA-binding protein associates with GABA receptors. J Biol Chem. 2004, 279: 13934-13943. 10.1074/jbc.M311737200.CrossRefPubMed

37.

Nishimura Y, Martin CL, Vazquez-Lopez A, Spence SJ, Alvarez-Retuerto AI, Sigman M, Steindler C, Pellegrini S, Schanen NC, Warren ST, Geschwind DH: Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Hum Mol Genet. 2007, 16: 1682-1698. 10.1093/hmg/ddm116.CrossRefPubMed

38.

Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ, Shen Y, Lally E, Weiss LA, Najm J, Kutsche K, Descartes M, Holt L, Braddock S, Troxell R, Kaplan L, Volkmar F, Klin A, Tsatsanis K, Harris DJ, Noens I, Pauls DL, Daly MJ, MacDonald ME, Morton CC, Quade BJ, Gusella JF: Disruption of neurexin 1 associated with autism spectrum disorder. Am J Hum Genet. 2008, 82: 199-207. 10.1016/j.ajhg.2007.09.011.PubMedCentralCrossRefPubMed

39.

Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, Liu XQ, Vincent JB, Skaug JL, Thompson AP, Senman L, Feuk L, Qian C, Bryson SE, Jones MB, Marshall CR, Scherer SW, Vieland VJ, Bartlett C, Mangin LV, Goedken R, Segre A, Pericak-Vance MA, Cuccaro ML, Gilbert JR, Wright HH, Abramson RK, Betancur C, Bourgeron T, Gillberg C, Leboyer M: Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007, 39: 319-328. 10.1038/ng1985.CrossRefPubMed

40.

Ching MS, Shen Y, Tan WH, Jeste SS, Morrow EM, Chen X, Mukaddes NM, Yoo SY, Hanson E, Hundley R, Austin C, Becker RE, Berry GT, Driscoll K, Engle EC, Friedman S, Gusella JF, Hisama FM, Irons MB, Lafiosca T, LeClair E, Miller DT, Neessen M, Picker JD, Rappaport L, Rooney CM, Sarco DP, Stoler JM, Walsh CA, Wolff RR: Children's Hospital Boston Genotype Phenotype Study Group: Deletions of NRXN1 (neurexin-1) predispose to a wide spectrum of developmental disorders. Am J Med Genet B Neuropsychiatr Genet. 2010, 153B: 937-947.PubMedCentralPubMed

41.

Gai X, Xie HM, Perin JC, Takahashi N, Murphy K, Wenocur AS, D'arcy M, O'Hara RJ, Goldmuntz E, Grice DE, Shaikh TH, Hakonarson H, Buxbaum JD, Elia J, White PS: Rare structural variation of synapse and neurotransmission genes in autism. Mol Psychiatry. 2011, doi: 10.1038/mp.2011.10

42.

Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, Zhang H, Estes A, Brune CW, Bradfield JP, Imielinski M, Frackelton EC, Reichert J, Crawford EL, Munson J, Sleiman PM, Chiavacci R, Annaiah K, Thomas K, Hou C, Glaberson W, Flory J, Otieno F, Garris M, Soorya L, Klei L, Piven J, Meyer KJ, Anagnostou E, Sakurai T: Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009, 459: 569-573. 10.1038/nature07953.PubMedCentralCrossRefPubMed

43.

Zweier C, de Jong EK, Zweier M, Orrico A, Ousager LB, Collins AL, Bijlsma EK, Oortveld MA, Ekici AB, Reis A, Schenck A, Rauch A: CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet. 2009, 85: 655-666. 10.1016/j.ajhg.2009.10.004.PubMedCentralCrossRefPubMed

44.

Zahir FR, Baross A, Delaney AD, Eydoux P, Fernandes ND, Pugh T, Marra MA, Friedman JM: A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha. J Med Genet. 2008, 45: 239-243.CrossRefPubMed

45.

Rujescu D, Ingason A, Cichon S, Pietilainen OP, Barnes MR, Toulopoulou T, Picchioni M, Vassos E, Ettinger U, Bramon E, Murray R, Ruggeri M, Tosato S, Bonetto C, Steinberg S, Sigurdsson E, Sigmundsson T, Petursson H, Gylfason A, Olason PI, Hardarsson G, Jonsdottir GA, Gustafsson O, Fossdal R, Giegling I, Moller HJ, Hartmann AM, Hoffmann P, Crombie C, Fraser G: Disruption of the neurexin 1 gene is associated with schizophrenia. Hum Mol Genet. 2009, 18: 988-996.PubMedCentralPubMed

46.

Wisniowiecka-Kowalnik B, Nesteruk M, Peters SU, Xia Z, Cooper ML, Savage S, Amato RS, Bader P, Browning MF, Haun CL, Duda AW 3rd, Cheung SW, Stankiewicz P: Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay. Am J Med Genet B Neuropsychiatr Genet. 2010, 153B: 983-993.PubMed

47.

Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper PB, Choi M, Crawford EL, Davis L, Davis Wright NR, Dhodapkar RM, Dicola M, Dilullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC: Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams Syndrome region, are strongly associated with autism. Neuron. 2011, 70: 863-885. 10.1016/j.neuron.2011.05.002.PubMedCentralCrossRefPubMed

48.

Duong L, Klitten LL, Moller RS, Ingason A, Jakobsen KD, Skjodt C, Didriksen M, Hjalgrim H, Werge T, Tommerup N: Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders. Am J Med Genet B Neuropsychiatr Genet. 2012, 159B: 354-358. 10.1002/ajmg.b.32036.CrossRefPubMed

49.

Gregor A, Albrecht B, Bader I, Bijlsma EK, Ekici AB, Engels H, Hackmann K, Horn D, Hoyer J, Klapecki J, Kohlhase J, Maystadt I, Nagl S, Prott E, Tinschert S, Ullmann R, Wohlleber E, Woods G, Reis A, Rauch A, Zweier C: Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1. BMC Med Genet. 2011, 12: 106-10.1186/1471-2350-12-106.PubMedCentralCrossRefPubMed

50.

Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T: Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet. 2003, 34: 27-29. 10.1038/ng1136.PubMedCentralCrossRefPubMed

51.

Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, Raynaud M, Ronce N, Lemonnier E, Calvas P, Laudier B, Chelly J, Fryns JP, Ropers HH, Hamel BCJ, Andres C, Barthelemy C, Moraine C, Briault S: X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet. 2004, 74: 552-557. 10.1086/382137.PubMedCentralCrossRefPubMed

52.

Ylisaukko-oja T, Rehnstrom K, Auranen M, Vanhala R, Alen R, Kempas E, Ellonen P, Turunen JA, Makkonen I, Riikonen R, Nieminen-von Wendt T, von Wendt L, Peltonen L, Jarvela I: Analysis of four neuroligin genes as candidates for autism. Eur J Hum Genet. 2005, 13: 1285-1292. 10.1038/sj.ejhg.5201474.CrossRefPubMed

53.

Yan J, Feng J, Schroer R, Li W, Skinner C, Schwartz CE, Cook EH, Sommer SS: Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr Genet. 2008, 18: 204-207. 10.1097/YPG.0b013e3282fb7fe6.CrossRefPubMed

54.

Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP: A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010, 465: 1033-1038. 10.1038/nature09144.PubMedCentralCrossRefPubMed

55.

Barnby G, Abbott A, Sykes N, Morris A, Weeks DE, Mott R, Lamb J, Bailey AJ, Monaco AP: Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. Am J Hum Genet. 2005, 76: 950-966. 10.1086/430454.PubMedCentralCrossRefPubMed

56.

Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA: Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009, 7: 62-10.1186/1741-7015-7-62.PubMedCentralCrossRefPubMed

Title: Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci
Authors: Dale J Hedges
Kara L Hamilton-Nelson
Stephanie J Sacharow
Laura Nations
Gary W Beecham
Zhanna M Kozhekbaeva
Brittany L Butler
Holly N Cukier
Patrice L Whitehead
Deqiong Ma
James M Jaworski
Lubov Nathanson
Joycelyn M Lee
Stephen L Hauser
Jorge R Oksenberg
Michael L Cuccaro
Jonathan L Haines
John R Gilbert
Margaret A Pericak-Vance
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Molecular Autism / Issue 1/2012
Electronic ISSN: 2040-2392
DOI: https://doi.org/10.1186/2040-2392-3-2

At a glance: The STEP trials

Springer Medicine

Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

Variation in the autism candidate gene GABRB3 modulates tactile sensitivity in typically developing children

Self-referential and social cognition in a case of autism and agenesis of the corpus callosum

Loci nominally associated with autism from genome-wide analysis show enrichment of brain expression quantitative trait loci but not lymphoblastoid cell line expression quantitative trait loci

Failure to deactivate the default mode network indicates a possible endophenotype of autism

High-functioning autism spectrum disorder and fragile X syndrome: report of two affected sisters

Common genetic variants, acting additively, are a major source of risk for autism