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Received: 2013-05-08

Revision Accepted: 2013-11-20

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Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.3 P.264-271

http://doi.org/10.1631/jzus.B1300133


Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population*


Author(s):  Shuang Liang1, Xue-lai Wang1, Ming-yang Zou1, Han Wang1, Xue Zhou1, Cai-hong Sun1, Wei Xia1, Li-jie Wu1, Takashi X. Fujisawa2, Akemi Tomoda2

Affiliation(s):  1. Department of Childrens and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, China; more

Corresponding email(s):   liangyouyou2004@163.com

Key Words:  Autism, ZNF533 , DOCK4 , IMMP2L , Northeastern Chinese Han population, Single-nucleotide polymorphism


Shuang Liang, Xue-lai Wang, Ming-yang Zou, Han Wang, Xue Zhou, Cai-hong Sun, Wei Xia, Li-jie Wu, Takashi X. Fujisawa, Akemi Tomoda. Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population[J]. Journal of Zhejiang University Science B, 2014, 15(3): 264-271.

@article{title="Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population",
author="Shuang Liang, Xue-lai Wang, Ming-yang Zou, Han Wang, Xue Zhou, Cai-hong Sun, Wei Xia, Li-jie Wu, Takashi X. Fujisawa, Akemi Tomoda",
journal="Journal of Zhejiang University Science B",
volume="15",
number="3",
pages="264-271",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300133"
}

%0 Journal Article
%T Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population
%A Shuang Liang
%A Xue-lai Wang
%A Ming-yang Zou
%A Han Wang
%A Xue Zhou
%A Cai-hong Sun
%A Wei Xia
%A Li-jie Wu
%A Takashi X. Fujisawa
%A Akemi Tomoda
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 3
%P 264-271
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300133

TY - JOUR
T1 - Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population
A1 - Shuang Liang
A1 - Xue-lai Wang
A1 - Ming-yang Zou
A1 - Han Wang
A1 - Xue Zhou
A1 - Cai-hong Sun
A1 - Wei Xia
A1 - Li-jie Wu
A1 - Takashi X. Fujisawa
A1 - Akemi Tomoda
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 3
SP - 264
EP - 271
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300133


Abstract: 
Objective: A study in a Caucasian population has identified two single-nucleotide polymorphisms (SNPs) in ZNF533, one in DOCK4, and two in IMMP2L, which were all significantly associated with autism. They are located in AUTS1 and AUTS5, which have been identified as autism susceptibility loci in several genome-wide screens. The present study aimed to investigate whether ZNF533, DOCK4, and IMMP2L genes are also associated with autism in a northeastern Chinese Han population. Methods: We performed a similar association study using families with three individuals (one autistic child and two unaffected parents). A family-based transmission disequilibrium test (TDT) was used to analyze the results. Results: There were significant associations between autism and the two SNPs of ZNF533 gene (rs11885327: χ 2=4.5200, P=0.0335; rs1964081: χ 2=4.2610, P=0.0390) and the SNP of DOCK4 gene (rs2217262: χ 2=5.3430, P=0.0208). Conclusions: Our data suggest that ZNF533 and DOCK4 genes are linked to a predisposition to autism in the northeastern Chinese Han population.

ZNF533、DOCK4和IMMP2L基因多态性与中国东北汉族孤独症的关联研究

研究目的:ZNF533DOCK4IMMP2L在大脑发育过程中起到非常重要的作用,是孤独症研究的候选基因。高加索人群的研究结果发现,ZNF533DOCK4IMMP2L基因的5个单核苷酸多态性(SNP)位点与孤独症高度相关。为了探讨上述位点是否与中国孤独症发生相关,我们开展了东北汉族孤独症的核心家系研究。
创新要点:孤独症候选基因多态位点的研究结果通常很难得到重复。本研究首次在中国东北汉族人群中验证了与高加索人群孤独症密切相关的候选位点。这一结果对孤独症的研究具有重要指导意义。
研究方法:利用SNaPshot的方法,检测了中国东北汉族370个核心家系中ZNF533(rs11885327、rs1964081)、DOCK4(rs2217262)和IMMP2L(rs12537269、rs1528039)的分布情况,利用传递不平衡检验(TDT)分析了这些多态位点与孤独症发生的相关性。
重要结论:ZNF533DOCK4基因多态性与中国北方汉族孤独症发生存在显著关联。

关键词:孤独症;ZNF533;DOCK4;IMMP2L;中国东北汉族;单核苷酸多态性

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

References

[1] American Psychiatric Association, 1994.  Diagnostic and Statistical Manual of Mental Disorder. American Psychiatric Association,Washington, DC :

[2] American Psychiatric Association, 2013.  Diagnostic and Statistical Manual of Mental Disorder. American Psychiatric Association,Washington, DC :

[3] Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators, 2012. Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 sites, United States, 2008. MMWR Surveill Summ, 61(3):1-19. 

[4] Badner, J.A., Gershon, E.S., 2002. Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7. Mol Psychiatry, 7(1):56-66. 


[5] Bailey, A., Le Couteur, A., Gottesman, I., 1995. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med, 25(1):63-77. 


[6] Baird, G., Simonoff, E., Pickles, A., 2006. Prevalence of disorders of the autism spectrum in a population cohort of children in south Thames: the special needs and autism project (SNAP). Lancet, 368(9531):210-215. 


[7] Barrett, S., Beck, J.C., Bernier, R., 1999. An autosomal genomic screen for autism. Collaborative linkage study of autism. Am J Med Genet, 88(6):609-615. 


[8] Battye, R., Stevens, A., Perry, R.L., 2001. Repellent signaling by slit requires the leucine-rich repeats. J Neurosci, 21(12):4290-4298. 


[9] Beaty, T.H., Hetmanski, J.B., Fallin, M.D., 2006. Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations. Hum Genet, 120(4):501-518. 


[10] Biersmith, B., Liu, Z.C., Bauman, K., 2011. The DOCK protein sponge binds to ELMO and functions in Drosophila embryonic CNS development. PLoS ONE, 6(1):e16120


[11] Brugha, T.S., Mcmanus, S., Bankart, J., 2011. Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry, 68(5):459-465. 


[12] Buxbaum, J.D., Silverman, J.M., Smith, C.J., 2001. Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. Am J Hum Genet, 68(6):1514-1520. 


[13] Daz-Anzalda, A., Joober, R., Rivire, J.B., 2004. Association between 7q31 markers and tourette syndrome. Am J Med Genet A, 127A(1):17-20. 


[14] Elsabbagh, M., Divan, G., Koh, Y.J., 2012. Global prevalence of autism and other pervasive developmental disorders. Autism Res, 5(3):160-179. 


[15] Fombonne, E., 2009. Epidemiology of pervasive developmental disorders. Pediatr Res, 65(6):591-598. 


[16] Hallmayer, J., Cleveland, S., Torres, A., 2011. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry, 68(11):1095-1102. 


[17] IMGSAC, 1998. A full genome screen for autism with evidence for linkage to a region on chromosome 7q. Hum Mol Genet, 7(3):571-578. 


[18] IMGSAC, 2001. A genomewide screen for autism: strong evidence for linkage to chromosomes 2q, 7q, and 16p. Am J Hum Genet, 69(3):570-581. 


[19] Khaniani, M.S., Kalitsis, P., Burgess, T., 2008. An improved diagnostic PCR assay for identification of cryptic heterozygosity for CGG triplet repeat alleles in the Fragile X gene (FMR1). Mol Cytogenet, 1(1):5


[20] Kim, Y.S., Leventhal, B.L., Koh, Y.J., 2011. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry, 168(9):904-912. 


[21] Kleefstra, T., Yntema, H.G., Oudakker, A.R., 2004.  Zinc finger 81 (ZNF81) mutations associated with X-linked mental retardation. J Med Genet, 41(5):394-399. 


[22] Kogan, M.D., Blumberg, S.J., Schieve, L.A., 2009. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics, 124(5):1395-1403. 


[23] Krug, D.A., Arick, J., Almond, P., 1980. Behavior checklist for identifying severely handicapped individuals with high levels of autistic behavior. J Child Psychol Psychiatry, 21(3):221-229. 


[24] Maestrini, E., Pagnamenta, A.T., Lamb, J.A., 2010. High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility. Mol Psychiatry, 15(9):954-968. 


[25] Miyamoto, Y., Yamauchi, J., 2010. Cellular signaling of Dock family proteins in neural function. Cell Signal, 22(2):175-182. 


[26] Monfort, S., Rosello, M., Orellana, C., 2008. Detection of known and novel genomic rearrangements by array based comparative genomic hybridisation: deletion of ZNF533 and duplication of charge syndrome genes. J Med Genet, 45(7):432-437. 


[27] Pagnamenta, A.T., Bacchelli, E., de Jonge, M.V., 2010. Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia. Biol Psychiatry, 68(4):320-328. 


[28] Petek, E., Windpassinger, C., Vincent, J.B., 2001. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am J Hum Genet, 68(4):848-858. 


[29] Petek, E., Schwarzbraun, T., Noor, A., 2007. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol Genet Genomics, 277(1):71-81. 


[30] Schellenberg, G.D., Dawson, G., Sung, Y.J., 2006. Evidence for multiple loci from a genome scan of autism kindreds. Mol Psychiatry, 11(11):1049-1060. 


[31] Schopler, E., Reichler, R.J., Devellis, R.F., 1980. Toward objective classification of childhood autism: childhood autism rating scale (cars). J Autism Dev Disord, 10(1):91-103. 


[32] Shao, Y., Wolpert, C.M., Raiford, K.L., 2002. Genomic screen and follow-up analysis for autistic disorder. Am J Med Genet, 114(1):99-105. 


[33] Shao, Y., Raiford, K.L., Wolpert, C.M., 2002. Phenotypic homogeneity provides increased support for linkage on chromosome 2 in autistic disorder. Am J Hum Genet, 70(4):1058-1061. 


[34] Spielman, R.S., Ewens, W.J., 1996. The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet, 59(5):983-989. 


[35] Spielman, R.S., Mcginnis, R.E., Ewens, W.J., 1993. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet, 52(3):506-516. 


[36] Szatmari, P., Paterson, A.D., Zwaigenbaum, L., 2007. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet, 39(3):319-328. 


[37] Trikalinos, T.A., Karvouni, A., Zintzaras, E., 2006. A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol Psychiatry, 11(1):29-36. 


[38] Xiao, Y., Peng, Y., Wan, J., 2013. The atypical guanine nucleotide exchange factor Dock4 regulates neurite differentiation through modulation of Rac1 GTPase and actin dynamics. J Biol Chem, 288(27):20034-20045. 


[39] Xu, L.M., Li, J.R., Huang, Y., 2012. AutismKB: an evidence-based knowledgebase of autism genetics. Nucl Acids Res, 40(D1):D1016-D1022. 


[40] Zhou, X., Xu, Y., Wang, J., 2011. Replication of the association of a MET variant with autism in a Chinese Han population. PLoS ONE, 6(11):e27428



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