Analysis of four DLX homeobox genes in autistic probands

被引:58
作者
Hamilton, SP
Woo, JM
Carlson, EJ
Ghanem, N
Ekker, M
Rubenstein, JLR [1 ]
机构
[1] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Ctr Human Genet, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Genom Core Facil, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Nina Ireland Lab, San Francisco, CA 94143 USA
[5] Univ Ottawa, Dept Biol, Ottawa, ON, Canada
关键词
D O I
10.1186/1471-2156-6-52
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Linkage studies in autism have identified susceptibility loci on chromosomes 2q and 7q, regions containing the DLX1/2 and DLX5/6 bigene clusters. The DLX genes encode homeodomain transcription factors that control craniofacial patterning and differentiation and survival of forebrain inhibitory neurons. We investigated the role that sequence variants in DLX genes play in autism by in-depth resequencing of these genes in 161 autism probands from the AGRE collection. Results: Sequencing of exons, exon/ intron boundaries and known enhancers of DLX1, 2, 5 and 6 identified several nonsynonymous variants in DLX2 and DLX5 and a variant in a DLX5/6intragenic enhancer. The nonsynonymous variants were detected in 4 of 95 families from which samples were sequenced. Two of these four SNPs were not observed in 378 undiagnosed samples from North American populations, while the remaining 2 were seen in one sample each. Conclusion: Segregation of these variants in pedigrees did not generally support a contribution to autism susceptibility by these genes, although functional analyses may provide insight into the biological understanding of these important proteins.
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页数:11
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共 57 条
[31]  
Marín O, 2000, J NEUROSCI, V20, P6063
[32]   Sequence, organization, and transcription of the Dlx-1 and Dlx-2 locus [J].
McGuinness, T ;
Porteus, MH ;
Smiga, S ;
Bulfone, A ;
Kingsley, C ;
Qiu, MS ;
Liu, JK ;
Long, JE ;
Xu, DW ;
Rubenstein, JLR .
GENOMICS, 1996, 35 (03) :473-485
[33]   No association between single nucleotide polymorphisms in DLX6 and Piccolo genes at 7q21-q22 and autism [J].
Nabi, R ;
Zhong, H ;
Serajee, FJ ;
Huq, AM .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2003, 119B (01) :98-101
[34]  
Palferman S, 2001, AM J HUM GENET, V69, P570
[35]  
Panganiban G, 2002, DEVELOPMENT, V129, P4371
[36]  
Pfeffer U, 2001, INT J ONCOL, V18, P1293
[37]   Genome-wide scan for autism susceptibility genes [J].
Philippe, A ;
Martinez, M ;
Guilloud-Bataille, M ;
Gillberg, C ;
Råstam, M ;
Sponheim, E ;
Coleman, M ;
Zappella, M ;
Aschauer, H ;
van Maldergem, L ;
Penet, C ;
Feingold, J ;
Brice, A ;
Leboyer, M .
HUMAN MOLECULAR GENETICS, 1999, 8 (05) :805-812
[38]   Analysis of the autism chromosome 2 linkage region:: GAD1 and other candidate genes [J].
Rabionet, R ;
Jaworski, JM ;
Ashley-Koch, AE ;
Martin, ER ;
Sutcliffe, JS ;
Haines, JL ;
Delong, GR ;
Abramson, RK ;
Wright, HH ;
Cuccaro, ML ;
Gilbert, JR ;
Pericak-Vance, MA .
NEUROSCIENCE LETTERS, 2004, 372 (03) :209-214
[39]   Neurobiology of autism [J].
Rapin, I ;
Katzman, R .
ANNALS OF NEUROLOGY, 1998, 43 (01) :7-14
[40]  
Rozen S, 2000, Methods Mol Biol, V132, P365