Mutation screening and imprinting analysis of four candidate genes for autism in the 7q32 region

Bonora, Elena; Bacchelli, Elena; Er, Levy; Blasi, Francesca; Marlow, Angela J.; Monaco, Anthony P.; Maestrini, Elena

doi:10.1038/sj.mp.4001004

Cited by 40 publications

(28 citation statements)

References 39 publications

(47 reference statements)

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“…These data represent one of the more significant association between a candidate gene and ASD in the publicly available AGRE data set (www.agre.org). [52][53][54][55][56][57][58][59][60][61] The triad data also define a minimal population for future family-based association studies that is both a powerful and cost-efficient alternative to using extended nuclear families.…”

Section: Discussionmentioning

confidence: 99%

Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder

et al. 2004

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Mouse mutants of the homeobox transcription factor Engrailed2 (En2) and autistic individuals display similar cerebellar morphological abnormalities, which include hypoplasia and a decrease in the number of Purkinje cells. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Human EN2 maps to 7q36, a chromosomal region that has demonstrated suggestive linkage to autism spectrum disorder (ASD). [20][21][22] To investigate EN2 for evidence of association with ASD, four single-nucleotide polymorphisms (SNPs) (rs3735653, rs1861972, rs1861973, rs2361689) that span the majority of the 8.0 kb gene were assessed by the transmission/disequilibrium test [23][24][25][26] . Initially, 138 triads of autistic individuals and their parents were tested. Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P ¼ 0.0018; rs1861973, P ¼ 0.0003; haplotype, P ¼ 0.000005). Flanking exonic SNPs (rs3735653 and rs2361689) did not display association. This analysis was then extended to include 167 small nuclear ASD pedigrees and significant association was again only observed for rs1861972 and rs1861973 under both the narrow and broad diagnostic criteria (narrow: rs1861972 P ¼ 0.0290, rs1861973 P ¼ 0.0073, haplotype P ¼ 0.0009; broad: rs1861972 P ¼ 0.0175, rs1861973 P ¼ 0.0107, haplotype P ¼ 0.0024). These data demonstrate association between a cerebellar patterning gene and ASD, suggesting a role for EN2 as a susceptibility locus and supporting a neurodevelopmental defect hypothesis in the etiology of autism.

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Section: Discussionmentioning

confidence: 99%

Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder

et al. 2004

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“…Screening of exons 25, 35, 44 and 51 was carried out using DHPLC as described; 29 and the conditions optimised for the position of the four variants in the corresponding exons. Fragments showing a variant pattern were subsequently reamplified and sequenced as described before.…”

Section: Dhplc Screening In German Samplementioning

confidence: 99%

“…For the promoter analysis, PCR products from genomic DNA were subjected to denaturing high-performance liquid chromatography (DHPLC) analysis using the WAVE TM DNA Fragment Analysis System (Transgenomic) as described. 29 Samples showing a variant DHPLC pattern were sequenced to determine the nature of the heterozygous change.…”

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confidence: 99%

Analysis of reelin as a candidate gene for autism

et al. 2003

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Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify relevant gene(s) and report here the analysis of reelin (RELN), a gene located under our peak of linkage. Screening RELN for DNA changes identified novel missense variants absent in a large control group; however, the low frequency of these mutations does not explain the relatively strong linkage results on 7q. Furthermore, analysis of a previously reported triplet repeat polymorphism and intragenic single nucleotide polymorphisms, using the transmission disequilibrium test, provided no evidence for association with autism in IMGSAC and German singleton families. The analysis of RELN suggests that it probably does not play a major role in autism aetiology, although further analysis of several missense mutations is warranted in additional affected individuals.

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“…PCR amplifications and DHPLC analysis were performed as described previously. 34 Samples showing a variant DHPLC pattern were reamplified and sequenced on both strands using BigDye v3.0 (Applied Biosystems) according to the manufacturer's instruction to determine the nature of the heterozygous changes. Sequences were loaded on ABI377 sequencing machines (Applied Biosystems) and analyzed using Sequence Navigator v3.1.…”

Section: Imgsac Multiplex and Singleton Familiesmentioning

confidence: 99%

Mutation screening and association analysis of six candidate genes for autism on chromosome 7q

et al. 2004

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Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect for this variant. Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility.

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Mutation screening and imprinting analysis of four candidate genes for autism in the 7q32 region

Cited by 40 publications

References 39 publications

Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder

Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder

Analysis of reelin as a candidate gene for autism

Mutation screening and association analysis of six candidate genes for autism on chromosome 7q

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