Here, we have investigated the association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/-) and rs6150410 (CGCATCCCC/-) in promoter region; rs1861972 (A/G) and rs1861973 (C/T) in the intron] of the gene with autism and ASD in Indian population using family-based approach.
The haplotype A-C of rs1861972 and rs1861973 is the core element of the observed haplotype association in this study, which plays a role as a protective factor against autism; in addition, the haplotype G-A-C is less frequent in male cases compared to controls (38.64 vs. 52.51%), which plausibly modulate disease vulnerability to autism.
Since the associated SNPs were in high linkage disequilibrium and shared similar minor allele frequencies, we chose to test whether one of the SNPs (rs1861972) was associated with autism in three recruiting sites from the NIH Collaborative Programs of Excellence in Autism (CPEA) network.
Our previous research involving 167 nuclear families from the Autism Genetic Resource Exchange (AGRE) demonstrated that two intronic SNPs, rs1861972 and rs1861973, in the homeodomain transcription factor gene ENGRAILED 2 (EN2) are significantly associated with autism spectrum disorder (ASD).
Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P=0.0018; rs1861973, P=0.0003; haplotype, P=0.000005).
Subsequent molecular analysis determined that the EN2 ASD-associated haplotype (rs1861972-rs1861973 A-C) functions as a transcriptional activator to increase gene expression.
Previously we demonstrated that an intronic haplotype (rs1861972-rs1861973 A-C) in the homeobox transcription factor ENGRAILED2 (EN2) is significantly associated with ASD.
Here, we have investigated the association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/-) and rs6150410 (CGCATCCCC/-) in promoter region; rs1861972 (A/G) and rs1861973 (C/T) in the intron] of the gene with autism and ASD in Indian population using family-based approach.
The haplotype A-C of rs1861972 and rs1861973 is the core element of the observed haplotype association in this study, which plays a role as a protective factor against autism; in addition, the haplotype G-A-C is less frequent in male cases compared to controls (38.64 vs. 52.51%), which plausibly modulate disease vulnerability to autism.
While Del-T haplotype formed from rs34808376-rs1861973 markers showed increased non-transmission, the Ins-C showed significant transmission suggesting protective effect and risk, respectively, conferred by these haplotypes in autism etiology.
Our previous research involving 167 nuclear families from the Autism Genetic Resource Exchange (AGRE) demonstrated that two intronic SNPs, rs1861972 and rs1861973, in the homeodomain transcription factor gene ENGRAILED 2 (EN2) are significantly associated with autism spectrum disorder (ASD).
Our previous research involving 167 nuclear families from the Autism Genetic Resource Exchange (AGRE) demonstrated that two intronic SNPs, rs1861972 and rs1861973, in the homeodomain transcription factor gene ENGRAILED 2 (EN2) are significantly associated with autism spectrum disorder (ASD).
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=0.0290, rs1861973 P=0.0073, haplotype P=0.0009; broad: rs1861972 P=0.0175, rs1861973 P=0.0107, haplotype P=0.0024).
Two intronic SNPs (rs1861972 and rs1861973) demonstrated significant association with autism (rs1861972, P=0.0018; rs1861973, P=0.0003; haplotype, P=0.000005).
Subsequent molecular analysis determined that the EN2 ASD-associated haplotype (rs1861972-rs1861973 A-C) functions as a transcriptional activator to increase gene expression.
Previously we demonstrated that an intronic haplotype (rs1861972-rs1861973 A-C) in the homeobox transcription factor ENGRAILED2 (EN2) is significantly associated with ASD.
Here, we have investigated the association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/-) and rs6150410 (CGCATCCCC/-) in promoter region; rs1861972 (A/G) and rs1861973 (C/T) in the intron] of the gene with autism and ASD in Indian population using family-based approach.
Our previous research involving 167 nuclear families from the Autism Genetic Resource Exchange (AGRE) demonstrated that two intronic SNPs, rs1861972 and rs1861973, in the homeodomain transcription factor gene ENGRAILED 2 (EN2) are significantly associated with autism spectrum disorder (ASD).
Here, we have investigated the association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/-) and rs6150410 (CGCATCCCC/-) in promoter region; rs1861972 (A/G) and rs1861973 (C/T) in the intron] of the gene with autism and ASD in Indian population using family-based approach.
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.