Table 2 Negated genes for Autism

EN2

Do the genetic data add to the overall hypothesized neurophysiological mechanism, or are the data less focused? In the end, RELN, 5 HTT and EN2 may not be major genes in the etiology of autism, either singly or in concert, but they are important models for pointing out the difficulties in these studies so that advances in understanding the genetic and developmental basis of autism can be attained.

GRIK2

After applying Bonferroni correction, these results were no longer statistically significant. The global 2 -test or association regarding the number of haplotypes (H) for 1 degree of freedom (d.f.) for haplotype transmission did not reveal an association between the GRIK2 locus and ASD (2 = 19.355, d.f. = 13). We also carried out the bootstrap significance test using 100,000 bootstrap samples.

SLC25A12

Furthermore, a strong association of autism with SNPs within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1), has been demonstrated, suggesting the potential etiological role of AGC1 in autism (Ramoz et al., 2004; Segurado et al., 2005). However, recent two studies using large samples did not confirm the association of SLC25A12 gene and autism, suggesting that the SLC25A12 gene is not a major contributor to genetic susceptibility of autism (Blasi et al., 2006; Rabionet et al., 2006). Second, it has been reported that blood levels of glutamate are altered in patients with autism (Rolf et al., 1993; Moreno-Fuenmayor et al., 1996; Aldred et al., 2003).

OXTR

We observed AEI in OXTR. The variation in AEI was driven, in part, by a SNP in intron 3 of OXTR (rs237897; p = 0.0265). rs237897 was not associated with autism in our sample. The addition of hormones did not appear to alter AEI significantly from the baseline.

SHANK3

In addition, our results also reinforce the need for the detailed LD mapping, mutation screening and CNV analysis of SHANK3 in different population or other neurodevelopmental disorders. The present study did not find strong evidence of SHANK3 polymorphisms and autism or identify any described non-synonymous mutations in our cohort. These might indicate that SHANK3 doesn't represent a major susceptibility gene for autism in the autism families ascertained from Chinese Han population.

SLC6A4

Based on these results, it appears unlikely that SLC6A4 play a significant role in the genetic predisposition to autism. In this study, no evidence was provided for an association between the SLC6A4 locus and autism in the Chinese Han trios. What reasons might be considered for the differences?

CADPS2

Despite positional, functional, and expression data supporting the role of CADPS2 as a candidate gene for autism, we were unable to identify any mutations in or around the coding regions that co-segregate with the disorder in 90 families multiplex for autism. The A297T mutation found in autism family AU427 does not occur in a conserved region of the gene (the amino acid at codon 297 differs between human CADPS2 and mouse cadps2), and does not occur within any known functional domains of the protein, and thus is unlikely to be functionally relevant. Human CADPS and CADPS2 were cloned from a brain cDNA library using the yeast two hybrid system with the C terminus of dystrophin as bait.

NLGN3

A family-based association study for rs2290488 in 101 trios did not reveal association of this polymorphism with autistic disorders on high functioning level. We conclude that there is no evidence for an involvement of NLGN3 and NLGN4X genetic variants with autism spectrum disorder on high functioning level in our study group.

GABRB3

Serotonin transporter (5 -HTT) and gamma-aminobutyric acid receptor subunit beta3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. The International Molecular Genetic Study of Autism Consortium.

MECP2

However, they were unable to confirm this change in mRNA. Vourc ? h et al. (50) failed to identify mutations in the MeCP2 coding sequence in a sample of 59 patients with autism, only 17 of which were females. Both of the mutations described in the current study have been noted in classic RTT patients.

UBE3A

A population-based study showed a high rate of ASD in AS (38). But, a mutation was not identified in the UBE3A putative promoter or coding region in 10 idiopathic ASD patients (39). Lack of expression of the maternally expressed UBE3A gene in the brain is thought to be the cause of AS.

RELN

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.