Transmission disequilibrium testing of the chromosome 15q11-q13 region in autism. American Journal of Medical Genetics
ABSTRACT Evidence implicates the serotonin transporter gene (SLC6A4) and the 15q11-q13 genes as candidates for autism as well as restricted repetitive behavior (RRB). We conducted dense transmission disequilibrium mapping of the 15q11-q13 region with 93 single nucleotide polymorphisms (SNPs) in 86 strictly defined autism trios and tested association between SNPs and autism using the transmission disequilibrium test (TDT). As exploratory analyses, parent-of-origin effects were examined using likelihood-ratio tests (LRTs) and genotype-phenotype associations for specific RRB using the Family-Based Association Test (FBAT). Additionally, gene-gene interactions between nominally associated 15q11-q13 variants and 5-HTTLPR, the common length polymorphism of SLC6A4, were examined using conditional logistic regression (CLR). TDT revealed nominally significant transmission disequilibrium between autism and five SNPs, three of which are located within close proximity of the GABA(A) receptor subunit gene clusters. Three SNPs in the SNRPN/UBE3A region had marginal imprinting effects. FBAT for genotype-phenotype relations revealed nominally significant association between two SNPs and one ADI-R subdomain item. However, both TDT and FBAT were not statistically significant after correcting for multiple comparisons. Gene-gene interaction analyses by CLR revealed additive genetic effect models, without interaction terms, fit the data best. Lack of robust association between the 15q11-q13 SNPs and RRB phenotypes may be due to a small sample size and absence of more specific RRB measurement. Further investigation of the 15q11-q13 region with denser genotyping in a larger sample set may be necessary to determine whether this region confers risk to autism, indicated by association, or to specific autism phenotypes.
- SourceAvailable from: Rong Chen
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- "Based on literature review, we selected nine ASD-related genes (GABRA4, GABRB1, TDO2, GABRB2, GABRA2, GABRB3, GABRA5, SLC25A12, and BDNF; details in Table 2) for this study; these genes had been found to be associated with ASD symptoms (Belmonte et al., 2004; Cheng et al., 2009; Freitag, 2007; S.-J. Kim et al., 2008; Nabi et al., 2004). We selected SNPs within each ASD-related candidate region and identified them from NCBI's SNP database (dbSNP) (http://www.ncbi.nlm.nih.gov/SNP). "
ABSTRACT: Autism is widely believed to be a heterogeneous disorder; diagnosis is currently based solely on clinical criteria, although genetic, as well as environmental, influences are thought to be prominent factors in the etiology of most forms of autism. Our goal is to determine whether a predictive model based on single-nucleotide polymorphisms (SNPs) can predict symptom severity of autism spectrum disorder (ASD). We divided 118 ASD children into a mild/moderate autism group (n = 65) and a severe autism group (n = 53), based on the Childhood Autism Rating Scale (CARS). For each child, we obtained 29 SNPs of 9 ASD-related genes. To generate predictive models, we employed three machine-learning techniques: decision stumps (DSs), alternating decision trees (ADTrees), and FlexTrees. DS and FlexTree generated modestly better classifiers, with accuracy = 67%, sensitivity = 0.88 and specificity = 0.42. The SNP rs878960 in GABRB3 was selected by all models, and was related associated with CARS assessment. Our results suggest that SNPs have the potential to offer accurate classification of ASD symptom severity.Journal of Autism and Developmental Disorders 07/2011; 42(6):971-83. DOI:10.1007/s10803-011-1327-5 · 3.06 Impact Factor
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ABSTRACT: The present summary reports about a dressed-state approach to optical phase conjugation (OPC) by resonant nearly degenerate four-wave mixing in vapors. The basic idea is to decouple the pump fields from the probe field by first treating the problem of the pump fields interacting with the atom and then consider the interaction with the probe field. From this model, the dip, observed in the OPC yield when the pump fields are tuned to an atomic resonance, can be interpreted as an interference effect between contributions to the polarization originating from two dressed-state transitions