An association analysis of candidate genes on chromosome 15 q11–13 and autism spectrum disorder

Curran, Sarah; Powell, John; Neale, Benjamin M.; Dworzynski, Katharina; Li, Tao; Murphy, Declan; Bolton, Patrick

doi:10.1038/sj.mp.4001839

Cited by 17 publications

(9 citation statements)

References 29 publications

(28 reference statements)

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“…There are several reports of markers from this interval being in linkage disequilibrium with ASD [111, 113 -118], although there are also studies in which no such association was observed [119,120]. Overall, the studies support the model that one or more genes in the AS/PWS region contribute to ASD, with a continued interest in GABRB3 [116,121]. In this regard, there are conflicting reports of whether GABRB3 is subject to genomic imprinting.…”

mentioning

confidence: 51%

Molecular epigenetics of Angelman syndrome

Lalande

Calciano

2007

Cell. Mol. Life Sci.

127

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Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, ataxia, seizures, EEG abnormalities and bouts of inappropriate laughter. AS individuals fail to inherit a normal active maternal copy of ubiquitin protein ligase E3A (UBE3A). UBE3A is subject to genomic imprinting, with predominant transcription of the maternal allele in brain. The known genetic causes of AS are maternal deletion of chromosome 15q11-q13, paternal chromosome 15 uniparental disomy, UBE3A mutation and an abnormality of the imprinting process, termed imprinting defect. There remain major questions concerning the molecular pathogenesis of AS, including: 1) the mechanisms underlying the imprinting defect class of AS, 2) the identity of proteins targeted by UBE3A, 3) the role of a noncoding antisense transcript in regulating UBE3A imprinting and 4) the contribution of other genes such as methyl-binding CpG-binding protein 2 and gamma-aminobutyric acid A receptor, subunit beta3 to the AS phenotype.

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mentioning

confidence: 51%

Molecular epigenetics of Angelman syndrome

Lalande

Calciano

2007

Cell. Mol. Life Sci.

127

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“…Most findings were negative in the GABRA5 and GABRG3 regions with ASD 15, 28, 32, 34, 45, 46 . However, Kim et al .…”

Section: Introductionmentioning

confidence: 97%

GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic spectrum disorders

Yang

Guo

Dong

et al. 2017

Sci Rep

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GABAA receptor subunit genes GABRB3, GABRA5, and GABRG3 located on chromosome 15q11-q13 have been implicated in the etiology of autistic spectrum disorders (ASD). This study intended to investigate the possible role of single-nucleotide polymorphisms (SNPs) present in GABRB3 (rs2081648 and rs1426217), GABRA5 (rs35586628), and GABRG3 (rs208129) genes in ASD susceptibility and symptom-based and developmental phenotypes of ASD in Chinese Han children and adolescents. 99 ASD patients and 231 age- and gender- frequency-matched typical developing (TD) controls were tested by TaqMan® genotyping assay. Symptom-based phenotypes were evaluated by Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC), and developmental phenotypes were assessed by Early Childhood Development Questionnaire (ECDQ) in ASD patients. Three haplotypes and global χ 2 test of all SNPs demonstrated significant associations between ASD and TD groups. Besides, GABRB3 rs2081648, GABRA5 rs35586628, and GABRG3 rs208129 polymorphisms were associated with symptom-based deficits in social interaction, sensorimotor and somatosensory coordination, visual response, imitation, activity level, language expression and adaptability. Developmental abnormalities in late emergences of social interaction and fine motor were detected in GABRB3 rs2081648 polymorphism. Overall results indicated that gene synergy may participate in ASD pathogenesis, and GABAA receptor gene polymorphisms can predict symptom-based and developmental deficits in ASD individuals.

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“…Other approaches described in the present literature propose genotyping of all the coding SNPs (Bergholdt et al, 2005) or a selection of (validated) intragenic SNPs (Curran et al, 2006;Moses et al, 2006), sequencing the gene and comparing discordant subjects (Dash et al, 2006;Lowe et al, 2007), using evenly spaced SNPs throughout the gene (Lou et al, 2007;Palmer et al, 2006), or combinations of the previous methods (Hinks et al, 2006;Nicolae et al, 2005;Wang et al, 2007;Wilson et al, 2006;Yang et al, 2005). This field is clearly evolving rapidly, but it is beyond the scope of this manuscript to go into detail on each of these methods.…”

Section: Snp Selectionmentioning

confidence: 99%

“…One often used strategy for fine mapping a region found by linkage analysis is to focus on a limited number of candidate genes because (a) only a limited number of genes is present under the linkage peak, or (b) some well established candidate genes are present (Bergholdt et al, 2005;Curran et al, 2006;Lou et al, 2007;Lowe et al, 2007;Palmer et al, 2006). This approach has many advantages: (1) Limiting the number of candidate genes also implies limiting the number of polymorphisms to be assessed; (2) by using established candidate genes, the chance of finding a real causative allele (as opposed to a false positive result) is augmented; (3) restricting the number of polymorphisms diminishes the number of statistical tests, avoids (more or less) stringent correction procedures for multiple testing, as well as limits the chance of a false positive result; and (4) complementary to statistical evidence for association between a gene variant and an examined trait, a real causality can be proven by functional (physiological or biological) evidence for an association.…”

mentioning

confidence: 99%

Selection of Genes and Single Nucleotide Polymorphisms for Fine Mapping Starting From a Broad Linkage Region

Windelinckx

Vlietinck

Aerssens³

et al. 2007

Twin Res Hum Genet

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Fine mapping of linkage peaks is one of the great challenges facing researchers who try to identify genes and genetic variants responsible for the variation in a certain trait or complex disease. Once the trait is linked to a certain chromosomal region, most studies use a candidate gene approach followed by a selection of polymorphisms within these genes, either based on their possibility to be functional, or based on the linkage disequilibrium between adjacent markers. For both candidate gene selection and SNP selection, several approaches have been described, and different software tools are available. However, mastering all these information sources and choosing between the different approaches can be difficult and time-consuming. Therefore, this article lists several of these in silico procedures, and the authors describe an empirical two-step fine mapping approach, in which candidate genes are prioritized using a bioinformatics approach (ENDEAVOUR), and the top genes are chosen for further SNP selection with a linkage disequilibrium based method (Tagger). The authors present the different actions that were applied within this approach on two previously identified linkage regions for muscle strength. This resulted in the selection of 331 polymorphisms located in 112 different candidate genes out of an initial set of 23,300 SNPs.

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An association analysis of candidate genes on chromosome 15 q11–13 and autism spectrum disorder

Cited by 17 publications

References 29 publications

Molecular epigenetics of Angelman syndrome

Molecular epigenetics of Angelman syndrome

GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic spectrum disorders

Selection of Genes and Single Nucleotide Polymorphisms for Fine Mapping Starting From a Broad Linkage Region

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