Autism and intellectual disability in a patient with two microdeletions in 6q16: a contiguous gene deletion syndrome?

Strunk, Daniela; Weber, Peter; Röthlisberger, Benno; Filges, Isabel

doi:10.1186/s13039-016-0299-8

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…Among the 5 significant genes after a stringent Bonferroni correction for all genes and all tissues in the analysis ( Figs 3 and S20 ), POU3F2 (also known as BRN2 ) is primarily expressed in the central nervous system ( S21 Fig ), especially in hippocampus and hypothalamus [ 25 ]. It encodes a transcription factor with important roles in neurogenesis and brain development [ 26 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder

Huang

Shin

et al. 2021

PLoS Genet

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Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p = 2.1E-7), a transcription factor mainly expressed in developmental brain. Gene targets regulated by POU3F2 showed a 2.7-fold enrichment for known ASD genes (p = 2.0E-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p = 7.1E-5). These results provide a novel connection between rare and common variants, whereby ASD genes affected by very rare mutations are regulated by an unlinked transcription factor affected by common genetic variations.

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Section: Resultsmentioning

confidence: 99%

Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder

Huang

Shin

et al. 2021

PLoS Genet

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“…PRDM13 is required to generate the precise number of GABA (gamma-aminobutyric acid) associated neurons (i.e., GABAegic neurons) 21 . There is a report that a microdeletion of PRDM13 locus has been implicated in autism and intellectual disability in human 22 . The QTL window on SSC1 at 58–59 Mb includes MAP3K7 , which is known to be involved in autophagy.…”

Section: Resultsmentioning

confidence: 99%

Single-step genome-wide association study for social genetic effects and direct genetic effects on growth in Landrace pigs

Hong

Lee

Ramayo-Caldas

et al. 2020

Sci Rep

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In livestock social interactions, social genetic effects (SGE) represent associations between phenotype of one individual and genotype of another. Such associations occur when the trait of interest is affected by transmissible phenotypes of social partners. The aim of this study was to estimate SGE and direct genetic effects (DGE, genetic effects of an individual on its own phenotype) on average daily gain (ADG) in Landrace pigs, and to conduct single-step genome-wide association study using SGE and DGE as dependent variables to identify quantitative trait loci (QTLs) and their positional candidate genes. A total of 1,041 Landrace pigs were genotyped using the Porcine SNP 60K BeadChip. Estimates of the two effects were obtained using an extended animal model. The SGE contributed 16% of the total heritable variation of ADG. The total heritability estimated by the extended animal model including both SGE and DGE was 0.52. The single-step genome-wide association study identified a total of 23 QTL windows for the SGE on ADG distributed across three chromosomes (i.e., SSC1, SSC2, and SSC6). Positional candidate genes within these QTL regions included PRDM13, MAP3K7, CNR1, HTR1E, IL4, IL5, IL13, KIF3A, EFHD2, SLC38A7, mTOR, CNOT1, PLCB2, GABRR1, and GABRR2, which have biological roles in neuropsychiatric processes. The results of biological pathway and gene network analyses also support the association of the neuropsychiatric processes with SGE on ADG in pigs. Additionally, a total of 11 QTL windows for DGE on ADG in SSC2, 3, 6, 9, 10, 12, 14, 16, and 17 were detected with positional candidate genes such as ARL15. We found a putative pleotropic QTL for both SGE and DGE on ADG on SSC6. Our results in this study provide important insights that can help facilitate a better understanding of the molecular basis of SGE for socially affected traits.

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“…It has been suggested as a candidate gene for ASD because of its localization in the autism specific region on chromosome 6q21 and the involvement of the receptor protein in cognitive functions like learning and memory [8,24]. Recently, a chromosomal microarray (CMA) analysis describing a 19-year old patient showed two de novo microdeletions that spanned 10 genes including GRIK2 [25]. Mutation screening revealed several SNPs, including one nucleotide variation changing the protein (M867I) of GRIK2 , which may be functionally relevant to the development of ASD [26].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of Ionotropic Glutamate Receptor-Related Genes and the Risk of Autism Spectrum Disorder in a Chinese Population

Xie

Hou

et al. 2019

Psychiatry Investig

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Objective To evaluate the association of GRIK2 and NLGN1 with autism spectrum disorder in a Chinese population. Methods We performed spatio-temporal expression analysis of GRIK2 and NLGN1 in the developing prefrontal cortex, and examined the expression of the genes in ASD cases and healthy controls using the GSE38322 data set. Following, we performed a case-control study in a Chinese population. Results The analysis using the publicly available expression data showed that GRIK2 and NLGN1 may have a role in the development of human brain and contribute to the risk of ASD. Later genetic analysis in the Chinese population showed that the GRIK2 rs6922753 for the T allele, TC genotype and dominant model played a significant protective role in ASD susceptibility (respectively: OR=0.840, p=0.023; OR=0.802, p=0.038; OR=0.791, p=0.020). The NLGN1 rs9855544 for the G allele and GG genotype played a significant protective role in ASD susceptibility (respectively: OR=0.844, p=0.019; OR=0.717, p=0.022). After adjusting p values, the statistical significance was lost (p>0.05). Conclusion Our results suggested that GRIK2 rs6922753 and NLGN1 rs9855544 might not confer susceptibility to ASD in the Chinese population.

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Autism and intellectual disability in a patient with two microdeletions in 6q16: a contiguous gene deletion syndrome?

Cited by 4 publications

References 35 publications

Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder

Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder

Single-step genome-wide association study for social genetic effects and direct genetic effects on growth in Landrace pigs

Polymorphisms of Ionotropic Glutamate Receptor-Related Genes and the Risk of Autism Spectrum Disorder in a Chinese Population

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