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Brain enhancer activities at the gene-poor 5p14.1 autism-associated locus
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Due to the vast clinical and genetic heterogeneity, identification of causal genetic determinants for autism spectrum disorder (ASD) has proven to be complex. Whereas several dozen ‘rare’ genetic variants for ASD susceptibility have been identified, studies are still underpowered to analyse ‘common’ variants for their subtle effects. A recent application of genome-wide association studies (GWAS) to ASD indicated significant associations with the single nucleotide polymorphisms (SNPs) on chromosome 5p14.1, located in a non-coding region between cadherin10 (CDH10) and cadherin9 (CDH9). Here we apply an in vivo bacterial artificial chromosome (BAC) based enhancer-trapping strategy in mice to scan the gene desert for spatiotemporal cis-regulatory activities. Our results show that the ASD-associated interval harbors the cortical area, striatum, and cerebellum specific enhancers for a long non-coding RNA, moesin pseudogene1 antisense (MSNP1AS) during the brain developing stages. Mouse moesin protein levels are not affected by exogenously expressed human antisense RNAs in our transgenic brains, demonstrating the difficulty in modeling rather smaller effects of common variants. Our first in vivo evidence for the spatiotemporal transcription of MSNP1AS however provides a further support to connect this intergenic variant with the ASD susceptibility.
- Subjects :
- 0301 basic medicine
Chromosomes, Artificial, Bacterial
Genotype
Moesin
Mice, Transgenic
Single-nucleotide polymorphism
Locus (genetics)
Genome-wide association study
Regulatory Sequences, Nucleic Acid
Biology
Polymorphism, Single Nucleotide
Article
Mice
03 medical and health sciences
Animals
Humans
Autistic Disorder
Enhancer
Gene
Genetic association
Genetics
Multidisciplinary
Genetic heterogeneity
Microfilament Proteins
Brain
Computational Biology
Genetic Variation
Oligonucleotides, Antisense
Cadherins
030104 developmental biology
Genetic Techniques
Chromosomes, Human, Pair 5
RNA, Long Noncoding
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....2eb14e9b0cd97dcc1e4a749a675c55f4