ArticleFrontiers in genetics2019
Evolution and Comprehensive Analysis of DNaseI Hypersensitive Sites in Regulatory Regions of Primate Brain-Related Genes.
Article in Frontiers in genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
- Chromatin Profiling Techniques: Exploring the Chromatin Environment and Its Contributions to Complex Traits.International journal of molecular sciences · 2021Review
- Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species.BMC genomics · 2020Review
- Characterization of a pathogenic variant in GBA for Parkinson's disease with mild cognitive impairment patients.Molecular brain · 2020Article
- Accelerated Evolution of the Regulatory Sequences of Brain Development in the Human Genome.Molecules and cells · 2020Article
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14 authors at 3 institutions in 1 country.
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Abstract
How the human brain differs from those of non-human primates is largely unknown and the complex drivers underlying such differences at the genomic level remain unclear. In this study, we selected 243 brain-related genes, based on Gene Ontology, and identified 184,113 DNaseI hypersensitive sites (DHSs) within their regulatory regions. To performed comprehensive evolutionary analyses, we set strict filtering criteria for alignment quality and filtered 39,132 DHSs for inclusion in the investigation and found that 2,397 (~6%) exhibited evidence of accelerated evolution (aceDHSs), which was a much higher proportion that DHSs genome-wide. Target genes predicted to be regulated by brain-aceDHSs were functionally enriched for brain development and exhibited differential expression between human and chimpanzee. Alignments indicated 61 potential human-specific transcription factor binding sites in brain-aceDHSs, including for CTCF, FOXH1, and FOXQ1. Furthermore, based on GWAS, Hi-C, and eQTL data, 16 GWAS SNPs, and 82 eQTL SNPs were in brain-aceDHSs that regulate genes related to brain development or disease. Among these brain-aceDHSs, we confirmed that one enhanced the expression of GPR133, using CRISPR-Cas9 and western blotting. The
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