Human evolved regulatory elements modulate genes involved in cortical expansion and neurodevelopmental disease susceptibility
| Autor: | Daniel H. Geschwind, Christopher Hartl, Carli K. Opland, Jerry Huang, Hyejung Won |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genetics of the nervous system General Physics and Astronomy 02 engineering and technology Epigenesis Genetic Neural Stem Cells 2.1 Biological and endogenous factors Developmental Regulatory Elements Transcriptional Aetiology lcsh:Science Epigenesis Regulation of gene expression Cerebral Cortex Multidisciplinary Gene Expression Regulation Developmental Brain Human brain 021001 nanoscience & nanotechnology Chromatin medicine.anatomical_structure Mental Health Neurological Transcriptional 0210 nano-technology Biotechnology Cell type Evolution Science 1.1 Normal biological development and functioning Biology Human accelerated regions General Biochemistry Genetics and Molecular Biology Article Evolutionary genetics Evolution Molecular 03 medical and health sciences Genetic Underpinning research MD Multidisciplinary medicine Genetics Humans Genetic Predisposition to Disease Epigenetics Gene Human Genome Neurosciences Molecular General Chemistry Regulatory Elements Gene regulation Brain Disorders 030104 developmental biology Gene Expression Regulation Neurodevelopmental Disorders lcsh:Q Neuroscience |
| Zdroj: | Nature communications, vol 10, iss 1 Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-11 (2019) |
| Popis: | Modern genetic studies indicate that human brain evolution is driven primarily by changes in gene regulation, which requires understanding the biological function of largely non-coding gene regulatory elements, many of which act in tissue specific manner. We leverage chromatin interaction profiles in human fetal and adult cortex to assign three classes of human-evolved elements to putative target genes. We find that human-evolved elements involving DNA sequence changes and those involving epigenetic changes are associated with human-specific gene regulation via effects on different classes of genes representing distinct biological pathways. However, both types of human-evolved elements converge on specific cell types and laminae involved in cerebral cortical expansion. Moreover, human evolved elements interact with neurodevelopmental disease risk genes, and genes with a high level of evolutionary constraint, highlighting a relationship between brain evolution and vulnerability to disorders affecting cognition and behavior. These results provide novel insights into gene regulatory mechanisms driving the evolution of human cognition and mechanisms of vulnerability to neuropsychiatric conditions. Different classes of human evolved regulatory elements are located in non-coding regions of the genome. The authors connect the expansion of the cortical surface and connectivity with human evolved elements and show that their target genes are involved in neurodevelopmental disease susceptibility. |
| Databáze: | OpenAIRE |
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