scholarly journals Genetic control of gene expression and splicing in the developing human brain

2018 ◽  
Author(s):  
Rebecca L. Walker ◽  
Gokul Ramaswami ◽  
Christopher Hartl ◽  
Nicholas Mancuso ◽  
Michael J. Gandal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Brain Development ◽  
Genetic Control ◽  
Allelic Variation ◽  
Fetal Brain ◽  
The Body ◽  
List Type ◽  
Control Of Gene Expression ◽  
Neuropsychiatric Diseases

SummaryMost genetic risk for human diseases lies within non-coding regions of the genome, which is predicted to regulate gene expression, often in a tissue and stage specific manner. This has motivated building of extensive eQTL resources to understand how human allelic variation affects gene expression and splicing throughout the body, focusing primarily on adult tissue. Given the importance of regulatory pathways during brain development, we characterize the genetic control of the developing human cerebral cortical transcriptome, including expression and splicing, in 201 mid-gestational human brains, to understand how common allelic variation affects gene regulation during development. We leverage expression and splice quantitative trait loci to identify genes and isoforms relevant to neuropsychiatric disorders and brain volume. These findings demonstrate genetic mechanisms by which early developmental events have a striking and widespread influence on adult anatomical and behavioral phenotypes, as well as the evolution of the human cerebral cortex.HighlightsGenome wide map of human fetal brain eQTLs and sQTLs provides a new view of genetic control of expression and splicing.There is substantial contrast between genetic control of transcript regulation in mature versus developing brain.We identify novel regulatory regions specific to fetal brain development.Integration of eQTLs and GWAS reveals specific relationships between expression and disease risk for neuropsychiatric diseases and relevant human brain phenotypes.

scholarly journals Sex differences in gene expression in the human fetal brain

2018 ◽  
Author(s):  
Heath E. O’Brien ◽  
Eilis Hannon ◽  
Aaron R. Jeffries ◽  
William Davies ◽  
Matthew J. Hill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Human Brain ◽  
Brain Development ◽  
Developmental Disorders ◽  
Fetal Brain ◽  
Human Fetal Brain ◽  
Human Brain Development ◽  
Early Human ◽  
Sex Biases

ABSTRACTWidespread structural, chemical and molecular differences have been reported between the male and female human brain. Although several neurodevelopmental disorders are more commonly diagnosed in males, little is known regarding sex differences in early human brain development. Here, we used RNA sequencing data from a large collection of human brain samples from the second trimester of gestation (N = 120) to assess sex biases in gene expression within the human fetal brain. In addition to 43 genes (102 Ensembl transcripts) transcribed from the Y-chromosome in males, we detected sex differences in the expression of 2558 autosomal genes (2723 Ensembl transcripts) and 155 genes on the X-chromosome (207 Ensembl transcripts) at a false discovery rate (FDR) < 0.1. Genes exhibiting sex-biased expression in human fetal brain are enriched for high-confidence risk genes for autism and other developmental disorders. Male-biased genes are enriched for expression in neural progenitor cells, whereas female-biased genes are enriched for expression in Cajal-Retzius cells and glia. All gene- and transcript-level data are provided as an online resource (available at http://fgen.psycm.cf.ac.uk/FBSeq1) through which researchers can search, download and visualize data pertaining to sex biases in gene expression during early human brain development.

scholarly journals Genetic control of gene expression in whole blood and lymphoblastoid cell lines is largely independent

2011 ◽  
Vol 22 (3) ◽  
pp. 456-466 ◽  
Author(s):  
J. E. Powell ◽  
A. K. Henders ◽  
A. F. McRae ◽  
M. J. Wright ◽  
N. G. Martin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genetic Control ◽  
Cell Lines ◽  
Whole Blood ◽  
Lymphoblastoid Cell Lines ◽  
Control Of Gene Expression

Translational control of gene expression in the human brain

1989 ◽  
Vol 13 (3-4) ◽  
pp. 469-479 ◽  
Author(s):  
Niklas Langstrom ◽  
Anders Eriksson ◽  
Bengt Winblad ◽  
William Wallace
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Translational Control ◽  
Control Of Gene Expression

scholarly journals Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following Maternal Respiratory Viral Infection

2018 ◽  
Vol 40 (2) ◽  
pp. 104-119 ◽  
Author(s):  
Adrienne M. Antonson ◽  
Bindu Balakrishnan ◽  
Emily C. Radlowski ◽  
Geraldine Petr ◽  
Rodney W. Johnson
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Brain Development ◽  
Hippocampal Neurons ◽  
Protein A ◽  
Fetal Brain ◽  
Respiratory Syndrome Virus ◽  
Maternal Infection ◽  
Ki 67 ◽  
Fetal Brain Development

Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses were removed by cesarean section at GD 111 (3 days before anticipated parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 levels and developed transient febrile and anorectic responses lasting approximately 21 days. Despite having a similar overall body weight, fetuses from the PRRSV-infected gilts had a decreased brain weight and altered hippocampal gene expression compared to fetuses from control gilts. Notably, maternal infection caused a reduction in estimated neuronal numbers in the fetal dentate gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, but the relative integrated density of GFAP+ staining was increased, in addition to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. Maternal viral infection caused an increase in fetal hippocampal gene expression of the inflammatory cytokines TNF-α and IFN-γ and the myelination marker myelin basic protein. MHCII protein, a classic monocyte activation marker, was reduced in microglia, while expression of the MHCII gene was decreased in hippocampal tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest that maternal viral infection at the beginning of the last trimester results in a reduction in fetal hippocampal neurons that is evident 5 weeks after infection, when fetal piglets are near full term. The neuronal reduction was not accompanied by pronounced neuroinflammation at GD 111, indicating that any activation of classic neuroinflammatory pathways by maternal viral infection, if present, is mostly resolved by parturition.

The Brain/MINDS project aimed at establishing the marmoset as a model organism for neurobiology and establishing the genetic and biochemical elements of their neural development

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 86-88
Author(s):  
Tomomi Shimogori
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Molecular Mechanisms ◽  
Mental Disease ◽  
Visual Stimuli ◽  
The Body ◽  
Proper Function ◽  
Newborn Mouse ◽  
Model Animal ◽  
The Brain

The brain is the most sophisticated and intricate organ in the body. Billions of neurons interconnect and form distinct regions which process different neural activities. The development of the brain during pregnancy and early post-natal life is extremely sensitive, complex and crucial to proper function over the life of a person. This is the most plastic time of the brain. It is changing constantly and reacting to the different stimuli encountered by the individual. The lack of a particular stimulus can have a profound effect on the later structure and function of the brain. For example, if a newborn mouse has an eye covered so it receives no light, visual cortex, where normally processes binocular visual stimuli, develops to process visual stimuli only from the open eye. This cannot be altered later on even when both eyes are opened; the mouse remains weak in one eye despite there being nothing wrong with the eye itself. Studying this early time period of brain development presents many problems. Investigation is hampered by the difficulty in accessing and manipulating the brain as well as the huge variety of factors that contribute to brain development. Currently, most work is conducted in rodents, primarily because there are a large range of genetic tools available. This is useful to an extent and has demonstrated key findings that appear to be relevant to most mammalian species. However, the human brain is quite different to the mouse brain. It has adapted to very different tasks required of mice compared to humans and therefore there is a knowledge gap to bridge in this area. In addition to this, examination of global gene expression in the brain has only truly become viable in the last 10 years. The same can also be said of the ability to analyse the development process at a biochemical level. Dr Tomomi Shimogori of the RIKEN Center for Brain Science, Japan, has been tackling these difficulties through her work on the molecular mechanisms of brain development. She has worked on rodents, but is now developing a model in the common marmoset based around the creation of a gene atlas. Working on the primate should help fill in the gap between rodent and human. Shimogori explains why the marmoset was chosen: 'One of the biggest advantages of using marmosets as a model animal is that many of its behaviours share similarities with human behaviours, and thus has potential for use in understanding the underlying mechanisms of human brain function and mental disease

The Influence of Thyroid Hormone on Ca2+ Signaling Pathways during Embryonal Development

2021 ◽  
Vol 21 ◽  
Author(s):  
Joachim Krebs
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Brain Development ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem Cell Line ◽  
Embryonic Stem ◽  
Fetal Brain ◽  
Mouse Embryonic Stem Cell ◽  
Dependent Manner ◽  
Transcription Activator

: Thyroid hormones influence brain development through regulation of gene expression. Ca2+-dependent gene expression is a major pathway controlled by the Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) which in turn is induced by the thyroid hormone T3 as also demonstrated in a mouse embryonic stem cell line. In addition, T3 is controlling the expression of neurexin, synaptotagmin2 (SYT2), synaptotagmin-related gene1 (SRG1) and a number of other genes, involved in neurotransmitter release in a Ca2+-dependent manner. It has been noticed that the development of dopaminergic neurons by evoking significant calcium entry occurs through TRPC calcium channels. It also was demonstrated that the T3-mediated development of an early neuronal network is characteristic for depolarizing GABAergic neurons concomitant with intracellular calcium transients. An important aspect of T3-dependent regulation of gene expression in the developing brain is its modulation by the transcription activator COUP-TF1. Regulation of alternative splicing by CaMKIV is another important aspect for embryonal neural development since it can lead to the expression of PMCA1a, the neuronal specific isoform of the plasma membrane calcium pump. Maternal hypothyroidism or CaMKIV deficiency can have a severe influence on fetal brain development.

scholarly journals Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100858 ◽  
Author(s):  
Veronica H. Ryan ◽  
Christopher T. Primiani ◽  
Jagadeesh S. Rao ◽  
Kwangmi Ahn ◽  
Stanley I. Rapoport ◽  
...  
Keyword(s):  
Gene Expression ◽  
Docosahexaenoic Acid ◽  
Human Brain ◽  
Brain Development ◽  
Human Brain Development ◽  
Development And Aging

scholarly journals Genetic control of gene expression at novel and established chronic obstructive pulmonary disease loci

2014 ◽  
Vol 24 (4) ◽  
pp. 1200-1210 ◽  
Author(s):  
Peter J. Castaldi ◽  
Michael H. Cho ◽  
Xiaobo Zhou ◽  
Weiliang Qiu ◽  
Michael Mcgeachie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Control ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Control Of Gene Expression ◽  
Disease Loci
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