2020-03-02

#schizophrenia and PsychENCODE's lab-grown human brain organoids

2020.3.2: psy/schiz/PsychENCODE
Dr. Thomas Lehner for PsychENCODE
claims that some of the genes for schizophrenia
are unique to humans; that makes sense,
because one advantage we have over other animals
is a bicameral mind
where cognitive functions were divided between
one part of the brain which appears to be "speaking",
and a second part which listens and obeys.
. the schiz'ic can use this arrangement
to hear the voice of a god and other telepathies.

. we are actually experimenting on
living human brains, grown in a vat!
Laura Sanders 2018:
"Lab-grown brain organoids
mimic the real thing, analyses suggest.
Along with other parts of a large research effort
called PsychENCODE,
the organoid results may offer new clues about
psychiatric diseases such as schizophrenia."

Dr. Thomas Lehner 2018:
PsychENCODE - the molecular architecture of the brain
"So with the PsychENCODE project,
we're actually able to identify several hundred new risk genes
for mental disorders. Schizophrenia in particular.
And they were actually able to see,
to identify human specific genes
that are expressed across development
that are risk genes for schizophrenia.
There are specific genes that are unique to humans.
And that these unique genes are involved in
the pathogenesis of this mental disorder."

The PsychENCODE Consortium:
Nat Neurosci. 2015 Nov 25; 18(12): 1707–1712.
The PsychENCODE project

Recent research on disparate psychiatric disorders
has implicated rare variants in genes involved in
global gene regulation and chromatin modification,
as well as many common variants located primarily in
regulatory regions of the genome.
Understanding precisely how these variants contribute to disease
will require a deeper appreciation for the mechanisms of gene regulation
in the developing and adult human brain.
The PsychENCODE project aims to produce a public resource of
multidimensional genomic data using
tissue- and cell type–specific samples
from approximately 1,000 phenotypically well-characterized,
high-quality healthy and disease-affected
human post-mortem brains,
as well as functionally characterize
disease-associated regulatory elements
and variants in model systems.

We are beginning with a focus on
autism spectrum disorder, bipolar disorder
and schizophrenia,
and expect that this knowledge will apply
to a wide variety of psychiatric disorders.
This paper outlines the motivation and design of PsychENCODE

The PsychENCODE project was founded to
to facilitate research on psychiatric diseases;
and perform comprehensive analyses of the regulatory regions,
epigenetic modifications and gene expression patterns
present across different ages, regions and cell types
in both the healthy and the disease-affected human CNS.
-- a systematic characterization
of the functional genomic elements
and noncoding RNAs linked to psychiatric disorders.
. see list of participating institutions and groups.

Key goals of the PsychENCODE project are to provide
an enhanced framework of regulatory genomic elements
(promoters, enhancers, silencers and insulators),
catalog epigenetic modifications
and quantify coding and non-coding RNA
and protein expression in tissue-and cell-type-specific samples
from healthy (neurotypical) control
and disease-affected post-mortem human brains.
These efforts will be complemented with integrative analyses,
as well as with functional characterizations of
disease-associated genomic elements
using human neural cells derived from
induced pluripotent cells (iPSCs)
or the developing mouse brain.

The PsychENCODE Consortium will share information among
consortium members and the broader research community
through a website www.psychENCODE.org

and a knowledge portal www.synapse.org/pec.
developed by the PsychENCODE data coordination core at
Sage Bionetworks.

CNON cells, fibroblasts and iPSCs
will be made available through the
NIMH Repository and Genomics Resource
(NIMH-RGR; nimhgenetics.org)
PsychENCODE investigators will ensure that data can be
visualized through genome browsers
such as the UCSC Genome Browser and/or IGV.

Nature. 2012 Sep 6; 489(7414): 57–74.
An Integrated Encyclopedia of DNA Elements
in the Human Genome
The ENCODE Project Consortium
. a “User’s Guide” including details of
cell type choice and limitations:
PLoS Biol. 2011 Apr;9(4):e1001046.
A user's guide to the encyclopedia of DNA elements (ENCODE).
ENCODE Project Consortium.

PsychENCODE Consortium's research papers:
Here, the PsychENCODE Consortium presents
11 research papers published in Science, Science Advances,
and Science Translational Medicine organized
around the themes of functional genomics in the
developing and adult brain
along with examinations of psychiatric disorders.
Studies of over 2000 individual brains
with bulk tissue analysis and at the single cell level
provide a rich resource for studies of gene expression,
epigenetics, and genomic regulation to better understand
the neurogenetics underlying development, health, and disease.

publications at psychencode.org.

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