Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Autism Spectrum Disorder (ASD)


One hypothesis is that autism may be influenced by premature shortening of especially long genes as a result of improperly functioning enzymes.


Research Study  —  Genes Disrupted in Autism

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes.


Research Study  —  Autism Linked to Transcription of Long Genes

Topoisomerases are expressed throughout the developing and adult brain and are mutated in some individuals with autism spectrum disorder (ASD). Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor, dose-dependently reduces the expression of extremely long genes in mouse and human neurons, including nearly all genes that are longer than 200kilobases. Our findings suggest that chemicals and genetic mutations that impair topoisomerases could commonly contribute to ASD and other neurodevelopmental disorders.


Research Study  —  Protein-Truncating Variants tabulated by GTEx Project

We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects.


Research Study —  Genotype-Tissue Expression (GTEx) pilot analysis

The majority of GWAS variants are noncoding, likely manifesting their effects via the regulation of gene expression. To facilitate the collection of multiple different tissues per donor, the project obtains recently deceased donors through consented next-of-kin donation, from organ donation and rapid autopsy settings.


Research Study —  Database Links Regulatory DNA to its Target Genes

By analyzing genetic material gleaned from more than 100 people who had died just hours before, the Genotype-Tissue Expression (GTEx) project portrays gene regulation in action, identifying the genes switched on or off by subtle changes in DNA within 2 million bases of any gene.


Research Study  —  Mutations in Autism Spectrum Disorder

By comparing affected to unaffected siblings, we show that 13% of de novo missense mutations and 43% of de novo likely gene-disrupting (LGD) mutations contribute to 12% and 9% of diagnoses of Autism Spectrum Disorder.


Research Study  —  Human Transcriptome across Tissues and Individuals

Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program.


Research Study  —  Schizophrenia Mutations in Synaptic Networks

Inherited alleles account for most of the genetic risk for schizophrenia. However, new (de novo) mutations, in the form of large chromosomal copy number changes, occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Genes affected by mutations in schizophrenia overlap those mutated in autism and intellectual disability, as do mutation-enriched synaptic pathways.


Research Study  —  Autism Spectrum Disorders Biology

Multiple studies have confirmed that rare and de novo point mutations and submicroscopic variations in chromosomal structure contribute to a considerable number of cases and have identified a growing number of specific genomic intervals and genes conferring risks. A set of newly discovered ASD proteins highlights a role for chromatin modifiers (CHD8), and DNA binding proteins (POGZ), ion channels (SCN2A), microtubule-associated proteins (KATNAL2), neurotransmitter receptors (GRIN2B), and phosphorylation-regulated tyrosine kinases (DYRK1A).


Research Study  —  Genetic Basis for Variation in Transcript Abundance

One of the big surprises reported is the discovery of module QTLs (modQTLs), which are regulatory variants that influence the co-regulation of gene expression. The idea is that most genes are organized into expression modules. Even though they are located on different chromosomes, they tend to be have similar expression levels.


Research Study  —  Autism Risk Identified with Regulatory Sites on the UBE3A Protein