Nagy - Functional genomic regulation

Question 1

What is the ultimate goal of molecular psychiatry?

Answer 1

Finding biological basis to psychiatric disorders

Question 1

What is the difference between genetics and genomics?

Answer 1

Genetics deal with genes and heredity
Genomics deal with the entire genome (DNA, chromatin, chromosomes, etc.)

Question 2

True or false: the majority of genetic variants fall into regions of the genome that code for gene.

Answer 2

False: promoter or non-coding, but mainly non-coding

Question 3

Is the genetic architecture of psychiatric diseases mendelian?

Answer 3

No, large number of small-effect variants primarily located in non-coding regions

Question 4

What are functional genomics?

Answer 4

Study of dynamic expression of gene products in a specific context.

Question 5

What are systems impacted by ELA?

Answer 5

HPA
Myelination
Opioid signalling
Growth factors and plasticity
E-I balance (GABAergic neurons primary subtype enrobed by PNNs)
Monoaminergic signalling

Question 6

What are epigenetics?

Answer 6

Processes that alter gene expression without altering the underlying DNA sequence

Question 7

What determines cell fate?

Answer 7

DNA methylation (transcriptome)

Question 8

True or false: all DNA methylation is-context dependent.

Answer 8

False, most of the DNA methylome is already established before the differentiation process, ensuring cell identity and genomic stability.

Question 9

True or false: DNA methylation is both permanent and mutable.

Answer 9

True.

Question 10

What are three central mechanisms of epigenetics?

Answer 10

DNA methylation
Post translational histone modifications
Long and short non-coding RNAs

Question 11

DNA cytosine methylation leads to different outcomes depending on its location, what are the options?

Answer 11

Gene promoter = repressive bc. interference with transcription factors

Gene body = expression still happening

Question 12

What are the key functions of DNA methylation in early development? In childhood and beyond?

Answer 12

Dev = genomic imprinting + differentiation

Later = mediates relationship between environment and gene expression

Question 13

What has been found for maternal care and methylation of the glucocorticoid recpetor (GR) promoter? What translational finding has been discovered?

Answer 13

Less maternal licking and grooming = increased methylation of GR promoter exon = decrease in GR expression = less negative feedback sensitivity (cortisol levels will rise)

Gene expression was reduced in suicide w/ abuse compared to suicide alone and controls (b) and specifically in the 1F promoter of homologous gene

Question 14

What is the difference between intergenerational and transgenerational inheritance?

Answer 14

Intergenerational = effect persists in immediate offsprings
Transgenerational = effect persists in generations beyond immediate offsprings

Question 15

What is an epigenetic consequence expected from epigenetic reprogramming (think of cell and embryonic development)?

Answer 15

Loss of DNA methylation (return to a pre-mature state)

Question 16

What is called the complex formed from the combination of DNA and histones?

Answer 16

Nucleosome

Question 17

What is the function of the histone code?

Answer 17

Regulation of transcription by modifications to histone tails (epigenetic modifications)

Question 18

How do nucleosomes and chromatin relate?

Answer 18

a nucleosome is the basic repeating unit of chromatin, consisting of DNA wrapped around a core of histone proteins, whereas chromatin encompasses the entire package of DNA, histone proteins, and associated non-histone proteins within the nucleus. Nucleosomes are the building blocks of chromatin structure, contributing to its organization and function.

Question 19

True or false: all cells differ in their epigenetic profile

Answer 19

True

Question 20

What is single cell ATAC?

Answer 20

Single-cell ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) is a cutting-edge technique used in molecular biology and genomics to study the accessibility of chromatin at the single-cell level. It provides insights into the regulatory landscape of individual cells by identifying regions of chromatin that are accessible to transposase enzymes.

Tn5 transposases which naturally (and randomly) cuts only where it has accesses to both strands of DNA.

Question 21

PAPER - What is a UMAP?

Answer 21

Uniform Manifold Approximation and Projection is a manifold learning technique for dimensionality reduction that is more efficient at maintaining the global structure of the dataset.

Question 22

PAPER - What are two ways to reveal cell type specific expression patterns?

Answer 22

Map OCR (open chromatin regions)

ATAC provides TF footprint -> Tn5 transposase cannot cleave double helix when TFs are bound -> drop of fragment mapping

Question 23

PAPER - Why is multi-model visualization useful to understand genomic interactions?

Answer 23

Allows to map primal and distal interactions enabled by different chromatin conformations = good broad picture

Question 24

PAPER - How are disease associated microglia analyses useful (DAM)?

Answer 24

Allows to map neuroinflammation

Question 25

PAPER - How can snATAC be used for cell taxonomy?

Answer 25

Modelling cell types

Question 26

How can chromatin structure influence the expression of genetic variants?

Answer 26

E.g. by folding on one exon

Question 27

What is an interpretation challenge that GWASes recurrently face? How could it be explained?

Answer 27

SNPs discovered map on non-coding regions

Might be bc. the non-coding regions concerned are altering chromatin structure, transcription factor binding sites, or long-range enhancer-promoter interactions.