Week 12 (GTEx and ENCODE)

Question 1

GTEx

Answer 1

Genotype Tissue Expression

Question 2

what was the purpose of GTEx?

Answer 2

create a comprehensive resource to understand how genetic variants influence gene expression across various human tissues

Question 3

how were tissues collected for GTEx?

Answer 3

pieces and parts were collected from (dead) humans

Question 4

what conclusion did GTEx draw about using blood as a sample to assay things?

Answer 4

blood is a bad tissue to use because it has the fewest transcribed genes

Question 5

GTEx used a small sample size so that examined _____ that act in cis to the gene as the expected effect size

Answer 5

eQTLs

Question 6

what tissue shows that the variant is affecting it?

Answer 6

the heart

Question 7

the number of ________ identified showed no signs of plateauing at current sample sizes in any of the tissues

Answer 7

eGenes

Question 8

what are eGenes?

Answer 8

These are genes whose expression levels are influenced by genetic variants, meaning that different versions of a gene can lead to different levels of expression in cells

Question 9

what type of genes would have a DNA variant that effects the expression in ALL tissues?

Answer 9

house keeping genes (genes necessary for normal operations)

Question 10

why are some variants found in all tissues while some are only found in one type of tissue?

Answer 10

some genes are only expressed in specific tissues

Question 11

what do we refer to the quantitative variation of gene structure due to genetic variation as?

Answer 11

splicing QTLs

Question 12

eQTLs

Answer 12

expression quantitative trait loci

Question 13

what are eQTLs?

Answer 13

genetic variants that are significantly associated with changes in gene expression levels in different human tissues, eQTLs are like “switches” that can affect how much a gene is expressed

Question 14

what is the difference between cis and trans eQTLs?

Answer 14

• cis (within the same gene)
• trans (affecting a different gene)

Question 15

what is the significance of eQTLs?

Answer 15

eQTLs provide valuable information about the genetic basis of complex traits and diseases, as well as the regulatory mechanisms that control gene expression

Question 16

genetic variants affecting gene expression and splicing patterns have been shown to fall within regulatory elements, providing a potential ______ ______ for their effects

Answer 16

molecular basis

Question 17

what is the value of eQTL information?

Answer 17

to establish functional links between regulatory elements and genes in the genome

Question 18

how can you increase the power of eQTL information?

Answer 18

adding additional tissues and subjects to the data set

Question 19

what is the purpose and future goals of individual-level transcriptome analysis?

Answer 19

it is likely to become a crucial addition to the personalized assessment of an individuals biology and likely disease status

Question 20

what was the ultimate goal of the GTEx project?

Answer 20

to provide a framework for biological interpretation of disease related variants
(a framework to help understand disease-related genetic changes)

Question 21

in GTEx, what could you increase to likely increase the number of detected GWAS-eQTL loci?

Answer 21

• sample sizes
• range of tissues

Question 22

GTEx found that ~13% of candidate genes proposed by GTEx eQTLs and in LD to genome wide significant GWAS SNPs, are _________ genes

Answer 22

noncoding

Question 23

when doing anything in genomics, why does more mean better?

Answer 23

the more more samples or individuals tested allow you to see more effects, see the variations and notice when things vary

Question 24

what does ENCODE stand for?

Answer 24

Encyclopedia of DNA Elements

Question 25

what was the purpose of the ENCODE Project?

Answer 25

the project provides new insights into the organization and regulation of out genes and the genomes and is an expansive resource of functional annotations for biomedical research

Question 26

define a functional element

Answer 26

a discrete genome segment that encodes a defined product or displays reproducible biochemical signature

Question 27

what is a discrete genome segment?

Answer 27

something that has a defined beginning and end (there are coordinates)

Question 28

ENCODE abbreviations: RNA-seq

Answer 28

isolation of RNA sequences (different purification techniques to isolate different fractions of RNA followed by high throughput sequencing)

Question 29

ENCODE abbreviations: CAGE

Answer 29

capture of the methylated cap at the 5' end of RNA

Question 30

ENCODE abbreviations: ChiP-seq

Answer 30

chromatin immunoprecipitation sequencing. a method used to identify the binding sites of DNA-associated proteins, often transcription factors, on a genome-wide scale.

Question 31

ENCODE abbreviations: RRBS

Answer 31

reduced representation bisulphoe sequencing. It's a method used to analyze DNA methylation patterns, particularly focusing on CpG islands and other CpG-rich regions of the genome.

Question 32

what is currently the preferred method for ENCODE?

Answer 32

ATAC-seq

Question 33

ENCODE abbreviations: ATAC-seq

Answer 33

Assay for Transposase-Accessible Chromatin sequencing. It's a technique used in molecular biology to map chromatin accessibility, meaning which parts of the DNA are open and accessible to proteins.

Question 34

major findings of the ENCODE project

Answer 34

- the discovery that a vast majority (80.4%) of the human genome is transcribed into functional RNA molecules, challenging the traditional view of "junk DNA" - identified numerous regulatory elements

Question 35

what did ENCODE reveal about noncoding regions of the genome?

Answer 35

ENCODE has further shown that non-coding regions are often functional and that many non-coding variants associated with disease lie within these functional regions

Question 36

____% of the genome relies within 8 kilo bases of a DNA-protein interaction

Answer 36

95%

Question 37

there are 5.6 times more enhancer regions that promoter-like regions. why?

Answer 37

likely due to the increased need for fine-tuning gene expression. Enhancers, which can be located far from their target promoters, allow for more complex and nuanced control of gene activity by interacting with a wider range of transcription factors and other regulatory elements. Promoters, on the other hand, are more directly involved in the initiation of transcription and are typically located closer to the gene they regulate

Question 38

how many protein coding genes in mammals?

Answer 38

20,000

Question 39

how many bp in mammalian genome?

Answer 39

3 bp

Question 40

what percentage of bp are protein coding?

Answer 40

2%

Question 41

there are 5.6 times more ________ than _______ like regions in the genome

Answer 41

enhancer; promoter

Question 42

there is more variation in non-coding regions than coding regions. Why?

Answer 42

coding regions carry the instructions for protein synthesis so they have to be able to maintain their functionality, so there is less variation while non-coding regions do not directly encode proteins so they do not have as significant of an impact on the organisms survival if a variant occurs, it does not break the function of the organism

Question 43

T/F: there are more "disease" variants outside coding regions than in coding regions

Answer 43

True

Question 44

on average, each "gene" has 3-4 alternative transcription start sites (TSS). why?

Answer 44

for regulation purposes

Question 45

there are lots of RNAs produced that don't code for proteins. What might these non-coding RNAs do?

Answer 45

Non-coding RNAs (ncRNAs) are functional RNA molecules that do not code for proteins but play crucial roles in regulating gene expression, maintaining cellular structures, and other cellular processes

Question 46

have we identified all the "genes"?

Answer 46

NO

Question 47

in ENCODE, wat did they use to identify transcription start sites at high confidence?

Answer 47

CAGE-seq

Question 48

why are there regions of histone modification?

Answer 48

integration of the different histone modification information can be used systematically to assign functional attributes to genomic regions

Question 49

ENCODE found that ____% of the human genome has a "functional" element

Answer 49

80%

Question 50

what was the 80% "functional" elements made up of?

Answer 50

- 62% RNA - 56% histone modifications - 15% open chromatin - 8% transcription factor binding

Question 51

what is the broadest element class that covers 62% of the genome?

Answer 51

RNA

Question 52

How is it that humans have about the same number of protein coding genes as “simpler” organisms but are more complex?

Answer 52

the use of alternative splicing, non-coding DNA, and complex gene regulation

Question 53

GWAS SNPs are particularly enriched in the segmentation classes associated with _______ and _______ across several cell types

Answer 53

enhancers and TSSs

Question 54

GWAS analysesbtypically associate disease to SNPs in large regions, what can a comparison to ENCODE non-coding functional elements do?

Answer 54

can help pinpoint casual variants