HGP and Biobanks - Genomics

Question 1

What is genetics?

Answer 1

The study of heredity

Question 2

What does a genetics experiment look at?

Answer 2

How traits on passed on, where and when a gene is expressed, what does a gene do, how does it interact with other genes

Question 3

What is genomics?

Answer 3

Studying whole genomes

Question 4

How long does it take to generate data from a genetics experiment? How easy is it to draw conclusions from it?

Answer 4

Takes a lot of time to get the data, but since clear-cut questions were asked it is easier to draw conclusions

Question 5

How long does it take to generate data from a genomics experiment? How easy is it to draw conclusions from it?

Answer 5

Quite easy and fast to generate the data, but is difficult to extract any meaningful conclusions

Question 6

What are 4 research goals in the post-genomic era?

Answer 6

1. Cataloging genomic variation among the human population
2. Connecting variations to phenotypes
3. Annotation and functional analysis
4. Developing new technologies to store and analyze genomic data

Question 7

What does research done to catalogue genomic variation aim to do? What does it look at?

Answer 7

Determine what is normal genetic variation among the population so we can figure out what variation is disease causing. They look at SNPs - single nucleotide polymorphisms

Question 8

What are single nucleotide polymorphisms?

Answer 8

10 million places in the human genome where one nucleotide varies between individuals in the population

Question 9

What does research done to connect variations to phenotypes aim to do? What does it look at?

Answer 9

They aim to determine which variations are normal and which ones are disease causing. They look for variations that appear to be linked to certain phenotypes in the population

Question 10

What is genome annotation?

Answer 10

Identifying which sequences are genes, coding regions, enhancers, promotors, etc. What encodes something

Question 11

What is functional analysis?

Answer 11

Determining if the gene is doing what we think it is doing

Question 12

Why is genome annotation necessary?

Answer 12

Without it, we just have a bunch of ACTG which means nothing

Question 13

Can we link genotype to phenotype for simple diseases?

Answer 13

Yes

Question 14

Why can we link genotype and phenotype for simple diseases?

Answer 14

They are caused by one or a few genes with large effects, so they have a strong, direct, and clear link

Question 15

Do most diseases follow simple inheritance?

Answer 15

No, most are complex inheritance

Question 16

Why is it difficult to link genotype and phenotype for complex diseases?

Answer 16

There are lots of genes each making very small contributions, can be hundreds of genes

Question 17

Why is linking risk alleles to phenotype difficult for complex diseases?

Answer 17

There are individuals with the phenotype that don’t have the risk allele, and unaffected individuals with the risk allele

Question 18

Can genomics studies conclude that a variation is causing a disease?

Answer 18

No, genomics studies can reveal a correlation between a variation and a phenotype, but can’t conclude that variation caused it

Question 19

What are the 5 things required to link genotype with phenotype?

Answer 19

1. Identify correlations between a variation and a phenotype
2. Characterize the function of the genetic sequences identified to correlate with a phenotype
3. Prove that variation caused the phenotype using animal models
4. Understand gene interactions at a genomic scale and how those interactions influence phenotype
5. Understand environmental influences and that effect on phenotype

Question 20

Which of the 5 steps to linking genotype and phenotype are we currently at?

Answer 20

Step 1 for most studies (determining correlation). Some are beginning step 2 (characterizing sequence function)

Question 21

What are the 3 high thoroughput approaches used to identify the genetic basis of diseases?

Answer 21

Genome wide association studies (GWAS), whole exome sequencing (WES), whole genome sequencing (WGS)

Question 22

Which of the 3 high thoroughput genomic study approaches is the most common?

Answer 22

GWAS

Question 23

What do genome wide association studies look at?

Answer 23

A large number of SNPs from a huge sample. The scan the genetic variation across the genome and look for differences between affected and unaffected people

Question 24

What can genome wide association studies tell us?

Answer 24

There is a correlation between a variation and a phenotype

Question 25

What are the limitations of genome wide association studies?

Answer 25

Requires huge samples, which is expensive and laborious. There can be thousands of risk loci and we still can’t predict with any confidence if a person will develop a disease. We can only say if they have an increased risk. GWAS also miss a lot of genetic variation

Question 26

What is the exome?

Answer 26

DNA sequences that are both transcribed and translated and thus expressed

Question 27

How much of the genome does whole exome sequencing examine?

Answer 27

1-2%

Question 28

What would be the advantage of using whole exome sequencing over genome wide association studies?

Answer 28

A lot cheaper

Question 29

When would it be advantageous to use whole genome sequencing to examine the genetic basis of a disease?

Answer 29

For small sample sizes like families to be able to draw meaningful conclusions about the genetic basis of a disease