KJB - Human Genome Project

Question 1

The HGP consists of how many chromosomes?

Answer 1

22 pairs of autosomes

1 pair of sec chromosomes

Question 2

Define karyotype.

Answer 2

A chromosome spread - a set of human chromosomes at the stage of mitosis (shortly before the cell divides)

Question 3

What does Giemsa staining do?

Answer 3

Allows you to see characteristics of banding patterns.

Question 4

How many bases of DNA are there?

Answer 4

3 billion

Question 5

How many genes are there?

Answer 5

20, 000 - 30, 000

Question 6

What version of the human genome sequence are we on?

Answer 6

38th version - still not complete

Question 7

State the goals of the HGP

Answer 7

1. Identify all the genes in human DNA
2. Sequence all base pairs that make human DNA
3. Store this information in a database
4. Improve tools for data analysis
5. Transfer technologies to private sector
6. Address ethical, legal and social issues that may arise from the project.

Question 8

Composition of the human genome project. Give %

Answer 8

Of the 3 billion base pairs, only:

• around 3% actually codes for DNA protein
• around 39% = single copy non coding DNA
• around 59% = repetitive DNA (containing transposons)

Question 9

Humans do not have much more genes than creatures such as nematodes, fruit flies or any other simple organism. Explain why.

Answer 9

In terms of gene numbers we are not that complex compared to a nematode worm but the way that we USE these genes we are a lot more complex in how we switch genes on and off, and how we make proteins from those genes.

Question 10

Although the sizes of bases in genes vary greatly, what is the average?

Answer 10

3000 bases per gene.

Question 11

Explain what epigenetic changes are.

Answer 11

Epigenetic changes do not involve DNA sequences but change the chemical structure of bases e.g. by adding a methyl group to C bases. A lot of methyl additions will silence the genes.
Epigenetic changes occur through environmental exposure and are frequently involved in human cancers.

Question 12

Modern drug discovery process order:

Answer 12

1. Target identification
2. Determine DNA and protein sequence
3. Elucidate structure and function of target
4. Proof of concept and assay development
5. Assay for high throughput molecular screen
6. Mass screening and/ or directed synthesis programme
7. Select lead structures

Question 13

Target identification requires genome information. The healthy cells are compared against diseased cells and the differences are noted. What are the 3 ways in which this can be done?

Answer 13

1. Genetic association studies - look at DNA SEQUENCE variation in diseased v.s healthy individuals
2. Gene expression studies (transcriptomics) - look for differences in GENE EXPRESSION in diseased v.s healthy individuals (i.e. which genes are ‘on’ and which are ‘off’
3. Protein expression studies (proteomics) - look for differences in PROTEIN EXPRESSION and modification in diseased v.s healthy individuals (i.e. which proteins are made and how they are modified)

Question 14

How do you elucidate the structure of the protein?

Answer 14

X-ray crystallography

Question 15

What are the two ways of analysing the role of a target protein in a disease?

Answer 15

1. OVEREXPRESSION - make lots more of the protein than normal and see what happens OR introduce a transgene i.e. a gene from a different organism
2. GENE KNOCKOUT - take the gene away (and therefore stop protein production) and see what happens

IF A PROTEIN IS REALLY INVOLVED IN THE DISEASE (IS A GOOD DRUG CANDIDATE), THEN ONE OF THESE APPROACHES WILL GIVE US AN EFFECT THAT SHOULD LOOK LIKE A PATHOLOGY