Using Genome Projects (A Level only) (AQA A Level Biology)

The Human Genome Project was created with the hopes of advancing personalised medicine.Personalised medicine involves the development of more targeted drugs to treat a variety of human diseases as well as the development of synthetic tissues.

Define the term genome.

Some aggressive cancers have been found to be associated with specific genetic mutations identified by the Human Genome Project. Drug Z has been developed to treat patients with a specific type of bowel cancer. Results from the clinical trials show that drug Z has caused a 45% shrinkage of cancerous tumours in only four months.

Suggest how work on the Human Genome Project has aided the development of drug Z.

Explain how drug Z can cause a large reduction in cancerous growths in only four months.

Suggest one advantage and one disadvantage of screening people for harmful alleles that can cause health problems.

Genome projects involve collecting DNA samples from many individuals to create a reference genome. The genomes of patients with diseases can then be compared to this reference genome to try and deduce if there are any genetic factors that affect the likelihood or severity of the disease.

Suggest why DNA samples are taken from multiple individuals for the creation of a reference genome.

When scientists initially studied the human genome, they found that certain genes showed some degree of variation between humans while other genes exhibited no variation between humans at all.

Suggest why some genes showed no variation in their base sequences between individuals.

Genome projects involving simpler organisms can be highly useful for human medicine. Plasmodium falciparum is a parasite which causes severe malaria. It’s genome is currently being studied by many scientists to see if particular variants are associated with insecticide and drug resistance. It is also the aim of scientists to use the information from the parasites genome to develop an effective vaccine against malaria. 

Suggest and explain how the antigenic genes could be identified within the parasites genome and used to speed up the development of a vaccine.

Scientists are able to determine the proteome of Plasmodium falciparum from its genome. Determining the proteome of humans from their genome has proved to be very difficult.

Suggest why.

Describe and explain the difference between the genome and proteome of a cell.

The speed of DNA sequencing methods have changed drastically within the last 20 years. New technology means that DNA sequencing can be done within a matter of hours. The length of DNA that can be sequenced in a given time is measured in base pairs. In 1982, the rate of DNA sequencing by a particular machine was approximately 550 base pairs per hour. In 2018 a machine was capable of sequencing approximately 550 million base pairs per hour. Calculate how many times faster the rate of DNA sequencing is in 2018 compared with 1980. Give your answer in standard form.

The term “junk DNA” became a common term in the 1960s. Scientist used it to describe the lengths of DNA that weren’t genes. It is estimated that approximately 98% of the human genome does not code for polypeptides. Further research involving genome projects have shown that “junk DNA” plays a vital role in genome regulation. As a result, scientists started to refer to it as non-coding DNA rather than junk DNA.
Describe the two different forms of non-coding DNA that are found in the cells of eukaryotes.

It was decided that all data generated for the Human Genome Project would be made publicly available prior to publication. Describe one advantage and one disadvantage of making scientific data public prior to publication.

Suggest two medical applications of genome projects like the Human Genome Project.

Genome projects have been used to investigate evolutionary relationships and population events for different species. Scientists compared the genomes of randomly sampled orangutans and humans. 

They studied a particular intron within a gene (ZFY) on the Y chromosome of male humans and male orangutans. They observed that there was a high degree of genetic variation within the samples taken from the orangutans but that there was absolutely no variation within the samples taken from the humans. Suggest an explanation for the lack of variation observed in the male humans.

When carrying out a genome project the DNA from individuals were obtained via blood samples. Name which cell the DNA is obtained from when using a blood sample. Explain your answer.

It has been suggested by some scientists that sequencing the genomes of all children at birth could be beneficial for prolonging life expectancy. Evaluate this suggestion.

Researchers want to investigate the possible genetic links or markers for prostate cancer. They have access to the reference genome and data from the Human Genome Project. They also have access to the genomes of over 1,500 NHS patients who have suffered from prostate cancer.

Suggest how they could use the data above to investigate the genetic links/markers for prostate cancer.

The human genome is approximately 3 billion base pairs long. A DNA sequencing machine allows for 5.5 x 10⁸ base pairs to be sequenced per hour. Using this information calculate the number of days it would take to sequence the 1500 genomes of the NHS patients using this machine.

Give your answer to the nearest day.

It has been discovered that men who carry a faulty BRCA2 gene (located on chromosome 13) are more likely to develop prostate cancer.

How can this information be used in the future to help with the early detection and treatment of prostate cancer.

Building on the success of multiple human genome projects a new project investigating the epigenome is currently underway. Scientists hope that the data collected will aid them in their understanding of epigenetics and its effect on cancers.

Discuss the use of bioinformatics as a tool for studying the genome.

There are around 3 x 10⁹ base pairs in the human genome. In the year 2000, a rough draft of the human genome was announced, however, it had an error rate of 1 error per 1000 base pairs. Three years later, in 2003, the final copy was published with an error rate of just 1 error per 12000 base pairs.

Use these figures to calculate how many fewer errors were presented in the final copy compared to the draft copy of the genome. Show your final answer in standard form.

Suggest how DNA sequencing can be used in the treatment of specific genetic diseases such as haemophilia.

Explain why the proteome of a human changes throughout their lifetime.

Distinguish between the genome, epigenome and proteome.

Outline the mechanism by which interactions between the genome and epigenome determine the proteome of an organism.

Explain why the genome of a bacterium is more simple to determine than the genome of a human.

The human genome project established that the human genome is made up of 26 564 genes and these genes contain 233 785 exons and 207 344 introns.

Use this information to calculate the average ratio of exons to introns per gene in the human genome.

The Sanger sequencing method was one of the methods used during the Human Genome Project to sequence fragments of human DNA. 

 The process requires the following:

1. An enzyme - DNA polymerase
2. A primer (1 single type)
3. The four DNA nucleotides
4. The template DNA (to be sequenced)
5. Fluorescently labelled dideoxynucleotide versions of the DNA nucleotides (needed for chain termination)

 The process occurs as follows:

1. The ingredients are added into a tube
2. The mixture is heated to separate the strands of the DNA fragments
3. The mixture is then cooled to allow the primers to anneal
4. The temperature is set at 37^oC so DNA polymerase can synthesize new DNA
5. The cycle is repeated many times

During the process, new DNA fragments are built using DNA nucleotides, every time a dideoxynucleotide is added, it terminates the sequence. After many cycles, it is likely that every single position on the target DNA has been occupied by a chain terminating nucleotide giving a range of different fragments. The process can be seen in Figure 1.

 Figure 1

Using the information provided, compare the Sanger sequencing method to PCR.

Justify the requirement for a primer in this sequencing method.

Gel electrophoresis was carried out on the DNA fragments produced after sequencing was carried out. The results can be seen in Figure 2.

Figure 2

Explain how electrophoresis separates the DNA fragments as shown in Figure 2.

Use Figure 2 and the information from part (a) to deduce the order of the base code of the DNA fragment.

The Sanger sequencing method was developed in 1977 by British Biochemist Fred Sanger. It was one of the methods used during the Human Genome Project to sequence fragments of human DNA before they were collated to form larger regions of DNA and then whole chromosomes.

 Table 1 shows some information about the Sanger sequencing method.

Scientists carried out five sequencing runs using the Sanger sequencing method. Each run sequenced 850 base pairs. Complete the table below to show the statistics for this procedure.

Per run, calculate the total time taken, the total cost and the number of potentially incorrect bases.

An overview of the Sanger sequencing method is shown in Figure 1.

 Figure 1

Describe and explain how the structure of DNA makes it possible to sequence the genome of an organism.  

The base sequences of the human, chimpanzee and a macaque are compared in Figure 2.

Calculate the percentage of the base code shown is identical across macaques and chimpanzees.

 Figure 2

Compare the base sequences of the human, chimpanzee and macaque. Suggest what conclusions we could make from this information.

Explain why knowledge of the human genome does not easily translate into the proteome of a human.

Genome projects involving simpler organisms can be highly useful for human medicine. Plasmodium falciparum is a parasite which causes severe malaria. All 5300 genes of the parasite have been sequenced and scientists are now using this information to develop a database of the plasmodium proteome.

Explain how sequencing of a the Plasmodium falciparum proteome may help us to develop an effective vaccination which can be used to combat Malaria.

Outline how DNA sequencing facilitates the process of genetic screening for a disease.

When the Human Genome Project set about producing a genetic map of the human genome, its intention was to allow earlier diagnosis of diseases and to facilitate the creation of effective new medicines. However, it was also apparent that genetic information could be used in ways which are harmful or unfair. In response to these concerns, a budget was set aside to manage any ethical, legal and social dilemmas

Discuss the ethical, legal and social considerations of DNA sequencing projects such as the Human Genome Project.