1. Higher Human Biology Unit 1 – Human Cells
Section 5 – Human Genomics

2. a – Human Genomics We will be learning… To define the term genome
To explain what is meant by the term human genomics
State that bioinformatics can be used to identify DNA sequences
To define potential uses of bioinformatics

3. Human Genomics
The genome is the whole hereditary information of an organism that is encoded in the DNA.
Human genomics is the study of the human genome
It involves determining the sequence of the nucleotide base molecules along the DNA and then relating this genetic information about genes to their functions.

4. What were the Aims of the Human Genome Project?
To identify all the approximately 20,000-25,000 genes in human DNA.
To find where each gene is located
To determine the sequences of the 3 billion chemical base pairs that make up human DNA.
Store this information in databases.
Estimated time 15 years. (started in 1980)
Estimated cost US$3 billion

5. The Human Genome Project
Started in 1986 (USA and UK) but officially ‘started’ in 1990, Europe and Japan joined in 1992
Completed in 14th April 2003 – under budget and 2 years early
The sequence is not that of one person, but is a composite derived from several individuals. Therefore, it is a "representative" or generic sequence. To ensure anonymity of the DNA donors, more blood samples (nearly 100) were collected from volunteers than were used, and no names were attached to the samples that were analysed. Thus, not even the donors knew whether their samples were actually used.
Also sequenced yeast and animals used in medical research e.g. zebra fish and rats.

6. Human Chromosomes
For a nice overview of how all the 3 billion bases in our genome were sequenced and why this is important click here
XY = male XX = female

7. Sequencing DNA
A portion of DNA with an unknown base sequence is chosen to be sequenced. Many copies of one of this DNA’s strands (the template) are synthesised using PCR.
Then, in order to make DNA that are complementary to these template strands, all the ingredients needed for synthesis are added to the preparation. These include DNA polymerase, primer and the four types of DNA nucleotide. In addition the preparation receives a supply of modified nucleotides (ddA, ddT, ddG and ddC), each tagged with a different fluorescent dye.
See here for animation

8. Every so often during the synthesis process, a molecule of modified nucleotide just happens to be taken up instead of a normal one. However, when a modified nucleotide is incorporated into the new DNA strand, it brings the synthesis of that strand to a halt because a modified nucleotide does not allow any subsequent nucleotide to become bonded to it. Provided that the process is carried out on a large enough scale, the synthesis of a complementary strand will have been stopped at every possible nucleotide position along the DNA template.

10. The DNA Fragments of various lengths(each with its modified nucleotide and its unique fluorescent tag) are separated using electrophoresis. The order of the nucleotides in the original DNA can then be worked out from the fluorescent dye that is used.
Usually a computer working as an automated sequence analyser, detects the four fluorescent dyes processes this information quickly and displays the sequence of bases in the DNA sample.
genome sequencing animation

11. Separating DNA fragments
DNA fragments can be separated by gel electrophoresis
Largest fragments
Smallest fragments
DNA moves to
the positive terminal
due to it’s overall
negative charge +
gel with DNA
fragments

12. Automated DNA sequencing
This gives a direct readout of the sequence and the process can be automated so that it is much faster than by conventional sequencing.

13. Separating DNA fragments
1. The final stage of the genome project is to determine and assemble the actual DNA sequence itself.
2. There are several critical requirements for this part:-
a. Single stranded DNA fragments must be generated as the templates;
b. sequencing technology must be accurate and fast;
c. computer hardware and software must be available to analyse the sequence data.
The unknown fragment to be sequenced is copied many times by
PCR ( see following lessons )
4. The unknown fragment base sequence is found using:-
a. a DNA polymerase;
b. a primer;
c. Four man-made nucleotides with the four bases
d. a fluorescent dye or radioactive element

14. What next?
After all 3 billion base pairs were sequenced there was more work to do
Scientists now had to understand the message and identify causes of disease, such as cancer, and then generate effective treatments.
300 disease causing genes exist and over 4000 genes express several different forms of the protein that they encode.
Being able to read genomes allows comparisons to be made between individuals and different species or personalised medicine

15. b – Pharmacogenetics and Personalised Medicine
We will be learning…
To explain what is meant by the term human genomics
To describe how an individuals genome can be analysed to predict the likelihood of developing certain diseases
Explain the role of genomics in personalised medicine
Explain what pharmacogenetics is and how it is used to select the most effective drugs and dosage to treat their disease.

16. Human Genomics
The sequence of bases can be determined for individual genes and entire genomes
This genetic information can be used to find the function of different genes.
Entire genomes can be compared using single nucleotide polymorphisms (SNPs). (These are differences between individuals due to base substitutions. )
SNPs

17. A variation in DNA sequence that affects a single base pair in a DNA chain is called a single nucleotide polymorphism (SNP). SNPs are one of the ways in which genomes are found to differ from one individual to another. For example, the DNA of two people might differ by the SNP shown below. This difference has arisen as a result of a point mutation where one base pair has been substituted for another. Two out of every three SNPs involve the replacement of cytosine (C) and with thymine (T). SNPs can occur in coding and non-coding regions of the genome.

18. SNP maps
Scientists have managed to catalogue more than a million SNPs. They believe that an SNP map will help them identify and understand the workings of genes associated with disease.
Some SNPs may indicate the likelihood of a person developing a particular illness.

19. Alzheimer’s Disease
One of the genes associated with this disease is called ApoE (Apolipoprotein E)
The gene is affected by two SNPs and different combinations of these produce three different forms of the gene (Apo E2, Apo E3 and Apo E4).
Research has shown that inheritance of the ApoE4 allele increases the chance of Alzheimer’s disease whilst inheritance of the Apo E2 allele makes the person less likely to develop the condition.

20. Bioinformatics
Is the use of computer technology to identify DNA sequences
The enormous amount of data produced by DNA and protein sequencing can be managed and analysed using computer technology and shared over the internet

21. Bioinformatics is the name given to the fusion of molecular biology, statistical analysis and computer technology. It is an ever-advancing area that enables scientists to carry out rapid mapping and analysis of DNA sequences on a huge scale and then compare them.

22. Bioinformatics Computer programs can be used to identify
Gene sequences by looking for coding sequences similar to know genes
Start sequences (there is a good chance that each of these will be followed by a coding sequence
Sequences lacking stop codons (a protein coding sequence is normally a very long chain of base triplets containing no stop codon except the one at its end

23. Bioinformatics
Computer programmes can also be used to search for base sequences that code for specific amino acid sequences of known proteins.
This can be useful in medicine, for example in genetic screening for diseases.

24. Videos BBC documentary (1 hour)
Ethics of genome project (5 mins) human-genome-project/8732.html
History of the world

25. Systematics
Video
This can be defined as the study of a group of living things with respect to their diversity, relatedness and classification. Data obtained by comparing human genome sequences are used in systematics to study the origins of modern humans and their evolutionary relationships. Unlike other primates such as orangutans, whose DNA differs among the members of the species by around 5%, the mean difference in genomic sequence among the members of the human race is only about 0.3%. This high degree of similarity indicates that all humans are more closely related to one another than other types of primate. Careful examination of the genetic differences that do exist between different human populations shows that the greatest variation occurs among populations in Africa rather than those on other continents. Furthermore, genetic evidence indicates that all human populations outside Africa possess only a small part of the total genetic diversity found among African populations. These findings support the “out of Africa” theory. This proposes that humans originated in Africa and underwent early evolutionary divergence in that continent over a very long period of time (e.g. millions of years) to form a variety of genetically different populations. Then small groups migrated out of Africa relatively recently (e.g. 100,000 years ago) and gave rise to all other human populations.

26. Personal Genome Sequence
Personalised Medicine
A complete sequencing of a person’s DNA bases is called a personal genome sequence. The branch of genomics involved in sequencing the genomes of individuals and analysing them using bioinformatics tools is called personal genomics. As a result of advances in computer technology, the process of sequencing DNA is rapidly becoming faster and cheaper. Sequencing an individual’s DNA for medical reasons will soon become a real possibility. In years to come, a person’s entire genome may be sequenced early in life and stored as an electronic medical record available for future consultation by doctors when required.
Having located the mutant variants present in a persons genome, it is important to distinguish between those altered sequences that are genuinely harmful.

27. Personalised Medicine
Personalised medicine is based on an individuals genome.
It would allow scientists to predict an individuals susceptibility to disease, select treatment that is more likely to be successful, and avoid adverse reactions to medication.
Video

28. Personalised Medicine
To make use of this technique, scientists need to:
Locate mutant variants in the genome
Distinguish between harmful and neutral variants
Establish a link between the mutation and a disease
The nature of the disease might depend on genetic and environmental factors.

29. Pharmacogenetics
This can be defined as the study of the effects (therapeutic, neutral or adverse) of pharmaceutical drugs on the genetically diverse members of the human population. Already it is known that one in ten drugs (e.g. the blood thinner warfarin) varies in effect depending on differences such as SNPs in the persons DNA profile. In the future it may be possible to use genomic information and
customise medical treatment to suit an individuals exact metabolic requirements. The most suitable drug and the correct dosage would be prescribed as indicated by personal genomic sequencing. Ideally this advance would increase drug efficacy while reducing side effects and “one-size-fits-all” approach would be consigned to history.

32. Now I can….. Define the term genome
Explain what is meant by the term human genomics
State that bioinformatics can be used to identify DNA sequences
Define potential uses of bioinformatics
Describe how an individuals genome can be analysed to predict the likelihood of developing certain diseases
Explain the role of genomics in personalised medicine
Explain what pharmacogenetics is and how it is used to select the most effective drugs and dosage to treat their disease.

33. Word
Meaning
Human Genomics
is the study of the human genome
Bioinformatics
use of computers and statistics in analysis of sequence data
Systematics
study of the diversification of living organisms past and present
Pharmacogenetics
the study of the effects (therapeutic, neutral or adverse) of pharmaceutical drugs on the genetically diverse members of the human population
SNP’s
A variation in DNA sequence that affects a single base pair in a DNA chain is called a single nucleotide polymorphism
DNA Probe
short piece of DNA complementary to a target sequence of DNA
DNA Profiling
use of DNA probes to produce a 'fingerprint' of an individual's DNA
Fluorescent Labelling
method of making a fragment of DNA show up under the ultraviolet light
Genome
total genetic material present in an organism
Genome Sequence Data
information about the nucleotide sequence of the entire human genome
Personalised Medicine
development in which treatment is based on the individual's genome

34. Revised Higher 2015 A Q7 B

36. Suggested activities
Ethical diamond 9
Close reading activity