(B) Amplification and detection of DNA sequences. (5) Human Genomics DNA (A) Sequencing DNA (B) Amplification and detection of DNA sequences.

Human Genomics (A) State what the Human Genome Project involved State what is meant by ‘bioinformatics’ State 2 benefits of using computer technology State 2 uses of computer programs State what is meant by ‘systematics’ State what is meant by ‘personalised medicine’ State what is meant by ‘pharmacogenetics’

The Human Genome Project What do you already know?

The Human Genome Project Aims: 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 Estimated cost: US $3 billion

The Human Genome Project Who was involved? 1986 – Scientists from USA and UK 1992 – Scientists from Europe and Japan joined Sequence is not just from one person More than 100 blood samples were taken from anonymous volunteers

The Human Genome Project Method: Single DNA strand: GCTATGCGG CGATACGCC Normal DNA replication Add labelled nucleotides which STOP replication instead… We now know the 3rd nucleotide is ADENINE! CGA

The Human Genome Project Method: A single strand of DNA is chosen DNA polymerase, primer, the four DNA nucleotides and modified nucleotides (fluorescent dye) are added to a tube containing the DNA strand. DNA replication occurs BUT… When a modified nucleotide binds to the DNA strand it halts the process, producing different lengths of DNA strands. These pieces are then put through a process called GEL ELECTROPHORESIS which sorts the strands out by size. Because we have added a dye to the nucleotides, we are able to begin to identify the order of nucleotides This process is carried out on many copies, eventually all the strands will have stopped at every possible position.

The Human Genome Project Method: How to Sequence the Human Genome Sequencing the DNA nucleotide order

The Human Genome Project Results: The entire human genome (all 3 billion nucleotides) were sequenced Completed in 2003 (2 years early) Under-budget of estimated US $3 billion

The Human Genome Project What’s next? Research does not stop after the sequencing is complete… 300 disease causing genes exist Over 4000 genes express several different forms of the protein that they encode Scientists now work to understand and identify the causes of disease (cancer) and generate effective treatments. However, the function of most genes still have to be identified…

Additional Video The Secret of Our Lives: The Human Genome Project (14:30)

The Human Genome Project It took 13 years, but in 2003, scientists from around the world had successfully sequenced the entire human genome (3 billion nucleotides). Genome is the word used to describe all of the DNA of a species. Research still continues to identify the function of all of the 20,000–25,000 genes which form the human genome.

> Have any other genomes been sequenced > Have any other genomes been sequenced? > Has the leap in technology improved the process? > How exactly has computer technology been useful?

> Have any other genomes been sequenced > Have any other genomes been sequenced? > Has the leap in technology improved the process? > How exactly has computer technology been useful?

Sequenced Human Genomes Craig Venter is known for being one of the first to sequence the human genome and in 2007, his own genome was published. Within it there were 4.1 million variations, 3.2 million being single nucleotide polymorphisms (SNPs), which are single-base substitutions, the rest being deletions, insertions and duplications. Over a million of these variations were previously unknown. The project took about 10 years and cost US $100 million.

Sequenced Human Genomes In 2008, James Watson's genome was published; it cost US $1.5 million and took just 4 months. It is interesting to note that Watson started to take cholesterol-lowering drugs straightaway after he had his DNA sequenced but did not want to know about any of his genes that might be linked to Alzheimer’s disease.

Sequenced Human Genomes In December of 2010 a personal genome machine, priced at less than 50,000 dollars came onto the market. This will sequence your genome in less than 2 weeks at a cost of less than US $10,000. No doubt as the technology advances hospitals or even health centres will be able to diagnose genetically complex predispositions such as cancers, diabetes and neurological disorders, and optimise treatments or advise on life management systems within the space of a day.

> Have any other genomes been sequenced > Have any other genomes been sequenced? > Has the leap in technology improved the process? > How exactly has computer technology been useful? 1. BIOINFORMATICS 2. SYSTEMATICS

Molecular Biology (genomic sequencing) BIOINFORMATICS Molecular Biology (genomic sequencing) Statistical Analysis Computer Technology Bioinformatics is the use of computer technology to identify DNA sequences. The sequence of bases can be determined for individual genes and entire genomes. The enormous amount of data produced by DNA and protein sequencing can be managed and analysed using computer technology and shared over the internet. Computer programs can be used to: Identify gene sequences by looking for coding sequences similar to known genes, start sequences or sequences lacking stop codons. Identify base sequences that correspond to the amino acid sequence of a protein.

Systematics Systematics compares human genome sequence data and genomes of other species to provide information on evolutionary relationships and origins.

Comparative genomics As of early 2011, the following genomes have been published: over 1000 prokaryotes (single celled organism that lacks a membrane bound nucleus) 300 eukaryotes (any organism whose cells contain a nucleus enclosed within membranes) have been published, with many more in the pipeline. Soon all the major crop and farm animals along with all their main disease-causing organisms will have their genome sequences stored in huge computer databases.

Comparative genomics Organism Estimated size (base pairs) Chromosome number Estimated gene number Human (Homo sapiens) 3 billion 46 ~25,000 Mouse (Mus musculus) 2.9 billion 40 Fruit fly (Drosophila melanogaster) 165 million 8 13,000 Plant (Arabadopsis thaliana) 157 million 10 25,000 Roundworm (Caenorhabditis elegans) 97 million 12 19,000 Yeast (Saccharomyces cerevisiae) 12 million 32 6,000 Bacteria (Escherichia coli) 4.6 million 1 3,200 Arabadopsis has a smaller genome than the fruit fly but twice as many genes: about the same as a human. So an important lesson is that genomic size, or the number of genes, is not proportional to the organism’s place on the evolutionary tree. However, by using powerful software it is possible to recognise individual genes within genomes and to compare these genes between species.

Comparative genomics The Japanese puffer fish (Fugu rubripes) has a genome eight times smaller than humans but with a similar number of genes: it lacks any lengthy repetitive sequences. About 75% of the puffer fish genes have a human equivalent, even though men and fish diverged from their common ancestor 450 million years ago. This has proved to be a useful model organism since the puffer fish genome project has revealed about 1000 new genes in the human genome.

Comparative genomics Fruit flies are thought to share 60% of their genes with humans; in other words we share a core set of genes with a fly. Furthermore, about two-thirds of genes known to be involved with cancer have also been found in fruit flies. So by studying how these genes work in a much simpler organism we should get a better understanding of how they operate in humans and therefore be able to control or prevent the onset of cancer.

Out of Africa Theory If you look hard enough, you'll find any number of theories about just where human beings originated. The prevailing theory among scientists, however, is that the first Homo sapiens evolved in Africa and, between 56,000 and 200,000 years ago, migrated into other lands

How is studying genomics beneficial for: THINK/PAIR/SHARE: How is studying genomics beneficial for: Agriculturalists Farmers Vets Doctors Pharmaceutical companies?

how is studying genomics beneficial for HUMANS? Agriculturalists will improve crop yields by engineering crops to be resistant to specific diseases, pests or environmental factors such as global warming or drought resistance. Farm animal production may be improved by the development of preventative medicines to treat their diseases. This branch of veterinary medicine will no doubt run in parallel with advances in human medicine Personalised medicine is based on an individual’s genome. Analysis of an individual’s genome may lead to personalised medicine through understanding the genetic component of risk of disease. The importance of distinguishing between neutral and harmful mutations and the complex nature of many diseases. Pharmacogenetics and the use of genome information in the choice of effective drugs.

How is knowing the variations between individuals of any use? What is the 1000 Genomes Project? 1000 Genomes Project Small genetic differences between individuals help explain why some people are at higher risk than others for developing illnesses such as diabetes or cancer. In October 2010, the 1000 Genomes Project, an international public-private consortium, published the most comprehensive map of these genetic variations, estimated to contain approximately 95 per cent of the genetic variation of any person on Earth. How is knowing the variations between individuals of any use?

Personalised Medicine https://www.youtube.com/watch?v=fEY3Khsmuak https://www.youtube.com/watch?v=fGjG_9EEeeA

Personalised medicine is based on an individual’s genome. By analysing an individual’s genome and understanding the genetic component of risk of disease, personalised medicine can be created. Pharmacogenetics is the study of how are genes affect how we respond to different drugs. Using the information from an individual’s genome will help doctors in the choice of effective drugs. The importance of distinguishing between neutral and harmful mutations is also important.

TASK: Read the information sheet on Personal Genomics and answer the questions which follow.

Human Genomics (A) State what the Human Genome Project involved State what is meant by ‘bioinformatics’ State 2 benefits of using computer technology State 2 uses of computer programs State what is meant by ‘systematics’ State what is meant by ‘personalised medicine’ State what is meant by ‘pharmacogenetics’