ZOO405 by Rania Baleela is licensed under a Creative Commons Attribution- NonCommercial-ShareAlike 3.0 Unported LicenseRania BaleelaCreative Commons Attribution- NonCommercial-ShareAlike 3.0 Unported License ZOO405, Week 5 lecture 9

This week The human genome project

YESTERDAY Half-century ago, very little was known about the genetic factors contributing to human diseases. In 1953, James Watson and Francis Crick described the double helix structure of DNA Methods to determine the order, or sequence, of the chemical letters in DNA were developed in the mid-1970s. In 1990, the National Institutes of Health (NIH) and the Department of Energy joined with international partners in a quest to sequence all 3 billion bp in the human genome, which is the complete set of DNA in the human body=> Human Genome Project.

Human Genome Project

Sequencing genomes: Sequencing genomes: 1. The Human Genome Project (HGP) 2. Khoisan & Bantu genomes from SA

Where do I start? ~ 230 Personnel

A USA govt. project coordinated by the Department of Energy & the NIH, launched in 1986 by Charles DeLisi. 6 main objectives: It has 6 main objectives: 1.Human gene maps & mapping of human inherited diseases 2.Development of new DNA technologies 3.Sequencing of the human genome 4.Development of bioinformatics 5.Comparative genomics 6.Functional genomics What is the Human Genome Project?

Human Chromosome No.3 1.Human gene maps & mapping of human inherited diseases: The genetic maps involves the production of fairly low-level resolution framework maps Integration with high-resolution physical maps.

2. Development of new DNA technologies The development of high-throughput automated capillary sequencers and robust fluorescent sequencing kits has helped transform the ease and cost of large-scale DNA sequencing projects. ABI 3700 “Prism” DNA Sequencer

3. Sequencing of the human genome The human genome contains large sections of repetitive DNA => technically difficult to clone and sequence. Expressed sequences or genes are most likely to be the regions of greatest medical and biological importance. A commercial approach: ‘shotgun’ sequence the whole of the human genome at random and then take the sequence information generated and assemble it by means of a computer program that recognizes overlapping DNA sequences.

4. Development of bioinformatics Is essential to the overall success of the Human Genome Project. Bioinformatics allow the identification of coding sequences and the determination of their likely function(s) from homologies to known genes Bioinformatics= the establishment of facilities for collecting, storing, organizing, interpreting, analyzing & communicating the data from the project

5. Comparative genomics Separate genome projects for a number of other species ‘model organisms’. Mapping of the human homologues of newly identified genes from other species provides new ‘candidate’ genes for inherited diseases in humans.

Compare whole chromosomesFind missing genes P. knowl esi conti gs P. falciparum Chr 3 P. yoelii contigs (TIGR) tblastx

7. Functional genomics Functional genomics or post-genomic genetics is the way in which model organisms are providing the means to follow the expression of genes & the function of their protein products in normal & in inherited disorders.

In April 2003, researchers successfully completed the Human Genome Project, under budget and more than two years ahead of schedule.

Map of South Africa. The figure shows ethnic grouping and localities of study participants, KB1, NB1, TK1, MD8 and ABT (a–e, respectively), areas of arid and desert climates and the geographic distribution of the Khoisan and Niger–Congo languages. The Khoisan languages are characterized by clicks, denoting additional consonants. (Schuster et al., 2010)

Benefits of Human Genome Project research Improved diagnosis. Research for fuel and environmental cleanup. DNA forensics. Improved agriculture and livestock. Better understanding of evolution and human migration. More accurate risk assessment.

Disease Genes Discovered: at least one disease- related mutation has been identified for 1100 genes Clinical disorders and gene mutations: Different mutations in the same gene can give rise to more or less distinct disorders (number of diseases for which there are known mutations is ~1500) Functional Classifications: Disease genes classed by function and their relative representations

Some diseases involve polygenic effects A number of classic “genetic diseases” are caused by mutations of a single gene: – Huntington’s, Cystic Fibrosis, Tay-Sachs, PKU, etc. Many diseases are the result of the interactions of many genes: – Asthma, Heart disease, Cancer

There are many socio-ethical implications of the HGP Three of the most important ones 1. Behavioral Genetics If genes that indicate susceptibility for criminality, intelligence, or homosexuality are discovered, how should we respond? 2. Gene Testing/Therapy 3. Privacy Issues

Ethical, legal & social implications of the Human Genome Project Some questions to consider: Fairness & privacy: who should have access to your genetic information? Psychological stigmatization: how does knowing your predisposition to disease affect an individual? Genetic testing: should screening be done when there is no treatment available? Reproductive issues: use of genetic information in decision making. Clinical issues: implementation of standards and quality control measures in testing procedures.

OUTCOME: TODAY It has fueled the discovery of more than 1,800 disease genes. Researchers can find a gene suspected of causing an inherited disease in a matter of days More than 2,000 genetic tests for human conditions. At least 350 biotechnology-based products resulting from the Human Genome Project are currently in clinical trials. Challenge: understand the produced data. A major step toward such comprehensive understanding was the development in 2005 of the HapMap (

HapMap & benefits Is a catalog of common genetic variation, or haplotypes, in the human genome. In 2010, the 3 rd phase of the HapMap project was published, with data from 11 global populations. HapMap data have accelerated the search for genes involved in common human diseases from age-related blindness to obesity. With the drastic decline in the cost of sequencing whole exomes or genomes, groundbreaking comparative genomic studies are now identifying the causes of rare diseases. Pharmacogenomics is a field that looks at how genetic variation affects an individual’s response to a drug. Pharmacogenomic tests can already identify whether or not a breast cancer patient will respond to the drug Herceptin, whether an AIDS patient should take the drug Abacavir, or what the correct dose of the blood-thinner Warfarin should be.