1. What is the Human Genome Project? Identify all the approximately 35,000 genes in human DNA Determine the sequences of the 3,000,000,000 bases ( = 200 phone books) in the haploid human genome Store this information in databases Develop tools for data analysis Address the ethical, legal, and social issues Study the genomes of lab organisms e.g. fruit fly, mouse, nematode worm, yeast

2. How is it being done? By many labs worldwide By cloning fragments of the human genome in bacteria and yeast (millions of clones with 1000-1,000,000 bp of DNA in each) By determining the DNA sequence of each fragment using automated apparatus By assembling the sequences of all the fragments back into the complete genome sequence using computers

3. How far has it got? Working draft of most of it has been done Whole sequence in the next 2 years First whole chromosome to be completed was 22, followed by whole genomegenome A private company in the USA (Celera) claimed it would get there first and patent a lot of it, but didn’t!

4. For what will it be useful? It will help us to understand common human diseases e.g. cancer, mental health It will show what makes us human, e.g. by comparing our genes with animals’ genes Genes make proteins so we can predict all human proteins, design new drugs, etc Variation in DNA between individuals can be used to study origins of human populations

5. Genetic variation and disease Some genes directly cause rare genetic diseases e.g. Cystic fibrosis, sickle-cell anemia - called “simple” or “Mendelian” genetic disease Many genes contribute to the risk of getting a common disease with genetic and environmental components - called “complex” or “multifactorial” disease e.g. cancer, heart disease, asthma, schizophrenia, diabetes The Human Genome Project will help us identify these genes

6. How do you find the disease genes? Look for variations in the DNA sequence that are found more often in patients than in healthy controls Go to the corresponding region of the genome (in the database) See what genes are nearby and whether they might have a role in the disease For example, associated with schizophrenia is a bit of chromosome 22...chromosome 22

7. What makes us human? Specifically human traits (language, planning, advanced cognitive skills) emerged after divergence of human and ape lineages Most of the human and chimp genomes are 99% identical and we are even very similar to mice - all mammals have about the same set of genes Subtle differences in structure or expression of a few genes that affect the development of the brain, are probably responsible for human-specific traits Detailed comparison of human and other genomes should enable these genes to be identified

8. What do all the proteins do? The DNA sequence is analysed by computer to identify the actual genes and translate them into the predicted protein amino-acid sequence Each protein sequence is compared (by computer) with all proteins in the database to look for “homology” with a known protein Homology means “having a similar structure, because of a common evolutionary origin” (e.g. bird’s wing and mammal’s forelimb) Functions of the novel protein and homologous, known protein might be the same

9. Homology and protein structure Proteins are homologous if they have >25% identical aminoacids over a length of >80:...ASFGHERTYHGTYRELLYHHG......ESFHILSDYGDHHEELYHFGG... Homologous proteins have the same 3-D structure A novel protein from the genome can be fitted on to a known protein structure...protein structure

10. Where did humans come from? “Genetic archaeology” is a new science that uses molecular genetics to study the origins of humans Different forms (alleles) of genes are compared in present populations More variation indicates an older population Most genetic variation is within populations, not between them - “races” do not have a real genetic basis

11. Human population migrations “Out of Africa” 50,000 years ago

12. Implications for society? Genes for disease susceptibility - should insurance companies have the right to know? Geneticists say “No” Will the HGP tell us everything about what makes a human? Absolutely not. Genes are important but they are not everything Genes for human traits - designer babies? Do parents have the right to a baby who will grow up like one of the characters above? Or clones of their parents?