What is the Human Genome Project

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 genome
• A private company in the USA (Celera) claimed it
  would get there first and patent a lot of it, but
  didnt!

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...

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.
  birds wing and mammals 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 gt25
  identical aminoacids over a length of gt80
• ...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...

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
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?