Why Sequence the Human Genome?

Question 1

Why was the human genome sequenced?

Answer 1

The human genome project, begun in 1990, aimed to:
- identify all human genes, and their roles
- analyse genetic variation between humans
- sequence the genomes of several model organisms used in genetics
- develop new sequencing techniques and computational analyses
- to share genome information with scientists and the general public as fast as possible

Question 2

What is a genome?

Answer 2

complete set of DNA of an organism, including all its genes

Question 3

What is genomics?

Answer 3

The study of genes

Question 4

What were the key findings of the human genome?

Answer 4

• There are fewer genes than expected
• Less than 2% of our genome codes for proteins
• The genome is dynamic
• We still don’t know what many of our protein coding genes do
• Most human genes are related to those of other animals
• All humans are 99.9% similar at sequence level

Question 5

What does the human reference genome include?

Answer 5

Nucelar DNA:
- 22 Autosomes, X and Y
- 6 million base pairs
- Half from each parent
- <20,000 genes

Mitochondrial DNA:
- Single, circular
- 16,569 base pairs
- all from mother
- 37 genes

Question 6

What did they find when they tried to identify all human protein coding genes, and their roles?

Answer 6

• Define a gene and look for things that look like genes in sequences
• <2% coding (exons)
• 20% introns (the splice out of the DNA before it was translated)
• ~20,000 genes
• Many (about 20%) still have unknown function

Question 7

While any two human genomes are 99.9% similar…

Answer 7

… across the population there is a lot of variation, and it is important

Question 8

Why are our genomes 0.1% different?

Answer 8

Single Nucleotide Polymorphisms (SNPs) - are sites in DNA that commonly vary within populations

• Between the human reference genome and Watsons genome there are 1.9 Million SNPs difference

Question 9

Describe SNPs

Answer 9

They are common single base pair changes or variants
- SNPs are common, around 1 in every 300 nucleotides
- Your SNPs are mostly different from your parents (occurred in your own DNA replication)
- Each genome sequence adds to the variation on record
- Diversity in genome sequencing adds to knowledge of variation
- Many SNPs don’t “do” anything, they are just inherited variations, but that doesn’t mean they aren’t useful

Question 10

What can analysing common variants (genotyping) tell you?

Answer 10

• Who you are related to
• Where (some of) your ancestors came from
• Disease risk/assosciation
• How you might respond to drugs
  This data can also be used to solve crime

Question 11

Describe what happens when an SNP is found in certain places on the DNA

Answer 11

• Linked SNP: is close to the gene so is more likely to be inherited with the gene (but if its not it won’t affect the gene itself)
• Non-coding SNP: if that SNP changes how the enzyme binds to the DNA then it can effect how much of that protein is made
• Coding SNP: If that SNP is at the start of the codon then it is more likely to change the amino acid. If the amino acid is in an important region of the protein then it will effect the proteins function. If it is not on an important area of the protein then it will not have an effect on the proteins function.

Question 12

Describe short tandem repeats (STRs) and DNA profiling

Answer 12

• STRs are repeats of 2-5 nucleotides, found in specific regions of the genome
• Each person inherits two alleles, one from each biological parent - which can be different lengths
• They can be used to create genetic profiles, or ‘DNA fingerprints’.

EG. 8 repeats of CAG from mother, 3 repeats of CAG from father. This person is 3,8 at STR 1.

Question 13

Describe the importance of InDels

Answer 13

InDels: small deletions or insertions
- Second most common variant type in the human genome
- Can cause a “frameshift” - change the way DNA is read, if in protein coding regions
- Between the human reference genome and Watsons genome there is a difference of 0.2 million InDels

One of the most common genetic human diseases, cystic fibrosis, is caused by CFTR deltaF508, which is a three nucleotide deletion.

Question 14

What are the structural variants that cause variation in the human genome?

Answer 14

CNV’s - copy number variants. chunks of DNA>500bp that are present at different amounts ‘or copy numbers’ relative to a reference genome
- can be deleted or duplicated
- can span multiple genes
- humans have 10,000 CNVs, found within and between genes
- many genes found in CNV are associated with sensory perception and immunity

Between the human reference genome and Watsons genome there is a difference of 23 large CNV (34 genes)