Block C Part 2: The Human Genome Project Flashcards
What is one genome?
A complete set of chromosomes
(Lecture 3, Slide 3)
How do human chromosomes range in size? (give values)
from 5.5x10^7 to 2.5 x10^8
(Lecture 3, Slide 3)
What were the 4 aims of the human genome project?
To determine the sequence of the 3 billion chemical base pairs in human DNA
Identify all genes in human DNA to their position on chromosomes
Attempt to predict their function of all genes
Utilise this info for understanding disease, developing better medicines and helping to understand human variability and how humans compare to other species
(Lecture 3, Slide 4)
How was the human genome project an international project?
Individual labs concentrated on a single chromosome all over the world , US, UK, Germany, China, Japan
(Lecture 3, Slide 7)
What was necessary to carry out the large number of PCR tests / sequencing reactions that were required for the human genome project?
Robotic production lines
(Lecture 3, Slide 7)
What is phase 1 of the human genome project?
Produce high resolution chromosomal maps - libraries of BAC clones for sequencing
(Lecture 3, Slide 8)
What is phase 2 of the human genome project?
Sequence each BAC DNA
(Lecture 3, Slide 8)
What is phase 3 of the human genome project
Assemble all sequences to produce a final draft and annotate to identify genes
(Lecture 3, Slide 8)
What did we have to wait on before completion of the human genome project?
Sequencing technology to improve
(Lecture 3, Slide 12)
What was the method of the old sanger sequencing?
Radiation, 4 separate dideoxy reactions (one for each base) and it was very slow and results had to be read manually off an x-ray film
(Lecture 3, Slide 13)
What is the new method of sanger sequencing?
Like PCR but with fluorescent terminators
(Lecture 3, Slide 14)
How were the advances in sanger DNA sequencing technology used in the second phase of the human genome project?
It reduced the cost and also enabled the computational assembly of all sequences into “contig”
(Lecture 3, Slide 18)
What approach did the IHGSC group use in the human genome project?
The clone-by-clone approach
(Lecture 3, Slide 19)
What are the 2 disadvantages of the clone-by-clone approach?
It’s a slow and expensive process
(Lecture 3, Slide 19)
What are the 2 advantageous of the clone-by-clone approach?
It’s very effective at getting over regions of highly repetitive DNA sequences and you are able to retrieve clones later
(Lecture 3, Slide 19)
What approach did Celera use for the human genome project?
Shotgun sequencing
(Lecture 3, Slide 20)
What is shotgun sequencing?
You blast the genome into small fragments, sequence each one and then use computers to reassemble the sequence
(Lecture 3, Slide 20)
What was the disadvantage of shotgun sequencing in the human genome project?
It had to rely on public databases of sequence and mapping information in order to assemble the sequence that was generated by this method
(Lecture 3, Slide 20)
When was a working draft of the human genome made available?
July 2000
(Lecture 3, Slide 22)
How has the size of the genome that we have discovered grown?
Around 20,000-25,000 genes in 2001 - ~ 1.5 - 5% of the genome
(Lecture 3, Slide 25)
Roughly how many base pairs and SNP variants does chromosome 16 contain?
~90,000,000 base pairs with ~ 1.7 million SNP variants
(Lecture 3, Slide 26)
What is gene ontology?
The study of finding out what our genes do
(Lecture 3, Slide 27)
What are the 5 most common functions of our genes in gene ontology?
Around 23.6 % are unclassified
~12% code for transcription factors
~8.8% code for transferases
~8.5% code for proteins involved in nucleic acid binding
~6.4% code for transporters
not necessary to remember percentages, just helps to visualise
(Lecture 3, Slide 27)
What is population genetics?
Genetic variation between humans is now visible at the genome scale
(Lecture 3, Slide 28)
How similar are human beings to each other (in percentage)?
99.9%
(Lecture 3, Slide 29)
How many people and chromosomes were sequenced during the human genome project?
4 (+1 at Celera privately) - 10 chromosomes
(Lecture 3, Slide 29)
How did these human beings sequenced during the human genome project give us a first glimpse at global human genetic variation?
As the various sequences were aligned, variants emerged which weren’t just mistakes in the sequence
(Lecture 3, Slide 29)
What were the 2 major types of revelation in the human genome project?
Single Nucleotide Polymorphisms (SNPs)
Copy Number Variants (CNVs)
(Lecture 3, Slide 29)
What was the next step after the human genome project?
SNP identification
(Lecture 3, Slide 30)
What was created in the quest to identify SNPs?
A public database to DNA differences - dbSNP
(Lecture 3, Slide 30)