Block C Part 2: The Human Genome Project Flashcards

1
Q

What is one genome?

A

A complete set of chromosomes
(Lecture 3, Slide 3)

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2
Q

How do human chromosomes range in size? (give values)

A

from 5.5x10^7 to 2.5 x10^8
(Lecture 3, Slide 3)

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3
Q

What were the 4 aims of the human genome project?

A

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)

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4
Q

How was the human genome project an international project?

A

Individual labs concentrated on a single chromosome all over the world , US, UK, Germany, China, Japan
(Lecture 3, Slide 7)

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5
Q

What was necessary to carry out the large number of PCR tests / sequencing reactions that were required for the human genome project?

A

Robotic production lines
(Lecture 3, Slide 7)

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6
Q

What is phase 1 of the human genome project?

A

Produce high resolution chromosomal maps - libraries of BAC clones for sequencing
(Lecture 3, Slide 8)

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7
Q

What is phase 2 of the human genome project?

A

Sequence each BAC DNA
(Lecture 3, Slide 8)

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8
Q

What is phase 3 of the human genome project

A

Assemble all sequences to produce a final draft and annotate to identify genes
(Lecture 3, Slide 8)

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9
Q

What did we have to wait on before completion of the human genome project?

A

Sequencing technology to improve
(Lecture 3, Slide 12)

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10
Q

What was the method of the old sanger sequencing?

A

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)

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11
Q

What is the new method of sanger sequencing?

A

Like PCR but with fluorescent terminators
(Lecture 3, Slide 14)

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12
Q

How were the advances in sanger DNA sequencing technology used in the second phase of the human genome project?

A

It reduced the cost and also enabled the computational assembly of all sequences into “contig”
(Lecture 3, Slide 18)

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13
Q

What approach did the IHGSC group use in the human genome project?

A

The clone-by-clone approach
(Lecture 3, Slide 19)

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14
Q

What are the 2 disadvantages of the clone-by-clone approach?

A

It’s a slow and expensive process
(Lecture 3, Slide 19)

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15
Q

What are the 2 advantageous of the clone-by-clone approach?

A

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)

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16
Q

What approach did Celera use for the human genome project?

A

Shotgun sequencing
(Lecture 3, Slide 20)

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17
Q

What is shotgun sequencing?

A

You blast the genome into small fragments, sequence each one and then use computers to reassemble the sequence
(Lecture 3, Slide 20)

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18
Q

What was the disadvantage of shotgun sequencing in the human genome project?

A

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)

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19
Q

When was a working draft of the human genome made available?

A

July 2000
(Lecture 3, Slide 22)

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20
Q

How has the size of the genome that we have discovered grown?

A

Around 20,000-25,000 genes in 2001 - ~ 1.5 - 5% of the genome
(Lecture 3, Slide 25)

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21
Q

Roughly how many base pairs and SNP variants does chromosome 16 contain?

A

~90,000,000 base pairs with ~ 1.7 million SNP variants
(Lecture 3, Slide 26)

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22
Q

What is gene ontology?

A

The study of finding out what our genes do
(Lecture 3, Slide 27)

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23
Q

What are the 5 most common functions of our genes in gene ontology?

A

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)

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24
Q

What is population genetics?

A

Genetic variation between humans is now visible at the genome scale
(Lecture 3, Slide 28)

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25
Q

How similar are human beings to each other (in percentage)?

A

99.9%
(Lecture 3, Slide 29)

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26
Q

How many people and chromosomes were sequenced during the human genome project?

A

4 (+1 at Celera privately) - 10 chromosomes
(Lecture 3, Slide 29)

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27
Q

How did these human beings sequenced during the human genome project give us a first glimpse at global human genetic variation?

A

As the various sequences were aligned, variants emerged which weren’t just mistakes in the sequence
(Lecture 3, Slide 29)

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28
Q

What were the 2 major types of revelation in the human genome project?

A

Single Nucleotide Polymorphisms (SNPs)
Copy Number Variants (CNVs)
(Lecture 3, Slide 29)

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29
Q

What was the next step after the human genome project?

A

SNP identification
(Lecture 3, Slide 30)

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30
Q

What was created in the quest to identify SNPs?

A

A public database to DNA differences - dbSNP
(Lecture 3, Slide 30)

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31
Q

What did SNP identification set the scene for?

A

Global genome analysis used to find gene variants associated with complex genetic disorders
(Lecture 3, Slide 30)

32
Q

Why were the 10 chromosomes from the 5 individuals sequenced in the human genome project?

A

To create a representative sample of the genetic diversity in the human population and it was the start of detailed analysis of sequence differences between individuals
(Lecture 3, Slide 31)

33
Q

What was the aim of the international HapMap project?

A

To find the more common SNP variants in the world’s population
(Lecture 3, Slide 32)

34
Q

How many SNPs did the HapMap project in 2005 locate?

A

> 1,000,000
(Lecture 3, Slide 32)

35
Q

What were the 4 populations of people studied and how many were studied at the start of the HapMap project?

A

Started off with 270 people from Nigeria (African), Japan + China (Asian) and Utah (Northern and Western European ancestry)
(Lecture 3, Slide 32)

36
Q

How many people are studied in the HapMap project now and where are they from?

A

1,301 individuals from across the world
(Lecture 3, Slide 32)

37
Q

Why are big human genome studies becoming routine?

A

As human genome sequencing is becoming very cheap
(Lecture 3, Slide 36)

38
Q

How long did it take to fill in the 8% gap in the original sequence of the human genome project and how was this achieved?

A

It took just over 20 years and was achieved using new technology
(Lecture 3, Slide 37)

39
Q

What does “T2T” stand for and when did it occur?

A

T2T stands for the Telomere to Telomere Consortium and it published results in spring 2022
(Lecture 3, Slide 37)

40
Q

Roughly how many base pairs of nuclear DNA do we have in the human genome, and therefore in our bodies?

A

~ 3,100,000,000 base pairs
(Lecture 3, Slide 37)

41
Q

Roughly how many base pairs is the mitochondrial genome, and hence is present in our bodies?

A

~ 16,500 base pairs
(Lecture 3, Slide 37)

42
Q

Roughly how many genes does the draft “T2T-CHM13” annotation total and roughly how many of these are predicted to be protein coding?

A

It contained roughly 63,500 genes and about 20,000 (~31.5%) of these are predicted to be protein coding
(Lecture 3, Slide 37)

43
Q

What are 3 types of non-coding genes that were contained in the Telomere-to-Telomere Consortium?

A

tRNAs, rRNAs involved in translation and micro RNAs (miRNAs) and Long Non-coding RNAs (IncRNAs) involved in transcription regulation
(Lecture 3, Slide 37)

44
Q

What percentage of genes in the human genome are only found in vertebrates?

A

~7%
(Lecture 3, Slide 38)

45
Q

What are 6 things we learned from the human genome project?

A

How do humans compare to other species?
Humans are still evolving
Fine-structure of inheritance
Human prehistory
The way in which our genes control our response to medication
What genes are linked to genetic diseases
(Lecture 3, Slide 45)

46
Q

How did the human genome project lead to us finding out evolutionary relatedness between humans and other animals?

A

Many species had their genome sequenced while the human genome project was waiting for it’s final push, and these were then compared to determine evolutionary relatedness
(Lecture 3, Slide 46)

47
Q

What do modular domains in proteins allow during evolution?

A

Novel genes / proteins
(Lecture 3, Slide 50)

48
Q

What is a novel gene or protein?

A

A gene or protein that has been newly identified or discovered
(Lecture 3, Slide 50)

49
Q

What pathways are high conserved (unchained) between species?

A

The ones that are important for life, such as ribosome proteins , tRNAs and ABC transporters
(Lecture 3, Slide 51)

50
Q

Higher organisms such as humans have selective expansion in particular protein families and domains - state 4 examples of this.

A

Answers Include:
Immune function
Intercellular signalling
Metabolic function
Olfaction - sense of smell
Haemostasis - the process to prevent or stop bleeding
mRNA splicing
Translation
(Lecture 3, Slide 52)

51
Q

How many genes do humans have with “human-specific features”?

A

850
(Lecture 3, Slide 52)

52
Q

How many genes do humans have that are entirely human-specific?

A

Over 50
(Lecture 3, Slide 52)

53
Q

What are 4 types of genes which show evidence for fast/recent evolution in humans?

A

Answers Include:
Pathogen response
Cell cycle / DNA metabolism
Protein metabolism
Reproduction
Neuronal activity
Skin pigmentation
(Lecture 3, Slide 53)

54
Q

How is FOXP2 gene an important human-specific variant in the gene sequence?

A

There are 2 amino acids changes between chimps and humans/Neanderthals/Denisovans - proving evolution
(Lecture 3, Slide 57)

55
Q

What is an example of human-specific loss of sequences?

A

Humans and chimps having less functional olfactory (sense of smell) genes than most animals that diverged earlier than humans
(Lecture 3, Slide 58)

56
Q

What is known as a “unit of inheritance”?

A

Linkage disequilibrium blocks (LD blocks)
(Lecture 3, Slide 60)

57
Q

What is a linkage disequilibrium block?

A

It refers to the non-random association of alleles at 2 or more loci in a population
(Lecture 3, Slide 60)

58
Q

Where are LD blocks located?

A

Chiasma formation in meiosis occurs at “hotspots” - an LD block is the space in-between
(Lecture 3, Slide 61)

59
Q

What is one piece of evidence supporting the “Out of Africa” theory of human migration?

A

African populations today are far more genetically diverse than the rest of the world
(Lecture 3, Slide 65)

60
Q

What percentage of a non-African genome derives from the genomes of Neanderthal and Denisovan archaic humans?

A

~2-2.5%
(Lecture 3, Slide 68)

61
Q

Roughly when did we diverge form our archaic Denisovan and Neanderthal ancestors?

A

500,000-700,000 years ago
(Lecture 3, Slide 69)

62
Q

Roughly when did humans in Africa achieve “anatomical modernity”?

A

A few hundred thousand years ago
(Lecture 3, Slide 69)

63
Q

Roughly when did humans start to expand out of Africa and the Near East?

A

50,000-70,000 years ago
(Lecture 3, Slide 69)

64
Q

Roughly when did humans start to admix with Denisovans and Neanderthals in Eurasia?

A

Shortly after humans migrated out of Africa and the Near East
(Lecture 3, Slide 69)

65
Q

When did multiple independent transitions from hunter-gatherer to food producing lifestyles occur?

A

Within the last 10,000 years
(Lecture 3, Slide 69)

66
Q

What 3 things happened after multiple independent transitions from hunter-gatherer to food producing lifestyles?

A

Large scale population growth, further migration and admixture
(Lecture 3, Slide 69)

67
Q

What is individual variation in the outcome of drug treatments often mediated by?

A

Genetic differences
(Lecture 3, Slide 72)

68
Q

What are 5 factors of a response to drug treatments that are under genetic control?

A

Inactivation/activation by oxidative pathways (cytochrome P450s)
Conjugation for excretion through the kidney (GST)
Target sensitivity
Side effects from toxicity
Disease mutation type
(Lecture 3, Slide 72)

69
Q

How do we tailor therapy to individual genotypes?

A

By more precisely identifying patients who will respond well to a drug treatment and avoid prescribing drugs to people with incompatible genomes who may react badly - this is known as pharmacogenetics
(Lecture 3, Slide 73)

70
Q

What is the DF508 mutation?

A

The most common mutation in the cystic fibrosis gene in europeans resulting in no functional protein being produced
(Lecture 3, Slide 77)

71
Q

What is the G551D mutation?

A

Makes up 5% of the mutations of the cystic fibrosis gene and results in a damaged protein with reduced function being produced
(Lecture 3, Slide 77)

72
Q

How is the protein function in cystic fibrosis restored?

A

By Ivacaftor drug
(Lecture 3, Slide 77)

73
Q

How did the human genome project lead to bioinformatics?

A

As all information about the human genome is now available publicly online - AI can even be used to solve many complex problems with it
(Lecture 3, Slide 80)

74
Q

How has the human genome project affected genetic studies?

A

Any study can now be “genome wide”
(Lecture 3, Slide 80)

75
Q

What do “genome-wide” genetic studies offer?

A

The best hope of cracking complex genetic disorders , such as cancer or diabetes
(Lecture 3, Slide 81)

76
Q

The human genome project made transcriptomics and proteomics possible - how does this benefit us?

A

It is now possible to identify disease/state biomarkers, consequences of illnesses and drug action
(Lecture 3, Slide 81)