Lecture 5: The Human Genome Project and How we got here[A] (learn how to do crosses!!))

Question 1

When did we enter the genomic era?

Answer 1

In 1995, as this was when we got the first complete prokaryotic genome sequencing (Haemophilus influenzae).

Question 2

What ratio is the expected genotype and phenotype ratio for monohybrid crosses [peas]?

Answer 2

genotype= 1:2:1

phenotype= 3:1

Question 3

What are both the parents in a monohybrid cross?

Answer 3

Hetrozygotes

Question 4

Who created the first ever genome sequence of any organism?

Answer 4

J. Craig Venter

Question 5

What did J. Craig Venter sequence the genome of?

Answer 5

The prokaryote Haemophilus influenza Rd

Question 6

When was the human genome project proposed?

Answer 6

In 1986, although it didn’t start till 1990.

Question 7

When was the genome of the first archaea sequenced?

Answer 7

In 1996 and it was of extremophile Methanococcus jannaschii

Question 8

When was the first eukaryotic genome sequenced?

Answer 8

In 1996

Question 9

When was the genome of the fruit fly first sequenced?

Answer 9

In 1999

Question 10

When was the first draft of the human genome almost complete?

Answer 10

In 2001

Question 11

When did the human genome project formally end?

Answer 11

In 2003

Question 12

When was the genome of the chimanzee sequenced?

Answer 12

In 2005

Question 13

What is our closest living ancestor?

Answer 13

Chimpanzees

Question 14

When were the mat and rouse genomes completed?

Answer 14

2002-2003: Allowed for direct comparisons with humans.

Question 15

When was the genome of Neanderthals sequenced?

Answer 15

In 2010.

Question 16

What did the sequencing of the Neanderthal genome reveal?

Answer 16

Revealed that there is 2% of Neanderthal DNA in modern non-Africans.

Question 17

What were some of the key findings of the human genome project?

Answer 17

• Gene Sharing: Humans share genes with archaea, yeast, and animals.
• Humans have approx 22,000 protein-coding genes, which is a lot lower than the prediction of 100,000
• Non-Coding DNA: Only 1.5% of human DNA encodes proteins; the rest plays regulatory roles.
• Comparative Insights: Genetic similarity to mice (~90%) and chimpanzees (~98%).

Question 18

What did the 1000 genomes project do?

Answer 18

It mapped all known genes involved in human variation

Question 19

What did the 100,000 genomes project do?

Answer 19

It mapped the genomes of people with genetic disease and of people who were more susceptible to genetic disease.

Question 20

What are some of the downsides of such large scale DNA sequencing?

Answer 20

• Sequencing required advancements in algorithms, storage systems, and statistical tools.
• Ethical concerns , such as privacy concerns and psychological impact.

Question 21

Is it true that although the human genome project was formally concluded in 2003, gaps persisted in the heterochromatin regions?

Answer 21

Yes

Question 22

How were the gaps in the human genome project sorted?

Answer 22

In 2022, there was the Telomere-to-Telomere (T2T) project, which filled these gaps, producing a truly complete human genome.

Question 23

What are some of the applications of the above genome sequencings?

Answer 23

• Can be used for the predicition of suceptability to certain diseases, like cancer.
• Can be used in personalised medicine, and so treatments can be tailored to individual genetic profiles.
• Provided some evolutionary insights: Chromosomal comparisons between humans and chimpanzees revealed structural differences like chromosome fusion events + Genetic data supports the “in and out of Africa” model, indicating extensive historical gene flow.

Question 24

What is heterochromatin?

Question 25

When was the genetic test on breast cancer developed?

Answer 25

In 2019

Question 26

What is 8% of our genome?

Answer 26

heterochromatin

Question 27

What does heterochromatin include?

Answer 27

• Centromeres
• Telomeres
• X and Y chromosomes

Question 28

When was the telomere-to-telomere project completed?

Answer 28

In 2022

Question 29

When was the origins of the japanese people published? (3 evolutionary origins)

Answer 29

In 2024

Question 30

What were the goals of the human genome project?

Answer 30

1) Identify all of the genes in human DNA

2) Determine the sequences of the DNA base pairs that make up the human genome

3) Store this information in databases

4) Improve tools for data analysis

5) Transfer related technologies to the private sector

6) Address the ethical, legal, and social issues that may arise from the project.

Question 31

How many genes did the human genome project say that humans have?

Answer 31

22,000, which is much lower than expected (100,000).

Question 32

What % of our genome codes for proteins?

Answer 32

Only 1.5 %

Question 33

How big is the human haploid genome?

Answer 33

3.2 X 10⁹ bp (3,200,000,000 )

(equates to 22,000 coding genes)

Question 34

Has the human genome project allowed us to understand our evolutionary history?

Answer 34

Yes

(Chromosomal comparisons between humans and chimpanzees revealed structural differences like chromosome fusion events + Genetic data supports the “in and out of Africa” model, indicating extensive historical gene flow.)

Question 35

What’s one difference between the chromosomes of humans and chimpanzees?

Answer 35

At the 2nd point of chromosomes, there’s 2 chromosomes in chimps and one chromosome in humans. (fusion event/breakage event)

Question 37

What are the benefits of the human genome project?

Answer 37

• Allows us to understand our evolutionary history.
• Allows us to make use of personalised medicine.
• Improved genetic screening i.e for breast cancer.

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Question 38

What does a faulty version of the BRCA1 gene increase the chances of breast cancer in women by?

Answer 38

A faulty version of the BRCA1 gene increases the chances of breast cancer in women from 12.5% to 60-90%.

Question 39

What does a faulty version of the BRCA1 gene increase the chances of ovarian cancer in women by?

Answer 39

A faulty version of the BRCA1 gene increases the chances of ovarian cancer in women from 1.9% to 11-40%.

Question 40

What are the ethical/legal issues with the knowledge of people’s genomes?

Answer 40

• Will genetic information be used fairly?
• Could an employer refuse to hire someone because of a health concern indicated by that person’s genome?
• Could health insurance companies refuse to provide insurance to some people?
• Psychological impact: imagine you have a genotype associated with a short life – do you want to know?
• Stigmatisation: do you want your neighbour to know?

Question 41

Who came up with the Central Dogma of molecular biology? (‘Once information has got into a protein it can’t get out again’.)

Answer 41

Francis Crick in 1958

Question 42

How does information flow in the central dogma?

Answer 42

DNA -> RNA -> Protein

DNA replicates itself, transcribes to RNA, and RNA translates to proteins.

Question 43

What regulates gene expression, coding DNA or non-coding DNA?

Answer 43

Non-coding DNA regulates gene expression. This is because non-coding DNA contains elements like: promoters, enhancers, and silencers that help determine: when a gene is turned on or off; where in the body a gene is active; where in the body a gene is active. This explains phenotypic differences between species with similar genes (although they share most genes, they are phenotypically different because their genes are regulated in different ways to each other).

Question 44

Describe the modern version of the central dogma

Answer 44

• DNA replication
• Transcription of DNA to RNA
• Information translated into a protein

Question 45

Who is known as the founder of genetics?

Answer 45

Gregor Mendel

Question 46

What is the scientific name for pea plants?

Answer 46

Pisum sativum

Question 47

Why did Mendel work with pea plants? [Watch vid on Mendel]

Answer 47

• They’re cheap
• They produce large numbers of offspring
• They have a relatively short generation time
• They can unergo both self-fertilisation and cross fertilisation.

Question 48

How do you cross-pollinate a pea plant?

Answer 48

• Transfer the pollen(male) from the anthers of one plant on a brush and rub it on the stigma(female) of another plant.
• Remove the anthers from the target plant. (prevents plant from self-pollinating)
• Pure-breeding lines with contrasting features were available.
• Only simple tools are needed

Question 49

How do you self-pollinate a pea plant?

Answer 49

• Use a brush to transfer pollen from the anthers to the stigma of the same flower.

Question 50

What does a monohybrid cross mean?

Answer 50

a breeding experiment that involves two organisms with different variations of a single genetic trait

Question 51

Describe Mendel’s experiment

Answer 51

• He crossed a pure breeding green plant(yy) with a pure breeding yellow plant (YY). This was the parental generation.
• In the next generation (F1), all the peas were yellow. Mendel then called the yellow pea colour a dominant trait.
• Mendel then crossed the F1 yellow pea plant with a pure green plant, and the offspring was a mixture of green and yellow peas in a one to one ratio.
• Mendel called the green peas a recessive trait.
• Mendel then crossed an F1 yellow with and F1 yellow and got a 3:1 ratio of yellow to green. (F2 generation)

Question 52

What was the first law of inheritance/ the law of segregation?

(read in book)

Answer 52

• Each individual has factors for each trait, one from each parent.
• If the factors are identical, the individual is homozygous for the trait.
• If the factors are different, the individual is heterozygous.

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Question 53

Is Mendel’s law of independent assortment/law of inheritance true?

Answer 53

No, only in special circumstances

Question 54

What did Sutton conclude?

Answer 54

• That sex was determined via chromosome-based inheritance.
• That Mendel’s ‘factors’ were carried on chromosomes.

Question 55

How did T.H Morgan make his career?

Answer 55

By studying fruit flies

Question 56

What is the scientific name for fruit flies?

Answer 56

Drosophila melanogaster

Question 57

What’s the difference between male and female fruit flies?

Answer 57

Males have black bottoms, females are striped and slightly bigger.

Question 58

What did Morgan notice about fruit flies in 1910?

Answer 58

Wild-type fruit flies have red eyes but some of his mutant flies had white eyes. So he decided to find out why these white eyes are inherited.

Question 59

Describe Morgan’s crosses

Answer 59

• He took a female with red eyes (wild-type) and crossed it with a male with white eyes(mutatnt). This gave all red-eyed offspring, showing that the red-eye trait is dominant to the white-eye trait. (F1)

reciprocal cross
- He then crossed a female with white eyes with a male with red eyes. The result was females with red eyes and males with white eyes. Very unexpected, non-reciprocal.

• Decided that sex and eye colour were inherited together, and that the gene for eye colour was on the X chromosome, but not the Y chromosome

Question 60

Define the key observations

Answer 60

The white-eye trait was carried on the X chromosome.

Males, having only one X chromosome (XY), expressed the trait if they inherited the mutant X from their mother.

Females, with two X chromosomes (XX), needed two copies of the mutation to express the trait, which was rarer.

The outcome of the cross depended on the sex of the parent carrying the mutant trait.

Morgan’s work provided direct evidence that genes reside on chromosomes.

Traits like eye color in fruit flies (and some in humans, such as color blindness) are inherited differently in males and females due to their location on sex chromosomes.