What does the human genome tell us? + The Human Genome & Disease

Question 1

What is comparative genomics used for?

Answer 1

To discover what is in common and what is different

Question 2

What are things in common called?

Answer 2

Conserved

Question 3

What may conserved things encode?

Answer 3

Biology in common between species

Question 4

What may things that are different encode?

Answer 4

Organism specific biology

Question 5

What do you learn by comparing genes?

Answer 5

A little bit about which bits of the genome do what

Question 6

How do you compare sequences?

Answer 6

By lining them up next to each other and marking each point where sequences are the same and different

Question 7

What is the method for comparing sequences called?

Answer 7

Aligning

Question 8

What does it mean when there are more differences between DNA sequences?

Answer 8

The further apart the organisms are in time

Question 9

What may differences in individuals be associated with?

Answer 9

Disease, characteristics of an individual or evolutionary history

Question 10

What can we learn about an organism if we compare its genome with others?

Answer 10

What sort of genes they have, how differences between species arise and relationships between species

Question 11

How long does DNA from dead things remain in the environment?

Answer 11

For up to 1 million years

Question 12

What happens to DNA in the environment?

Answer 12

It degrades and is masked by more modern DNA which may also show up when sequenced

Question 13

When can ancient DNA be extracted?

Answer 13

In very special circumstances (for example if it is preserved in a cold environment such as a cave)

Question 14

How many neanderthal nucleotides were found?

Answer 14

4 billion

Question 15

What was done with modern contamination of the Neanderthal bits?

Answer 15

It was identified and discounted

Question 16

How many neanderthals were sequences gathered from?

Answer 16

Probably 3 individuals

Question 17

How much neanderthal sequence was obtained?

Answer 17

Enough sequence to compare with modern human genome sequences from around the world

Question 18

What was identified from the neanderthal sequencing?

Answer 18

Bits of DNA that differ between Neanderthals and us

Question 19

What was the most amazing finding from the neanderthal DNA sequencing?

Answer 19

Some of us carry neanderthal DNA

Question 20

Which humans carry neanderthal alleles?

Answer 20

Modern humans from Europe and asia while those from Africa show no sign of these alleles

Question 21

What is the most likely cause of africans showing no neanderthal DNA?

Answer 21

Neanderthals and homo sapiens have a common ancestor but Neanderthals left Africa before Homo sapiens. Then when Homo sapiens left Africa they interbred with neanderthals when they met

Question 22

What does it mean that humans have some neanderthal DNA?

Answer 22

It doesn’t mean that those of us with Neanderthal DNA have a different set of genes, it just means that our DNA holds variants that arose in neanderthals

Question 23

How much of the genome of non-africans is made up of variants that arose in neanderthals?

Answer 23

2-4%

Question 24

What does Neanderthal DNA do?

Answer 24

Add to our variation in our genome and might be related to our phenotype

Question 25

What was also found in Denisova?

Answer 25

A finger bone whose mitochondrial DNA doesn't match Neanderthal or modern human DNA (Denisovam)

Question 26

What was the genome from the species of archaic human sequenced from?

Answer 26

A tooth found in the same cave in 2010

Question 27

How much Denisovans variation is found in the human genome?

Answer 27

4-6% in present day melanesians

Question 28

What has sequencing our genomes helped?

Answer 28

Us to better understand who we are and where we came from

Question 29

What is the key technology?

Answer 29

Being able to compare genomes

Question 30

What can we do by comparing genomes from multiple species?

Answer 30

We can start to understand where our characteristics came from

Question 31

What is this the same approach to?

Answer 31

Modern disease genetics- data rich and statistically intense analysis

Question 32

What are our extinct relatives?

Answer 32

Not just fossils in our museums, but they also live on as variants in our genomes which affect our biology

Question 33

What can mutations be?

Answer 33

Inherited or acquired

Question 34

What are mutations?

Answer 34

Permanent changes to the DNA sequence

Question 35

What are inherited mutations called?

Answer 35

Germline mutations

Question 36

How are germline mutations passed on?

Answer 36

Via the gametes (eggs and sperm)

Question 37

How can mutations be acquired?

Answer 37

If DNA gets damaged or is copied incorrectly

Question 38

Are acquired mutations inherited?

Answer 38

No, these mutations are not passed on to the next generation

Question 39

What is the driving force for evolution?

Answer 39

Genetic variations and mutations

Question 40

What effects can mutations have?

Answer 40

They can have a beneficial effect, have no effect or a deleterious (damaging or harmful) effect on the organism

Question 41

What effect do majority of mutations have?

Answer 41

No effect at all

Question 42

What does the outcome of a mutation also depend on?

Answer 42

Environmental effects and other genes

Question 43

What is not consistent?

Answer 43

The molecular basis of a mutation

Question 44

What do we talk about when thinking about mutations?

Answer 44

Alleles

Question 45

Why do we talk about alleles rather than genes?

Answer 45

Because mutations in a single gene can have different effects

Question 46

What are the two ways of thinking about mutations?

Answer 46

Dominant vs Recessive and Loss of function vsGain of function

Question 47

What can mutations (alleles) be?

Answer 47

heterozygous (one mutant, one wild type allele) or homozygous (both alleles mutant)

Question 48

What is a dominant mutation?

Answer 48

One that causes a phenotype when heterozygous

Question 49

What is a recessive mutation?

Answer 49

One that causes a phenotype when only homozygous

Question 50

What must a mutation do to have a phenotype?

Answer 50

Affect the function of a gene

Question 51

What can a mutation do negatively to a gene?

Answer 51

Break a gene to cause it to not work as well as normal, or not work at all

Question 52

What is the mutation that breaks a gene to cause it to not work as well as normal or not work at all called?

Answer 52

Loss of function

Question 53

What are loss of function mutations often?

Answer 53

Recessive mutations

Question 54

What are loss of function mutations often recessive?

Answer 54

Because a normal copy of the gene exists on the other chromosome which can replace the lost function

Question 55

What can a mutation do positively to a gene?

Answer 55

It can cause a gene to work too well, or to do something unexpected

Question 56

What is a mutation called that can cause a gene to work too well or to do something unexpected?

Answer 56

Gain of function

Question 57

What are gain of function mutations often?

Answer 57

Dominant

Question 58

Why are gain of function mutations often dominant?

Answer 58

Because having an allele that works too well or does something novel will not be replaced by the normal copy of the gene

Question 59

Gain of function doesn't always mean it is...

Answer 59

something good

Question 60

What can we do by examining the inheritance pattern of something?

Answer 60

Determine if it is dominant or recessive. Also if it is x-linked, y-linked or autosomal

Question 61

What are examples of autosomal recessive mutations?

Answer 61

Inability to taste PTC, cystic fibrosis

Question 62

What are characteristics of autosomal recessive mutations?

Answer 62

Typically not seen in every generation of an affected family, passed on by two asymptomatic carriers, males and females are equally likely to inherit

Question 63

What are examples of autosomal dominant mutations?

Answer 63

Widows peak, Huntington's disease

Question 64

What are characteristics of autosomal dominant mutations?

Answer 64

Occurs commonly in a pedigree, affected individuals have an affected parent, males and females equally likely to inherit.

Question 65

What are examples of x-linked recessive mutations?

Answer 65

Haemophilia A and Haemophilia B

Question 66

What are the characteristics of x-linked recessive mutations?

Answer 66

Fathers can not pass on x-linked traits to their sone, no male to male transmission, most often affects males

Question 67

How do we determine the inheritance pattern? Step 1

Answer 67

Examine the pedigree and look for individuals that break the rules to find out some possibilities

Question 68

How do we determine the inheritance pattern? Step 2

Answer 68

Identify carriers who do not have the condition, if there are none, this might mean the condition is dominant

Question 69

How do we determine inheritance pattern? Step 3

Answer 69

Find the inheritance pattern that explains all the disease occurrence in a pedigree

Question 70

How do we find potential disease genes?

Answer 70

Sequence genome>>>Map to the human reference>>>Find common and novel variants>>>Work out if novel variants are predicted to be harmful or benign>>>validate and test the variants predicted to be harmful

Question 71

How do most disorders appear?

Answer 71

To have a genetic basis but do not follow straight forward inheritance patterns

Question 72

What do polygenic disorders involve?

Answer 72

Several genes acting together or environmental factors interacting with genes

Question 73

What is identifying polygenic genes?

Answer 73

Very hard

Question 74

How are polygenic genes identified?

Answer 74

Cases (10-100K) and controls (10-100K) are compared to identify variation

Question 75

What is identified when caring cases and controls?

Answer 75

Common variants and shared variants which are in cases but not controls are identified

Question 76

What happens after common and shared variants are identified?

Answer 76

The shared variants in cases not in controls are validated and tested to decide if variants in genes are likely to be associated with the disease

Question 77

What does having a disease-related variation mean?

Answer 77

For most diseases it doesn't mean you will get the disease

Question 78

How do diseases come about?

Answer 78

Through a combination of variants and the environment

Question 79

Different sufferers have...

Answer 79

different disease mechanisms

Question 80

What are most genetic disorders?

Answer 80

Probabilistic, not deterministic

Question 81

What is also probabilistic, not deterministic?

Answer 81

Most traits with a genetic component, your genes do not direct your destiny