Genome Variation

Question 1

How many bases does the human genome contain?

Answer 1

→ 3 billion bases

Question 2

How much of the genome codes for proteins?

Answer 2

→ 2%

Question 3

What are 2 examples of macro level differences associated with disease?

Answer 3

→ Aneuploidy

→ Translocations

Question 4

What are micro level differences associated with disease?

Answer 4

→ point mutation

→ SCA

Question 5

How much DNA is the same between 2 people?

Answer 5

→ 99.7%

Question 6

What is a variant?

Answer 6

→ Any position in the genome that varies between individuals

Question 7

What does a reference sequence do?

Answer 7

→ Summarize what base the vast majority of people have at that position (expected base sequence)

Question 8

What is a reference allele?

Answer 8

→ The most common and major allele

Question 9

What are all the assumptions of what is normal and a variant based on?

Answer 9

→ the human genome mapping project

Question 10

What is a SNP?

Answer 10

→ change in a single base

Question 11

How many SNVs are there in the human genome?

Answer 11

→ 17 million

Question 12

How are SNVs generated?

Answer 12

→ Faulty replication of DNA during mitosis

→ Mismatch repair mechanisms

Question 13

What is the frequency of a SNP in an individual?

Answer 13

→ 1 in every 1000 bases differ from the reference sequence

Question 14

Describe the faulty replication that leads to a SNV/SNP in a strand that is GTTC (1) and the other strand (2) is CGGT?

Answer 14

→ Two strands separate during replication
→ 2nd A in strand two of (1) gets replaced with a G
→ The mismatch repair mechanism identifies this and corrects it so the bases are a Watson Crick pair
→ The T on (1) is replaced with a C
→ The bases match but it is not the original sequence

Question 15

What does biallelic mean?

Answer 15

→ Two possible alleles present at a site

Question 16

In what 3 regions can SNVs be in?

Answer 16

→ Genes
→ promoter
→ Non coding region

Question 17

What 4 changes can SNVs cause within genes?

Answer 17

→ Synonymous
→ Non-synonymous
→ Nonsense
→ Affect where splicing occurs

Question 18

What are the two things that can cause SNVs to disappear?

Answer 18

→ Deleterious effect

→ Population annihilation

Question 19

Why is it better to use the term SNV and not polymorphism?

Answer 19

→ Polymorphism can imply no pathogenic effect

Question 20

What change does Sickle cell anaemia have?

Answer 20

→ Codon GAG to GTG

→ Glutamic acid to valine

Question 21

What is the criteria for an allele to be a polymorphism?

Answer 21

→ if the minor allele frequency is > 1%

→ at least one every 100 has a non reference allele then it can be called a polymorphism

Question 22

What is the criteria for an allele to be a mutation?

Answer 22

→ Minor allele frequency of less than 1%

Question 23

What is the criteria for a rare polymorphism?

Answer 23

→ 1-5%

Question 24

What affects whether a variant remains or not?

Answer 24

→ Evolution

Question 25

Why are rare variants damaging or recent?

Answer 25

→ rarity means the individuals don't reproduce → mortality/ can't reproduce → recent means they haven't had the chance to reproduce

Question 26

Why do all variants start off rare?

Answer 26

→ They take time to spread if they are not damaging

Question 27

How do new alleles arise?

Answer 27

→ Mutation

Question 28

What is gene flow?

Answer 28

→ Migration leading to the introduction of a variant into another population

Question 29

What is genetic drift?

Answer 29

→ Random change in variant allele frequency between generations

Question 30

What is selection and why does it occur?

Answer 30

→ Non- random change in a variant allele frequency between generations → because the presence is either pathogenic (negative selection) → or beneficial (positive selection)

Question 31

When are genetic variants most likely to be neutral?

Answer 31

→ If they are within the non coding region | → If they are a gene that has minor effects eg pigmentation and not developmental

Question 32

What is a microsatellite?

Answer 32

→ An area that is repeated (many repeating base pairs)

Question 33

What are microsatellites also called?

Answer 33

→ Short tandem repeats

Question 34

What are microsatellites like across individuals?

Answer 34

→ Highly variable

Question 35

Why are microsatellites not biallelic?

Answer 35

→ they are multiallelic → Can be 10 or 12 different alleles → There can be more than 1 repeat it is not binary

Question 36

Describe the polymerase slippage model?

Answer 36

→ Polymeras slips and causes the new strand to unpair from the template → If the slip happens at a region that has many repeats it has many identical codons to reattach to → The new strand may reattach to the template at the wrong codon → It can reattach at a more distant point than it was attached to before → because of this the new strand forms a bubble of unpaired bases → The repair mechanisms open the bubble and replace the baes

Question 37

Where in the genome can microsatellites be found in?

Answer 37

→ Intronic - UTR → Intergenic → Exonic

Question 38

What type of disorder is Huntingtons?

Answer 38

→ Trinucleotide repeat expansion disorder

Question 39

What is a copy number variant?

Answer 39

→ Variation in the number of copies of the same gene between people

Question 40

What is the simplest type of copy number variant?

Answer 40

→ Presence or absence of a gene

Question 41

How many copies does a normal person have of a gene and why?

Answer 41

→ 2 | → there are a pair of homologous chromosomes and every locus should be diploid (mother and father)

Question 42

Describe non allelic homologous recombination in meiosis?

Answer 42

→ Sometimes chromosomes misalign → You can get sequence similarity between different parts of the chromosomes → When chromosomes align they look for sequence similarity → There can be deletion of one and a copy number change in the other

Question 43

Why are there some identical parts of genes in maternal and paternal chromosomes?

Answer 43

→ Viral or bacterial genomes that have been incorporated through evolution

Question 44

What % of the genome is a copy number variant?

Answer 44

→ 12%

Question 45

What is an example of a microdeletion disorder?

Answer 45

→ diGeorge syndrome

Question 46

List the types of genetic variants and their incidence

Answer 46

→ SNP - 17 million detected → Microsatellites - 3% → CNV - > 2000 identified

Question 47

What do common variants contribute to?

Answer 47

→ Personality → looks → sporting ability

Question 48

What are some diseases/trait associations that come from common variants?

Answer 48

``` → height → allergies → Haemochromatosis → diabetes → alzheimers → anxiety → Dyslexia → Memory → sexual desire → ageing → nicotine dependance ```

Question 49

What are the three possible effects of variants?

Answer 49

→ Beneficial → Pathogenic → Most are neutral

Question 50

What can variants be used for?

Answer 50

→ Markers to help find disease causing genes and mutations