6. Normal Genetic Variation

Question 1

What can reduce diversity

Answer 1

Genetic bottlenecks

Question 2

What is a genetic bottleneck caused by

Answer 2

Speciation, migration, environment, disease

Reduction in population

Question 3

What promotes diversity

Answer 3

Mutation

Question 4

What is a mutagen

Answer 4

Agents that cause mutations eg, physical/ chemical

Question 5

How can UV light cause melanoma

Answer 5

Too much UV light = causes pyrimidine dimers to form = abnormalities in subsequent replication

Question 6

In what way do alkylating agents cause mutation

Answer 6

Transfer methyl/ ethyl to backbone phosphate = causes G to T

Question 7

How many base pairs do we all have

Answer 7

3 x 10^9

Question 8

What percent of human genome differs between people

Answer 8

0.1%

6 x 10^6 different base pairs

Question 9

Which genetic testing technique can show frequency of mutations

Answer 9

WGS

Question 10

What happens to the rate of germ line mutations with paternal age

Answer 10

Increases

Question 11

Where is a germ line mutation present

Answer 11

Egg or sperm = heritable = all cells affected in offspring

Question 12

Are somatic mutations inheritable and where do they occur

Answer 12

In non germ line tissues

Cannot be inherited

Question 13

What are the two types of origins of genetic variation and give examples fir each

Answer 13

• exogenous (eg, radiation, chemicals, mostly somatic)

- endogenous ( segregation/aneuploidys , recombination/trasnoclations, DNA replication errors, inadequate DNA repair

Question 14

What types of mutations dont alter teh DNA content

Answer 14

• Single nucleotide replacements

- balanced translocations/ inversions

Question 15

What percentage of our DNA is poorly conserved

Answer 15

90%

Small DNA changes don’t always result in an obvious effect on phenotype

Question 16

What is a SNP

Answer 16

Single nucleotide polymorphism = if a single nucleotide variation occurs in more than 1 % of population

Question 17

What is the most common SNP

Answer 17

C —> T

Question 18

Indel meaning

Answer 18

Insertion or deletion of one or more nucleotides

Question 19

What is a CNV

Answer 19

Large indels

Changes in copy number of sequences greater than 100 in length

Question 20

Are silent variations of SNPs more common

Answer 20

Yes

Question 21

What is minor allele frequency- MAF

Answer 21

The frequency of the less common variant in a population (of a SNP)

Question 22

What % of all human genome variation do SNPs make up

Answer 22

90%

Question 23

What is a diallelic SNP

Answer 23

When the base can change to one other base eg:

C —> T

Question 24

What is a triallleic SNP

Answer 24

When the base can change to two other bases eg,

C—> A or T

Question 25

What are Intronic/ intergenic variants

Answer 25

- Variants that occur between genes/ exons | - dont affect protein directly

Question 26

Why can intronic variantions still be bad

Answer 26

Can affect the regulation of transcription/ splicing

Question 27

What are three types of coding ‘extronic’ variants

Answer 27

- missense = nonsynmous = a.a change - nonsense = stop= change of a.a to stop codon = leads to truncation of protein - silent = synonymous = codon for a.a is changed but some same a.a still coded for, eg: GGC = Glycine and GGU = Glycine

Question 28

Which type of mutation leads to truncation of protein

Answer 28

Nonsense

Question 29

Which type of protein leads to the same amino acid being coded for

Answer 29

Silent

Question 30

What are SSRs

Answer 30

Simple repeat sequences/ micro satellites = repeated region of DNA = occur at thousands of locations on the gene - unstable, prone to replication slippage

Question 31

What is genetic anticipation

Answer 31

When the repeat length of variant in a gene can increase in meiosis so the longer sequence is passed onto child = earlier onset in child

Question 32

What is microsatelltie DNA

Answer 32

A tract of repetitive DNA motifs are repeated, about 5 to 50 times

Question 33

Give 3 examples of a disease which is subject to genetic anticipation

Answer 33

Huntington’s disease Fragile X syndrome Spinocerebellar ataxia = progressive, degenerative involving loss of full control of bodily movements

Question 34

What does the CNV map show

Answer 34

Documents teh extent and characteristics of CNV among healthy populations

Question 35

Which regions of a chromosome show a particularly high rate of CNV variation

Answer 35

- pericentromeric (near/ on each side of the centromere) | - subtelomeric (segments of DNA between telomeric caps and chromatin)

Question 36

Which genes are the least affected by CNVs

Answer 36

Genes that are associated with disease

Question 37

How many genes can be comepletly removed from the genome without producing apparent phenotypic consequences

Answer 37

More than 100

Question 38

Give an example of cells where CNVs are enriched n why

Answer 38

In cells involved in immune response - need to be diverse to respond to different pathogens etc

Question 39

What a percentage of teh human genome isn’t functionally restrained n generally permissive of variation

Answer 39

90%

Question 40

What are deleterious mutations eliminated by

Answer 40

Natural selection | Eg, mutations that compromise early dev/ neonatal health wont persist in population

Question 41

What is postive selection of CNVs

Answer 41

When a beneficial adaptation spreads

Question 42

What does teh human AMY1A gene code for n how is it an example of postive selection of CNVs

Answer 42

- codes for salivary amylase which hydrolyses starch - people in populations with high starch diets have more copies of this AMY1A gene = spread as human diets became increasingly rich in insoluble starch

Question 43

What % of human genetic variation is found within populations

Answer 43

85 to 90%

Question 44

What % of human genetic variation is found between populations

Answer 44

Only 10 to 15%