Genetic Variations in Individuals and Populations

Question 1

What is the difference between a genome mutation and a chromosome mutation?

Answer 1

Genome mutations involve chromosome misaggragation (for example: Aneuploidy) resulting in abnormal numbers of chromosomes

Chromosome mutations are smaller scale mutations due to errors in rearangements (for example: translocation)

Question 2

Translate m.8393C>T into laymans terms

Answer 2

A point mutation on mitochondrial DNA base number 8393 occured in which a C was converted into a T

Question 3

Translate c.1257_1261delACGTC into layman’s terms

Answer 3

A deletion of bases 1257 to 1261 (sequence: ACGTC) occured on cDNA

Question 4

What does IVS stand for ?

Answer 4

Intervening sequence

Question 5

What parameters impact the likelihood that a germline mutation will occur?

Answer 5

Gene size (larger genes, greater risk)

Presence of CG sequences

Mutation phenotype

Parental age

Parental gender

Question 6

Why is there an increased risk for nondisjunction in the germline with age of a female?

Answer 6

The oocytes are sitting from puberty until fertilization, so with more time there is a greater risk for an abnormal crossing over event to occur.

Question 7

Which meiotic division contributes a greater percentage of the total germline mutations in females?

Answer 7

The first meiotic division

Nondisjunction during meiosis I results in 4 gametes with abnormal number of chromosomes (2 with n+1 and 2 with n-1)

Question 8

What type of mutation is most common in male germline production?

Answer 8

Replication errors

Question 9

What are polymorphisms?

Answer 9

Variant sequences that occur in more than 1% of the population

Question 10

What is the difference btween a STRP indel and a VNTR indel?

Answer 10

STRP indel = short tandem repeat polymorphism, 5-25 copies of a 2-3 nucleotide repeat

VNTR indel = variable number tandem repeat sequence, up to 1000s of copies of a 10-100 nucleotide tandem repeat

Question 11

What are microsatellites and why are they useful for identifying individuals?

Answer 11

Microsatellite markers are stretches of DNA containing tandem repeats of 2, 3, or 4 (STRPs)

Different people have different number of repeats, so they can be used for forensic purposes

Question 12

What are minisatellites?

Answer 12

Multiple copies of DNA sequences of 10-100 basepairs present in tandem

Larger segments than microsatellites. Difficult to detect with PCR.

Question 13

What are the different possible blood types?

Answer 13

O, A, B and AB

Question 14

How do the sugars attached to galactose in the H-protein oligosaccharide differ between blood types?

Answer 14

O: none

A: N-acetylgalactosamine

B: Galactose

AB: both types are present

Question 15

How do antibodies in serum differ between individuals with different blood types?

Answer 15

O type: anti-A and anti-B

A type: anti-B

B type: anti-A

AB: no antibodies

Question 16

Which blood type is considered universal donors? Universal recipients?

Answer 16

O is universal donors (no sugars present)

AB is universal recipients (no antibodies present)

Question 17

What is the rhesus factor?

Answer 17

RhD is found on the surface of red blood cells

Mutations are inherited as an autosomal recessive trait

Rh+ individuals do have the D antigen on their RBCs, wheras Rh- individuals do not.

Rh- individuals have antibodies agains Rh+ red blood cells, which can be problematic in Rh- mothers carrying Rh+ children

Question 18

Where are the MHC genes found?

Answer 18

In a gene rich region on chromosome 6p

Question 19

Why is the variability in the MHC gene problematic for transplantation?

Answer 19

Because there are so many different possible genes, it is very difficult to find a match between donor and recipient

Question 20

What is the role of MHC class I?

Answer 20

It presents intracellular proteins including viral proteins

These proteins are degraded and presented to HLA I molecules in the endoplasmic reticulum, they are then expresed on the cell surface and if the presented protein is considered foreign, an immune response would be triggered

Question 21

What is the role of MHC class II?

Answer 21

Extracellular proteins and bacteria can be taken up and presented on MHC class II

Professional antigen presenting cells express MHC II on their surface, help immune system to detect when foreign protein is present extracellularly

Question 22

What is a haplotype?

Answer 22

A group of alleles in coupling at closely linked loci that are inherited as a unit

Because of the proximity of genes, there is a very low chance that a cross over event will separate them.

Example: MHC genes

Question 23

What are the odds that a sibling will inherit the same two copies of MHC genes?

Answer 23

1/4

Simple mendellian genetics, group of MHC genes are inherited as a haplotype

Question 24

What is the Hardy-Weinberg equilibrium equation?

Answer 24

Estimates the genotype frequencies from allele frequencies and vice versa

p² + 2pq + q² = 1

Question 25

Assuming brown eyes are dominant over blue eyes, in a population of 200 people, 168 have brown eyes.

What is the value of p? q?

Answer 25

Blue eyed people are homozygous recessive (q²), q = sqrt((200-168)/200) = sqrt(0.16) = 0.4

p+q = 1, so p = 0.6

Question 26

For an X-linked disease, how is the incidence of disase among males calculated?

Answer 26

The incidence of disease among males equals q because males only have 1 X chromosome

Males with the gene will all have the disease

Question 27

What are the exceptions to the Hardy-Weinberg equilibrium?

Answer 27

Genetic drift

Founder effect

Reduced fitness

Question 28

What are the assumptions for meeting Hardy-Weinberg equilibrium?

Answer 28

Large population: not influenced by chance fluctuations

Random mating: no preference based on phenotype similarities

No mutation: no conversion of P allele to Q allele

No selection: all genotypes are equally capable of mating and producing offspring

Question 29

What can compensate for reduced fitness to lead to population equilibrium?

Answer 29

The new mutation rate can compensate for reduced fitness

M=sq, where M=mutation rate, s= selection coefficient = 1-f