Population Genetics (Taylor L3)

Question 0

Define polymorphism

Answer 0

a genetic variant (mutation) which is “common” (greater than or = 1%) in the population

Question 1

Give 3 classes of Genetic mutations, describe each and give their mechanisms

Answer 1

1. Genome Mutation - Affects the # of intact chroms in the cell, Chromosome missegregation
2. Chromosome Mutation - Alters the structure of individual chromosomes, Chromosome rearrangement
3. Gene Mutation - alters individual genes, Base pair mutation

Question 2

Define Founder effect

Answer 2

a high frequency of a mutant allele in a population founded by a small ancestral group when one or more of the original founders was a carrier of the mutant allele

Question 3

Define Genetic Drift

Answer 3

random fluctuation of allele frequencies, usually in small populations

Question 4

Define selection

Answer 4

active selection of favorable alleles over non-favorable alleles

Question 5

Define genetic Fitness

Answer 5

a measure of the chance that an allele will be transmitted to the next generation
scale is 0 to 1
measures reproductive success

Question 6

How does migration and gene flow work?

Answer 6

when two populations with different allele frequencies for a disorder mix (as in immigration) then allele frequencies can change.

alters the HW equilibrium estimates

Question 7

How do doctors affect the frequency of a mutant allele (in theory)?

Answer 7

If a medical care improves the reproductive fitness of a person with a disease, then the frequency of the mutation in the population may rise.

Question 8

Increase in allele frequencies for _________ diseases is usually slow while increases in allele frequencies for ____________ and ___________ diseases are usually higher (faster).

Answer 8

recessive

dominant and X-linked

Question 9

Of the three (genome, chromosome, gene) mutation types, which is the most common and what is its frequency in humans?

Answer 9

Genome mutations (chromosomal aneuploidy)

rate of 1 missegregation per 25-50 meiotic cell divisions

Question 10

What is the rate of chromosome mutations in the human population?

Answer 10

1 rearrangement per 1700 cell divisions

seems high, but usually not compatible with life

Question 11

Why would the rate of increase of recessive alleles be slower than dominant alleles and/or X-linked alleles?

Answer 11

Dominant alleles are always expressed when present (as are hemizygous X-linked alleles in males) and so are subject to selective forces.

Recessive alleles (in heterozygotes) are silent and not necessarily subject to selective forces. Exception is the heterozygote advantage.

Question 12

Describe the two main ways a DNA gene mutation can occur.

Answer 12

1. errors during replication

2. failure to repair DNA after introduction of a mutation (damage)

Question 13

It is estimated that between ________ and _______ nucleotides are damaged per human cell per day via spontaneous processes such as ____(list 5 causes)_____.

Answer 13

10,000 to 1,000,000

deamination, depuriation, demethylation
rxn with mutagens (natural or environmental)
ultraviolet or ionizing radiation

Question 14

What is a dynamic mutation?

Give two examples (from the text) that are a result of this type of mutation.

Answer 14

Expansion (amplification) of a repeat region of a gene during gametogenesis. Resulting expansion interferes with normal function (transcription or translation)

ex: 10 CAG repeats in exon 1 of HD gene expanded to 12 CAG repeats in the next generation.
ex: fragile X syndrome - CGG repeats in the 5’UTR of the FMR1 gene

Question 15

How does a dynamic mutation in the coding region of a gene interfere with gene expression?

Answer 15

Abnormal protein product.

Question 16

How does a dynamic mutation in the 5’UTR or 3’UTR region of a gene interfere with gene expression?

Answer 16

Interferes with transcription, mRNA production or translation

Question 17

Define mutation rate of a gene

Answer 17

number of new mutations per locus per generation

Question 18

Achondroplasya, has a relatively high mutation rate (1.4x10^-5 mutations per locus per generation). Why is this high mutation rate surprising / interesting?

Answer 18

The high mutation rate results almost exclusively from mutation at one particular nucleotide: Gly380Arg in a fibroblast growth factor receptor

In general, we expect high mutation rates in larger genes and at many different nucleotide positions

Question 19

methylated CpG repeats (islands) are often mutational ________.

Answer 19

hotspots

Question 20

Given a mutation rate of 10^-6 per locus per generation and 25,000 genes in the human genome we can calculate that 1 in _________ people will have a new mutation from either maternal or paternal germline.

Answer 20

1 in 40

Question 21

Why is it more likely that trisomies of chromosomes 13, 18, 21 and X are more likely to come from the maternal germline?

Answer 21

The primary oocyte is paused in meiosis I for many years. Nondisjunction (lack of ability to handle nondisj. or breakage of homologue linkages) is more likely the older the oocyte is.

Paternal gametogeneis occurs throughout the lifetime of the individual so all sperm are “new”.

Question 22

Give 4 diseases where mutations in the paternal germline is more common.

Answer 22

Cainosynostoses (Apert, Pfeiffer, Crouzon syndromes)
Achondroplasia
Apert syndrome
X-linked hemophilia B
Huntington disease (CAG expansions)

Question 23

As a male or female ages, contrast their increased risk of passing a mutation through the germline.

Answer 23

As females age, there is increased risk of nondisjunction in the mieosis I suspended oocytes.

As a male ages, there is increased risk of replication errors as spermatogonia undergo 20-25 mitotic divisions per year before entering their final meiosis to become spermatozoa.

Question 24

Take two individuals and grab a random 1000 bp sequence from homologous chromosomes. What is the expected number of bp differences?

Answer 24

1

Question 25

Take two individuals and grab a random bp sequence from two homologous protein coding regions. What is the expected variation rate?

Answer 25

1 bp per 2500

Question 26

Why might the protein coding regions of different individuals be more similar than a random (likely non-coding) region of the DNA?

Answer 26

It is likely that protein coding regions are under more tight scrutiny. Mutations with band phenotypic effects are more likely to be selected agains. Mutations that are silent (in the non-coding regions, for example) are less likely to be “corrected.”

Question 27

Differentiate between a polymorphism and a rare variant.

Answer 27

polymorphism: present in 1% or more of the population

rare variant: present in less than 1% of the population

Question 28

The assumptions of the Hardy-Weinberg Equlibrium

Answer 28

1. Large population with random matings (wrt locus in question)
2. Allele frequency remains constant
   a. no mutations,
   b. no selections, all individuals are equally capable of mating
   c. no immigration of new allele frequencies into the population

Question 29

What is positive selection for heterozygotes (the heterozygote advantage)?

Answer 29

pretty self explanatory…

Increased fitness of heterozygotes under certain environmental conditions.
Classic Example: resistance to malaria due to heterozygous for sickle cell mutation (as well as some other hemoglobinopathies)

Question 30

Give three examples (as presented in the text p. 201) of the Founder Effect.

Answer 30

1. Type I Tyrosinemia - Lac Saint Jean region of Quebec
2. Ellis-van Creveld syndrome - Old Order Amish populations
3. Choroideremia (X-linked degenerative eye disorder) - Finland
   Hyperornithinemia -Finland

Question 31

What is a balanced polymorphism?

Answer 31

Selective forces operate to both maintain a deleterious allele and to remove it from the gene pool so that the end result is that the disease sticks around in a large number of heterozygotes.

Question 32

NextGen sequencing as (to date) sequenced ___________ exomes representing ___% of the entire genome.

NextGen sequencing found _____________ single nucleotide variants.

Answer 32

2,440
1.3%

503,481