Clinical Genetics Exam 2 PP 4 (Population Genetics)

Mutation Gene flow/migration Non-random mating Genetic drift Natural selection

5 factors that can alter allele frequencies

founder effect

A ___ occurs when a new colony is started by a few members of the original population.

There are 40 total alleles in the 20 people of which 2 alleles are for Tay Sachs. So, 2/40 = .05 (5%) of the alleles are for Tay Sachs. That represents p. Thus, tt or p2 = (.05)2 = 0.0025 or 0.25% of the F1 population will be born with Tay Sachs

After graduation, you and 19 of your closest friends (let's say 10 males and 10 females) charter a boat to go on a three-hour tour. Unfortunately, you crash (safely) on a deserted island. No one finds you and you start a new population totally isolated from the rest of the world. Two of your friends are Cajun and carry (i.e. are heterozygous for) the recessive Tay Sachs allele (t). Assuming that the frequency of this allele does not change as the population grows, what will be the incidence of Tay Sachs on your island?

gene (flow) migration

Any movement of genes from one population to another.

bottleneck

Because genetic drift acts more quickly to reduce genetic variation in small populations, undergoing a ___ can reduce a population's genetic variation by a lot, even if the ___ doesn't last for very many generations.

copy number variants

CNV stands for

single nucleotide polymorphisms

Cataloged in the HapMap database

specific diseases

Characterization of SNPs may help in identifying subsets of individuals at risk for _____

carriers in the population is much larger than the number of homozygous affected individuals

For rare recessive diseases, the number of _______ in the population is much larger than the number of _______

larger

For rare recessive diseases, the number of carriers in the population is much ___ than the number of homozygous affected individuals

- mutation - gene flow - genetic drift - nonrandom mating - natural selection

Forces that can lead to evolutionary change, creating circumstances in which the Hardy-Weinberg law may fail to apply. what are the 5?

copy number variants

Genes that were thought to always occur in two copies per genome have now been found to sometimes be present in one, three, or more than three copies.

observable traits

Genome-wide association studies look for variation across the entire human genome in order to identify genetic associations with ______ (such as blood pressure or weight)

evolution

Hardy-Weinberg equilibrium is only an ideal situation because ______ is always occurring within populations

heterozygotes

However, individuals with the heterozygous condition (Ss) have some sickling of red blood cells, but generally not enough to cause mortality. In addition, malaria cannot survive well within these "partially defective" red blood cells. Thus, ___ tend to survive better than either of the homozygous conditions.

9% =.09 = ss = q2. To find q, simply take the square root of 0.09 to get 0.3. Since p = 1 - 0.3, then p must equal 0.7. 2pq = 2 (0.7 x 0.3) = 0.42 Therefore, 42% of the population are heterozygotes (carriers)

If 9% of an African population is born with a severe form of sickle-cell anemia (ss), what percentage of the population will be more resistant to malaria because they are heterozygous (Ss) for the sickle-cell gene?

42%

If 9% of an African population is born with a severe form of sickle-cell anemia (ss), what percentage of the population will be more resistant to malaria because they are heterozygous (Ss) for the sickle-cell gene?

genetic balance

If all of the assumptions are correct, then the population is in __ aka Hardy Weinberg equilibrium

genetic variation

If genes are carried to a population where those genes previously did not exist, gene flow can be a very important source of _______

gene copy number (CNV)

In 2004, researchers published findings that showed large-scale variations in ______ were common and occurred in hundreds of places in the human genome

Single base pair polymorphisms

SNPs are ____

drug responses/adverse reactions

SNPs may predict ____

Spread throughout the genome Spaced about 1,000 bases apart

SNPs spread throughout the ________ and are spaced about _______ bases apart

hemoglobin

Sickle-cell anemia is a genetic disease caused by a mutation in the ___ gene that may provide a survival advantage.

PCR

The normal allele on the CCR5 gene can be distinguished from the 32bp deletion using _____

stratification

When a population has subgroups that are relatively genetically separate

stratification

When mate selection is restricted to members of a particular subgroup, that results in excess homozygotes

assortative mating

When the choice of mate is made based on possessing a particular trait.

basic biological proceses

Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of ___ affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine.

- basic biological processes affecting human health - improvement in the prediction of disease and patient care - the realization of the promise of personalized medicine

Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of: - basic _______ affecting human health - improvement in the _____ of disease and patient care - the realization of the promise of ________

genetic drift

___ affects the genetic makeup of the population but through an entirely random process.

environmental influences

___ can select for or against a phenotype

SNPs

___ may eventually be diagnostic of disease risk

population bottlenecks

_____ occur when a population's size is reduced for at least one generation.

gene migration

______ includes lots of different kinds of events, such as people moving to new cities or countries.

32bp deletion

a ________ in the CCR5 gene results in in nonfunctional protein

- reduced genetic variation from the original population. - a non-random sample of the genes in the original population.

a small population size produced from a founder effect means that the colony may have: - reduced _______ from the original population. - a _____ sample of the genes in the original population.

- mutant allele= DCCR - normal allele = CCR5 - heterozygote= DCCR/CCR

abbreviation on the CCR5 gene for: - the mutant allele - the normal allele - the heterozygote

adaptations

although genetic drift is a mechanism of evolution, it doesn't work to produce _____

?

cases vs controls?

homozygous for a deleterious recessive gene

consanguity and inbreeding have a higher risk of producing offspring that are _______ for a _____ gene

homozygotes

consanguity and inbreeding increases the proportion of _________

polygenic or multifactorial disease or birth defect

consanguity and inbreeding may produce offspring with increased susceptibility for ______ or ______ disease or birth defect

genetic diversity and susceptibility to certain diseases

copy number variants are suspected to underlie _____ and ______ to certain diseases

- Human populations do NOT randomly *mate* - Human populations are large but often distributed in *small groups* - Human populations have *mutations* and frequently new mutations - Human populations are highly *mobile* and introduce new *alleles* - Human populations are under a variety of *natural selection* stressors (malaria, HIV, etc)

exceptions to H-W: - Human populations do NOT randomly _____ - Human populations are large, but often distributed in _______ - Human populations have _____ and frequently new ones - Human populations are highly _____ and introduce new _______ - Human populations are under a variety of n______ stressors

natural selection

genetic drift affects the genetic makeup of the population but, unlike _____, through an entirely random process.

- interaction with environment (development and epigenetic) - interaction with environment competition (selection and evolution)

genotype --> interaction with _______ --> phenotype --> interaction with ________ --> new population

Hardy Weinberg in Autosomal Recessive Disease

hardy Weinberg in _________ diseases can be used to help estimate the frequency of *carriers* in a population

*carriers*

hardy Weinberg in autosomal recessive diseases can be used to help estimate the frequency of ______ in a population

p+q=1 OR p^2 + 2pq + q^2

how do we calculate the frequency of CCR5 genotypes within a population?

Tendency to choose partners with similar medical problems, such as dwarfism and deafness

in assortative mating there is a tendency to choose partners based on what?

what to what would be predicted

in stratification, there is also a deficiency of heterozygotes compared with...

non random

large populations often have _______ matings

frequency of three genotypes

p+q=1 or p2 + 2pq + q2

one generation.

population bottlenecks occur when a population's size is reduced for at least ...

how different disease genes are more common in different populations

population genetics Is the basis for understanding what?

frequency

population genetics looks at how the ________ of genes is maintained or changes

statistical distribution

population genetics looks at the ___________ of genes in a particular population

experimental gene therapy

some ________ plan to mimic the 32 bp deletion in the CCR5 gene in AIDS patients

homozygotes

stratification is when mate selection is restricted to members of a particular subgroup, that results in excess _______

1 - random mating 2- a large population size 3 - no mutations 4- no new alleles are introduced/lost 5 - no natural selection.

the H-W theorem states that allelic frequencies will remain constant if what 5 assumptions are true?

the allele frequencies p and q remain constant

the hardy Weinberg equation means that: population genotype frequencies from generation to generation will remain constant (at equilibrium) if ....

CCR5

this gene encodes a cell surface cytokine receptor which is the entry point for HIV

- malaria - HIV

what are some examples of natural selection stressors that human populations are under?

- stratification - assortive matings - consanguinity and inbreeding

what are the 3 different types of non random matings?

or rare recessive traits (q2 < 0.0001), p approximates 1 2pq is approximately 2q (twice the frequency of the mutant allele)

what does the p equal in hardy Weinberg for RARE recessive traits? 2pq?

Homozygotes for the mutation do not have the receptor and are resistant to HIV infection

what happens to homozygotes for the 32 bp deletion (mutation) on the CCR5 gene?

(NF1 has 50% new mutation rate)

what is an example of a frequently new mutation that human populations have, which is an exception to H-W equilibrium

amish in Ohio originated from 10 families

what is an example of founder effect?

generating the frequency of carriers within a given population

what is one of the most important medical applications of hardy Weinberg?

the size of the gene pool is twice the number of individuals in the population because each genotype consists of two alleles

what is the frequency of CCR5 For an autosomal locus?

p^2 (AA) + 2pq (Aa) + q^2 (aa) = 1

what is the hardy Weinberg equation

autosomal recessive

what type of inheritance is the CCR5 32 bp deletion?

bottleneck effect

when a chance event greatly reduces the size of a population. the surviving individuals have allele frequencies different from those of the original population so they generate a new population with a strong dominance of the new alleles

disease-causing alleles

when using the hardy Weinberg equation in autosomal recessive diseases: - Usually put all ______ together (whether compound, heterozygotes, or homozygotes)

affected = q^2

when using the hardy Weinberg equation in autosomal recessive diseases: Start with the frequency of?

q= 0.6 p + q= 1 1- 0.6= .40 so 40%

you have sampled a population in which you know the percentage of homozygous recessive genotype (aa) is 36%. calculate the frequency of the "A"

the frequency of aa is 36%, which means that q^2= 0.36. this means q= 0.6 q= frequency of the allele so the frequency is 60%

you have sampled a population in which you know the percentage of homozygous recessive genotype (aa) is 36%. calculate the frequency of the "a"

Aa= 2pq 2pq= 2x 0.4 (p) x 0.6 (q) = 0.48 or 48%

you have sampled a population in which you know the percentage of homozygous recessive genotype (aa) is 36%. calculate the genotype of Aa (carriers)

36%

you have sampled a population in which you know the percentage of homozygous recessive genotype (aa) is 36%. using that 36%, calculate the frequency of the aa genotype