BSCI222 - After Exam 3 - Final

50% of final composed of this content.

Mendelian Traits are continuous or discontinuous?

Discontinuous (qualitative) traits because individual displays one phenotype or the other.

• Example: Green vs Yellow pea

What is quantitative genetics?

The study of traits that show continuous variation that are influenced by multiple genes and environmental factors.

Env Factors: Climate, living conditions

Continuous Variation

Traits that fall between 2 extremes on a spectrum.

“How the trait is distributed.”

• Additive genetic variation

• More genes that influence trait will have a stronger effect on the phenotype

Why are quantitative traits considered additive?

Traits are considered additive because each gene has a small contribution to the phenotype (Additive Genetic Variation). The environment can also affect phenotype.

Meristic Characters

Vary in whole numbers

• Number of pups in litter

• Number of fingers

Threshold Characteristics

Traits that only appear once a certain genetic/environmental level is reached

• Below the threshold → trait doesn’t show

• Above the threshold → trait appears

Examples:

Type 2 diabetes (genetic risk + lifestyle)

Polygenic inheritance can be explained by rules of ______________.

Mendelian genetics.

The number of genes involved can be estimated from the number of parental phenotypes observed.

In Polygenic inheritance, what happens to the parental phenotype in the offsprings when there are more genes involved?

When more genes are involved, the chances of offspring displaying parental phenotype decrease.

What does (1/4)ⁿ represent in a cross?

The proportion of offspring with the parents’ genes in the F2 hybrid cross. Where n is the number of genes.

Midparent value

Offspring phenotype in between parental phenotypes

Frequency Distribution

A representation showing how different trait values occur in a population

True or False: Sampling is used to estimate mean (average) and variance (spread).

True

Population sampling requires: (2 things)

Random Sampling: Uses a random sample to estimate the population

Large Sample Size

Standard Deviation

Used to measure how much values deviate from mean

Normal Distribution

Symmetrical bell-shaped curve where the mean is in the center and values are spread out on both sides equally

Correlation

Correlation Coefficient

Regresstion

Heritability

How much of the variation is due to genetics

Phenotypic Variance (V_P) is equal to

the total variation in a trait in the population (INCLUDES GENETIC + ENVIRONMENTAL VARIATION)

Genetic Variance (V_G)

Includes:

Variation due to genotype (3 types)

1. Additive Genetic Variance (V_A): Sum of effects of different alleles

2. Dominance Genetic Variance (VD): Dominant allele masks other allele (non-additive)

3. Gene Interaction Variance (V_I): Genetic variance resulting from one gene influencing another.

Additive Genetic Variance (V_A)

Phenotypic variance is explained by summing the effects of different alleles in a genotype.

• Explains codominant alleles

Dominance Genetic Variance (V_D)

Dominant allele masks other allele (non-additive)

Example:

• In heterozygotes: Aa (dom A masks the effect of rec a)

Gene Interaction Variance (V_I)

Genetic variance resulting from one gene influencing another.

Total Genetic Variance =

V_G = V_A + V_D + V_I

Environmental Variance (V_E)

Variation caused by environment

Gene-by-environment Interaction (V_GE)

Effect of a genotype on a trait changes depending on environment

What is broad-sense heritability? How can broad sense heritability be calculated?

Broad Sense Variability: How much variation due to genetics alone?

H₂ = V_G / V_P

• Use experiments to get V_G and V_E individually.

• V_P is usually given.

How can you estimate genetic variance? How can you estimate environmental variance?

Since V_P = V_G + V_E

Controlling Genetic Variance:

• Control the environment that sets V_E = 0. (SAME env for all)

• Same env for entire experiment.

Controlling Environmental Variance:

• Control genotypes by cloning ind or using twins or inbred lines

• Different environments for genotypes

What is Narrow Sense Heritability?

Narrow Sense Heritability: Variation in trait due to additive effects of alleles.

h₂ = V_A / V_P

What does Parent-Offspring regression analysis estimate?

Estimates narrow-sense heritability by plotting parent vs offspring phenotype.

Slope of h = 1 indicates offspring phenotype matches parent phenotype

Slope of h = 0 indicates trait is not heritable (variation due to environmental effects)

Explain how genome-wide association studies can be used to identify genes contributing to a quantitative trait. Explain Quantitative Trait Loci.

GWAS: Scans ind for SNPs

QTLs: Genomic regions that control variation of a quantitative trait.

GWAS identifies regions of the genome contributing to phenotypic variation, which can then be traced to specific genes influencing the quantitative trait.

Use information about selection pressure on phenotypic variation to calculate narrow sense heritability.

h² = R/S

Change in trait mean after one generation.

R = Response to selection

• Measures how much the offspring actually change

• Mean of offspring - Mean of original pop

S = Selection Pressure

• Measures how strong selection is on parents

• Mean of parents - Mean of original pop

Population Genetics

Study of allele and genotype frequencies in populations, and how or why they change over time

Allele frequency is _____.

Formula is ________.

What do p and q represent?

How common allele is

p = Freq of dominant allele

q = Freq of recessive allele

Genotype Frequency is _____.

Formula is ______.

How common a genotype combination is

True or False: If there are only two alleles, p + q = 1.

True

List the conditions for Hardy-Weinberg equilibrium. What are consequences of violating these assumptions?

Conditions:

Random mating, no migration, no selection, no mutation, very large population size.

• Allele frequencies (p + q) must remain constant

Consequence:

Any of the above (migration or mutation to new alleles) results in variation that changes allele frequencies.

What is the equation for genotype frequencies with two alleles? (Used for Hardy Weinberg Equilibrium)

p² + 2pq + q²

What indicates a population is in Hardy-Weinberg equilibrium?

Allele frequencies do not change over time (p and q).

Genotype frequencies do not change over time.

How can we test if a population deviates from the Hardy-Weinberg equilibrium?

Using the chi-square test for goodness of fit.

• Find p and q (allele freq)

• Use that to find genotype freq (p², q², 2pq)

• Multiply genotype freq by appropriate observed counts to get expected

• Use observed and expected to get chi square

Chi squared Formula

Degrees of Freedom

df= number of genotypes possibilities−number of alleles

How do you interpret chi-squared value to determine HWE?

Use critical value at p = 0.05

Chi-Square < critical value

• Population at HWE

• “Difference is NOT statistically significant”

  
  

Chi-Square > critical value

• Population not at HWE

• “Difference is statistically significant”

Non-Random Mating

Individuals do not choose mate randomly = bias in offspring

3 Types of Non-Random Mating

Assortative

Assortative: Preference for mates with similar traits

• Increases Homozygptes

• Decreases Heterozygotes

F= 1 (?????)

3 Types of Non-Random Mating

Disassortative

Disassortative: Preference for mates with different traits

• Increases Heterozygotes

• Decreases Homozygotes

F= -1 (?????)

3 Types of Non-Random Mating

Consanguineous Mating

Inbreeding (Of closely related individuals)

• Increases Homozygotes

• Increases the chance of inheriting a recessive deleterious allele (harmful allele)

Effect on Inbreeding Coefficient:

F= Greater than 0 (usually 0.25 for sibling-sibling mating)

Coefficient of Inbreeding (F) or Fixation Index.

F is the probability of 2 alleles coming from 1 common ancestor (shared by both parents)

F=1 (COMPLETELY INBRED, FOR MULTIPLE GENS, USUALLY THE CASE FOR CELL LINES)

Large F = Fast elimination of heterozygotes

Inbreeding Depression

Reduced fitness (survival and fertility) due to closely related individuals mating.

• Increases homozygotes

• Exposes recessive deleterious alleles (harmful alleles) ——> can be lethal

What is hybrid vigor?

Normal mating (genetically different individuals mate)

• Heterozygotes increase

• Homozygotes decrease

• Fitness increases because the deleterious recessive alleles are masked

Natural Selection

Environmental factors create a reproductive advantage of one genotype over another, creating a difference in fitness.

Directional Selection

Selection against one allele

Selection increases frequency of one homozygote relative to the other.

Disruptive Selection

Selection against heterozygotes increases homozygotes.

Stabilizing Selection

Selection favors heterozygotes, which decreases homozygotes.

Define Fitness (W).

What is the formula? What does W=1 indicate?

Relative measure of reproductive success for a genotype

“how good genotype is at reproducing”

W=1 BEST GENOTYPE

Define Selection Coefficient (s).

What is the equation?

How strongly selection acts against genotype (alleles)

“How much a genotype loses in fitness”

S= 1 - W

Genetic Drift

Small population size —> random fluctuation in allele frequency ——-> causes changes in genotype frequency

Founders Effect

New population establishes from small # of individuals —> alleles of new pop completely dependent on genotypes of ind that migrated

“When a small group breaks off from a larger population and starts a new population, the new group has allele frequencies that are just a random sample of the original population.”

Bottleneck Effect

Population size is drastically reduced (natural disaster), and many alleles are lost to chance. Causes less genetic diversity in the new population.

Recognize how migration and mutation can increase or maintain genetic variation in a population.

Migration = Alleles move into and out of populations (creates gene flow)—> increases genetic diversity

Mutation = Spontaneous (random) introduction of new alleles ———> Slowly increases genetic variation

• Mutations can be lethal, beneficial, or neutral

• Not strong driver of allele freq

Eukaryotic Cell Cycle

Comprised of:

1. Interphase: Cell grows, and DNA is replicated.

2. Mitosis: Forms identical daughter cells through division.

Identify the checkpoints in Eukaryotic Cell Cycle.

G1: Cell grows

• Each cell has one chromatid per chromosome.

• G1 CHECKPOINT:

S: DNA synthesis.

G2: Cell grows

• Each cell has two chromatids per chromosome.

How is Eukaryotic Cell Cycle regulated?

Checkpoint Proteins: prevent continuation if there is DNA damage.

Cyclins: Activate CDKs (cyclin level rises and falls)

Cyclin-Dependent Kinases (CDKs): CDKs phosphorylate proteins that activate M or S phase.

Cancer Cells

Have loss of cell regulation

Explain how loss of cell cycle regulation results in cancer.

Cancers fail to regulate the cell cycle:

1. Rapid Division

2. Lack Inhibition

Cancer Cell Developmental Stages:

What is a primary tumor? What is a secondary tumor (METASTASIS)?

Primary Tumors: Original region where cancer cells divide + replicate

Benign: Abnormal cells that divide continuously (non-cancerous)

(Metastasis) Secondary Tumor: Cancer cells invade other cells in other tissues (malignant).

Relate stages of cancer cell development to the multigene model.

Multigene Model: Several mutations accumulate over time in different genes to develop cancerous cells.

Causes of Somatic Cell Cancer: ________

Consequences of mutations in Somatic Cells: _______

Causes of Gametic Cell Cancer: ________

Consequences of mutations in Gametic Cells: _______

(*Use genetic predisposition)

Causes of Somatic Cell Cancer: Random (stochastic) damage occurs over time in somatic cells (body cells)

Consequences of mutations in Somatic Cells: Can lead to cell death, abnormal cells, or cancer (if multiple mutations occur in same cell)

Causes of Gametic Cell Cancer: Replication error in cell division

Consequences of mutations in Gametic Cells: Heritable mutations that will be found in offspring. Genetic predisposition for certain cancers, which increases risk in offspring due to genetic makeup.

Oncogene

Mutated genes that make cells divide excessively

(Promote cell division)

Proto-oncogene

A normal gene that controls cell regulation, growth, and division.

Explain different ways to get gain-of-function mutations in proto-oncogenes.

Gain-of-function mutations in proto-oncogenes create oncogenes.

3 Different Ways to get Gain-of-Function:

• Altered transcriptional regulation > too much protein

• Tandem duplications > too much protein

• Amino acid change > hyperactive protein

Define Tumor Suppressor Genes. What is the significance of a loss-of-function mutation?

Normally prevent advancement through the cell cycle if there is damage. (INHIBIT CELL DIVISION)

Loss-of-function mutations cause tumor suppressor genes to lose ability to control cell cycle

• = Rapid cell division of damaged cells = inc risk of cancer

Recognize different types of proteins that can act as oncogenes.

1. Growth factors: Signals that tell cells to grow and divide

2. Receptors: Receptor always on and continue dividing

3. Signaling proteins: Continuous division signal

4. Transcription factors: Turn on growth genes

5. Cell cycle activators: Cyclin, CDKs, uncontrolled division

Discuss how impaired epigenetic mechanisms, chromosomal rearrangements, and viral infection might contribute to cancer.

Epigenetic Gene Regulation: Can alter DNA Methylation and histone modification which leads to loss of cell cycle regulation

Chromosomal Alterations: Deletion, inversion, translocations.

• Deletions can remove tumor suppressor genes

Viral Infection: Viral DNA can integrate into host DNA, which can cause rapid cell division.