Midterm Flashcards
Law of Equal Segregation
During production of gametes, each allele gets equally partitioned between egg/sperm.
Law of Independent Assortment
Alleles on different chromosomes assort independently at meiosis
Exceptions to Law of Equal Segregation
Complex Traits
Exceptions to Law of Independent Assortment
Linked Genes, Alleles far apart on same chromosomes
Prophase
- DNA condenses
- spindle forms
Prometaphase
- nuclear envelope disintegrates
- some microtubules bind to kinetochors
Metaphase
- chromosomes line up on metaphase plate
Anaphase
- sister chromatids get pulled back
Telophase
- nucleus reforms
- cleavage furrow forms
- cytokenesis
Cross-over happens when?
Prophase 1
When does independent assortment happen?
Metaphase 1
Bivalent
pair of synapsed dyads
Dyad
pair of sister chromatids
Tetrad
four chromatids making up bivalent
Consanguinity
incest
Dominant Trait Pedigree Analysis
- seen every generation
- affected offspring => affected parents
- 50% of heterozygote children are affected
- unaffected does not transmit trait
Recessive Trait Pedigree Analysis
- skips generations
- 25% of heterozygote children affected
SRY Gene
gene on Y chromosome determining male characteristics
pseudoautosomal regions
homologous regions on both X and Y chromosomes (near telomeres) allowing pairing in meiosis
sex determination in mammals vs Drosophila
Mammals: determined by having Y chromosome
Drosophila: determined by ratio of X chromosomes
Kleinfelter syndrome
XXY (male)
Turner Syndrome
X0 (female)
Gene Dosage in humans vs Drosophila
Mammals: X chromosome disactivation during embryogenesis
Drosophila: single X chromosome gene is hyperactivated
X Linked Recessive Pedigree Analysis
- usually males affected
- affected sons usually born from carrier mothers
- skips generations
- 50% of sons of heterozygous mothers are affected
- never passed from father to son (zig-zag inheritance)
- all daughters of affected fathers are carriers
Loss of function mutant allele
- aka null allele
- produces protein which is non-functional
Haplo-sufficiency
- one functional copy is enough to produce phenotype
- mutation is recessive
Haplo-insufficiency
- one functional copy is not enough to produce phenotype
- mutation is dominant
Dominant negative
- mutation that impedes the nonmutant protein
- usually seen in dimers
- effect is that mutation is dominant
Gain of function mutant allele
- aka hyperactive
- produces protein which has much greater effect than non-mutant allele
Incomplete Dominance
- type of haplo-insufficiency
- intermediate phenotype in heterozygotes
Codominance
- heterozygotes have two different simultaneous traits
Allelic series
- more than 2 alleles
- can have complex dominance relationship
Pleiotropy
- gene affecting multiple traits
- can be upstream of many processes
Recessive lethal
Dies before being able to reproduce, or in utero
Penetrance
presence or absence of phenotype
Expressivity
strength or variability of phenotype
Gene Modifiers
genes that affect expressivity or penetrance of another gene
Genetic Dissection
Using mutants to investigate biological processes
Genetic Screen
Looking through natural or mutagenized population to identify mutant phenotypes
Mutant Analysis Overview
- dominant or recessive?
- check phenotype of F1 of two inbred lines
- how many genes are affected in each mutant?
- check distribution of F2 phenotypes (ex: 3:1, 9:3:3:1)
- how many genes have I isolated in my screen?
- complementation test
- how do the genes interact with each-other to give wild type?
- double mutant analysis
Complementation Test
test for allelism
- mutant x mutant
- mutant phenotype => same gene (alleles of each-other)
- wild type phenotype => different gene
Complementation Group
- contains mutants that don’t complement each-other
- group === alleles of a particular gene
Double Mutant Analysis
- analyses interaction between two genes
- look at F1 x F1 = F2 cross from complementation test
Possibilities: - Additive: 9:3:3:1
- Complementarity: 9:7
- Epistasis (dominant): 12:3:1
- Epistasis (recessive): 9:3:4
Additive Gene Action
Genes working independently on same trait (9:3:3:1 on F2)
Complementary Gene Action
Need both genes to get trait (9:7 ratio)
Epistasis
A mutation masks another (double mutant looks same as one other)
- Recessive (9:3:4)
- Dominant (12:3:1)
Possible Complementary Gene Action Mechanisms
Linear pathway, Parallel Pathway, Regulatory Pathway
Recombination
Production of new combination of alleles of different genes by meiosis
Independent Assortment meaning for recombination
Same amount of parental and recombinant gametes
Degree of Linkage
- when genes are close together on same chromosome, parental alleles tend to stay together
- consequence is more parental gametes (skewed 9:3:3:1 ratio)
Prophase 1 Recombination
Pairs of homologous chromosomes synapse, causing crossing-over events
- only way to get recombinant gametes for genes on same chromosome
Evaluating Degree of Linkage
Test Cross AB/ab x ab/ab
- calculate recombinant frequency (RF)
Recombinant Frequency
# recombinants / # total offspring RF of 50% is unlinked, <50% is linked
Gene Mapping Units
cM (centimorgans) or m.u. (map units)
- proportional but not equal to physical distance
Population Genetics
Studying why populations:
- differ (allele frequency)
- change over time
Forces affecting Populations
- mutations
- selection
- migration
- genetic drift
Types of Genetic Variation
- SNP
- indel (insert, delete)
- microsatellite (# repeats)
Haplotype
DNA sequence for section of chromosome
- used to classify
- can be organized phylogenetically
Genotype Pool
frequency of genotypes of an allele
Gamete Pool
frequency of an individual allele
Calculating allele frequency
p = Fmm + 1/2Fmn q = Fnn + 1/2Fmn
Hardy-Weinberg Conditions
random mating no selection no migration no mutation infinitely large population
Hardy-Weinberg Proportions
Freq(AA) = p^2 Freq(Aa) = 2pq Freq(aa) = q^2
Hardy-Weinberg Theory
When HW conditions hold, allele frequency stays the same after X generations
Inbreeding Consequences
increases frequency of homozygotes
lowering of population’s fitness
increase change of inheriting recessive disorders
HW Proportions with Inbreeding
Freq(AA) = p^2 + pqF Freq(Aa) = 2pq(1 - F) Freq(aa) = q^2 + pqF
Inbreeding Coefficient
probability that two alleles inherited by an individual are identical by descent
F = (1/2)^2 (1 + Fa)
(assumption is full sib mating, for half sib, divide by two)
Fa is prob that ancestor is identical by descent
Inbreeding Depression Factor
Increased chance of inheriting a recessive disorder
(q^2 + pqF)/q^2
Mutation Rate in Population
very slow
10^9 mutation/bp/generation in humans, much higher if whole gene is considered
Genetic Drift
When population is small or fragmented (population bottleneck), random chance causing drastic loss of genetic variation in a population
Population Bottleneck
Quick reduction or fragmentation of population
Probability of allele fixation
P^(2N)
Natural Selection
- Directional shift in allele frequency due to environment conditions
- Can be rapid
- Works by favouring higher relative fitness
Relative Fitness
fitness compared to max absolute fitness
Selection Coefficient
aka “s”
difference between relative fitness and 1
Balancing Selection
Happens when heterozygotes are favoured
- consequence is balancing of alleles until equilibrium
WAA = 1 - s1 WAa = 1 Waa = 1 - s2 Freq(AA) = s1 / (s1 + s2)
Balancing Mutation Rate against Natural Selection
u = mutation rate
q^2 = u/s
(q at equilibrium)
Multifactorial Hypothesis Conditions
Complex traits caused by:
- several loci
- no dominance effects
- how environment reacts with genotype
Meristic Trait
based on a count of something (hairs, bristles)
Threshold Trait
how liable you are to develop a certain disease/condition
Statistical Formulas
Mean = 1/n (Sum of Xs)
Variance, Vx = 1/n (Sum of Xs - X)^2
Covariance, COVxy = 1/n (Sum of (Xi - X)(Yi - Y))
Correlation, Rxy = COVxy = Sqrt(VxVy)
Multifactorial Hypothesis Formulas
Xi = Mean(X) + g + e g = genetic deviation e = environmental deviation
Vx = Vg + Ve
Multifactorial Model
- Make two inbred lines
- Calculation variation in two lines (Ve)
- Make F2 generation
- Calculation variation of F2 (Vx)
Broad Sense Heritability
Proportion of phenotype variability due to genetics
Value depends on the experimental setup (inbred lines, environments chosen, etc)
H^2 = Vg/Vx (0 to 1, dimensionless)
Twin Studies
Used to get heritability estimates for humans
Need to separate at birth
Calculate correlation between traits:
H^2 = COVx’x’’ / Vx
Narrow Sense Heritability
Measure of degree which an individual’s genetics determines phenotype of offspring (additive effects)
Vg = Va + Vd h^2 = Va / Vx
Breeder’s Equation
Do selection experiment
S = difference between population and selection means
R = difference between old and new populations
h^2 = R / S
QLT Mapping
Using genetic markers to find QLTs in genome
- ex: SNPs, minisatellites, other known loci
- start with two inbred lines (P1, P2)
- make F1 hybrid line
- background F1 with P1 (BC1)
- examine BC1 trait and market phenotypes
Compare trait values across recombinant classes, find correlation between markers and traits
Lod score
Higher means better likelihood of nearby QTL
Genome-Wide Association Studies
GWAS
Using data from large populations to find QTLs, relying on natural meiosis
