population genetics exam 3

1st key point for natural selection

individuals of a species exhibit variations in genotype/phenotype

2nd key point for natural selection

many of these variations are heritable and passed to offspring

3rd key point for natural selection

organisms reproduce in exponential fashion (more offspring is produced than can survive and reproduce)

4th key point for natural selection

organisms that have a certain genotype phenotype are more likely to survive and reproduce

natural selection is more effective in shifting allele frequencies in

large populations

fitness (w) measures

individual’s ability to contribute genetic material to future generations (probability of survival and reproduction)

absolute fitness of a genotype measures

the proportional change for each genotype (survivability)

calculation for absolute fitness

survivors / original # at birth

relative fitness of a genotype measures

the probability of survival compared to another genotype (one genotype would be the standard and equal to 1)

calculation for relative fitness

absolute fitness / highest absolute fitness

percentage of surviving genotypes

p²w_AA

2pqw_Aa

q²w_aa

the total percentage of surviving offspring is also called the

mean fitness (w-bar)

mean fitness equation

p²w_AA + 2pqw_Aa + q²w_aa

normalized genotype frequencies for AA

p²w_AA / w-bar

normalized genotype frequencies for Aa

2pqw_Aa / w-bar

normalized genotype frequencies for aa

q²w_aa / w-bar

the selection coefficient measures

the selective pressures against a genotype

equation for selection coefficient (s)

1 - w

directional selection - effects on quantitative traits

genotype conferring to phenotypic extremes are selected

results in a change in population mean over time

common in plant and animal breeding

occurs in nature as a result of change in environment

only moves in one direction or another

directional selection - effects on discrete traits

occurs when one allele or trait is favored over another

with no other acting force, favored all will become fixed

will reach equilibrium (no change in allele frequency from one generation to the next) when the more fit allele fixes in the population

stabilizing/balancing selection - effects on quantitative traits

intermediate phenotypes are favored

both extreme phenotypes are selected against

will reduce the population variance over time but not the mean

stabilizing selection acts to keep a population well adapted to its envrionment

stabilizing/balancing selection - effects on discrete traits

occurs in the case of overdominance

the fitness of the heterozygotes is higher than the two homozygotes (heterozygote advantage)

population with some heterozygotes always have a larger mean fitness than homozygotes

to maintain a certain percentage of heterozygotes, both alleles must be present, which will tend to an equilibrium with a p between 0-1

disruptive selection - effects on quantitative traits

both phenotypic extremes are selected for

intermediates are selected against

will result in a population with an increasingly bimodal distribution for the trait

opposite of stabilizing selection

disruptive selection - effects on discrete traits

occurs when there is underdominance

heterozygote is less fit than two homozygotes (heterozygote disadvantage)

leads to unstable equlibrium

the BLANK explains why many chromosomes carry rare mutations that slightly reduce fitness in heterozygotes and are strongly deleterious or even lethal when homozygotes

mutation-selection balance

DNA profiling is an

approach used by forensic scientists to distinguish between individuals of the same species based on their DNA (AKA DNA fingerprinting and typing)

who invented DNA fingerprinting in 1984 using VNTRs

Sir Alec Jeffreys

ways Jeffreys’ approach was different from today:

used a multi-locus VNTR

southern blotting, not PCR

required large quantities of DNA

minisatellite/VNTRs

repeated sequence contains 6-100 bp

microsatellite/STRs

repeated sequence contains 1-5bp

the genotype of a person for each locus is shown as

the number of repeat units he/she carries

homozygous genotype

(7,7)

heterozygous genotype

(6,8)

parts of PCR-based DNA profiling

relies upon PCR amplification of short tandem repeats (STRs)

at least 20 STRs used to generate a DNA profile

single PCR reaction with a multiple fluorescently labeled primers

can obtain a DNA profile from minute quantities of DNA

PCRs amplifies DNA exponentially

gel electrophoresis

separates DNA fragments by size

DNA loaded onto a porous gel

electrical current passed through gel

shorter strands move quicker than larger strains

gel strained with DNA binding dye

capillary electrophoresis

glass capillary tubes filled with a gel matrix

advantages of capillary electrophoresis

higher resolving power

higher throughput

faster separation

automation & online detection

amelogenin gene occurs on both the

X and Y chromosome (X will be shorter)

amelogenin enables the X and Y amplicons to be

distinguished from one another

advantages of STRs

100,000 STRs identified in human genome

multiple alleles & individuals are highly heterozygous (high power of discrimination)

tetra- or pentanucleotides

found in different chromosomes or far enough apart that they are in linkage equilibrium

small size 100-400bp (good for PCR)

relatively low mutation rates

nut under selective pressure

can be co-amplfied/multiplexed

identification only

importance of HW equilibrium

allele frequencies & genotype frequencies can be estimated from population data

stable allele frequencies allows allele frequency databases to be developed

these can be used to calculate how common or rare a DNA profile is

important legal implicationsim

importance of linkage equilibrium

linkage equilibrium means that loci are inherited independently of each other

when 2 events are independent, the probability of both events happening together is calculated by multiplying each probability

product rule to be used to calculate DNA profile estimates

STR profiles are highly discriminating

the human genome contains 3.2 billion base pairs (bp) which is equal to

approximately 3pg of DNA (haploid)

commercial DNA profiling kits require

0.5-2.0ng of input DNA (1ng is standard - approximately 167 diploid cells)

DNA analysis for identity requires

a reference sample for comparison

questioned samples (Q)

evidence samples where you do not know who contributed the DNA

known sample (K)

the reference samples that have been collected from the victim, suspects, etc

questioned samples MUST be analyzed before the reference samples to protect against

contamination & bias

steps for accessing STR profiles

1. is the profile from 1 individual or a mixture?

2. what alleles are present in profile?

3. determine the genotype of the profile

4. compare to a reference

single source profiles have a

maximum of 2 alleles at each locus

mixture profiles have

more than 2 alleles at each locus

steps for statistical calculations

1. survey desire population groups to generate data sets

2. determine the allele frequencies at each locus

3. allele frequency information is used to estimate the frequency of a particular DNA profile

   • use produce rule

statistics are performed on the evidence NOT

the subject/reference profile

a conservative minimum allele frequency is used to

have a reliable estimate of an allele frequency, since it is important to have several observations that allele

minimum allele frequency equation

5/2N

(*) and (-) means what in population database

use minimum allele frequency

random match probability (RMP)

the probability of selecting the observed profile from a population of random, unrelated individuals

underlying assumption of RMP

1. the 2 alleles inherited at a locus from an individual’s parents are independent (locus in HW)

2. the alleles at different loci are independent of one another (linkage equilibrium)

3. the true perpetrator is not a relative of subject (possibility of matching an unrelated individuals)

4. appropriate population data are used for genotype frequency estimates ad there are no significant subpopulation difference in allele frequencies used to calculate the profile frequency estimate

what is the consequence of ancestral/ethnic groups being composed of subgroups within the sample population

causes a decrease in heterozygotes and increase homozygotes (more likely to be IBD)

NCRII recommends using BLACK to adjust population substructure

Theta (Θ) correction factor

Theta (Θ) correction factor equation

p² + p(1-p)Θ

Θ = 0.01 for

typical at large populations

Θ = 0.03 for

smaller, isolated populations

RMP is not

chance someone is guilty

chance someone left evidence

chance someone is not guilty

(WORDING MATTERS)

RMP is simply the

estimated frequency at which a particular STR profile would be expected to occur in a population given the allele frequencies of that population group

inclusion wording involves

match

is consistent with

cannot be excluded

match

complete agreement between 2 single source profiles

is consistent with

agreement with genotype seen in Q profile (which is incomplete)

cannot be excluded

alleles/genotypes from K sample are present in an evidentiary Q sample

excluded

mismatch at even a single locus, Q & K came from different sources

inconclusive

inability to clearly include or exclude a suspect’s DNA profile from an evidence DNA profile

the greater size of the database

the greater chance of adventitious match

adventitious match

match that occurs by chance

2 questions when a match is derived from database

1. what is the rarity of the DNA profile? (deals with RMP)

2. what is the probability of finding such a match in the database searched? (depends on RMP & size of database)

database match probability (DMP) equation

RMP x number of profiles in database

birthday problem

in a group of 23 randomly chosen individuals, there is a greater than 50% chance that 2 will share a birthday (month and date)

as databases expand, the chance of finding adventitious matches

increase, especially in cases of partial, mixed and related profiles