Announcements

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BIOL223 Genetics Evolution March 9,
2009 Intro to Population Genetics FRI The
equilibrium population Assumptions and utility
of Hardy-Weinberg MON Relaxing the assumptions,
one by one Mutations Wed Selection
Announcements Reading Freeman Herron Monday
Ch. 5, pp. 143-160 Ch. 6, pp. 210-212 Wed Ch.
6, pp. 182-194 Homework assignment Q6 (p. 219)
and Q14 (p. 220) Links to PDFs of J. Heredity
51-7 and Stansfield, 2005. under Lecture 17
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Goals

• Understand Hardy-Weinberg (HW) equilibrium model
• Be able to estimate allele frequencies from a
  population sample and test for H-W proportions
• Understand expected genotypic and phenotypic
  frequencies for sex-linked loci

• Be able to answer the question
• Is population under consideration in
  Hardy-Weinberg equilibrium?

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Assumptions of Hardy-Weinberg model 1. Random
mating. 2. No mutation. 3. Large (infinite)
population size (no genetic drift). 4. No
differential survival or reproduction (no natural
selection). 5. No migration (no gene flow)
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• If assumptions of the Hardy-Weinberg model are
  met, then the following will be true
• The population will not evolve
  i.e., allele frequencies will be constant from
  generation to generation. ? Hardy-Weinberg
  equilibrium.
• 2. Genotypes will be in binomial proportions.
• ? Hardy-Weinberg proportions

p2 2pq q2
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1. Hardy-Weinberg equilibrium (Null model ? no
evolution)
Wheel 1 generation
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2. Zygote genotypes will be in binomial
proportions. Hardy-Weinberg
proportions Gametes Zygote genotypes A
a AA Aa aa
p q p2 2pq q2
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Testing for Hardy-Weinberg proportions To test
whether a population is in Hardy-Weinberg
proportions, we (1) determine allele
frequencies from observed genotypes numbers,
(2) calculate expected genotype numbers under
HW model, (3) compare observed numbers to
expected numbers using the chi-square test.
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(1) What are the allele frequencies
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(2) What are the expected genotype numbers?
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(3) Chi-square test
degrees of freedom genotypes - alleles 1
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accept null hypothesis
reject
0.91 lt 3.84 Therefore, we accept these as H-W
proportions Recall, Hardy-Weinberg
IS the null model
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Occurrence of cystic fibrosis Autosomal
recessive (cc)
1/600 white Americans 1/3,500 African
Americans 1/2,000 Hispanics
1/20,000 Asians
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Assume that this class of 200 students comes from
a population in which 1/600 people are aflicted
(cc) with cystic fibrosis. How many carriers
(Cc, heterozygotes) do we expect in this
class? (a) Less than one (b) 1 (c) 5 (d)
10 (e) 15
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• Can we estimate frequency of recessive alleles
• Cystic fibrosis occurs in 1/600 births of white
  Americans (cc)
• What is the frequency of c allele?
• (2) How many carriers (Cc, heterozygotes) do we
  expect in this class of 200 people?

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(1) If population is in H-W equilibrium, then
allele frequency easily computed from genotype
frequency. CC Cc cc
p2 2pq q2
(599/600) 1/600 q2 1/600
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(2) If there are only 2 alleles and you know the
frequency of 1, simple arithmetic gives you the
other.
q 0.041 p 1 q 0.959
CC Cc cc p2
2pq q2 0.92 0.08
0.00 (0.0017)
(3) And if population in H-W Eq, its easy to
compute frequency heterozygotes (Hz)
2pq N (0.08) (200) 15.7
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Hardy-Weinberg with 3 alleles A1, A2, A3
Sperm pool
A1 p0.3
A2 q0.5
A3 r0.2
A1 p0.3
A2 q0.5
Egg pool
A3 r0.2
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X-linked traits e.g., color blindness
c-b
Females Males CC normal
CY normal Cc normal cY
color-blind cc color-blind
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X-linked traits
Y-bearing sperm
X-bearing sperm
XA (p)
Xa (q)
Y
XA (p)
XA Xa (pq)
XA XA (p2)
XA Y (p)
Eggs
Xa (q)
Xa Y (q)
Xa Xa (q2)
XA Xa (pq)
Assumptions? Large, panmictic population, no bias
in sex ratio
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Now, one by one, lets relax the assumptions of
Hardy-Weinberg model 1. Random mating. 2. No
mutation 3. Large (infinite) population size (no
genetic drift). 4. No differential survival or
reproduction (no natural selection). 5. No
migration (no gene flow)
Today
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Mutation

• Molecular basis of mutation
• Phenotypic effects of mutations
• Rates of mutation
• Effect of mutation on HW Eq
• Variation in mutation rate

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(No Transcript)
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Mutation is heritable change in genetic
information. Our focus change in the DNA
sequence of genes.
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Mutations can happen either in somatic cells or
in cells that will form gametes (germ-line)

• Before we move on
• Are somatic cells reproducing?
• 2. Are they reproducing sexually or asexually?
• 3. Are mutations heritable within that clonal
  lineage?
• 4. What can result from mutations?
• 5. Are such cancers heritable?
• 6. No, although predisposition can be.

In animals, the germ-line is separate (few
divisions)
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Mutations can happen in somatic cells or in
cells that will form gametes (germ-line)
In plants, somatic mutations can enter the
germ-line!
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In microbes reproducing by binary fission,
potentially any mutation can enter population
Vertical transmission of genes within lineages
over generations
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Recall DNA replicates at mitosis and meiosis
? Opportunity for error repair
mismatch must be repaired if C ? G, no
mutation If not repaired, C ?T
next replication mutation
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Point mutations (changes to a single nucleotide)
Any of these point mutations can give rise to
SNPs Single Nucleotide Polymorphisms
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Types of single nucleotide mutations in genes
Missense mutation (transition)
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Types of single nucleotide mutations in genes
Missense mutation (transition) Amino acid
substitution
(b) Missense mutation (transition) ?
Missense mutation (transversion)