Population Genetics

1
Population Genetics
2
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
3
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
4
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
Avery, McCarty, and MacLeod Genes are DNA
5
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
6
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
Modern Genetics Heres how DNA influences the
expression of traits from molecule to phenotype
throughout development
7
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
How does evolution work at a genetic level?
Population Genetics and the Modern Synthesis
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
Modern Genetics Heres how DNA influences the
expression of traits from molecule to phenotype
throughout development
8
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
How does evolution work at a genetic level?
Population Genetics and the Modern Synthesis
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
How can we describe the patterns of evolutionary
change through DNA analyses? Evolutionary Genetics
Modern Genetics Heres how DNA influences the
expression of traits from molecule to phenotype
throughout development
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The Darwinian Naturalists
The Modern Synthesis
The Mutationists
Ernst Mayr
Selection is the only mechanism that can explain
adaptations mutations are random and cannot
explain the non-random fit of organisms to
their environment
T. H. Morgan
R. Goldschmidt
The discontinuous variation between species can
only be explained by the discontinuous variation
we see expressed as a function of new mutations
the probabilistic nature of selection is too weak
to cause the evolutionary change we see in the
fossil record
10
Sewall Wright Random chance was an important
source of change in small populations
The Modern Synthesis
J. B. S. Haldane Developed mathematical models
of population genetics with Fisher and Wright
R. A. Fisher
Multiple genes can produce continuous variation,
and selection can act on this variation and cause
change in a population
Theodosius Dobzhansky Described genetic
differences between natural populations
described evolution as a change in allele
frequencies.
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Population Genetics I. Basic Principles
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Population Genetics I. Basic Principles
A. Definitions - Population a group of
interbreeding organisms that share a common gene
pool spatiotemporally and genetically defined
- Gene Pool sum total of alleles held by
individuals in a population - Gene/Allele
Frequency of genes at a locus of a particular
allele - Gene Array of all alleles at a
locus must sum to 1. - Genotypic Frequency
of individuals with a particular genotype -
Genotypic Array of all genotypes for loci
considered 1.
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)



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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)
Genotypic Array 60/200 0.30 80/200 .40 60/200 0.30 1


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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)
Genotypic Array 60/200 0.30 80/200 .40 60/200 0.30 1
''A' alleles 120 80 0 200/400 0.5

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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)
Genotypic Array 60/200 0.30 80/200 .40 60/200 0.30 1
''A' alleles 120 80 0 200/400 0.5
'a' alleles 0 80 120 200/400 0.5
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array 2.
Short Cut Method - Determining the Gene Array
from the Genotypic Array a. f(A) f(AA)
f(Aa)/2 .30 .4/2 .30 .2 .50 b.
f(a) f(aa) f(Aa)/2 .30 .4/2 .30 .2
.50 KEY The Gene Array CAN ALWAYS be computed
from the genotypic array the process just counts
alleles instead of genotypes. No assumptions are
made when you do this.
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium 1. If a population
acts in a completely probabilistic manner,
then - we could calculate genotypic arrays
from gene arrays - the gene and genotypic
arrays would equilibrate in one
generation
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium 1. If a population
acts in a completely probabilistic manner,
then - we could calculate genotypic arrays
from gene arrays - the gene and genotypic
arrays would equilibrate in one generation 2.
But for a population to do this, then the
following assumptions must be met (Collectively
called Panmixia total mixing) -
Infinitely large (no deviation due to sampling
error) - Random mating (to meet the basic
tenet of random mixing) - No selection,
migration, or mutation (gene frequencies must not
change)
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium Sources of
Variation Agents of Change Mutation N.S. Re
combination Drift - crossing
over Migration - independent
assortment Mutation Non-random Mating
VARIATION
So, if NO AGENTS are acting on a population, then
it will be in equilibrium and WON'T change.
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium 3. PROOF - Given a
population with p q 1. - If mating is
random, then the AA, Aa and aa zygotes will be
formed at p2 2pq q2 - They will grow up and
contribute genes to the next generation - All
of the gametes produced by AA individuals will be
A, and they will be produced at a frequency of p2
- 1/2 of the gametes of Aa will be A, and thus
this would be 1/2 (2pq) pq - So, the frequency
of A gametes in the gamete/gene pool will be p2
pq p(p q) p(1) p - Likewise for the
'a' allele (remains at frequency of q). - Not
matter what the gene frequencies, if panmixia
occurs then the population will reach an
equilibrium after one generation of random
mating...and will NOT change (no evolution)
22
Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq.
Genotypes, F1
Gene Freq's
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1
Gene Freq's
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1 p2 .36 2pq .48 q2 .16 1.00
Gene Freq's
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1 p2 .36 2pq .48 q2 .16 1.00
Gene Freq's f(A) p .36 .48/2 0.6 f(A) p .36 .48/2 0.6 f(a) q .16 .48/2 0.4 f(a) q .16 .48/2 0.4
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1 p2 .36 2pq .48 q2 .16 1.00
Gene Freq's f(A) p .36 .48/2 0.6 f(A) p .36 .48/2 0.6 f(a) q .16 .48/2 0.4 f(a) q .16 .48/2 0.4
Genotypes, F2 .36 .48 .16 1.00
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility 1. If
no real populations can explicitly meet these
assumptions, how can the model be useful?
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility 1. If
no real populations can explicitly meet these
assumptions, how can the model be useful? It is
useful for creating an expected model that real
populations can be compared against to see which
assumption is most likely being violated.
30
Example CCR5 a binding protein on the surface
of white blood cells, involved in the immune
response. CCR5-1 functional allele CCR5 D32
mutant allele 32 base deletion Curiously,
homozygotes for D32 are resistant to HIV, and
heterozygotes show slower progression to AIDS.
The HIV virus binds to wbcs with the normal
protein, but less so to cells with the deletion
protein.
Mutant allele interrupts viruss ability to
infect cells.
31
Example CCR5 a binding protein on the surface
of white blood cells, involved in the immune
response. CCR5-1 functional allele CCR5 D32
mutant allele 32 base deletion Curiously,
homozygotes for D32 are resistant to HIV, and
heterozygotes show slower progression to AIDS.
32
GENOTYPES
32 base-pair deletion, shortening one of the
fragments digested with a restriction enzyme
33
GENOTYPE OBSERVED EXPECTED O - E (O E)2 (O E)2/E
1/1 223 224.2 -1.2 1.44 0.006
32/1 57 55.4 1.6 2.56 0.046
32/32 3 3.4 -0.4 0.16 0.047
283 X2 0.099
1/1 223/283 0.788 p 0.788 0.201/2
0.89 32/1 57/283 0.201 32/32 3/283
0.011 q 0.011 0.201/2 0.11 Expected 1/1
p2 x 283 (0.792) x 283 224.2 Expected 1/32
2pq x 283 (0.196) x 283 55.4 Expected 32/32
q2 x 283 (0.0121) x 283 3.4
34
So this population is in HWE at this locus. HIV
is still rare, and is exerting too small a
selective pressure on the whole population to
change gene frequencies significantly.
This is the percentage of CCR5 delta 32 in
different ethnic populations European Descent
16 African Americans 2 Ashkenazi Jews 13
Middle Eastern 2-6
Why does the frequency differ in different
populations? Drift or Selection?
35
Allelic frequency of CCR5-d32 in Europe
Galvani, Alison P. , and John Novembre. 2005. The
evolutionary history of the CCR5-D32
HIV-resistance mutation. Microbes and Infection 7
(2005) 302309
36
Why Europe? - the allele is a new mutation -
was it selected for in the past?
Spread of the Bubonic Plague
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Why Europe? - the allele is a new mutation -
was it selected for in the past?
Smallpox and CCR5
Smallpox in Europe
In the 18th century in Europe, 400,000 people
died annually of smallpox, and one third of the
survivors went blind (4). The symptoms of
smallpox, or the speckled monster as it was
known in 18th-century England, appeared suddenly
and the sequelae were devastating. The
case-fatality rate varied from 20 to 60 and
left most survivors with disfiguring scars. The
case-fatality rate in infants was even higher,
approaching 80 in London and 98 in Berlin
during the late 1800s. Reidel (2005). The WHO
certified that smallpox was eradicated in 1979
38
Relationships Between Smallpox and HIV
1. Smallpox, on the other hand, was a
continuous presence in Europe for 2,000 years,
and almost everyone was exposed by direct
person-to-person contact. Most people were
infected before the age of 10, with the disease's
30 percent mortality rate killing off a large
part of the population before reproductive age.
ScienceDaily (Nov. 20, 2003) 2. The HIV
epidemic in Africa began as vaccination against
smallpox waned in the 1950s 1970s. Perhaps
vaccinations for smallpox were working against
HIV, too. 3. In vitro studies of wbcs from
vaccinated people had a 5x reduction in infection
rate of HIV compared to unvaccinated controls.
Weinstein et al. 2010
So, resistance to smallpox (or vaccination
against smallpox) may have been selected for in
Europe, and now confer some resistance to HIV.
39
Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility 1. If
no real populations can explicitly meet these
assumptions, how can the model be useful? It is
useful for creating an expected model that real
populations can be compared against to see which
assumption is most likely being violated. 2.
Also, If HWCE is assumed and the frequency of
homozygous recessives can be measured, then the
number of heterozygous carriers can be estimated.

40
Example Cystic fibrosis (cc) has a frequency of
1/2500 0.0004 in people of northern European
ancestry.
More than 1,000 different mutations in the CFTR
gene have been identified in cystic fibrosis
patients. The most common mutation (observed in
70 of cystic fibrosis patients) is a three-base
deletion in the DNA sequence, causing an absence
of a single amino acid in the protein. 0.0004 x
0.7 0.00028
In normal cells, salt is pumped out, water
follows and dilutes mucus
41
Example Cystic fibrosis (cc) has a frequency of
1/2500 0.0004 in people of northern European
ancestry common allele 0.00028.
Mucus in lungs reduces respiration, increases
bacterial infection In pancreas/liver, reduces
flow/efficacy of digestive enzymes In
intestine, reduces nutrient uptake
42
Example Cystic fibrosis (cc) has a frequency of
1/2500 0.0004 in people of northern European
ancestry, common allele 0.00028 How many
carriers are there? q2 0.00028, so q2
q 0.017. p q 1, so p 0.983 So, the
frequency of heterozygous carriers for this
allele 2pq 0.033 3 This calculation can
only be performed if HWE is assumed.
43
Population Genetics I. Basic Principles II.
Deviations from HWE A. Mutation
44
II. Deviations from HWE A. Mutation 1.
Basics
45
II. Deviations from HWE A. Mutation 1.
Basics a. Consider a population with f(A)
p .6 f(a) q .4
46
II. Deviations from HWE A. Mutation 1.
Basics a. Consider a population with f(A)
p .6 f(a) q .4 b. Suppose A' mutates
to a' at a realistic rate of µ 1 x 10-5

47
II. Deviations from HWE A. Mutation 1.
Basics a. Consider a population with f(A)
p .6 f(a) q .4 b. Suppose A' mutates
to a' at a realistic rate of µ 1 x 10-5
c. Well, what fraction of alleles will
change? A' will decline by µp .6 x 0.00001
0.000006 a' will increase by the same
amount.
48
II. Deviations from HWE A. Mutation 1.
Basics a. Consider a population with f(A)
p .6 f(a) q .4 b. Suppose A' mutates
to a' at a realistic rate of µ 1 x 10-5
c. Well, what fraction of alleles will
change? A' will decline by µp .6 x 0.00001
0.000006 a' will increase by the same
amount. d. So, the new gene frequencies will
be q1 q µp .400006 p1 p - µp
p(1-µ) .599994
49
At this realistic rate, it takes thousands of
generations to cause appreciable change.
Mutation is the source of new alleles, but it
does not change the frequency of alleles very
much. Were the mutationists wrong?
50
II. Deviations from HWE A. Mutation 1.
Basics 2. Other Considerations
51
II. Deviations from HWE A. Mutation 1.
Basics 2. Other Considerations -
Selection Selection can BALANCE mutation...
so a deleterious allele might not accumulate as
rapidly as mutation would predict, because it is
eliminated from the population by selection each
generation.
52
II. Deviations from HWE A. Mutation 1.
Basics 2. Other Considerations -
Selection - Drift The probability that a
new allele (produced by mutation) becomes fixed
(q 1.0) in a population 1/2N (basically,
it's frequency in that population of diploids).
In a small population, this chance becomes
measureable and likely. So, NEUTRAL mutations
have a reasonable change of becoming fixed in
small populations... and then replaced by new
mutations.
53
II. Deviations from HWE A. Mutation B. Migration
1. Basics - Consider two populations
p2 0.7 q2 0.3
p1 0.2 q1 0.8
54
II. Deviations from HWE A. Mutation B. Migration
1. Basics - Consider two populations
p2 0.7 q2 0.3
p1 0.2 q1 0.8
suppose migrants immigrate at a rate such that
the new immigrants represent 10 of the new
population
55
II. Deviations from HWE A. Mutation B. Migration
1. Basics - Consider two populations
p2 0.7 q2 0.3
p1 0.2 q1 0.8
suppose migrants immigrate at a rate such that
the new immigrants represent 10 of the new
population
56
II. Deviations from HWE A. Mutation B. Migration
1. Basics - Consider two populations
IMPORTANT EFFECT, BUT MAKES POPULATIONS SIMILAR
AND INHIBITS DIVERGENCE AND ADAPTATION TO LOCAL
CONDITIONS (EXCEPT IT MAY INTRODUCE NEW ADAPTIVE
ALLELES)
p2 0.7 q2 0.3
p1 0.2 q1 0.8
suppose migrants immigrate at a rate such that
the new immigrants represent 10 of the new
population
p(new) p1(1-m) p2(m) P(new) (0.2).9
(0.7)0.1 0.25
57
Frequency of the B allele of the ABO blood
group locus, largely as a result of the Mongol
migrations following the fall of the Roman Empire
58
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating 1. Positive
Assortative Mating "like phenotype mates with
like phenotype"
59
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating 1. Positive
Assortative Mating "like phenotype mates with
like phenotype" a. Pattern
AA Aa aa
.2 .6 .2
offspring

F1
60
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating 1. Positive
Assortative Mating "like phenotype mates with
like phenotype" a. Pattern
AA Aa aa
.2 .6 .2
offspring ALL AA 1/4AA1/2Aa1/4aa ALL aa

F1
61
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating 1. Positive
Assortative Mating "like phenotype mates with
like phenotype" a. Pattern
AA Aa aa
.2 .6 .2
offspring ALL AA 1/4AA1/2Aa1/4aa ALL aa
.2 .15 .3 .15 .2
F1 .35 .3 .35
62
a. Pattern
AA Aa aa
.2 .6 .2
offspring ALL AA 1/4AA1/2Aa1/4aa ALL aa
.2 .15 .3 .15 .2
F1 .35 .3 .35
b. Effect - reduction in heterozygosity at this
locus increase in homozygosity.
63
Groth, J. 1993. Call matching and positive
assortative mating in Red Crossbills. The Auk
110L 398-401.
male
female
64
Type 2
Type 1
65
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating 1. Positive
Assortative Mating 2. Inbreeding - reduction
of heterozygosity across the entire genome, at a
rate that correlates with the degree of
relatedness. - full sibs, parent/offspring
lose 50of heterozygosity each generation.
66
White tigers in the U.S. are all descendants of a
brother-sister pair from the Cincinnati Zoo. The
AZA has outlawed captive breeding of white tigers.
BigCatRescue
67
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating 1. Positive
Assortative Mating 2. Inbreeding - reduction
of heterozygosity across the entire genome, at a
rate that correlates with the degree of
relatedness. - full sibs, parent/offspring
lose 50of heterozygosity each generation.
CAN INCREASE PROBABILITY OF DIVERGENCE BETWEEN
POPULATIONS, AND CAN ALSO BE A WAY TO PURGE
DELETERIOUS ALLELES (ALTHOUGH AT A COST TO
REPRODUCTIVE OUTPUT).
68
II. Deviations from HWE A. Mutation B.
Migration C. Non-Random Mating D. Genetic Drift -
Sampling Error 1. The organisms that actually
reproduce in a population may not be
representative of the genetics structure of the
population they may vary just due to sampling
error (chance).
69
D. Genetic Drift - Sampling Error 1. The
organisms that actually reproduce in a population
may not be representative of the genetics
structure of the population they may vary just
due to sampling error (chance). - most dramatic
in small samples. 2. effects
70
D. Genetic Drift - Sampling Error 1. The
organisms that actually reproduce in a population
may not be representative of the genetics
structure of the population they may vary just
due to sampling error (chance). - most dramatic
in small samples. 2. effects 1 - small pops
will differ more, just by chance, from the
original population
71
D. Genetic Drift - Sampling Error 1. The
organisms that actually reproduce in a population
may not be representative of the genetics
structure of the population they may vary just
due to sampling error (chance). - most dramatic
in small samples. 2. effects 1 - small pops
will differ more, just by chance, from the
original population 2 - small pops will vary more
from one another than large populations
72
D. Genetic Drift - Sampling Error 1. most
dramatic in small samples. 2. effects 3.
circumstances when drift is very important
73
D. Genetic Drift - Sampling Error 1. most
dramatic in small samples. 2. effects 3.
circumstances when drift is very important -
Founder Effect
The Amish, a very small, close-knit group
decended from an intial population of founders,
has a high incidence of genetic abnormalities
such as polydactyly
74
- Founder Effect and Huntingtons Chorea
HC is a neurodegenerative disorder caused by an
autosomal lethal dominant allele. The fishing
villages around Lake Maracaibo in Venezuela have
the highest incidence of Huntingtons Chorea in
the world, approaching 50 in some communities.
75
- Founder Effect and Huntingtons Chorea
HC is a neurodegenerative disorder caused by an
autosomal lethal dominant allele. The fishing
villages around Lake Maracaibo in Venezuela have
the highest incidence of Huntingtons Chorea in
the world, approaching 50 in some communities.
The gene was mapped to chromosome 4, and found
the HC allele was caused by a repeated sequence
of over 35 CAGs. Dr. Nancy Wexler found
homozygotes in Maracaibo and described it as the
first truly dominant human disease (most are
incompletely dominant and cause death in the
homozygous condition).
76
- Founder Effect and Huntingtons Chorea
HC is a neurodegenerative disorder caused by an
autosomal lethal dominant allele. The fishing
villages around Lake Maracaibo in Venezuela have
the highest incidence of Huntingtons Chorea in
the world, approaching 50 in some communities.
By comparing pedigrees, she traced the incidence
to a single woman who lived 200 years ago. When
the population was small, she had 10 children who
survived and reproduced. Folks with HC now trace
their ancestry to this lineage. Also a nice
example of coalescence convergence of alleles
on a common ancestral allele.
77
D. Genetic Drift - Sampling Error 1. most
dramatic in small samples. 2. effects 3.
circumstances when drift is very important -
Founder Effect - Bottleneck
78
- Genetic Bottleneck If a population crashes
(perhaps as the result of a plague) there will be
both selection and drift. There will be
selection for those resistant to the disease (and
correlated selection for genes close to the genes
conferring resistance), but there will also be
drift at other loci simply by reducing the size
of the breeding population.
Cheetah have very low genetic diversity,
suggesting a severe bottleneck in the past. They
can even exchange skin grafts without rejection.
European Bison, hunted to 12 individuals, now
number over 1000.
Fell to 100s in the 1800s, now in the 100,000s