GENES IN POPULATIONS

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GENES IN POPULATIONS
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There are three main levels of Genetic
Analysis 1. The Individual genotype, haplotype,
cytogenetics, somatic cell genetics 2. The
Family segregation, linkage, familial
aggregation, heritability concepts 3. The
Population frequency of alleles, genotypes,
haplotypes, Hardy-Weinberg,gametic, or linkage
disequilibrium
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Mutation versus polymorphism Every polymorphism
is a mutation but not every mutation is a
polymorphism A polymorphism is a mutation that
occurs in the population at a relative frequency
of greater than 1. SNPs - single nucleotide
polymorphisms VNTRs - variable nucleotide repeats
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The CCR5 deletion that confers immunity to HIV
AIDS Whats the probability of carrying the
allele?
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Allele frequency through allele counting
2( of aa) of Aa 2 x N
Freq of A q
60 190 2000
0.11
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Hardy-Weinberg Principle
?That in a stable randomly mating population
allele frequencies stay constant and can predict
the genotype frequencies of the next generation.
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A Punnet square showing the ratio p2 2pq
q2 Characteristic of random mating
Female Gametes
p
q
A
a
A
p
p2 AA
pq Aa
Male Gametes
q
a
pq Aa
q2 aa
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Assumptions of the Hardy-Weinberg Principle

• Mating is random there are no sub-populations
  that differ in allele frequency
• Allele frequencies are the same in males and
  females
• All the genotypes are equal in viability and
  fertility (selection does not operate)
• Mutation does not occur
• Migration into the population is absent
• The population is sufficiently large, such that
  the frequencies of alleles do not change from
  generation to generation simply because of chance.

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Testing Hardy-Weinberg Equilibrium The purpose of
HW testing is to see if the genotypes follow the
p2 2pq q2 ratio because if they dont then
one of the assumptions for HW has been violated
e.g. 1) Population stratification (ethnic groups
that arent randomly mating across groups) 2)
Genotyping errors 3) Major mutation or selection
events are occurring at that locus 4) Major
admixture or segregation distortion
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Testing Hardy Weinberg Equilibrium 1. Take
observed genotype frequencies and estimate
relative allele frequencies (e.g. CCR5
example) 2. Take allele frequencies and estimate
the expected relative genotype frequencies
Expected f(AA) (0.89)2 0.7921 Expected
f(Aa) 2(0.89)(0.11) 0.1958 Expected f(aa)
(0.4575)2 0.0121
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3. Multiply the relative genotype frequencies by
the size of the sample (N) to get the expected
genotype frequencies 4. Perform Chi-square
goodness of fit test
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Other disequilibrium concepts gametic
disequilibrium - the frequency of alleles at two
different loci are not independent linkage
disequilibrium - the frequency of alleles at two
different linked loci are not indepent
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Alleles at site 1 G and T f(G), f(T) Alleles
at site 2 C and A f(C), f(A) Haplotype GC
f(G, C) GA f(G, A) TC f(T,
C) TA f(T, A) Disequilibrium f(G,C) -
f(G)f(C)
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MOLECULAR DIVERSITY AND EPIDEMIOLOGY OF COMMON
DISEASE (MDECODE) A Research Project Supported
by National Heart, Lung, and Blood Institute
(NHLBI) RO1 HL58238, 39, and 40

Established 1996
U. Of Michigan Ann Arbor,
MI Charlie Sing (Project Director) Sharon
Kardia Kathy Klos Alan Templeton (Wash. U.)
U. Of Washington Seattle, WA Debbie
Nickerson Scott Taylor
Penn State U. State College, PA Ken Weiss Anne
Buchanan Andy Clark S. Malia Fullerton
U. Of Texas Health Science Center
Houston, TX Eric Boerwinkle Andrew Brown
(U.Mississippi)
National Public Health Institute, Finland
Helsinki, Finland Jari Stengard
Erkki Vartiainen Veikko Salomaa
Pekka Puska
Mayo Clinic Rochester, MN Steve Turner
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MDECODE Project to study variation in 13 CVD
genes gt 7.7 Million bp Genotyped (N72)
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Distribution of 88 variable DNA sites in 10 kb of
the LPL gene
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Distribution of 101 variable DNA sites in the
ApoAI/CIII/AIV gene complex
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Relationship between SNPs and haplotypes
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Average Allele Effects
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Quebec, Canada (N201)
Nancy, France (N223)
Munster, Germany (N1000)
Helsinki, Finland (N207)
Rochester, MN, USA (N226)
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Cholesterol (mg/dl)
-10
-20
.15
.22
.16
.13
.14
Relative Frequency of Alleles
.77
.75
.78
.74
.80
.08
.03
.06
.13
.06
-30
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