Complications
Theta correction
Mutation
Silent alleles
Theta correction, mutations, silent alleles
Thore Egeland(1),(2)
(1) Norwegian University of Life Sciences, (2) NIPH
Athens Feb 11-12 2016
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Complications
Theta correction
Mutation
Silent alleles
Beyond standard cases
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Complex pedigrees Large, inbred
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Theta corrrection If e.g. Hardy-Weinberg does not apply
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Mutation If e.g. parent and child share no alleles
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Silent alleles Homozygote or silent allele?
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Drop out Homozygote or drop out?
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Complications
Theta correction
Mutation
Silent alleles
Dispute laid to rest
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Complications
Theta correction
Mutation
Silent alleles
Hardy Weinberg
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Complications
Theta correction
Mutation
Silent alleles
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Fraction homozygotes increases with θ
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Complications
Theta correction
Mutation
Silent alleles
Previous example
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Complications
Theta correction
Mutation
Silent alleles
Fst=Theta=0.01. Input: Pedigrees > Parameters
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LR = 2.298 · 1.764 = 4.1 when θ = 0.01
LR = 2.450 · 1.805 = 4.4 when θ = 0.00.
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Complications
Theta correction
Mutation
Silent alleles
Mutation: Exercise 2.2, 2.7
AF
14/15
Mother
−/−
Child
16/17
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Complications
Theta correction
Mutation
Silent alleles
Mutation: Results, simillar to Exercise 2.9
System
D3S1358
TPOX
D6S474
3 markers
22 (1 mut)
Child
17/17
8/8
16/17
AF
17/18
8/8
14/15
...
...
LR
2.450
1.805
0.000
0.000
...
0.000
LR(mut)
2.449
1.804
0.001
0.0045
...
25070642
Table 1: Genotype data for a Child and alleged father (AF) along with
LR-s. The rightmost column is based on a stepwise unstationary
mutation model (expained below) with mutation rate 0.001 and range
0.5 for all markers.
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Complications
Theta correction
Mutation
Silent alleles
Equal model
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P(no mutation) = 0.999
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Problem: P(14 → 17) = P(15 → 16) = 0.0002.
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Complications
Theta correction
Mutation
Silent alleles
Mutation: Biology
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Mutation rates:
http://www.cstl.nist.gov/strbase/mutation.htm
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Complications
Theta correction
Mutation
Silent alleles
Mutation: Input
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Complications
Theta correction
Mutation
Silent alleles
Mutation Matrix. Range
Range =
15 → 17
0.00015385
=
= 0.5
15 → 16
0.0030769
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Complications
Theta correction
Mutation
Silent alleles
Silent alleles. Input: General DNA data > . . . > Options
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Complications
Theta correction
Mutation
Silent alleles
Exercise 2.11
AF
B/−
mother
A/−
child
A/−
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I
I
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Enter genotypes as homozygous.
pB = 0.1, pS = P(“Silent allele”) = 0.05. Now e.g.
P(B/−) = pB2 + 2 · pB pS = 0.02.
Statistics for silent alleles:
http://www.cstl.nist.gov/strbase/NullAlleles.htm
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