7.

03
Exam
3
–
Spring
2010
–
Solution
Key

Instructors:
Aviv
Regev
&
Chris
Kaiser

TAs:
Christoph
Engert,
Jared
Owen,
Mitchell
Guttman,
Ambar
Mehta,
Pear

Sanglimsuwan



(For
typos
&
questions
on
notation,
contact
Christoph
Engert
with
“7.03
Exam
3”
in

the
subject)



1)
Hardy­Weinberg,
Selection
&
Inbreeding



A)



S
=
1



B)




With
S
=
1,
q
=
h
=
10^‐2



C)




As
the
fitness
of
(M/M)
=
(m/M):
without
heterozygote
advantage
in
the
population

the
allele
frequency
q,
changes
as
under
standard
homozygous
selection:


 Δq
=
‐S*q^2
=
‐1*(10^‐2)^2
=
‐10^‐4



D)




µ
=
S*q^2
=
1*(10^‐5)^2
=
10^‐10



E)



F(1
allele)
=
(½)^4
*
¼
=
½^6

There
are
only
2
alleles
that
can
contribute
to
homozygosity
by
descent
in
half‐
cousins:

F(half‐first
cousins)
=
2
*
(½)^4
*
¼
=
1/2^5
=
1/32



F)




Scenario
1:

F
=
1/8

f(m/m)
=
f(m/m
|
inbreeding)
*
P(inbreeding)




=
F
*
q
*
1
=
1/8
*
10^‐5
=
1.25
x
10^‐6



The
techs
performed
all
niece/uncle
matings
as
the
frequency
of
homozygous

individuals
is
1/8
of
the
allele
frequency.
Important
to
note
here
is
that
NO
random

mating
occurs.
Therefore
f(m/m)
=
f(m/m
|
inbreeding)



2)
Linkage
Disequilibrium



A)



qa
=
(f1(aB)
+
f2(aB))/2
+
(f1(ab)+f2(ab))/2
=
(540+140+60+1260)/4000
=
0.5



 after
1
generation
of
random
mating:
f2(a/a)
=
qa^2
=
0.25

 after
2
or
7
generations
nothing
changed
with
respect
to
the
frequency
f(a),

due
to
HWE,
and
therefore
with
the
frequency
of
the
homozygous

GENOTYPE:
f7(a/a)
=
q^2
=
0.25



B)



fmix(X)
=
fsen(X)
+
fhar(X)



f(AB)
=
(1260/2000
+
60/2000)/2
=
0.33

f(Ab)
=
(140/2000
+
540/2000)/2
=

0.17

f(aB)
=
(540/2000
+
140/2000)/2
=
0.17

f(ab)
=

(60/2000
+
1260/2000)/2
=
0.33



C)



Monoallelic
frequencies
in
the
mixed
population:

f(A)
=
0.33
+
0.17
=
0.5

f(a)
=
1
–
f(A)
=
0.5

f(B)
=
0.33
+
0.17
=
0.5

f(b)
=
1
–
f(B)
=
0.5



Alleles
 Observed
 Expected
 O‐E
 (O‐E)^2/E

AB
 1320
 1000
 320
 102.4

Ab
 680
 1000
 ‐320
 102.4

aB
 680
 1000
 ‐320
 102.4

ab
 1320
 1000
 320
 102.4


 
 
 Chi­Squ.:
 409.6



From
the
Chi‐Squared
statistic
for
the
full
sample‐size
we
are
very
confident
(p‐
value
<<
10^‐6)
that
the
mixed
population
is
in
LD.



D)



D
=
f(AB)
*
f(ab)
–
f(Ab)
*
f(aB)
=
0.33^2
–
0.17^2
=
0.08

As
D>0:
D’
=
D/
Dmax

Dmax
=
min{(pA*qb),(qapB)}
=
0.25,
as
(pA*qb)
=
(qa*pB)
=
0.5^2
=
0.25



D’
=
0.08/0.25
=
0.32



After
2
generations,
using:



D(n)
=
(1‐r)^n
*
D0

D(2)
=
0.5^2
*
0.08
=
0.02



D(2)’
=
D(2)
/
Dmax
=
0.02/0.25
=
0.08




(also
possible
to
calculate
directly
by
applying
the
recombination‐dependent
decay

to
D(0)’)
Note
that
we
assume
to
have
no
changes
in
the
mono‐allelic
frequencies
to

make
this
calculation.




3)
Sequence
Alignment
&
Conservation



A)


Traceback:









Alignment
Score
=
+7
(red
square)



Best
global
alignment:

--PAALPGTSD
|| || ||
QWPA-LP-TS-
B1)

Sequences
that
reoccur
are
shown
in
red
with
the
arrows
indicating
the
direction
of

their
first
occurrence.
















































 

B2)



Candidate
Regions
for
red‐causing
enzymes
on
the
red‐aphid
genome
are
the

duplicated
regions,
as
we
need
a
lot
of
gene‐product
to
make
the
aphid
red:

Chr
1:
3‐6,
6‐9,
12‐15


Chr
2:
9‐12,
12‐15,
15‐18

Chr
3:
3‐6,
6‐9,
9‐12



C)



Shown
here
are
the
parts
of
the
GREEN
APHID
chromosomes
that
have
exact

counterparts
on
the
red
aphid
chromosomes
in
blue,
gaps
are
grey:



1/A





2/B



3/C
 
 



Chr
A
&
B
are
exactly
equivalent
to
1
&
2
–
we
can
see
this
directly
from
the

symmetry
of
the
dot‐plots
&
the
also
explicitly
from
the
fact
that
the
2
dot‐plots
in

D)
are
the
same
as
in
B).
Chr
C
of
the
green
aphid
is
missing
the
duplicated
regions

3‐12
of
the
red
aphid
chromosome
3
(indicated
here
as
a
grey
empty
arrow),
while

the
regions
around
this
deletion
are
equivalent
to
each
other
(indicated
as
blue

arrows
for
corresponding
sequence).



D)



The
3‐12
region
deleted
on
Chr.
C
of
the
green
aphid
is
unique
&
duplicated
in
the

red
aphid,
making
it
our
primary
region
of
interest.



E)




The
duplicated
region
of
interest
is
the
Chromosome
from
Fungus
C.
It
is
also

amplified
in
the
red
aphid
through
duplication.