Download Genetics 418 Pedigrees 1.2

Genetics 418 Problem Set #1
Due Wednesday January 21 at 1:00 pm
Name:
ID Number:
-5% per day for late assignments
Note: a BRIEF explanation is required for each question. This explanation can be simplified by indicating on the
autoradiograph the parent of origin of each band, and if it is linked to an affected allele or to a normal allele. The pedigrees on the
following pages should be handed in along with your answers. Attach additional pages if necessary. Each question is based on a
pedigree that shows segregation of a genetic disorder where DNA was obtained from each individual and genotyping analysis was
carried out for the loci indicated. Each lane of bands on the autoradiograph corresponds to the individual above it in the pedigree.
Unless otherwise stated all affected individuals are indicated. Assume 100% penetrance.
1. This pedigree shows the segregation of a rare autosomal recessive disorder. Two polymorphic markers, K and L, that are linked to
the disease locus were used for this analysis. Biochemical testing has shown individual III-1 to be a carrier. II-1 was not a
carrier.
a). From the following autoradiogram, identify all carriers. Briefly explain your answer, including the parent of origin of the mutant
allele. (8)
b). Predict the disease status of IV-1 Explain. (2)
I
1
3
2
II
1
2
4
3
5
III
1
IV
K
L
3
2
1
?
4
6
7
4
2. The following figure shows a pedigree of a family with a rare autosomal recessive disorder. All affected individuals are indicated.
DNA was collected from other family members and two probes closely linked to the disease locus, D and E, were used for
RFLP analysis. Individuals III-2, III-3 and III-5 have undergone a new biochemical test that identifies carriers. III-3 was
found to be normal. No other members of the family have been tested.
a). Identify any additional carriers of this disorder and briefly explain your answer. (5)
b). Fill in the missing bands for this RFLP analysis. If there is more than one possibility for an individual then illustrate all the
possible patterns. (5)
I
1
2
II
1
2
3
4
5
III
1
D
E
2
3
4
5
3. Four microsatellite markers on chromosome 1 (in the order shown) were used to study the inheritance of a rare autosomal recessive
condition in the family below. The four separate autoradiograms were compiled and are presented below the pedigree with a
legend indicating how many copies of the repeat is present at each locus. The gene responsible for the condition is unknown,
but linkage analysis has revealed that it is likely to be within a 20.0 Mb interval defined by the markers A and D. It is also
quite likely that one will discover evidence for meiotic crossing-over in this large interval when studying any family.
Helpful hint: There has been no crossing over between generations I and II.
A
B
C
D
a). Assemble each person’s haplotype. (8) See the box to the right for an example.
I
II
1
2
3
3
1
4
11 14
15 16
12 12
17 15
PN MA
Chromosome 1
4
5
6
A
B
C
D
2
III
1
IV
1
A
17
16
15
14
13
12
11
B
18
17
16
15
14
13
12
C
9
8
7
6
5
4
3
2
1
D
8
7
6
5
4
3
2
?2
2
3
4
5
3
b). Which chromosomes in generations III and IV definitely or possibly represent crossing-over? Briefly explain your answer. (7)
c). Identify those people in generation I that definitely or possibly are carriers. Explain. (3)
d). Upon analysis, can one narrow the region which contains the gene responsible for the disease? Explain. (4)
e). What is the diagnosis for the fetus, IV-2? Explain. (3)
4. The following pedigree shows the inheritance pattern of an X-linked recessive disorder. Two microsatellite markers, A and B are
linked to the disease locus are used for this analysis.
a). Predict the carrier status of the females in this pedigree. Briefly explain your answer including the parent of origin of the affected
allele. ( 6 )
b). What assumption(s) are you making in your analysis? (2)
I
II
III
1
1
2
3
4
2
3
5
6
7
?
1
A
B
c). What is the simplest, non-molecular explanation for the RFLP pattern observed for individual II-6? Explain.(2)
d) Predict the sex and disease status of individual III-1. Explain. (2)
8