Problem 1
• Among 4.5 million births in one population
during a period of 40 years, 41 children
diagnosed with the autosomal dominant
condition aniridia were born to normal parents
• a. Assuming that these cases were due to new
mutations, what is the estimated mutation rate at
the aniridia locus? On what assumptions is this
estimate based, and why might this estimate be
either too high or too low?
Note: problem 1 from chapter 6 page 94
Answer Problem 1
• a. Assuming that these case were due to new mutations, what is the
estimated mutation rate at the aniridia locus? On what assumptions
is this estimate based, and why might this estimate be either too
high or too low?
• Assume 40 years is one generation. Then 41 mutations/9 million
alleles=4.55x10-6. This is based on the following assumptions
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ascertained cases result from new mutations
the disease is fully penetrant
all new mutant are liveborn and ascertained
only a single locus at which the mutation can lead to anirida
• If there are multiple loci
– then the estimate is too high
• If some mutation are not ascertained (because of death or lack of
penetrance)
– the estimate is to low
Note: problem 1 from chapter 6 page 94
Problem 2
•
The gel to the left is a diagnostic method used
to determine the size of the CGG repeat in the
FMR1 gene. The positions of normal alleles are
indicated by the white arrows while the
positions of diagnostic alleles are indicated by
the gray arrows
•
Lane 1 is a Normal male 2.8 Kbp unmethylated
EcoR1/Eag1 fragment.
Lane 2 is a Premutation male Slightly increased
size 2.8 Kbp EcoR1/Eag1 fragment due to slight
increase in CGG repeat number.
If lanes 3 and 4 are males do they have fragile X
syndrome. If they are affected which males do you
thinks has the most sever symtoms.
Lane 5 is a Normal female 5.2 Kbp methylated
(inactive X chromosome) and 2.8 Kbp unmethylated
(active X chromosome) EcoR1/Eag1 fragments.
Lane 6: Premutation carrier female Slightly
increased size 2.8 Kbp and 5.2 Kbp EcoR1/Eag1
fragments due to slight increase in the FMR1 CGG
repeat number carried by one X chromosome.
Some methylated and some unmethylated.
If Lanes 7 and 8 are females do they have fragile X
syndrome. If they are affect who do you think would
have the most sever degree of impairment..
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•
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•
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Answer Problem 2
•
The gel to the left is a diagnostic method used to determine the size of
the CGG repeat in the FMR1 gene. The positions of normal alleles are
indicated by the white arrows while the positions of diagnostic alleles
are indicated by the gray arrows
•
Lane 1 is a Normal male This indicates the size of a FMR1 fragment for an
unaffected male
Lane 2 is a Premutation male This indicates the size of a FMR1 fragment for
an unaffected male whose children are likely to receive a fragile X
chromosome when the repeat expands
If lanes 3 and 4 are males do they have fragile X syndrome.
•
•
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•
•
•
The individual in has the largest fragment so may be
the most severely affected.
Lane 5 is a Normal female 5.2 Kbp methylated (inactive X chromosome) and
2.8 Kbp unmethylated (active X chromosome) These are the size of the
fragments for an unaffected female
Lane 6: Premutation carrier female Slightly increased size 2.8 Kbp and 5.2
Kbp EcoR1/Eag1 fragments due to slight increase in the FMR1 CGG repeat
number carried by one X chromosome. Some methylated and some
unmethylated. These are the fragment size for a female who is
unsymptomatic but whose children will have a larger repeat size and are
more likely to be affected
If Lanes 7 and 8 are females do they have fragile X syndrome.
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•
The individual in lanes 3 and 4 have very large
fragment. They almost certainly have fragile X
syndrome.
If they are affected which males do you thinks has the most sever symtoms.
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•
•
In gel electrophoresis larger DNA fragments travel
slower in the gel. Therefore small DNA fragments will
be closer to the bottom of the gel and larger DNA
fragments will be closer to the top.
Both have much larger repeat sizes and are at least
carrier of the disease. In all likely hood they are mildly
affect
If they are affect who do you think would have the most sever degree of
impairment..
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Difficult to tell
The female in lane 8 has the largest repeat but one
normal chromosome. This person may have the most
sever symptoms
The female in lane 7 has two affected chromsomes but
the repeat sizes are small. Because both
chromosomes are affected she may have more sever
symptoms than individula 7.
In this gel we are looking at DNA fragments from the 5’
region of the FMR1 gene. The larger the DNA fragment
the larger the CGG repeat. In fact the difference in the
size of the DNA fragments is caused by changes in the
CGG repeat size.