PCB 3063 EXAM 3 CONTENT
Study Content and Questions for remaining topics in Chapter 4
Please first view video lectures (4,5,6,7) by Dr. El-Rady completely and take good notes to summarize
what you learn, review the discussed concepts and study the tophat questions discussed in synchronous
Teams sessions followed by the concepts in McGraw Hill Connect homework assignments. Finally test
what you have learned by answering the questions given below.
1. Be able to define a lethal allele.
Lethal Allele: an allele that may cause the death of an organism. These alleles are typically the result of
mutations in essential genes. They are usually inherited in a recessive manner.
2. Be able to define an essential gene.
Essential genes: genes that encode proteins that are absolutely required for survival.
● The absence of a specific essential protein results in a lethal phenotype.
● About 1/3 of all genes are essential for survival.
3. Be able to define a non-essential gene. If a gene is non-essential, be able to explain why
the genome of the organism may still carry this gene.
Nonessential Genes: genes that are not absolutely required for survival, although they are likely to be
beneficial to the organism.
● Examples of nonessential genes include hair color and eye color.
● A loss-of-function nonessential gene, for example, will not usually cause death.
● On rare occasions, however, a nonessential gene may acquire a gain-of-function
mutation that causes the gene product to be abnormally expressed in a way that may
interfere with normal cell function and lead to a lethal phenotype.
● Not all lethal mutations occur in essential genes (even though the majority do).
4. Is it possible for a non-essential gene to undergo mutations and turn into a lethal allele?
Yes. As stated in the question above, on rare occasions, a nonessential gene may acquire a
gain-of-function mutation that causes the gene product to be abnormally expressed in a way that may
interfere with normal cell function and lead to a lethal phenotype. Not all lethal mutations occur in
essential genes (even though the majority do).
5. Be able to distinguish between recessive lethal allele and a dominant lethal allele.
Recessive lethal alleles are when the heterozygous state is tolerated.
Dominant lethal alleles are when the heterozygous state leads to death.
If the mutation is caused by a dominant lethal allele, the homozygote and heterozygote for the allele will
show the lethal phenotype (as long as the dominant gene is expressed). If the mutation is caused by a
recessive lethal allele, the homozygous for the allele will have the lethal phenotype. Most lethal genes are
recessive.
, 6. Why do recessive lethal alleles giv no e a ratio of 2:1 (phenotype: normal) for a second
trait that the allele may be associated when heterozygotes are crossed to one another?
For this second trait the allele behaves in a dominant manner. (examples agouti and yellow
mice, Manx cats, etc)
¼ of the offspring are homozygous for the dominant mutant allele, and they die during embryonic
development. In the case of Manx cats, the Manx phenotype is dominant in heterozygotes, whereas the
dominant mutant allele is lethal in the homozygous condition.
7. How did Castle and Little conclude that the yellow allele is a lethal allele? (hint: where did
they look and see dead progeny)
Cuénot's crosses resulted in what appeared to be non-Mendelian ratios because he had discovered a
lethal gene. Castle and Little concluded that the yellow allele is a lethal allele by showing that ¼ of the
offspring from crosses between heterozygotes died during embryonic development (Castle & Little, 1910;
Paigen, 2003). This was why Cuénot never observed homozygous yellow. Yellow is dominant for coat
color but recessive for lethality.
8. Given any other similar example be able to pinpoint the presence of a lethal allele that
behaves recessively for the lethality phenotype and dominantly for a different phenotype.
If the heterozygous state is tolerated, it is a recessive lethal allele
If the heterozygous state leads to death, it is a Dominant lethal allele
9. Be able to define conditional lethal alleles and semi-lethal alleles. Given a set of
experimental data be able to pinpoint the presence of such alleles. (eg. Temperature
sensitive alleles)
Conditional Lethal Allele: an allele that is lethal, but only under certain environmental
conditions.
● Example: some conditional lethal alleles, called temperature-sensitive lethal alleles,
cause an organism to die only in a particular temperature range. This includes
Drosophila.
, ● The ts lethal allele is fatal for larva developing in 30 degrees C. Larva that grow at lower
temperatures (22 degrees C) survive.
Caused by mutations that alter the structure of the protein at the nonpermissive temperature.
Semilethal Alleles: lethal alleles that kill some individuals but not all.
● Environmental factors and other genes may help prevent the detrimental effects of
semilethal genes.
● Example: The X-linked white-eyed allele in fruit flies. Depending on the growth
conditions, approximately ¼ to ⅓ of the flies that carry the white-eyed allele die during
early stages of development.
10. Be able to explain the dominant lethal nature of the Huntington allele (Look at the
dominant allele in heterozygote and does it lead to death due to the neurodegenerative
disease). In this case of heterozygote, the individual is able to be born and enter
adulthood, however thereafter he or she begins to develop neurodegeneration that is
100% fatal by 65 years and therefore it is categorized as a lethal allele). What is the nature
of the mutation carried in the disease allele and what is the consequence on the
Huntingtin protein?
Huntington Disease is caused by a dominant lethal allele. It is a degenerative disorder
characterized by progressive dementia and increasingly uncontrollable movement of limbs. Homozygous
dominant individuals die in utero, heterozygous individuals develop normally but get the disease later in
life, and homozygous recessive individuals develop normally.
11. Be able to explain how this lethal mutation continues to be maintained in the human
population.
This lethal mutation is able to be maintained because the age of onset of the disease occurs after
the reproductive age.
12. What is the probability of passing this allele to the next generation if one of the two
parents carries the disease allele and will be definitely affected in adulthood. What would
be the probability of a child who is born, being affected in adulthood if both his/her
parents have the disease allele and will start developing the disease in their adulthood? In
this case look at how the disease allele behaves in homozygotes and whether they survive
during embryogenesis. Do you appreciate some similarity with lethal alleles or Manx
Study Content and Questions for remaining topics in Chapter 4
Please first view video lectures (4,5,6,7) by Dr. El-Rady completely and take good notes to summarize
what you learn, review the discussed concepts and study the tophat questions discussed in synchronous
Teams sessions followed by the concepts in McGraw Hill Connect homework assignments. Finally test
what you have learned by answering the questions given below.
1. Be able to define a lethal allele.
Lethal Allele: an allele that may cause the death of an organism. These alleles are typically the result of
mutations in essential genes. They are usually inherited in a recessive manner.
2. Be able to define an essential gene.
Essential genes: genes that encode proteins that are absolutely required for survival.
● The absence of a specific essential protein results in a lethal phenotype.
● About 1/3 of all genes are essential for survival.
3. Be able to define a non-essential gene. If a gene is non-essential, be able to explain why
the genome of the organism may still carry this gene.
Nonessential Genes: genes that are not absolutely required for survival, although they are likely to be
beneficial to the organism.
● Examples of nonessential genes include hair color and eye color.
● A loss-of-function nonessential gene, for example, will not usually cause death.
● On rare occasions, however, a nonessential gene may acquire a gain-of-function
mutation that causes the gene product to be abnormally expressed in a way that may
interfere with normal cell function and lead to a lethal phenotype.
● Not all lethal mutations occur in essential genes (even though the majority do).
4. Is it possible for a non-essential gene to undergo mutations and turn into a lethal allele?
Yes. As stated in the question above, on rare occasions, a nonessential gene may acquire a
gain-of-function mutation that causes the gene product to be abnormally expressed in a way that may
interfere with normal cell function and lead to a lethal phenotype. Not all lethal mutations occur in
essential genes (even though the majority do).
5. Be able to distinguish between recessive lethal allele and a dominant lethal allele.
Recessive lethal alleles are when the heterozygous state is tolerated.
Dominant lethal alleles are when the heterozygous state leads to death.
If the mutation is caused by a dominant lethal allele, the homozygote and heterozygote for the allele will
show the lethal phenotype (as long as the dominant gene is expressed). If the mutation is caused by a
recessive lethal allele, the homozygous for the allele will have the lethal phenotype. Most lethal genes are
recessive.
, 6. Why do recessive lethal alleles giv no e a ratio of 2:1 (phenotype: normal) for a second
trait that the allele may be associated when heterozygotes are crossed to one another?
For this second trait the allele behaves in a dominant manner. (examples agouti and yellow
mice, Manx cats, etc)
¼ of the offspring are homozygous for the dominant mutant allele, and they die during embryonic
development. In the case of Manx cats, the Manx phenotype is dominant in heterozygotes, whereas the
dominant mutant allele is lethal in the homozygous condition.
7. How did Castle and Little conclude that the yellow allele is a lethal allele? (hint: where did
they look and see dead progeny)
Cuénot's crosses resulted in what appeared to be non-Mendelian ratios because he had discovered a
lethal gene. Castle and Little concluded that the yellow allele is a lethal allele by showing that ¼ of the
offspring from crosses between heterozygotes died during embryonic development (Castle & Little, 1910;
Paigen, 2003). This was why Cuénot never observed homozygous yellow. Yellow is dominant for coat
color but recessive for lethality.
8. Given any other similar example be able to pinpoint the presence of a lethal allele that
behaves recessively for the lethality phenotype and dominantly for a different phenotype.
If the heterozygous state is tolerated, it is a recessive lethal allele
If the heterozygous state leads to death, it is a Dominant lethal allele
9. Be able to define conditional lethal alleles and semi-lethal alleles. Given a set of
experimental data be able to pinpoint the presence of such alleles. (eg. Temperature
sensitive alleles)
Conditional Lethal Allele: an allele that is lethal, but only under certain environmental
conditions.
● Example: some conditional lethal alleles, called temperature-sensitive lethal alleles,
cause an organism to die only in a particular temperature range. This includes
Drosophila.
, ● The ts lethal allele is fatal for larva developing in 30 degrees C. Larva that grow at lower
temperatures (22 degrees C) survive.
Caused by mutations that alter the structure of the protein at the nonpermissive temperature.
Semilethal Alleles: lethal alleles that kill some individuals but not all.
● Environmental factors and other genes may help prevent the detrimental effects of
semilethal genes.
● Example: The X-linked white-eyed allele in fruit flies. Depending on the growth
conditions, approximately ¼ to ⅓ of the flies that carry the white-eyed allele die during
early stages of development.
10. Be able to explain the dominant lethal nature of the Huntington allele (Look at the
dominant allele in heterozygote and does it lead to death due to the neurodegenerative
disease). In this case of heterozygote, the individual is able to be born and enter
adulthood, however thereafter he or she begins to develop neurodegeneration that is
100% fatal by 65 years and therefore it is categorized as a lethal allele). What is the nature
of the mutation carried in the disease allele and what is the consequence on the
Huntingtin protein?
Huntington Disease is caused by a dominant lethal allele. It is a degenerative disorder
characterized by progressive dementia and increasingly uncontrollable movement of limbs. Homozygous
dominant individuals die in utero, heterozygous individuals develop normally but get the disease later in
life, and homozygous recessive individuals develop normally.
11. Be able to explain how this lethal mutation continues to be maintained in the human
population.
This lethal mutation is able to be maintained because the age of onset of the disease occurs after
the reproductive age.
12. What is the probability of passing this allele to the next generation if one of the two
parents carries the disease allele and will be definitely affected in adulthood. What would
be the probability of a child who is born, being affected in adulthood if both his/her
parents have the disease allele and will start developing the disease in their adulthood? In
this case look at how the disease allele behaves in homozygotes and whether they survive
during embryogenesis. Do you appreciate some similarity with lethal alleles or Manx
