Huntington Disease Pedigree Problem

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SUMMARY

The discussion centers on the interpretation of a pedigree for Huntington disease, specifically regarding the genotypes of individuals II.1 and II.2. It is established that person II.1, despite being indicated as unaffected, likely has the genotype A/- due to the dominant nature of Huntington disease. The discussion clarifies that the presence of slashes indicates deceased individuals, not those affected by the disease. Furthermore, it emphasizes that the likelihood of Susan developing Huntington disease is low, primarily because her mother is likely homozygous recessive (aa) given her lack of symptoms.

PREREQUISITES
  • Understanding of Mendelian genetics, particularly dominant and recessive alleles.
  • Familiarity with the inheritance patterns of late-onset disorders, specifically Huntington disease.
  • Knowledge of pedigree analysis and its symbols, including the significance of filled and unfilled shapes.
  • Ability to interpret genotypes and their implications in genetic counseling.
NEXT STEPS
  • Research the genetic basis of Huntington disease and its inheritance patterns.
  • Learn about pedigree construction and analysis techniques in genetic studies.
  • Explore the implications of genotype determination in genetic counseling for families with a history of Huntington disease.
  • Investigate the impact of age and environmental factors on the expression of late-onset genetic disorders.
USEFUL FOR

Genetic counselors, medical students, and anyone involved in genetic research or familial health history analysis will benefit from this discussion, particularly those focused on Huntington disease and pedigree analysis.

Sunwoo Bae
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Homework Statement
This pedigree is for Huntington disease, a late-onset disorder of the nervous system. The slashes indicate deceased family members.

a) Is this pedigree compatible with the known mode of inheritance for Huntington disease?
b) Form an opinion on the likliehood that Susan and Alan will develop Huntington disease. Assume for the sake of the discussion that praents have children at age 25.
Relevant Equations
None
The first picture is the image given in the question, and the second picture is the possible genotypes given in the solution manual.

1659534834124.png
1659534631361.png


How is it possible that person II.1 (first male in the second generation) has the genotype A/- when he is unaffected? I thought that because person II.1 and person II.2 are both unaffected, their corresponding genotypes would be aa and aa, and the possibility of Susan having the disease would thus be 0. However, the solution manual suggests that the possibility of Susan developing the disease is very low, because her great-grandmother (person II.2 is 75 years old but is still alive, and thus is unlikely to have Huntigton disease).

In short, my question is:
1. person II.1 is deceased, yet is indicated as normal male (uncolored square). Is he affected or not? How should I indicate his genotype?
 
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Important note: the slashes mean deceased (i.e., dead), not diseased. The fact that the answer key got this wrong indicates that maybe you’re using a low-quality textbook. The slash indicates these individuals have died, but says nothing about why they died. The filled in shapes indicate that they have Huntington’s disease.

As for your questions:
Sunwoo Bae said:
Homework Statement:: This pedigree is for Huntington disease, a late-onset disorder of the nervous system. The slashes indicate deceased family members.

a) Is this pedigree compatible with the known mode of inheritance for Huntington disease?
b) Form an opinion on the likliehood that Susan and Alan will develop Huntington disease. Assume for the sake of the discussion that praents have children at age 25.
Relevant Equations:: None

How is it possible that person II.1 (first male in the second generation) has the genotype A/- when he is unaffected?
This seems incorrect, and makes me further doubt the quality of your textbook. In fact, since this person is not a descendant of the first generation (he “married into” the family, so to speak), there isn’t really anything you can deduce about him from the earlier generation. The fact that none of their kids have Huntington’s means that this individual must have at least one recessive allele (since HD is dominant). So if anything, his genotype is a/-.
Sunwoo Bae said:
Homework Statement:: This pedigree is for Huntington disease, a late-onset disorder of the nervous system. The slashes indicate deceased family members.

a) Is this pedigree compatible with the known mode of inheritance for Huntington disease?
b) Form an opinion on the likliehood that Susan and Alan will develop Huntington disease. Assume for the sake of the discussion that praents have children at age 25.
Relevant Equations:: None

However, the solution manual suggests that the possibility of Susan developing the disease is very low, because her great-grandmother (person II.2 is 75 years old but is still alive, and thus is unlikely to have Huntigton disease).
Strictly speaking, this is more accurate, because you don’t know with any confidence whether Susan’s mother is aa or Aa. Since Susan’s mother has not developed symptoms, it is very likely that she is aa, but there is a small chance that she is Aa.

The other thing to note is that the genotype for the male in the first generation is likely aa, rather than the Aa indicated in the answer key, as Aa would very likely have developed HD symptoms later in life. One disadvantage of a genogram like this is that it gives no indication of cause of death. If the first gen male was Aa but died in a car wreck at age 30, he likely would have been too young to develop HD symptoms, whereas if he had lived to age 50, he likely would have begun to develop signs of the disease.
 
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TeethWhitener said:
Important note: the slashes mean deceased (i.e., dead), not diseased. The fact that the answer key got this wrong indicates that maybe you’re using a low-quality textbook. The slash indicates these individuals have died, but says nothing about why they died. The filled in shapes indicate that they have Huntington’s disease.

As for your questions:

This seems incorrect, and makes me further doubt the quality of your textbook. In fact, since this person is not a descendant of the first generation (he “married into” the family, so to speak), there isn’t really anything you can deduce about him from the earlier generation. The fact that none of their kids have Huntington’s means that this individual must have at least one recessive allele (since HD is dominant). So if anything, his genotype is a/-.

Strictly speaking, this is more accurate, because you don’t know with any confidence whether Susan’s mother is aa or Aa. Since Susan’s mother has not developed symptoms, it is very likely that she is aa, but there is a small chance that she is Aa.

The other thing to note is that the genotype for the male in the first generation is likely aa, rather than the Aa indicated in the answer key, as Aa would very likely have developed HD symptoms later in life. One disadvantage of a genogram like this is that it gives no indication of cause of death. If the first gen male was Aa but died in a car wreck at age 30, he likely would have been too young to develop HD symptoms, whereas if he had lived to age 50, he likely would have begun to develop signs of the disease.
Thank you for your explanation. My confusion has been cleared! :)
 
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