Adrenoleukodystrophy

Adrenoleukodystrophy

Genetics and Inheritance pattern

Please cite your sources in intext citations after each question and a full reference list, using proper APA format.

Lorenzo Odone was born into a family in which neither of his parents showed the disease.

1. Assuming there was no spontaneous mutation, can you determine whether the trait is dominant or recessive? Why or why not? (1 pt)

According to the National Organization for Rare Disorders, ALD affects between 1 in 10,000 and 1 in 17,000 individuals. (X-Linked Adrenoleukodystrophy, 2020). ALD is a disease that is expressed differently in different individuals.

There are 4 forms of the disease seem in males:

• Childhood cerebral ALD which affects about 1/3 of affected males during early childhood (ages 3- 10). This is the most severe form and affects neurological functions, leading to loss of cognitive function, visual, motor skills, and more. The adrenal gland may also be affected, leading to Addison’s disease. Patients eventually lose all neurological functions and die within several years of onset.

• Adrenomyeloneuropathy (AMN) which begins in early adulthood and affects peripheral nerves and adrenal gland.

• Adult cerebral ALD affects 20% of males with ALD, and often develops in adults who have developed AMN, resulting in the same symptoms as childhood cerebral ALD.

• Addison’s only ALD affects 10% of males and affects the adrenal gland only.

Female carriers of ALD may show symptoms, though lesser than males, and often occurring later in life. Only 20% of female carriers show symptoms of ALD prior to age 40. By age 60, 90% of females will show symptoms. Females rarely show cerebral or adrenal gland involvement.

All males will show elevated levels of VLCFA’s in their blood, while only around 80% of carrier females will show elevated levels.

Watch the video below to see how ALD affects families.

2. Based on this information, is ALD an X-linked or autosomal trait? Why? (1 pt)

3. If X^A represents the normal allele and X^a represents the allele for ALD, write the genotypes for each of the following: (3 pts)

Lorenzo:

Lorenzo’s mother:

Lorenzo’s father:

4. a. What is the likelihood that Lorenzo’s parents would have another son with ALD? Please give the expected %. (1 pt)
5. What is the likelihood that Lorenzo’s parents would have a daughter with ALD? Please give the expected %. (1 pt)
6. Lorenzo most likely inherited the allele from which parent? (1 pt)
7. Lorenzo’s aunt (his mother’s sister) also was a carrier of the trait. No one in the immediate family had ALD. Assuming this was not a spontaneous mutation, it is likely that his aunt and his mother both inherited the trait from their ______? (1 pt)

7. What is X inactivation? How can this account for the lesser symptoms seen in some female carriers of ALD? (2 pts)

8. What would happen if a female had 2 copies of the mutated allele? (1 pt)

9. Assume the pedigree below shows the inheritance of ALD. Individuals with colored in boxes have ALD.

List all of the individuals who are definite carriers for ALD. Write both the generation and the number (II – 1 for example) (3 pts)