Answer ALL the yes/no questions concerning each of the following 4 pedigrees by
ID: 101780 • Letter: A
Question
Answer ALL the yes/no questions concerning each of the following 4 pedigrees by highlighting your answer in BOLD RED. [Circles -females, Squares-males, shaded indicates trait is expressed, e.g. a disease trait]. Assume that none of these traits is the result of a spontaneous mutation in the pedigree. Also assume that partners unrelated to the original grandparents are NOT carriers of mutations, unless they show the trait (shaded). Also assume 100% penetrance for all pedigrees. That is, dominant alleles will always be expressed in both homozygous and heterozygous genotypes and recessive alleles will only and always be expressed in homozygous genotypes. Hint: the best way to approach answering these questions is to take a given hypothesis (e.g. "this trait could be inherited as a simple autosomal dominant"), and assign genotypes to the pedigree individuals to see if that hypothesis is viable.Explanation / Answer
We will solve each of these pedigrees separately:
Let us first revise the clues that help us understand which pattern of inheritance the pedigree shows:
Autosomal dominant: Regardless of which parent (mother or father) is affected, one affected heterozygous can cause 50% of its progeny to have the disorder. One affected homozygous will have all of its progeny to be diseased. There are no carriers in this pattern.
Autosomal recessive: Regardless of which parent (mother or father) is affected, one affected heterozygous will have 50% healthy and 50% carrier progeny. The clue is, such a pattern will never have affected progeny, unless, one partner is carrier and the other diseased/carrier.
X-linked recessive: Males carrying the mutation will always be diseased because they have only one X chromosome. Females carrying one disease gene will be carriers and if they carry two affected genes they will be diseased.
X-linked dominant: Males carrying the mutation will always be diseased. Hence, it is not possible to identify whether the X-linked disease is dominant or recessive by looking at the male. It is the female which will help us identify. A female carrying one or two disease alleles will express the disease, there are no carriers in this pattern.
Since we understand the pattern now, we will look at each pedigree:
1. If you look at the bottom part where an affected male with an unaffected female give birth to one unaffected male and one unaffected female, we can find a clue:
a. Autosomal recessive? – To eliminate the chances that one of the partners is a carrier, we should find a place where either the male or the female is unaffected and unrelated to the original pedigree and we will take advantage of the fact that these can’t be carriers. Since the affected father and unaffected mother (non-carrier, unrelated) have no affected children, yes, it could be autosomal recessive.
b. Autosomal dominant? – 50% progeny will be affected. No, it couldn’t be autosomal dominant.
c. X-linked dominant? – All daughters should be affected because they carry X from father. This is not the case. No, it couldn’t be X-linked dominant.
d. X-linked recessive? – All daughters should be carriers, all sons should be healthy. Nobody should be diseased. Yes, it could be X-linked recessive.
You can confirm these cases by looking at the other side where an unaffected male and an affected female give birth to two affected males and one unaffected female.
2. Let’s take a look at the part where an affected male and an unaffected female give birth to an affected female, an unaffected female, and an unaffected male.
a. Autosomal recessive? – Since one of the child (regardless of sex) is affected, it couldn’t be autosomal recessive. Also, if you look at the part where an unaffected father (unrelated to the pedigree) and an unaffected mother (related to the pedigree) give birth to an affected son and an unaffected daughter, you may reassure the claim.
b. Autosomal dominant? – Since one out of three children are affected, it could be autosomal dominant looking at this part of the pedigree. However, it should be noted that there are no carriers in autosomal dominant disorders. If you look at the other part of the pedigree where an unaffected male and an unaffected female give birth to one affected male and one unaffected female, we can deduce that it couldn’t be autosomal dominant since none of the parents had any disorder (and they can’t be carriers either).
c. X-linked recessive? – We will get back to focus on the part where an affected male and an unaffected female give birth to an affected female, an unaffected female, and an unaffected male. In order for one daughter to be affected, the mother must be a carrier, who got her affected X chromosome from her affected father. Yes, it could be X-linked recessive.
d. X-linked dominant? – In X-linked dominant, an affected father would have all affected. Since this is not the case, it couldn’t be X-linked dominant.
3. Let’s focus on the part where an unaffected male and an affected female give birth to two unaffected daughters, one unaffected male, and one affected male.
a. Autosomal recessive? – Since there are affected progeny (while the male is not a carrier), it couldn’t be autosomal recessive.
b. Autosomal dominant? – Are there affected progeny? Yes. Are there any signs of carriers in the whole pedigree? No. Therefore, yes, it could be autosomal dominant.
c. X-linked recessive? – For X-linked recessive, the affected female should have both alleles affected. This means that all of her sons (who inherit one of her X chromosomes) must be affected too. Since one of the sons is not affected, it couldn’t be X-linked recessive.
d. X-linked dominant? – Let’s take a look at the top where an affected male and an unaffected female give birth to two unaffected males, one affected male, one unaffected female, and one affected female. Since the male has an X chromosome affected, all of his daughters must be affected too since they will carry his X chromosome. We see that it isn’t the case so it couldn’t be X-linked dominant.
4. We need to focus on the part where an unaffected male (related) and an unaffected female (unrelated) give birth to two unaffected sons, one affected son, one unaffected daughter, and one affected daughter.
a. Autosomal recessive? – The progeny shouldn’t be affected if a diseased individual mates with an unaffected (non-carrier) individual. However, there is no way for us find out whether the unaffected male is a carrier or not. He being a carrier provides a 50% probability that the progeny will be affected. Our inability to refute the claim that it is not autosomal recessive compels us to keep the possibility that it could be autosomal recessive.
b. Autosomal dominant? – Are there affected progeny? Yes. Are there signs of carriers? No. Yes, it could be autosomal dominant. It is interesting to see that if that unaffected male is a carrier, we can dismiss the claim that it is autosomal dominant. If the unaffected male isn’t a carrier, we can dismiss the claim that it is autosomal recessive. Since, we don’t have any way to find out, we must keep both the possibilities.
c. X-linked recessive? – For X-linked recessive, the affected female must have both affected X chromosomes. This would mean that all the males should be affected but we can observe an unaffected male. Hence, it is not X-linked recessive.
d. X-linked dominant? – If you look at the top of the pedigree where an affected male mates with an unaffected female, you will see that none of the progeny was affected. Since all females inherit the X chromosome from the father, they should be affected too if the father was affected. This isn’t the case here and hence, it is not X-linked dominant.