Determining mode of inheritance from pedigrees
Part of the HSC Biology course involves interpreting pedigrees and determining the mode of inheritance of a particular trait. The key is to look for patterns and analyse the pedigree systematically.
We determine the mode of inheritance by ruling out all other possibilities as much as possible.
To show a trait is recessive, we need to see that it cannot be dominant. If two parents without the trait have one or more offspring with the trait, this is a good indication that the trait is recessive. If the trait were dominant, the child must have gotten the dominant allele from at least one parent, who would express the trait is they had that allele. But since neither parent expresses the trait, it cannot be dominant.
Once we have decided that the trait is recessive, we can determine whether it is autosomal or sex-linked. Y-linked traits are extremely rare and can be ruled out as soon as we see a female expressing the trait (coloured circle). So then it is a matter to choosing between autosomal and X-linked inheritance.
To show a trait is autosomal recessive, we need to show it is not X-linked recessive. This can be clearly spotted when a female with the trait has parents without the trait. If the trait were X-linked, the father would only have one copy of the allele – the dominant allele (XD) , since he does not express the trait. He would then inevitably pass on this dominant allele to his daughter, but she cannot possibly possess this allele since she does express the trait (so she would be XdXd). Therefore it is impossible for the trait to be sex-linked.
Another way to disprove X-linkage is if a male without the trait and a female with the trait have either female offspring with the trait or male offspring without. If the trait were X-linked, the male parent would be XDY and the female parent would be XdXd, which means all male offspring would express the trait (XdY) and all female offspring would not (XDXd). Since this is not the case, the trait cannot be sex-linked.
It is not usually possible to definitively rule out autosomal inheritance to confirm X-linkage. However, there are certain patterns that strongly suggest X-linkage. For example, a family where a male parent without the trait (XDY) and a female parent expressing the trait (XdXd) with 100% male expression and 0% female expression implies X-linkage. This is because all male offspring would inherit the recessive allele from their mother (and be XdY) while all female offspring would inherit the dominant allele from their father (and be XDXd).
To show a trait is dominant, we need to find some evidence to show that it is not recessive. The most obvious way we see this is if two parents with the trait have one or more offspring without the trait. This would be impossible if the trait were recessive, as both parents would be homozygous recessive, so it would not be possible for a child to have the dominant allele.
Once we have established that a trait is dominant, in order to show that it is autosomal, we need to rule out the possibility of X-linkage.
The pattern where a male with the trait and a female without the trait produce a male with the trait or a female without the trait is one that can rule out X-linkage. If the trait were X-linked, the male parent would have the dominant allele (XDY) and the female parent would be homozygous recessive (XdXd). Therefore all male offspring would not express the trait (XdY) and all female offspring would (XDXd). As this is not the case, it would be impossible for the trait to be X-linked dominant.
Once again, it is not usually possible to definitively rule out autosomal inheritance but there are some patterns that strongly imply X-linkage. For example, a male with the trait (XDY) and a female without (XdXd) who have 100% of female offspring expressing the trait (XDXd) and 100% of male offspring not expressing the trait (XdY) is strongly suggestive of X-linked dominant inheritance.