After a long day of studying for the MCAT, you decide to finish up with some quick biology practice. You turn to the first passage in your prep book and see this:
“Disease X is a blood disorder caused by a mutation in a clotting factor gene. Jane’s father, sister, and brothers have Disease X, but her mother does not. Jane’s male cousin also suffers from Disease X, even though his parents are healthy; her uncle has the disease, but has a healthy son…”
Your eyes start to glaze over, so you take a look at the associated figure:
Figure 1 Pedigree of Jane’s family (J = Jane); dark shading represents disease phenotype; circles = females and squares = males
Panic sets in – you don’t know anything about Disease X! How can you even tell what mode of inheritance it follows? Autosomal recessive? Dominant? Sex-linked?
Luckily, you can use a few simple tricks to recognize modes of inheritance quickly. Commit these to memory, and you’ll be attacking MCAT genetics problems in no time!
1. If the disease or condition skips generations, it must be recessive. In other words, if two healthy parents have a child with the condition, it cannot possibly be a dominant trait. For a child to have the disease, he or she must have inherited at least one disease allele from a parent, and if the disease were dominant, that parent would show the disease phenotype. Since the parent does not, it must be recessive. Returning to Jane’s family pedigree, we see that this is the case (below); Disease X is a recessive condition.
2. If more males than females have the disease or condition, it is more likely to be X-linked recessive. This isn’t a guarantee; due to simple chance, more males than females could have a condition even if it were autosomal (located on a non-sex chromosome). However, remember that females have two X chromosomes, so they will not display the disease phenotype if they have only one recessive disease allele. In contrast, males have only one X chromosome, so one “disease” allele is enough for them to have the condition. Most of Jane’s affected relatives are male, so Disease X is looking like a good candidate to be X-linked.
3. Furthermore, if a disease is X-linked recessive, fathers will never pass it down to their sons. Fathers give sons their Y chromosomes, not X! For this reason, affected males must always receive their disease allele from their mothers, who could be either carriers or fully affected themselves. Jane’s cousin and uncle didn’t inherit Disease X from their fathers, but what about her brothers? Pay close attention – since Jane’s sister has Disease X (and thus must have two disease alleles), Jane’s mother must be a carrier and easily could’ve given her sons her disease allele. X-linked recessive it is!
Other useful tips:
4. If only males have the condition, it’s probably Y-linked, though these conditions are very rare. Only males carry Y chromosomes!
5. If all children of affected mothers have the condition, but no children of affected fathers and healthy mothers do, it’s probably mitochondrial. Mitochondria have their own genetic material, which is passed down through the maternal line. A number of diseases are inherited in this fashion.
We hope you find these tips helpful, and good luck studying!