Tutorial Two Model Answer

You were expected to have looked at the tutorial beforehand and to have come with prepared answers. This is not because the work forms part of the in course assessment (which it does not) but to enable the group to spend time discussing the more remote possibilities…

Pedigree 1

This is most likely to be an X linked recessive. It is clearly not too severe - might be something like colour blindness.

Points to notice:
1. the cousin marriage has allowed the expression of the condition in a female. In the case of severe XR conditions (e.g. DMD) it would be most unusual to find an affected female. How might an affected female arise?
   1. Non disjunction leading to uniparental disomy
   2. non random X inactivation… perhaps caused by an X-autosome translocation remember the DMD story
   3. new mutation in the paternal gamete
2. Could this be an autosomal recessive? Yes if four carriers have entered the pedigree. Who? I1, I2, II1 & II6. What chance of this? Depends on the gene frequency. Lets say that (like colour blindness) the condition affects one birth in 24. If XR then the gene frequency must be 0.083 (one male in 12 affected which displays the frequency of mutated X chromosomes directly) so the chance of the pedigree is roughly 1 in 6 (0.167) (I2's chance of carrying an affected X) (really it's 2pq so it's 2 × 11/12 × 1/12 = 0.153 which is about 2 in 13). If AR then carrier frequency is found from Hardy-Weinberg and is about 1 in 3. Chance of all four people who have married into this pedigree all being carriers is approximately (1/3)⁴ which is 1 in 81.

Pedigree 2

This is most likely to be an autosomal recessive. There's not much that you can add except perhaps to point out that if you have one affected person the people who are most likely also to be affected are his/her siblings. e.g. cystic fibrosis

Pedigree 3

This also looks like an X linked recessive. Its unlucky that all three sisters in the second generation are carriers but not impossible. An example of an X linked recessive lethal is haemophilia

Pedigree 4

Probably autosomal dominant but only because X linked dominants are so very rare. Look at the way that females pass it to both sexes whereas males transmit it to all their daughters and none of their sons. Looks very X linked doesn't it! How do you know it's not mitochondrial? An example of an X linked dominant is chondrodysplasia punctata

Pedigree 5

A strange one. If you guessed that it's X linked recessive because only males are affected you are wrong. There is transmission through a female (II₂) which is OK.  But there is also transmission from male to male, twice, which is impossible if X linked. A possible answer might be autosomal dominant with sex limited expression. e.g. androgenetic alopecia (male pattern baldness)

Risk Calculation

	For the Bayes Theorem calculation see these notes:
	And the additional information on Bayes theorem: