Sib pair studies are a quite common design when looking
for linkage. But recently these studies have been finding false positives
and excess sharing even in discordant sib pairs. This suggests that siblings
actually share more than the 50% of the genome that we would expect under
Mendelian inheritance. One possible explanation for this phenomenon might
be the existence of recessive lethals that persist in the genome. The existence
of a recessive lethal would cause patterns of inheritance which consist
of an increase in overall proportion of IBD sharing, an increase in proportion
of siblings sharing both parental genes IBD, but a decrease in the proporion
sharing one or none of their genes IBD. Using a hidden Markov model we
can calculate probabilities of IBD states between two and three sibs jointly
over regions of the chromosome. A Monte Carlo test can give us an indication
of regions where there is more or less sharing than expected. |
