Past exam of the mathematics course of the University of Cambridge / 2005 / iii / Paper 45 / 1 / vi

Put $N=n_0+n_1+n_2$ and $s=2x=2\theta (1-\theta )$. The usual recombination fraction range $0\le \theta \le 1/2$ gives $0\le s\le 1/2$, and the preceding likelihood function becomesTo see its relation to nonparametric linkage analysis, use Bayes' theorem and the constant disease probability $1/16$ to obtain the affected-pair marker-sharing probabilitiesTheir multinomial likelihood has exactly the same $s$-dependent kernel, since its extra factor $2^{n_1}$ is constant. Set $A=2n_0+n_1$ and $B=2n_2+n_1$. Then $A+B=2N$, and $B$ is the total number of shared ancestral copies. At fixed $N$, the Fisher-Neyman factorization theorem makes $B$ a sufficient statistic. The observed mean shared proportion is $\hat{p}=B/(2N)$, and the binomial likelihood kernel givesThe unlinked null is $s=1/2$, whereas linkage corresponds to $s<1/2$, or expected shared proportion $1-s>1/2$. If $\hat{p}\le 1/2$, the constrained likelihood is maximized at the unlinked null. For $\hat{p}>1/2$, its log likelihood ratio iswhose derivative in $\hat{p}$ is $2N\log [\hat{p}/(1-\hat{p})]>0$. Hence it orders samples exactly by excess IBD sharing. Under this fully penetrant recessive model, parametric linkage testing and a one-sided test of the overall IBD-sharing proportion use the same information. This is allele-sharing sufficiency for recessive linkage, not a general equivalence for all disease models. Use limiting values for terms such as $0\log 0$, and assume $N>0$ for the estimators.