Sequence recognition P(M|s) = P(M)* P(s|M) / P(s) (Bayes' theorem) (from Apr 12 ppt) Recognition question - What is the probability that the sequence s is from the start site model M ? P(M|s) = P(M)* P(s|M) / P(s) (Bayes' theorem) P(M) and P(s) are prior probabilities and P(M|s) is posterior probability.

Trait prediction P(M|s) = P(M)* [P(s|M) / P(s)] Probability of trait M given sequence s P(M|s) = P(M)* [P(s|M) / P(s)] Posterior = Prior * [standardized likelihood] Probability predicts unknown outcomes based on known parameters. Likelihood estimates unknown parameters based on known outcomes.

Trait prediction Monogenic: 1 = 1E-4 *[7E-2 /7E-7] Probability of trait M given sequence s P(M|s) = P(M)* [P(s|M) / P(s)] Monogenic: 1 = 1E-4 *[7E-2 /7E-7] “Monogenic forms of obesity at present account for approximately 7% of children with severe, young-onset obesity (3), but as this severity of obesity is only seen in <0.01% of the population .. 66% of the U.S. population had a BMI ≥ 25 kg/m2 and 32% were obese .. FTO: The 16% of adults who are homozygous for the risk allele weighed about 3 kilograms more and had a 1.67-fold increased risk of obesity” . --Frayling et al. Science 12 April 2007 FTO: 1.67*0.32 = .32 * [ .265/.16]

Trait prediction given diploid s A likely scenario: Not in OMIM & heterozygous P(deleterious | s) e.g. polyphen P(dominant | s) P(epistatic | s)

OMIM stats Dominant= 4170, recessive 3674 hits Autosomal X-Linked   Autosomal X-Linked Y-Linked Mitochondrial Total Gene with known sequence 10812 500 48 37 11397 Known sequence & phenotype 351 31 382 Phenotype, molecular basis known 1892 176 2 26 2096 Phenotype, molecular basis unknown 1423 133 4 1560 Suspected mendelian Phenotypes 2000 144 2146 16478 984 56 63 17581 Dominant= 4170, recessive 3674 hits

Genotype % chances if a subject has one copy of a (co)dominant allele "Aa" & most people are "aa". Family Risks

Genotype % chances if a subject has 2 copies of a (co)dominant allele "AA" & most people are "aa". Family Risks

Hardy–Weinberg equilibrium Assumptions: Diploid Trait is autosomal Is sexually reproducing, either monoecious or dioecious Discrete generations Random mating within a single population Population size sufficiently large so to minimize effect of genetic drift No selection, mutation, migration

PhenotypeGenetics allele interactions, epistasis http://galitski.systemsbiology.net//