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Understanding Sequence Recognition and Trait Prediction in Genetics

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This presentation delves into the principles of sequence recognition and trait prediction using Bayes' theorem. It explains how to calculate the posterior probability of a trait M given a sequence s (P(M|s)) by considering prior probabilities and standardized likelihoods. The importance of monogenic traits, such as obesity, is discussed alongside their statistical significance. Models of genotype predictions are illustrated, emphasizing Hardy-Weinberg equilibrium and the factors that influence genetic traits. Key terms and foundational concepts are briefly outlined for clarity.

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Understanding Sequence Recognition and Trait Prediction in Genetics

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Presentation Transcript

  1. Sequence recognition (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.

  2. Trait prediction 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.

  3. Trait prediction 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]

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

  5. OMIM stats Dominant= 4170, recessive 3674 hits

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

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

  8. 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

  9. PhenotypeGeneticsallele interactions, epistasis http://galitski.systemsbiology.net//

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