Sequence recognition

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(Ms) P(M) P(sM) / P(s)
• (Bayes' theorem)
• P(M) and P(s) are prior probabilities and P(Ms)
  is posterior probability.

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Trait prediction

• Probability of trait M given sequence s
• P(Ms) P(M) P(sM) / P(s)
• Posterior Prior standardized likelihood
• Probability predicts unknown outcomes based on
  known parameters. Likelihood estimates unknown
  parameters based on known outcomes.

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Trait prediction

• Probability of trait M given sequence s
• P(Ms) P(M) P(sM) / 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 lt0.01 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 1.670.32 .32 .265/.16

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Trait prediction given diploid s
A likely scenario Not in OMIM
heterozygous P(deleterious s) e.g.
polyphen P(dominant s) P(epistatic s)
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OMIM stats
  Autosomal X-Linked Y-Linked Mitochondrial Total
Gene with known sequence 10812 500 48 37 11397
Known sequence phenotype 351 31 0 0 382
Phenotype, molecular basis known 1892 176 2 26 2096
Phenotype, molecular basis unknown 1423 133 4 0 1560
Suspected mendelian Phenotypes 2000 144 2 0 2146
Total 16478 984 56 63 17581
Dominant 4170, recessive 3674 hits
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Family Risks
Genotype chances if a subject has one copy of a
(co)dominant allele "Aa" most people are "aa".
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Family Risks
Genotype chances if a subject has 2 copies of a
(co)dominant allele "AA" most people are "aa".
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HardyWeinberg 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

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PhenotypeGenetics allele interactions,
epistasis
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