9 lines
2.3 KiB
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9 lines
2.3 KiB
Markdown
## Heterozygosity
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http://gatkforums.broadinstitute.org/gatk/discussion/8603/heterozygosity
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<h3>Heterozygosity in population genetics</h3>
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<p>In the context of population genetics, heterozygosity can refer to the fraction of individuals in a given population that are heterozygous at a given locus, or the fraction of loci that are heterozygous in an individual. See the Wikipedia entries on <a href="http://en.wikipedia.org/wiki/Zygosity#Heterozygosity_in_population_genetics">Heterozygosity</a> and <a href="https://en.wikipedia.org/wiki/Coalescent_theory">Coalescent Theory</a> as well as the book "Population Genetics: A Concise Guide" by John H. Gillespie for further details on related theory.</p>
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<h3>Heterozygosity in GATK</h3>
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<p>In GATK genotyping, we use an "expected heterozygosity" value to compute the prior probability that a locus is non-reference. Given the expected heterozygosity <code>hets</code>, we calculate the probability of N samples being hom-ref at a site as <code>1 - sum_i_2N (hets / i)</code>. The default value provided for humans is <code>hets = 1e-3</code>; a value of 0.001 implies that two randomly chosen chromosomes from the population of organisms would differ from each other at a rate of 1 in 1000 bp. In this context <code>hets</code> is analogous to the parameter <code>theta</code> from population genetics. The <code>hets</code> parameter value can be modified if desired.</p>
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<p>Note that this quantity has nothing to do with the likelihood of any given sample having a heterozygous genotype, which in the GATK is purely determined by the probability of the observed data P(D | AB) under the model that there may be an AB heterozygous genotype. The posterior probability of this AB genotype would use the <code>hets</code> prior, but the GATK only uses this posterior probability in determining the probability that a site is polymorphic. So changing the <code>hets</code> parameters only increases the chance that a site will be called non-reference across all samples, but doesn't actually change the output genotype likelihoods at all, as these aren't <em>posterior</em> probabilities. The one quantity that changes whether the GATK considers the possibility of a heterozygous genotype at all is the <em>ploidy</em>, which describes how many copies of each chromosome each individual in the species carries.</p> |