I'm doing a theoretical project on haplotype assembly, and I need a reasonable method for generating a realistic diploid stretch of DNA. For example, if the density of heterozygous alleles is approximately one every thousand bases, then I would generate a diploid version by randomly mutating every position with probability 1/1000.
So in a typical human genome, what is the density of heterozygous alleles? Or in other words, what is the mean number of base pairs between heterozygous alleles?
•
written
by
Ryan Thompson
It is 1e-3 for Africans and ~0.8e-3 for typical non-Africans. If a population went through a severe bottleneck recently, the heterozygosity is smaller. Uniformly generating heterozygotes in a random way is good enough for some purposes, but if you want a more realistic simulation, you should use a coalescent simulator, such as ms or MaCS. In a coalescent process, which approximates human evolution quite well, the distance between adjacent heterozygotes follows a distribution much fatter than a poisson distribution. As a result, you more frequently get a region with a lot of heterozygotes or a very long stretch of homozygosity.
Another way is to take the consensus sequence from a published personal genome, which is more realistic to some extend, but also has more bias.
Thanks, Heng. I went for simple in my answer, but clearly there is much more detail in "doing this right".
You could generate intervals between variants using a poisson distribution. You could use sampling from known snp allele frequencies for genotype probabilities, with the knowledge that "known" snps are skewed toward common snps.
Log in to answer this question.
