What Is The Typical Density Of Heterozygous Alleles In A Diploid Human Genome?
2
4
Entering edit mode
10.1 years ago
Ryan Thompson ★ 3.5k

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?

genomics haplotype • 4.5k views
ADD COMMENT
9
Entering edit mode
10.1 years ago
lh3 32k

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.

ADD COMMENT
0
Entering edit mode

Thanks, Heng. I went for simple in my answer, but clearly there is much more detail in "doing this right".

ADD REPLY
0
Entering edit mode
10.1 years ago

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.

ADD COMMENT

Login before adding your answer.

Traffic: 2054 users visited in the last hour
Help About
FAQ
Access RSS
API
Stats

Use of this site constitutes acceptance of our User Agreement and Privacy Policy.

Powered by the version 2.3.6