Zygosity Of A Copy Number Variant

Question

[Pascal]

This question is similar to the one I wrote yesterday (Frequency of homozygous indels vs heterozygous indels) but this one is specific to Copy Number Variants.

So, do we observe more heterzygous CNV than homozygous ones in population?

[Sean Davis]

Perhaps it would be helpful to define what a heterozygous or homozygous CNV actually is. A copy number variant can actually arise in several ways. For example, not all sequence objects that give rise to a CNV are in cis, so het versus hom might not actually make sense for many CNVs.

[Larry_Parnell]

I don't know that it really matters, but I have to ask. Are you asking about human or other populations? Dogs, which tend to be inbred, may show different patterns, for example than "wild" fruit flies. Many crop species are highly inbred.

[Pascal]

Well I'm asking for human but this is an interesting point.

[Larry_Parnell]

Right. And partial overlap of "independent" CNVs could lead to a number of switches from het to hom across the CNV region.

[Matt Shirley]

From personal experience with human Affy microarray data, mostly hemizygous states are observed. But, as noted above, this has almost nothing to do with underlying biological mechanisms. For example, a conservative rearrangement to another chromosome could produce something that you would consider a homozygous deletion functionally, but you would not see that based on SNP array data.

Answer 1

[QVINTVS_FABIVS_MAXIMVS]

In accordance to HWE you expect to see more HET alleles than HOM alleles. Once you start including mCNV it gets confusing and selection can muck things up (say if a HOM deletion is advantageous)

If you're interested in finding the zygosity of a CNV you can use my script which assigns copy number to (assumed) biallelic CNV gtCNV