Hello,
I am working on a case which patient is diagnosed with PD. In their WES results, a total homozygous deletion of 3rd and 4th exomes of the PARK2 gene is present. There is consanguinity in paitent's parents and they do not show any symptomes of the disease.
Can the genotypes of the parents (both are estimated to carry the deletion in one alelle) be estimated with WES results? We used IGV to detect the patient's, however this does not seem to work with the cases that patient carries only one damaged alelle.
Hi
According to recent research, DNA variations outside the exons can also lead to genetic disorders.
But first you can start with WES result analysis. If that does not yield desired outcome you can move to further analysis of the genome.
You can refer this article for help in this regard: https://www.ncbi.nlm.nih.gov/m/pubmed/25535679/
Hope it was helpful.
Hi,
It sounds like you have a trio-samples from a family. You saw a DELETION of two exons of PARK2 in child's sample.
If the deletion is de-novo event (which means happened only in the child's body), you would not see any signal in samples of the parent.
else, the deletion is GERMLINE mutation passed from the parent. In this case,
homozygous deletions can be observed directing from gap in reads depth in IGV. But heterozygous deletions might be difficult to determine as there are reads in these two exons. In this case, you need a mutation calling for copy number variation in this region.Many software can do this job. please refer this abstract:
http://www.cidr.jhmi.edu/nih/CNV_IGES2015.pdf
or maybe more recent reviews.
CNVkit is a good software with automatic plotting, while it's installation might be painful without advance bioinformatics experiences. Also there are some CNV tools designed for trio-data : PLINK/SEQ , you can find heterozygous deletions through a pitfall of reads depths.
https://www.biostars.org/p/289370/
Using CNV-array is another choice. It is less expensive to validate if you are confident about the pathogenic role of this deletion.
Best,
Shuo
It depends.
If a deletion is much smaller than the size of your reads then yes, it is possible. In that case, your variant caller of choice will have probably also picked it up and tagged it as 'indel' (insertion/deletion) and you could then use IGV to visualise it and its context.
On the other hand, if your deletion is much larger than the size of your reads, which means you're most likely dealing with a copy number variant (CNV), you might be able to make out a drop in read depth on IGV, but you could never be sure if that was truly due to a CNV or the uneven read depth typical of WES. In this case, instead of IGV, you should use tools designed to identify CNVs, such as ExomeDepth:
https://omictools.com/exomedepth-tool
(For the best results you will have to compare your sequencing data to other data originating from the same platform and, ideally, the same physical machine)
Hope this helps.
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