**Edit 1:** The following is Y/Auto depth versus age in a cohort. Individuals in this cohort are not known to be cancer patients.

![enter image description here][1]

**Original question:**

In WGS/WES studies I read and studies I participated in analyzing, I notice that the average sequencing depth on Y chromosome vary a lot more than X chromosome, and the depth is mostly less than the average depth on autosomes (see the figure for an example; from [Turro et al. 2020][2]). Most individuals that got sampled do not have diseases involving large deletion of Y chromosome. 

What causes the variability in the sequencing depth on Y chromosome? Why is the average depth on Y almost always less than that on autosomes?

![enter image description here][3]

  [1]: /media/images/50b4a58e-0c41-4919-890c-49cd71bc
  [2]: https://www.nature.com/articles/s41586-020-2434-2.pdf
  [3]: /media/images/835d5568-c6e1-4f3f-a0b0-2836db5b
Hi Samuel,

I would guess it is the age related "Loss of the Y chromosome" you see in the data, which is a known effect.
See:
[Loss of Chromosome Y and Its Potential Applications as Biomarker in Health and Forensic Sciences][1]
for example.

"Loss of chromosome Y (LOY) is a mosaic aneuploidy that can be detected mainly in blood samples of male individuals. Usually, LOY occurrence increases with chronological age in healthy men."

"The mechanism by which LOY occurs is yet to be elucidated. It is not known whether the Y chromosome is lost as a whole or if it is a gradual deletion process during the lifespan."

We see that quite a lot  in our WES data of older men.


  [1]: https://www.karger.com/Article/FullText/508564