I am investigating novel variants in two male sibs under X-linked inheritance model. When looking at the shared novel functional variants on X-chromosome between the sibs I found many heterozygous variants which doesn't make sense (I expect most to be hemizygous).
The possible explanations I came up so far:
A possible swap with female samples -> but there are variants on Y-chromosome in both samples.
Variants are on one of the two pseudoautosomal regions (PARs) which are exact duplicates:
chrY:10001-2649520 and chrY:59034050-59363566
chrX:60001-2699520 and chrX:154931044-155260560 (from UCSC GRCh37)
-> Yes, this explained about third of those variants found on X-chromosome but the rest are on different regions.
The variants were called using SamTools/GATK using hg19 reference genome.
I would like to know if you've faced similar issue, what is your explanation and what would you do to verify your explanation/hypothesis.