I am looking at possible modifications to mapping software that could make variant calling in the X and Y chromosome regions more accurate. Perhaps an example would shed more light on the issue I'm trying to get at.

The pseudoautosomal regions in Y (PAR1 & PAR2) exchange DNA with homologous regions in X, thus acting diploid. It would seem ideal for variant calling to be likewise diploid here, making homozygous or heterozygous calls based on ALL the reads aligning well to these regions, as is done for the autosomal chromosomes, with the MAPQ of these reads being high unless they align nearly as well to other unrelated regions. But if full X and Y reference sequences are used, then supporting reads will map arbitrarily to the homologous X and Y regions, and even if variant calling tools merge them back into a single pileup, their maximum-likelihood analysis would be crippled by near-zero MAPQ scores. It seems plausible to me that if these regions were masked to N’s in the Y chromosome, for example, associated reads would get mapped into only the X regions, with meaningful MAPQ, and accurate diploid variant calling would thereby be facilitated. I know that Complete Genomics, for example, does make bi-allelic variant calls in the pseudoautosomal regions of the X and Y chromosomes, with positions always reported in the X chromosome. I am trying to discover whether something like the Y masking I imagine, or some other method, is used in current practice to achieve accurate variant calling in pseudoautosomal or other homologous regions of the X and Y chromosomes. Rather than manipulating the reference genome to mask out certain regions of Y, it might make sense to build that intelligence into the mapper via a list of regions to mask in Y.