Fig. 1

Homology between the human X and Y chromosomes where misaligning could occur. a High sequence homology exists between the human X and Y chromosomes in three regions: 100% sequence identity for the pseudoautosomal regions (PARs), PAR1, and PAR2, and ~ 99% sequence homology in the X-transposed region (XTR). The X chromosome PAR1 is ~ 2.78 million bases (Mb) extending from X:10,001 to 2,781,479 and the X chromosome PAR2 is ~ 0.33 Mb extending from X:155,701,383 to 156,030,895. The X chromosome PAR1 and PAR2 are identical in sequence to the Y chromosome PAR1 Y:10,001 to 2,781,479 and PAR2 Y:56,887,903 to 57,217,415. b Using a standard alignment approach will result in reads misaligning between regions of high sequence homology on the sex chromosomes. c Using a reference genome that is informed by the genetic sex of the sample may help to reduce misaligning between the X and Y chromosomes. In humans, samples without evidence of a Y chromosome should be aligned to a Y-masked reference genome, and samples with evidence of a Y should be aligned to a YPAR-masked reference genome