A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts.

Background: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1 deletions that did not arise via homologous recombination but most probably via non-homologous recombination (NHR) between palindromes. In the current study, we set out to identify deletions in the azoospermia factor c (AZFc) region caused by NHR between palindromes.

Methods: We screened 1237 men using plus/minus and quantitative real-time polymerase chain reaction, fluorescence in situ hybridization and Southern blot analyses for deletions caused by NHR. These 1237 men originated from two series: one series of 237 men with azoospermia or severe oligozoospermia and 148 with normozoospermia and one series of 852 consecutively included men of subfertile couples unselected for sperm count.

Results: We identified eight unrelated men with deletions caused by NHR. These deletions could be categorized into four classes termed P3a, P3b, P3c and P3d. The P3a and P3b deletions were found in single instances whereas the P3c and P3d deletions were found in three men. Men with a P3c deletion had a higher total sperm count than those without a deletion (median 378.8 × 10(6) versus 153.9 × 10(6), P = 0.040). We did not find an association of the other P3 deletions with altered sperm counts.

Conclusions: We have found a novel subclass of partial AZFc deletions that results from NHR. One deletion, the P3c deletion, might be associated with increased sperm count.