Development of a high-resolution Y-chromosome microarray for improved male infertility diagnosis

To develop a novel clinical test using microarray technology as a high-resolution alternative to current methods for detection of known and novel microdeletions on the Y chromosome.

Custom Agilent 8x15K array comparative genomic hybridization (aCGH) with 10,162 probes on an average probe spacing of 2.5 kb across the euchromatic region of the Y chromosome.

Clinical diagnostic laboratory.

Men with infertility (n = 104) and controls with proven fertility (n = 148).

Microarray genotyping of DNA.

Gene copy number variation determined by log ratio of probe signal intensity against a DNA reference.

Our aCGH experiments found all known AZF microdeletions as well as additional unbalanced structural alterations. In addition to complete AZF microdeletions, we found that AZFc partial deletions represent a risk factor for male infertility. In total, aCGH-based detection achieved a diagnostic yield of ∼11% and also revealed additional potentially etiologic copy number variations requiring further characterization.

The aCGH approach is a reliable high-resolution alternative to multiplex polymerase chain reaction for the discovery of pathogenic chromosome Y microdeletions in male infertility.