Structural variation of the human genome: mechanisms, assays, and role in male infertility

Abstract

Genomic disorders are defined as diseases caused by rearrangements of the genome incited by a genomic architecture that conveys instability. Y-chromosome related dysfunctions such as male infertility are frequently associated with gross DNA rearrangements resulting from its peculiar genomic architecture. The Y-chromosome has evolved into a highly specialized chromosome to perform male functions, mainly spermatogenesis. Direct and inverted repeats, some of them palindromes with highly identical nucleotide sequences that can form DNA cruciform structures, characterize the genomic structure of the Y-chromosome long arm. Some particular Y chromosome genomic deletions can cause spermatogenic failure likely because of removal of one or more transcriptional units with a potential role in spermatogenesis. We describe mechanisms underlying the formation of human genomic rearrangements on autosomes and review Y-chromosome deletions associated with male infertility.

Keywords:

• AZF
• DNA rearrangements
• genomic disorders
• non-allelic homologous recombination
• Y chromosome

Acknowledgments

This work was supported in part by the National Institute of Neurological Disorders and Stroke (National Institutes of Health) grant R01NS058529 to J.R.L., Texas Children's Hospital General Clinical Research Center grant M01RR00188, and Intellectual and Developmental Disabilities Research Centers grant P30HD024064.