Genomics of the human Y-chromosome: 1. Association with male infertility

Abstract

The human Y chromosome contains over 60 million nucleotides, but least number of genes compared to any other chromosome and acts as a genetic determinant of the male characteristic features. The male specific region, MSY, comprising 95% of the Y chromosome represents a mosaic of heterochromatic and three classes of euchromatic (X-transposed, X-degenerate and ampliconic) sequences. Thus far, 156 transcription units, 78 protein-coding genes and 27 distinct proteins of the Y chromosome have been identified. The MSY euchromatic sequences show frequent gene conversion. Of the eight massive palindromes identified on the human Y chromosome, six harbor vital testis specific genes. The human male infertility has been attributed to mutations in the genes on Y chromosome and autosomes and failures of several physical and physiological attributes including paracrine controls. In addition, deletion of any one or all the three azoospermia (AZFa, AZFb or AZFc) factor(s) and some still unidentified regulatory elements located elsewhere in the genome result in infertility. Characterization of palindromic complexes on the long arm of Y chromosome encompassing AZFb and AZFc regions and identification of HERV15 class of endogenous retroviruses close to AZFa region have facilitated our understanding on the organization of azoospermia factors. Considerable overlap of the AZFb and AZFc regions encompassing a number of genes and transcripts has been shown to exist. However, barring details on AZF, information on the exact number of genes or the types of mutations prevalent in the infertile male is not available. Similarly, roles of sizable body of repetitive DNA present in close association with transcribing sequences on the Y chromosome are yet not clear. In a clinical setting with known cases of infertility, systematic search for loss or gain of these repeat elements would help understand their biological role(s). We present a brief overview on the genetic complexity of the human Y chromosome in the context of human male infertility.