“Micro-deletions” of the human Y chromosome and their relationship with male infertility

a.
Renji Hospital, School of Medicine, Shanghai Jiaotong University; Shanghai Institute of Andrology, Shanghai 200001, China
b.
Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China

More Information

Corresponding author: E-mail address: ybhan@cuhk.edu.hk (Yibing Han)

摘要

- /
- /
Abstract: The Y chromosome evolves from an autochromosome and accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes. The human Y chromosome (60 Mb long) is largely composed of repetitive sequences that give it a heterochromatic appearance, and it consists of pseudoautosomal, euchromatic, and heterochromatic regions. Located on the two extremities of the Y chromosome, pseudoautosomal regions 1 and 2 (PAR1 and PAR2, 2.6 Mb and 320 bp long, respectively) are homologs with the termini of the X chromosome. The euchromatic region and some of the repeat-rich heterochromatic parts of the Y chromosome are called “male-specific Y” (MSY), which occupy more than 95% of the whole Y chromosome. After evolution, the Y chromosome becomes the smallest in size with the least number of genes but with the most number of copies of genes that are mostly spermatogenesis-related. The Y chromosome is characterized by highly repetitive sequences (including direct repeats, inverted repeats, and palindromes) and high polymorphism. Several gene rearrangements on the Y chromosome occur during evolution owing to its specific gene structure. The consequences of such rearrangements are not only loss but also gain of specific genes. One hundred and fifty three haplotypes have been discovered in the human Y chromosome. The structure of the Y chromosome in the GenBank belongs to haplotype R1. There are 220 genes (104 coding genes, 111 pseudogenes, and 5 other uncategorized genes) according to the most recent count. The 104 coding genes encode a total of about 48 proteins/protein families (including putative proteins/protein families). Among them, 16 gene products have been discovered in the azoospermia factor region (AZF) and are related to spermatogenesis. It has been discovered that one subset of gene rearrangements on the Y chromosome, “micro-deletions”, is a major cause of male infertility in some populations. However, controversies exist about different Y chromosome haplotypes. Six AZFs of the Y chromosome have been discovered including AZFa, AZFb, AZFc, and their combinations AZFbc, AZFabc, and partial AZFc called AZFc/gr/gr. Different deletions in AZF lead to different content spermatogenesis loss from teratozoospermia to infertility in different populations depending on their Y haplotypes. This article describes the structure of the human Y chromosome and investigates the causes of micro-deletions and their relationship with male infertility from the view of chromosome evolution. After analysis of the relationship between AZFc and male infertility, we concluded that spermatogenesis is controlled by a network of genes, which may locate on the Y chromosome, the autochromosomes, or even on the X chromosome. Further investigation of the molecular mechanisms underlying male fertility/infertility will facilitate our knowledge of functional genomics.
- human Y-chromosome /
- micro-deletion /
- male infertility

HTML全文

参考文献(34)

[1]	A.Z.C., Yang, Y., Zhang, S.Z. et al. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia Acta Genet. Sin., 33 (2006),pp. 111-116
[2]	Aitken, R.J., Marshal, G.J.A. Human spermatozoa: The future of sex Nature, 415 (2002),p. 963
[3]	Bachtrog, D. A dynamic view of sex chromosome evolution Curr. Opin. Genet. Dev., 16 (2006),pp. 578-585
[4]	Baker, H.W.G.
[5]	Charlesworth, B. The evolution of chromosomal sex determination and dosage compensation Curr. Biol., 6 (1996),pp. 149-162
[6]	Charlesworth, B., Charlesworth, D. The degeneration of Y chromosomes Phil. Trans. R. Soc. Lond. B., 355 (2000),pp. 1563-1572
[7]	Chen, J., Li, H., Qin, Z.D. et al. Y-chromosome genotyping and genetic structure of Zhuang population Acta Genet. Sin., 33 (2006),pp. 1060-1072
[8]	Cram, D.S., Osborne, E., McLachlan, R.I. Y chromosome microdeletions: implications for assisted conception Mol. J. Androl., 185 (2006),pp. 433-434
[9]	Ellis, P.J., Clemente, E.J., Ball, P. et al. Deletions on mouse Yq lead to upregulation of multiple X- and Y-linked transcripts in spermatids Hum. Mol. Genet., 14 (2005),pp. 2705-2715
[10]	Foresta, C., Moro, E., Ferkin, A. Y chromosome microdeletions and alterations of spermatogenesis Endocr. Rev., 22 (2001),pp. 226-239
[11]	Graves, J.A. The degenerate Y chromosome—can conversion save it? Reprod. Fertil. Dev., 16 (2004),pp. 527-534
[12]	Hughes, J.F., Skaletsky, H., Pyntilova, T. et al. Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee Nature, 437 (2005),pp. 101-104
[13]	Jobling, M.A., Tyler-Smith, C. The human Y chromosome: an evolutionary marker comes of age Nat. Rev. Genet., 4 (2003),pp. 598-612
[14]	Krausz, C., Wuitana-Murci, L., Rajpert-De-Meyts, E. et al. Identification of a Y chromosome haplogroup associated with reduced sperm counts Hum. Mol. Genet., 10 (2001),pp. 1873-1877
[15]	Kuroda-Kawaguchi, T., Skaletsky, H., Brown, L.G. et al. The AZFc region on the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men Nat. Genet., 129 (2001),pp. 279-286
[16]	Kuroki, Y., Iwamoto, T., Lee, J. et al. Spermatogenic ability is different among males in different Y chromosome lineage J. Hum. Genet., 44 (1999),pp. 289-292
[17]	Lahn, B.T., Page, D.C. Four evolutionary strata on the human X chromosome Science, 286 (1999),pp. 964-967
[18]	Lepretre, A.C., Patrat, C., Mitchell, M. et al. No partial DAZ deletions but frequent gene conversion events on the Y chromosome of fertile men J. Assist. Reprod. Genet., 22 (2005),pp. 141-148
[19]	McElreavey, K., Krausz, C., Bishop, C.E. The human Y chromosome and male infertility Results Probl. Cell. Differ., 28 (2000),pp. 211-232
[20]	McElreavey, K., Ravel, C., Chantot-Bastaraud, S. et al. Y chromosome variants and male reproductive function Int. J. Androl., 29 (2006),pp. 298-303
[21]	Mumm, S., Molini, B., Terrell, J. et al. Evolutionary features of the 4-Mb Xq21.3 XY homology region revealed by a map at 60-kb resolution Genome Res., 7 (1997),pp. 307-314
[22]	Nazareko, S.A., Puzyrev, V.P., Lemza, S.V. Y Chromosome heterochromatin and human morphophysiological variability Acta Genet. Sin., 18 (1991),pp. 424-430
[23]	Page, D.C., Harper, M.E., Love, J. et al. Occurrence of a transposition from the X-chromosome long arm to the Y-chromosome short arm during human evolution Nature, 311 (1984),pp. 119-123
[24]	Repping, S., Skaletsky, H., Lange, J. et al. Recombination between palindromes P5 to P1 on the human Y chromosome causes massive deletions and spermatogenic failure Am. J. Hum. Genet., 71 (2002),pp. 906-922
[25]	Repping, S., van Daalen, S.K., Korver, C.M. et al. A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region Genomics, 83 (2004),pp. 1046-1052
[26]	Rice, W.R. Evolution of the Y sex chromosome in animals Bioscience, 46 (1996),pp. 331-343
[27]	Rozen, S., Skaletsky, H., Marszalek, J.D. et al. Abundant gene conversion between arms of palindromes in human and ape Y chromosomes Nature, 423 (2003),pp. 873-876
[28]	Samli, H., Murat, S.M., Solak, M. Natural transmission of AZFb Y-chromosomal microdeletion from father to his three sons Arch. Androl., 52 (2006),pp. 423-426
[29]	Skaletsky, H., Kuroda-Kawaguchi, T., Minx, P.J. et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes Nature, 423 (2003),pp. 825-837
[30]	Tiepolo, L., Zuffardi, O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm Hum. Genet., 34 (1976),pp. 119-124
[31]	Underhill, P.A., Shen, P., Lin, A.A. et al. Y chromosome sequence variation and the history of human populations Nat. Genet., 26 (2000),pp. 358-361
[32]	Vogt, P.H. AZF deletions and Y chromosomal haplogroups: History and update based on sequence Hum. Reprod. Update., 11 (2005),pp. 319-336
[33]	Yu, M., Zhang, Y.L., Chen, F. et al. Y chromosome variations and haplogroups from 15 biallelic markers in six Chinese populations Acta Genet. Sin., 29 (2002),pp. 283-289
[34]	Zhang, F., Li, Z., Wen, B. et al. A frequent partial AZFc deletion does not render an increased risk of spermatogenetic impairment in East Asians Annal. Human Genet., 70 (2005),pp. 304-312