Ali Sher, Hasnain Seyed E
National Institute of Immunology, Molecular Genetics Laboratory, Aruna Asaf Ali Marg, New Delhi 110 067, India.
Gene. 2003 Dec 4;321:25-37. doi: 10.1016/j.gene.2003.08.006.
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.
人类Y染色体包含超过6000万个核苷酸，但与其他任何染色体相比基因数量最少，是男性特征的遗传决定因素。男性特异区域（MSY）占Y染色体的95%，是异染色质和三类常染色质（X易位、X退化和扩增子）序列的嵌合体。到目前为止，已鉴定出Y染色体的156个转录单位、78个蛋白质编码基因和27种不同蛋白质。MSY常染色质序列显示频繁的基因转换。在人类Y染色体上鉴定出的8个大型回文序列中，有6个含有重要的睾丸特异性基因。人类男性不育归因于Y染色体和常染色体上基因的突变以及包括旁分泌控制在内的多种物理和生理属性的缺陷。此外，任何一个或所有三个无精子症（AZFa、AZFb或AZFc）因子的缺失以及基因组其他位置一些仍未鉴定的调控元件都会导致不育。对包含AZFb和AZFc区域的Y染色体长臂上的回文复合体进行表征，以及鉴定靠近AZFa区域的内源性逆转录病毒HERV15类别，有助于我们了解无精子症因子的组织情况。已经证明AZFb和AZFc区域存在大量重叠，包含许多基因和转录本。然而，除了关于AZF的细节外，关于不育男性中确切的基因数量或普遍存在的突变类型的信息尚不可用。同样，与Y染色体上转录序列紧密相关的大量重复DNA的作用仍不清楚。在已知不育病例的临床环境中，系统搜索这些重复元件的缺失或增加将有助于了解它们的生物学作用。我们在人类男性不育的背景下简要概述了人类Y染色体的遗传复杂性。
