Mosaic loss of the Y chromosome and men's health.
Mosaic loss of the Y chromosome and men's health.
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DOI：
10.1002/rmb2.12445
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Miyado M
中科院分区：
文献类型：
--
作者：
Fukami M;Miyado M
虽然Y染色体基因与男性性发育、精子发生和身高生长有关，但这些基因在体细胞的存活或有丝分裂中不起作用。因此，缺乏Y染色体的体细胞可以在体内停留和增殖。几种分子技术，包括下一代测序和基于多重PCR的检测，用于检测男性血液中Y染色体的嵌合丢失（mLOY）。越来越多的证据表明，mLOY是人类最常见的获得性染色体改变，影响超过40%的70岁以上的男性。已知高龄、吸烟和细胞周期基因中的一些SNP会增加mLOY的频率。mLOY在老年男性中的发育过程仍有待澄清，但它可能反映了Y染色体的周期性有丝分裂消除或45，X细胞系的克隆扩增。在极少数情况下，mLOY也发生在年轻男性和胎儿中。MLOY与老年男性的早期死亡、癌症和其他疾病、育龄男性的不孕症以及儿童的发育缺陷有关。男性的Y染色体可能在每个生命阶段丢失，Y染色体丢失与各种健康问题有关。男性的体细胞总是有丢失Y染色体的风险。老年男性中频繁的Y染色体丢失是否是由于反复的有丝分裂染色体丢失或45，X细胞系的克隆扩增引起的，目前还不清楚。
Although Y chromosomal genes are involved in male sex development, spermatogenesis, and height growth, these genes play no role in the survival or mitosis of somatic cells. Therefore, somatic cells lacking the Y chromosome can stay and proliferate in the body. Several molecular technologies, including next‐generation sequencing and multiplex PCR‐based assays, are used to detect mosaic loss of the Y chromosome (mLOY) in the blood of men. Accumulating evidence suggests that mLOY represents the most common acquired chromosomal alteration in humans, affecting >40% of men over 70 years of age. Advanced age, tobacco smoking, and some SNPs in cell cycle genes are known to increase the frequency of mLOY. The developmental process of mLOY in elderly men remains to be clarified, but it possibly reflects recurrent mitotic elimination of Y chromosomes or clonal expansion of 45,X cell lineages. In rare cases, mLOY also occurs in young men and fetuses. MLOY has been associated with early death, cancers, and other disorders in elderly men, infertility in reproductive‐aged men, and developmental defects in children. Y chromosomes in men can be lost at every life stage and Y chromosomal loss is associated with various health problems. Somatic cells in men always have a risk to lose their Y chromosome. It remains unknown whether the frequent Y chromosomal loss in elderly men results from recurrent mitotic chromosomal loss or clonal expansion of a 45,X cell lineage.
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发表时间：
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