HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation
HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation
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DOI：
10.1093/humrep/der421
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发表时间：
2012-02-01
影响因子：
6.1
通讯作者：
Mitchell, Michael J.
中科院分区：
文献类型：
--
作者：
Kichine, Elsa;Roze, Virginie;Mitchell, Michael J.
背景：人类Y染色体上反复发生的AZFb缺失与精子的缺失有关，这是由于减数分裂成熟停滞导致生殖细胞不能进入单倍体阶段。部分缺失的极端罕见阻碍了对正常减数分裂阶段所需的AZFb基因的鉴定。通过两个与完全精子发生相关的重叠缺失(AZFc和b1/b3)来细化关键区间，其长度超过4Mb，包含13个编码基因：CDY2、XKRY、HSFY1、HSFY2、CYORF15A、CYORF15B、KDM5D、EIF1AY、RPS4Y2和4个RBMY副本。方法和结果：我们从1186对不育夫妇中筛选出Y染色体缺失，发现3名无关的少精子症男性和1名无精子症男性携带相同的768kb缺失，导致整个P4回文缺失，包括两个HSFY基因，仅在缺失区间内的编码基因。该768kb缺失在1179名对照男性中未发现。缺失断裂点只有4个碱基的核苷酸同源性，表明缺失不是反复发生的，而是建立时缺失的后代。证实了这一点，我们发现所有四名男性都携带着同一个高度定义的单倍组(R1b1b1a1b)的Y染色体(在法国南部发生率为30%)，尽管进一步的单倍型分析表明他们没有密切的血缘关系。结论：虽然HSFY缺失仅限于我们的不育群体，但它已经在许多世代中自然传播，表明HSFY基因对男性生育能力的贡献很小。重要的是，我们的研究正式排除了HSFY基因作为AZFb因子在减数分裂过程中的作用。
BACKGROUND: Recurrent AZFb deletions on the human Y chromosome are associated with an absence of ejaculated spermatozoa consequent to a meiotic maturation arrest that prevents the progression of germ cells to haploid stages. The extreme rarity of partial deletions has hampered the identification of the AZFb genes required for normal meiotic stages. The critical interval, refined by two overlapping deletions associated with full spermatogenesis (AZFc and b1/b3), measures over 4 Mb and contains 13 coding genes: CDY2, XKRY, HSFY1, HSFY2, CYORF15A, CYORF15B, KDM5D, EIF1AY, RPS4Y2 and four copies of RBMY.METHODS AND RESULTS: We screened 1186 men from infertile couples for Y chromosome deletions, and identified three unrelated oligozoospermic men and one azoospermic man who carry an identical 768 kb deletion resulting in loss of the entire P4 palindrome, including both HSFY genes, the only coding genes within the deletion interval. This 768 kb deletion was not found in 1179 control men. The deletion breakpoints share only 4 bp of nucleotide identity, revealing that the deletions are not recurrent, but are descendants of a founding deletion. Confirming this, we find that all four men carry a Y chromosome of the same highly defined haplogroup (R1b1b1a1b) (incidence 30% in Southern France), although further haplotype analyses showed that they were not closely related.CONCLUSIONS: Although the HSFY deletion is restricted to our infertile group, it has been transmitted naturally over many generations, indicating that HSFY genes make only a slight contribution to male fertility. Importantly, our study formally excludes HSFY genes as the AZFb factor required for progression through meiosis.