男性不育中1号染色体断点过多。

An excess of chromosome 1 breakpoints in male infertility.

作者信息

Bache Iben, Assche Elvire Van, Cingoz Sultan, Bugge Merete, Tümer Zeynep, Hjorth Mads, Lundsteen Claes, Lespinasse James, Winther Kirsten, Niebuhr Anita, Kalscheuer Vera, Liebaers Inge, Bonduelle Maryse, Tournaye Herman, Ayuso Carmen, Barbi Gotthold, Blennow Elisabeth, Bourrouillou Georges, Brondum-Nielsen Karen, Bruun-Petersen Gert, Croquette Marie-Francoise, Dahoun Sophie, Dallapiccola Bruno, Davison Val, Delobel Bruno, Duba Hans-Christoph, Duprez Laurence, Ferguson-Smith Malcolm, Fitzpatrick David R, Grace Elizabeth, Hansmann Ingo, Hultén Maj, Jensen Peter Ka, Jonveaux Philippe, Kristoffersson Ulf, Lopez-Pajares Isidora, McGowan-Jordan Jean, Murken Jan, Orera Maria, Parkin Tony, Passarge Eberhard, Ramos Carmen, Rasmussen Kirsten, Schempp Werner, Schubert Regine, Schwinger Eberhard, Shabtai Fiorella, Smith Kim, Stallings Raymond, Stefanova Margarita, Tranebjerg Lisbeth, Turleau Catherine, van der Hagen Carl Birger, Vekemans Michel, Vokac Nadja Kokalj, Wagner Klaus, Wahlstroem Jan, Zelante Leopoldo, Tommerup Niels

机构信息

Wilhelm Johannsen Centre for Functional Genome Research, Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark.

出版信息

Eur J Hum Genet. 2004 Dec;12(12):993-1000. doi: 10.1038/sj.ejhg.5201263.

DOI:10.1038/sj.ejhg.5201263

PMID:15367911

Abstract

In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.

摘要

在寻找可能通过染色体断点聚集而揭示的潜在不育基因座的过程中，我们从孟德尔细胞遗传学网络数据库（MCNdb）中收集了464名具有平衡重排的不育男性，并将他们的核型与丹麦全国队列的核型进行了比较。我们排除了罗伯逊易位、涉及性染色体的重排和常见变异。我们确定了10个常染色体带，其中5个在1号染色体上，不育组中的断点大量过剩。其中一些可能潜在地含有男性特异性不育基因座。然而，在不育男性中观察到1号染色体上几乎处处都存在断点普遍过剩的情况：队列中分别为26.5%和14.5%。无论是易位携带者还是倒位携带者，尤其是臂间倒位携带者，无论是已发表还是未发表的病例，都观察到了这种过剩情况，并且与无精子症显著相关。报道的断点数量最多的是在1q21；对其中四个断点的荧光原位杂交（FISH）定位显示，它们在分子水平上并不涉及同一区域。我们认为1号染色体含有一个关键区域，其完整性对男性生育能力至关重要。