Prueitt R L, Chen H, Barnes R I, Zinn A R
McDermott Center for Human Growth and Development and Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cytogenet Genome Res. 2002;97(1-2):32-8. doi: 10.1159/000064052.
Balanced translocations with breakpoints in a critical region of the X chromosome, Xq13-->q26, are associated with premature ovarian failure (POF). Translocations may cause POF either by affecting expression of specific X-linked genes essential for maintenance of normal ovarian function or by a chromosomal effect such as inhibition of meiotic pairing or altered X inactivation. We previously mapped seven Xq translocation breakpoints associated with POF to approximately 75-kb intervals. One translocation disrupted an aminopeptidase gene, XPNPEP2. We have now refined the map location of the remaining six breakpoints with respect to known genes and transcription units predicted from the draft human genome sequence. Only one of the six breakpoints disrupts a gene, DACH2, the human ortholog of a mouse gene expressed in embryonic nervous tissue, sensory organs, and limbs. DACH2 has no obvious relationship to ovarian function. The other five breakpoints fall in apparently intragenic regions. Our results are most consistent with models for POF associated with X;autosome translocations that involve generalized chromosome effects.
X染色体关键区域Xq13→q26发生平衡易位与卵巢早衰（POF）相关。易位可能通过影响维持正常卵巢功能所必需的特定X连锁基因的表达，或通过染色体效应，如抑制减数分裂配对或改变X染色体失活，从而导致POF。我们之前将7个与POF相关的Xq易位断点定位到大约75 kb的区间。其中一个易位破坏了一个氨肽酶基因XPNPEP2。现在，我们根据人类基因组序列草图预测的已知基因和转录单元，进一步精确了其余6个断点的图谱位置。这6个断点中只有一个破坏了一个基因DACH2，它是在胚胎神经组织、感觉器官和四肢中表达的小鼠基因的人类同源基因。DACH2与卵巢功能没有明显关系。其他5个断点位于明显的基因内区域。我们的结果与涉及广义染色体效应的X；常染色体易位相关的POF模型最为一致。
