BIOCHEMICAL GENETICS OF MALE SEXUAL DETERMINATION

男性性别决定的生化遗传学

• 批准号: 3319000
• 负责人: ROBERT P ERICKSON
• 金额: $ 13.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1989-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3319000
• 关键词: XYY syndrome; genetic mapping; molecular cloning; molecular genetics; sex chromosomes; sex differentiation; sex linked trait

We seek to understand molecular events involved in the differentiation of the mammalian male embryonic gonad. Such knowledge should be of benefit for improved diagnosis, and possibly prenatal diagnosis, of human intersex conditions as well as increasing our understanding of normal human development. Our studies will use both mouse models and human material. Studies in mice will focus on genetic loci in the proximal arm of chromosome 17 which interact with the mouse Y chromosome (which also has variants) to try and elucidate how these autosomal loci interact with the Y chromosome and other autosomal loci in contributing to normal testicular development. Among the loci on chromosome 17 may be those containing Banded krait minor satellite (Bkm) sex specific sequences. Since certain large deletions (T-Or1 and T-Hp) in this area of chromosome 17 can cause hermaphroditism, we will determine whether or not these deletions alter the amounts of Bkm-sequences detected on chromosome 17 by in situ hybridization. We will use the Bkm probe to look for mRNAs containing Bkm sequences in mouse and human fetal gonads and appropriate other tissues. Cosmid clones from the proximal region of mouse chromosome 17 and lambda clones from the human X chromosome will be screened with a Bkm probe. Subportions of positive clones will be used to screen fetal gonad RNA. The human Y chromosomal clones previously obtained, and new ones obtained by PERT and chromosome "hop" techniques, will be used to study XX males and their parents in an attempt to determine the source of the Y chromosomal DNA usually found in such XX males. The work on human material will also use human Y chromosome clones to look for expressed Y sequences in the male fetal gonad. Genomic clones corresponding to mouse or human male fetal gonad specific expressed sequences will be sought by screening cDNA libraries with the identified probe and using the cDNA clone to screen genomic clones (when the probe is not unique sequence).

我们试图了解参与分化的分子事件 哺乳动物雄性胚胎性腺。 这些知识应该是有益的 改进人类间性人的诊断，甚至可能进行产前诊断 条件以及增加我们对正常人类的了解 发展。 我们的研究将使用小鼠模型和人体材料。 对小鼠的研究将集中于近端臂的遗传位点 17 号染色体与小鼠 Y 染色体（也有 变体）来尝试阐明这些常染色体基因座如何与 Y 相互作用 染色体和其他常染色体位点有助于正常睾丸 发展。 17 号染色体上的基因座可能包含以下基因座： 带状金环蛇小卫星 (Bkm) 性别特定序列。 由于某些 17 号染色体该区域的大缺失（T-Or1 和 T-Hp）可导致 雌雄同体，我们将确定这些删除是否会改变 原位检测在 17 号染色体上检测到的 Bkm 序列数量 杂交。 我们将使用 Bkm 探针来寻找包含 Bkm 的 mRNA 小鼠和人类胎儿性腺以及适当的其他组织中的序列。 来自小鼠 17 号染色体和 lambda 近端区域的粘粒克隆 来自人类 X 染色体的克隆将用 Bkm 探针进行筛选。 阳性克隆的亚部分将用于筛选胎儿性腺 RNA。 先前获得的人类Y染色体克隆以及新获得的克隆 通过 PERT 和染色体“跳跃”技术，将用于研究 XX 男性和 他们的父母试图确定Y染色体的来源 DNA 通常存在于此类 XX 男性中。 关于人体材料的工作也将 使用人类 Y 染色体克隆来寻找男性中表达的 Y 序列 胎儿性腺。 对应于小鼠或人类男性胎儿的基因组克隆 通过筛选 cDNA 寻找性腺特异性表达序列 具有已识别探针的文库并使用 cDNA 克隆进行筛选 基因组克隆（当探针不是唯一序列时）。