IMMUNOGENETICS OF SPERMATOZOA, EGGS, AND EMBRYOS

精子、卵子和胚胎的免疫遗传学

• 批准号: 3311355
• 负责人: DOROTHEA BENNETT
• 金额: $ 17.21万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-05-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311355
• 关键词: HY antigen; antigens; cell differentiation; chromosome aberrations; chromosome complement; developmental genetics; early embryonic stage; egg /ovum; embryo /fetus; gene expression; genetic mapping; haploidy; homozygote; immunogenetics; mammalian embryology; membrane activity; mutant; nucleic acid sequence; sex chromosomes; sperm; spermatogenesis

The genetic controls of early mammalian embroygenesis should be approachable through the study of complex loci, such as those in t-haplotypes, which regulate differentiation. These chromosomes contain a variety of mutations which are embedded in a long region of chromosome, which includes the H-2 complex, in which recombination is suppressed. The embryological effects of lethal t-mutations suggest that they define genes that function sequentially to control switch points at which specific cell lineages become committed to diverge into separate pathways. Genetically, t-lethals appear to be members of a multigene family with related functions. We have recently shown that recombination occurs freely between two complementing t-haplotypes, which suggests that they are mismatched with respect to wild type, either in gene order or DNA sequences, but are structurally similar to one another. This has been confirmed in a preliminary way by findings that the H-2 complex, for example, is transposed or inverted in t-haplotypes. Furthermore, when t-haplotypes are analyzed with H-2 cDNA on Southern blots after digestion with restriction enzymes they are almost identical, whereas normal chromosomes from inbred strains are very different. We will use classical genetic analysis to obtain a detailed map of the many mutant genes trapped in lethal haplotypes. Specifically the position and number of lethal mutations will be determined, and the genes responsible for male transmission distortion and sterility will be identified and mapped. Concurrent cloning and analysis of the structure of t-specific DNA should lead to an understanding of the nature and relationships of the various interacting mutations contained in t-haplotypes. Also, the reason for defective complementation between different lethal t-haplotypes. Also, the reason for defective complementation between different lethal t-haplotypes will be explored in experiments designed to identify deleterious isoalleles. Other experiments will define the extent of several chromosome 17 deletions which will be useful in mapping experiments.

早期哺乳动物胚胎发生的遗传控制应为 通过研究复杂基因座的研究，例如 T-Haplotypes，调节分化。 这些染色体含有 嵌入长染色体区域的各种突变， 其中包括抑制重组的H-2复合物。 这 致命T-突变的胚胎学作用表明它们定义了基因 该功能顺序控制特定单元格的开关点 谱系致力于分流到单独的途径。 从遗传上， T致死者似乎是一个具有相关性的多基因家族的成员 功能。 我们最近表明，重组是在 两个补充T-Haplotypes，这表明它们不匹配 关于野生型，无论是基因顺序还是DNA序列，但 结构上相似。 这已在 例如，通过发现H-2复合物的初步方式是 在T-Haplotypes中转移或倒置。 此外，当T-Haplotypes是 消化后用H-2 cDNA在南部印迹上分析 酶几乎是相同的，而近交的正常染色体 菌株非常不同。 我们将使用经典的遗传分析来 获取被困在致命中的许多突变基因的详细图 单倍型。 特别是致命突变的位置和数量 确定，以及负责男性传播失真的基因 和无菌性将被识别和映射。 并发克隆和 对T特异性DNA结构的分析应导致理解 各种相互作用突变的性质和关系 包含在t-haplotypes中。 另外，互补缺陷的原因 在不同的致命T-haplotypes之间。 另外，有缺陷的原因 将在不同的致命T-haplotypes之间进行互补。 旨在识别有害的同级的实验。 其他实验 将定义几个染色体17染色的程度 用于映射实验。