IMMUNOGENETICS OF SPERMATOZOA, EGGS, AND EMBRYOS

早期哺乳动物胚胎发生的遗传控制应该是 通过研究复杂的基因座，如那些在 t-单倍型，调节分化。 这些染色体含有一个 嵌入染色体长区域的各种突变， 包括H-2复合物，其中复合被抑制。 的 致死性T突变的胚胎学效应表明它们定义了基因 其顺序地起作用以控制特定单元 血统变得致力于分歧成独立的路径。 从遗传学上讲， t-致死基因似乎是一个多基因家族的成员， 功能协调发展的 我们最近已经表明，重组发生之间的自由 两个互补的t单倍型，这表明它们是错配的， 相对于野生型，无论是在基因顺序或DNA序列，但 在结构上彼此相似。 这一点已在一份 初步的方法，发现H-2复合物，例如， 在t-单倍型中转座或倒置。 此外，当t-单倍型是 用限制性内切酶消化后在Southern印迹上用H-2 cDNA分析 酶，他们几乎是相同的，而正常的染色体从近交系 菌株非常不同。 我们将使用经典的遗传分析， 获得了许多突变基因的详细图谱， 单倍型。 具体来说，致命突变的位置和数量将 而导致男性传播失真的基因 和不育性将被识别和映射。 并行克隆和 对t细胞特异性DNA结构的分析应该能帮助我们理解 各种相互作用的突变的性质和关系 包含在t-单倍型中。 此外，缺陷互补的原因 不同的致命t单倍型之间的联系 此外，缺陷的原因 不同致死性t-单倍型之间的互补将在 旨在鉴定有害等位基因的实验。 其他实验 将确定几个染色体17缺失的程度， 在绘图实验中很有用。

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.