THE J-C INTRON: A MUTATION INDICATOR IN BOVINE V GENES

描述(改编自申请者摘要)：重排和体细胞 突变导致牛的主要抗体库多样化。 未模板化的体细胞突变、基因转换或两者的组合 被认为是牛科剧目多样化的主要来源。 然而，牛和牛的重链和轻链V基因的大部分谱系 绵羊仍然不为人所知。因此，很难确定， 表达的抗体基因的特定变异是否是由于突变 或者重新编排。也很难区分基因转化和 和未模板化的体细胞点突变。建议的研究需要实验。 这将使用J-C内含子序列的变异来解决这些问题。这个 列出了以下具体目的：1)使用J-C内含子作为诊断 牛Lambda轻链突变机制的指示剂 多元化。2)使用牛重链J-C内含子作为中性 牛重链突变多样化的指标。3)J-C的使用 内含子作为牛突变机制的诊断指标 重链突变多样化。对J-C内含子的研究提供了 既是突变的中性指标，也是区分基因的一种方法 转化(模板化突变)和体细胞突变(非模板化突变)。 轻、重链J-C内含子的特征及其验证 它们作为检测红斑狼疮的发生和机制的“变异计”的效用 牛抗体基因的突变将建立一种有用的分析工具 牛免疫球蛋白基因的变异。申请人提出，这种方法可以 为今后牛体细胞突变的研究提供了一种简便的检测方法 器官和细胞培养中的免疫球蛋白基因。

DESCRIPTION (Adapted from the Applicant's Abstract): Rearrangement and somatic mutation contribute to primary antibody repertoire diversification in cattle. Untemplated somatic mutation, gene conversion, or a combination of both, is thought to be the major generator of repertoire diversification in the Bovidae. However, much of the repertoire of heavy and light chain V genes in cattle and sheep remains unknown. Thus, it is difficult to determine, definitively, whether particular variations in expressed antibody genes are due to mutation or rearrangement. It is also difficult to discriminate between gene conversion and untemplated somatic point mutation. The proposed studies entail experiments that will use variation in J-C intron sequences to resolve these issues. The following specific aims were listed: 1) Use of the J-C intron as a diagnostic indicator of the mutational mechanisms used in bovine lambda light chain diversification. 2) Use of the bovine heavy chain J-C intron as a neutral indicator of bovine heavy chain mutational diversification. 3) Use of the J-C intron as a diagnostic indicator of the mutational mechanism employed in bovine heavy chain mutational diversification. Examination of the J-C intron provides both a neutral indicator of mutation and a way a to discriminate between gene conversion (templated mutation) and somatic mutation (untemplated mutation). Characterization of light and heavy chain J-C introns and demonstration of their utility as "mutometers" for detecting the occurrence and mechanism of mutation in bovine antibody genes will establish a useful tool for analysis of variation in bovine Ig genes. The applicant proposes that this approach may provide a convenient assay for future study of somatic mutation of bovine immunoglobulin genes in organ and cell culture.