HUMAN T COMPLEX TESTES-EXPRESSED GENES & MALE STERILITY

人类 T 复合体测试表达基因

• 批准号: 3324953
• 负责人: LEE M SILVER
• 金额: $ 12.64万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3324953
• 关键词: artificial chromosomes; evolution; female; fertility; gel electrophoresis; gene expression; gene frequency; gene mutation; genetic library; genetic manipulation; genetic mapping; genetic polymorphism; haploidy; histocompatibility gene; human genetic material tag; human subject; hybrid cells; laboratory mouse; male; molecular cloning; nucleic acid hybridization; nucleic acid sequence; nucleobase; testis

The major objective of this proposal is the identification and characterization of human analogues of mouse t complex genes expressed in a testes-specific manner (referred to generically as Tcte genes). Variant forms of the t complex, known as t haplotypes, carry a set of mutant Tcte genes that interact to the detriment of sperm function. To date, a total of 16 t-complex testes-expressed gene have been defined by cloning or phenotypic expression. Six independent Tcte genes/gene families have been cloned, and four of these show cross-hybridization to human DNA and map to human chromosome 6. We will determine if the untested mouse Tcte genes also hybridize with human DNA. Our working hypothesis is that most, if not all, Tcte genes will be localized to human chromosome 6, and that a subset of male sterilities are a result of mutation in these genes. Representative clones for each human Tcte gene will be obtained and sequenced for comparison with the known mouse sequences (both wild-type and mutant). DNA will be obtained from a random population of individual for a survey of the type and frequency of polymorphisms associated with each Tcte gene. Three independent methods - in situ hybidization, somatic cell hybrid analysis, and pedigree studies - will be used for high resolution mapping of all chromosome 6-associated Tcte genes. The gene order of human chromosome 6 will be compared with that of mouse chromosome 17 to formulate models for chromosomal evolution. Since there is evidence for at least two separate clusters of Tcte genes in the mouse, we will use the techniques of pulse field gel electrophoresis and yeast artificial chromosome cloning to determine the possible presence of Tcte gene clusters in humans. Finally, once we have completed a basic characterization of the human Tcte system, our long-range goal will be to analyze the segregation of chromosome 6 alleles with familial cases of male infertility.

这项建议的主要目的是确定和 小鼠t复合体基因的人类似物的表征 以测试特异性方式表达（一般称为 Tcte基因）。 t复合体的变体形式，称为t 单倍型，携带一组突变的Tcte基因， 损害精子功能。 到目前为止，共有16个T-复合体 已经通过克隆或表型鉴定确定了测试表达基因 表情 六个独立的Tcte基因/基因家族已经被发现。 克隆，其中四个显示与人类DNA交叉杂交 并映射到人类6号染色体。 我们将确定 未经测试的小鼠Tcte基因也与人DNA杂交。 我们的工作假设是，大多数，如果不是全部，Tcte基因将是 位于人类6号染色体上， 不育是这些基因突变结果。 代表 将获得每个人Tcte基因的克隆并测序 为了与已知的小鼠序列（均为野生型 突变体）。 DNA将从一个随机的人口， 调查的类型和频率 与每个Tcte基因相关的多态性。 三 独立方法-原位杂交、体细胞杂交 分析和谱系研究-将用于高分辨率 所有6号染色体相关Tcte基因的定位。 基因 人类6号染色体的顺序将与 小鼠17号染色体， 进化 因为有证据表明至少有两个独立的 Tcte基因簇的小鼠，我们将使用的技术， 脉冲场凝胶电泳与酵母人工染色体 克隆以确定Tcte基因簇的可能存在 在人类身上。 最后，一旦我们完成了一个基本的 人类TCTE系统的表征，我们的长期目标 将分析6号染色体等位基因的分离， 男性不育的家族性病例。

项目成果

Genetic mapping of three human homologues of murine t-complex genes localizes TCP10 to 6q27, 15 cM distal to TCP1 and PLG.

小鼠 t 复合体基因的三个人类同源物的遗传图谱将 TCP10 定位于 6q27，距 TCP1 和 PLG 远端 15 cM。

• DOI: 10.1016/0888-7543(92)90317-l
• 发表时间: 1992
• 期刊: Genomics
• 影响因子: 4.4
• 作者: Blanché,H;Wright,LG;Vergnaud,G;deGouyon,B;Lauthier,V;Silver,LM;Dausset,J;Cann,HM;Spielman,RS
• 通讯作者: Spielman,RS

New reproductive technologies in the treatment of human infertility and genetic disease.

治疗人类不孕症和遗传病的新生殖技术。

• DOI: 10.1007/bf00489454
• 发表时间: 1990
• 期刊: Theoretical medicine
• 作者: Silver,LM