FETAL GLOBIN GENES EVOLUTION OF ONTOGENETIC PROGRAMS

胎儿珠蛋白基因个体遗传程序的进化

• 批准号: 6219726
• 负责人: MORRIS GOODMAN
• 金额: $ 7.46万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219726
• 关键词: Mammalia; growth /development; hematology; human tissue; inborn metabolism disorder; nucleic acids

This project has two closely related aims (1) to seek a better understanding of the evolutionary relationship of the primates through analysis of the structure and expression of the globin genes during embryonic and fetal development; and (2) to follow clues about the controlling gene elements that determine when genes are turned on and off during gestation by observing differences in the timing of gene expression in these closely related animals. The research focuses on the globin genes, since they undergo a well-characterized sequence of switches during gestation in humans, and the control (reversal) of these switches may have significant medical benefits in hematological diseases such as sickle cell anemias and thalassemia. Expression profiles in the two branches of simian primates, catarrhines (Old World Monkeys, hominoids) and platyrrhines (New World Monkeys), suggests that more than one step was involved in the evolutionary transition. We are (1) localizing fe tal-speci fic sequences within the human ( gene; (2) using the strategy called differential phylogenetic footprinting to identify specific base changes that may be responsible for the three different patterns of ( expression seen in nonanthropoid primates; and (3) documenting the in vivo expression patterns of ( genes in extant platyrrhine and catarrhine primates. This work has important implications for clarifying the mechanisms that control new patterns of gene expression as well as for the understanding of factors that regulate hemoglobin switching. Using samples from the University of Washington Primate Center, we have found that globin gene expression is very similar in M. nemestrina and in humans (1) the expression is fetal; (2) (1 is expressed to a much higher level than (2; and (3) the intergenic distance is 11 kb. FUNDING NIH grants HL33940 and RR00166 and NSF grant INT-9602913. Goodman, M., Porter, C.A., Czelusniak, J., Page, S.L., Schneider, H., Shoshani, J., Gunnell, G., and Groves, C.P. Toward a phylogenetic classification of primates based on DNA evidence complemented by fossil evidence. Mol. Phylogenet. & Evol. 9:585-598, 1998. Goodman, M. The Genomic Record of Humankind's Evolutionary Roots. Am. J. Hum. Genetics 64:31-39, 1999.

这个项目有两个密切相关的目标(1)寻求更好的 通过对灵长类进化关系的理解 珠蛋白基因的结构和表达分析 胚胎和胎儿发育；以及(2)跟踪关于 控制基因元件，这些基因元件决定了基因何时启动和 通过观察基因计时的差异在怀孕期间关闭 在这些亲缘关系密切的动物身上表达。研究的重点是 珠蛋白基因，因为它们经历了一个很好的特征序列 人类在怀孕期间的开关，以及控制(逆转) 这些开关在血液学方面可能有显著的医疗益处。 镰状细胞性贫血和地中海贫血等疾病。表达式 猴灵长类两个分支的剖面图(旧) 世界猴子、人科动物)和鸭嘴兽(新世界猴子)， 表明在进化过程中不止一个步骤参与 过渡。我们正在(1)定位特定于 人类(基因；(2)使用称为差异的策略 确定特定碱基变化的系统发育足迹 对(所见表情的三种不同模式负责 在非类人型灵长类动物中；以及(3)记录在体内的表达 现存的白颈鹿和卡他灵长类动物的(基因)模式。 这项工作对阐明这一机制具有重要意义 控制新的基因表达模式，以及 对调节血红蛋白转换的因素的理解。vbl.使用 来自华盛顿大学灵长类中心的样本，我们有 发现珠蛋白基因在根结线虫中的表达非常相似 在人类中，(1)表达是胎儿的；(2)(1)表达为 高于(2)；(3)基因间距离为11kb。 资助国家卫生研究院拨款HL33940和RR00166，以及国家科学基金会拨款INT-9602913。 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 Shoshani，J.，Gunnell，G.和Groves，C.P.走向系统发育 基于DNA证据的灵长类分类 化石证据。摩尔。亲缘关系。&Evol.1998年9：585-598。 《人类进化根源的基因组记录》。上午好。 J.嗯。：遗传学：31-39,1999。