基因组研究的三个突出方面-文档资料

二、干细胞是功能基因组研究的最佳选材
1. 是各种不同组织和细胞类型的共同的源; 2. 可代表个体发育的各个阶段; 3. 是人体材料但很少涉及伦理学和法律学问题； 4. 具有重要的应用价值。
第三部分：SNP研究
DOE在一篇介绍SNP文章中写到：
Why does one man live to celebrate his hundredth birthday with a glass of wine in one hand and a cigar in the other while another succumbs in midlife to cancer or heart disease? And why may one woman's breast cancer be effectively eradicated while another's shows no significant response to the same treatment?
五、干细胞的应用价值


人类胚胎干细胞研究的重要性至少表现在以下几个方面： • 一、生物学与医学基础研究： 人类干细胞是机体早期发育的极好模型。过去，人类发育生 物学研究经常受到很多实际问题和伦理学的限制，因此只有使用 动物模型。有了胚胎干细胞就可以直接在人类组织上研究早期发 育出现的复杂事件和细胞分化的原初过程。关键是找到特定的因 子，它们控制着与发育和分化过程相关的基因的打开和关闭。这 一研究也必然为了解非正常细胞分化（如：肿瘤等）的原因提供 线索。 • 二、医疗实践 • 细胞移植 • 药物设计

干细胞培养过程
三：干细胞研究的一些最新成果


1. Dr. Ira Black of the University of Medicine and Dentistry of New Jersey reported the stem cells, treated with growth factors and antioxidants in tissue culture experiments, quickly divided into two cells - another stem cell and a nerve cell. Black and his colleagues were able to turn 80 percent of the bone marrow cells taken from rats and humans into nerve cells. 2. The Macklis group in HMS was able to induce stem cells deep in the cerebral cortex of adult mice to replace damaged neurons. The new neurons grew from already present immature precursor cells into fully formed, connected, and mature replacements.
The population is now about 6 x 109. A catalog of all sequence differences would require 18 x 1015 entries. This catalog may be needed to find the rarest or most complex disease genes.
前言：2000年基因组研究的三个突出方面
1. 干细胞作为基因组研究的重要选材
Celera Genomics And Geron Corporation Announce Collaboration For Human Pluripotent Stem Cell Genomics June 12, 2000
The objective of the collaboration is to identify and assign function to genes important in early human development, and to utilize the information to develop small molecule pharmaceuticals, protein therapeutics, cell and gene therapies, diagnostics, and tools for use in drug discovery and testing.
从成年小白鼠未发育的脑干细胞转变为肌肉细胞从成年小白鼠未发育的脑干细胞转变为肌肉细胞angelovescovigiuliocossustemcellresearchmilan200020他们也用成年人志愿者的神经干细胞实现了同样的工作newbraincellsinduced病人自身基因组有遗传缺陷
2000年基因组研究的三个突 出方面
With A Song In Their Heads -- Birth of new brain cells induced in birds

2. 影响成体干细胞应用的某些因素： A. 当前并没有在所以人体组织中发现成体干细胞； B. 成体干细胞含量极少，很难分离与纯化； C. 对某些病人来说，可能： 疾病的进程等不到足量干细胞的培养； 病人自身基因组有遗传缺陷；
SNP研究是基因组领域理论成果走向应用的关键步骤。是 联系基因型和表现型之间关系的桥梁。
HUMAN GENETIC DIVERSITY: The Ultimate Human Genetic Database
Any two individuals differ in about 3 x 106 bases (0.1%).
第二部分：干细胞和基因组研究
一、生物学领域两项新进展的结合

国际上很多新闻单位都把基因组和干细胞的研究进展评 为2000国际十大科技成果。很快这两项研究就结合在一 起了。
"Celera's agreement with Geron is important because we will be using human pluripotent stem cells-the most basic form of human cells that contain a diverse set of genes not expressed in high abundance in other cells-as a source to better understand the human genome," said J. Craig Venter, Ph.D., Celera's president and chief scientific officer. "By combining Celera's high-throughput sequencing facility, computational power, and bioinformatics expertise with Geron's human pluripotent stem cell technology, our goal is to enable the development of new approaches to prevent, diagnose and treat some of our most devastating diseases such as heart disease, Parkinson's disease, and cancer."
下边的几个最新的研究成果进一步说明包括人在内的高 等生物的成体干细胞依然有明确的分化能力。

从成年小白鼠未发育的脑干细胞转变为肌肉细胞
Angelo Vescovi 和 Giulio Cossu, 在 the Institute for Stem Cell Research in Milan 2000 9 20 他们也用成年人志愿者的神经干细胞实现了同样的工作
1998年美国有两个小组分别培养出了人多能( pluripotent ) 干细胞：
James A. Thomson在 Wisconsin大学领导一个研究小组从人胚胎组 织中培养出了干细胞株。他们使用的方法是：人卵体外受精后，将 胚胎培育到囊胚阶段，提取 inner cell mass细胞，建立细胞株。经 测试这些细胞株的细胞表面 marker 和酶活性，证实它们就是胚胎 干细胞。用这种方法，每个胚胎可取得15－20个细胞用于培养。 John D. Gearhart在 Johns Hopkins大学领导另一个研究小组也从人胚 胎组织中建立了干细胞株。他们的方法是：从受精后5－9周人工流 产的胚胎中提取生殖母细胞( primordial germ cell )。由此培养的细 胞株，证实具有巨能干细胞的特征。
The explanations may reside in the cumulative effect of a small number of differences in DNA base sequence called single-nucleotide polymorphisms (SNPs), which underlie individual responses to environment, disease, and medical treatments. SNPs are the most common type of sequence variation.
Human Genome Project and SNP Consortium Announce Collaboration
3. DNA芯片的广泛使用
第一部分：干细胞研究进展


一、什么是细胞？
干细胞是具有无限期产生各种分化细胞能力的细胞。 它是各种干细胞的统称。通常认为干细胞有几个主要 特征： • 它们是未分化的，但具有分化成各种特定细胞的 能力； • 它们可无限地分裂产生大量后裔; • 其子细胞有两种命运，保持为干细胞或分化为特 定细胞。
四：成年个体的干细胞研究



成体干细胞研究是干细胞研究中最激动人心的部分。它 可以有效地防止组织排斥，可以避免伦理学、法律系方 面的争论。 1. 成体干细胞是否具有胚胎干细胞那样的分化潜力？
大量的动物实验证明了成体干细胞具有很强的分化能力。如：

Recent experiments in mice suggest that when neural stem cells were placed into the bone marrow, they appeared to produce a variety of blood cell types. Studies with rats have indicated that stem cells found in the bone marrow were able to produce liver cells.
干细胞分类
Totipotent stem cell: 全能干细胞, 如受精卵 pluripotent stem cell: 多能干细胞，如囊胚中

的内囊细胞

multipotent stem cell: 专能干细胞，如造血干
细胞
二、怎样得到 pluripotent stem cell?


2. SNP研究的国际大协作
The SNP Consortium Ltd. is a non-profit foundation organized for the purpose of providing public genomic data. Its mission is to develop up to 300,000 SNPs distributed evenly throughout the human genome and to make the information related to these SNPs available to the public without intellectual property restrictions. 856,666 mapped SNPs, is now available. July 11, 2000