The human genome project, HGP) was first proposed by American scientists in 1985 and officially launched in 199. Scientists from the United States, Britain, France, Germany, Japan and China participated in this human genome project with a budget of $3 billion. According to this plan, in 25, all the codes of about 2,-25, genes in the human body will be unlocked, and at the same time, the spectrum of human genes will be drawn. In other words, it is to uncover the secret of 3 billion base pairs that make up 2,-25, genes of human beings. The Human Genome Project, Manhattan Atomic Bomb Project and Apollo Project are also called the three major scientific projects. Known as the "moon landing program" of life science.
The Human Genome Project, HGP) is a large-scale, transnational and interdisciplinary scientific exploration project. Its purpose is to determine the nucleotide sequence of 3 billion base pairs contained in the human chromosome (haploid), so as to draw the human genome map, identify the genes and their sequences contained in it, and achieve the ultimate goal of deciphering human genetic information. Genome project is an important step for human beings to explore their own mysteries, and it is another great project in the history of human science after Manhattan project and Apollo moon landing project. By 25, the sequencing of the human genome project has been completed. Among them, the publication of the draft human genome work in 21 (the International Human Genome Project funded by the public fund and the private company Celera Genome Company independently completed and published separately) is considered as a milestone in the success of the Human Genome Project.
The significance of gene mapping
lies in that it can effectively reflect the Shi Kongtu of the whole gene expressed under normal or controlled conditions. Through this picture, we can know the expression of a gene in different tissues and levels at different times. We can also know the different levels of expression of different genes in a tissue at different times, and we can also know the different levels of expression of different genes in different tissues at a specific time.
The human genome is an international cooperation project: characterizing the human genome, sequencing and mapping the DNA of selected model organisms, developing new technologies for genome research, improving the ethical, legal and social issues involved in human genome research, training scientists who can use these technologies and resources developed by HGP to conduct biological research, and promoting human health.
Folding and editing other materials in this paragraph
Contribution of folding to the study of human disease genes
Genes related to human diseases are the vital information for the structural and functional integrity of the human genome. For monogenic diseases, the new ideas of "location cloning" and "positional candidate cloning" have led to the discovery of a large number of genes causing monogenic diseases such as Huntington's chorea, hereditary colon cancer and breast cancer, which laid the foundation for gene diagnosis and gene therapy of these diseases. At present, polygenic diseases such as cardiovascular diseases, tumors, diabetes, neuropsychiatric diseases (senile dementia, schizophrenia) and autoimmune diseases are the focus of disease gene research. Health-related research is an important part of HGP. In 1997, it was put forward one after another: "Tumor Genome Anatomy Plan" and "Environmental Genomics Plan".
contribution of folding to medicine
gene diagnosis, gene therapy and treatment based on genome knowledge, disease prevention based on genome information, identification of disease-prone genes, lifestyle of risk population and intervention of environmental factors.
Contribution of folding to biotechnology
Genetic engineering drugs
Secreted proteins (polypeptide hormones, growth factors, chemokines, coagulation and anticoagulation factors, etc.) and their receptors.
(2) diagnostic and research reagent industry
gene and antibody kits, biochips for diagnosis and research, disease and drug screening models.
Promoting cell, embryo and tissue engineering
Embryo and adult stem cells, cloning technology and organ reconstruction.
Contribution of folding to pharmaceutical industry
Screening drug targets: combining combinatorial chemistry and natural compound separation technology, establishing Qualcomm's receptor and enzyme binding test; knowledge-based drug design: advanced structural analysis, prediction and simulation of gene and protein products-drug action "pocket".
Individualized drug therapy: pharmacogenomics.
The important influence of folding on social economy
Biological industry and information industry are two economic pillars of a country; Social and economic benefits of discovering new functional genes; Genetically modified food; Genetically modified drugs (such as diet pills and diet pills)
The influence of folding on the study of biological evolution
The evolutionary history of organisms is engraved in the "heavenly book" of each genome; Paramecium is a relative of human beings-1.3 billion years; Man evolved from a kind of monkey 3-4 million years ago. Humans "walked out of Africa" for the first time-2 million years of ancient apes; The human "Eve" came from Africa, 2, years ago-the second "out of Africa"?
Negative effects of folding
Jurassic Park is not just a science fiction story; Racial selective genocidal biological weapons; Gene patent war; Predatory war of genetic resources; Genes and personal privacy.
folding editing application example of this paragraph
folding disease genes
A key application of human genome research is to find disease genes with unknown biochemical functions through positional cloning. This method includes mapping the chromosome region containing these genes through linkage analysis of the affected families, and then examining the region to find the genes.
positional cloning is very useful, but it is also very boring. When this method was first proposed in the early 198s, researchers who wanted to achieve positional cloning had to generate genetic markers to track inheritance, walk chromosomes to get genomic DNA covering this region, and analyze the region of about 1Mb by direct sequencing or indirect gene identification. The first two obstacles were removed in the mid-199s with the development of the genetic and physical atlas of human chromosomes with the support of the Human Genome Project. However, the remaining obstacles are still difficult.
All these will change with the practicality of the draft human genome sequence. The human genome sequence in the public database makes it possible to quickly identify candidate genes by computer, and then the mutation detection of related candidate genes needs the help of gene structure information.
Now, for Mendel's hereditary diseases, a gene search is often realized in a research group of appropriate size within several months. At least 3 disease genes have been located and cloned directly by the genome sequence provided by the public. Because most human sequences have only been obtained in the past 12 months, many similar findings may not have been published.
In addition, in many cases, genome sequence plays a supporting role, such as providing candidate microsatellite markers for good genetic linkage analysis. (In 21, scientists in China, Shanghai and Beijing discovered the hereditary Koga essential type II gene)
Genome sequence is also helpful to reveal the mechanism leading to many common chromosome deletion syndromes. In several cases, recurrent deletions were found, resulting from unequal crossover of homologous weight combinations replicated in large almost identical chromosomes. Examples include the degeorge/Velocidal syndrome region on chromosome 22 and the repeated deletion of Williams-Beuren syndrome on chromosome 7.
The availability of genomic sequences also allows rapid identification of collateral homology of disease genes, which is valuable for two reasons. First of all, the mutation of collateral homologous genes can cause related genetic diseases. A good example found through the use of genome sequences is color blindness (complete color blindness).
CNGA3 gene, which encodes the A subunit of GMP-gated channel in photoreceptor ring of optic cone, shows that there are mutants in some color-blind families. The computer search of genome sequence revealed that the collateral homologous gene encoded the corresponding B subunit, CNGB3 (which did not appear in EST database). CNGB3 gene was quickly identified as the cause of color blindness in other families. Another example is provided by premature senility 1 and premature senility 2 genes, and their mutations may lead to the early occurrence of Alzheimer's disease.
The second reason is that collateral homologues can provide opportunities for treatment. For example, in individuals with sickle cell disease or β thalassemia, an attempt is made to reactivate the hemoglobin gene expressed in embryos, which is caused by the mutation of β -globulin gene.
we systematically searched 971 known collateral homologues of human disease genes in online human mendelian genetic database (OMIM) and SwissProt or TrEMBL protein database. We identified 286 potential collateral homologues (at least 5 amino acids matched, with more than 7% but less than 9% identity on the same chromosome and less than 95% identity on different chromosomes). Although this analysis may identify some pseudogenes, 89% of the matches show homology of more than one exon in the new target sequence, which means that many of them are functional. This analysis shows the potential to quickly identify disease genes in computers.
folding drug targets
in the past century, the pharmaceutical industry has largely relied on limited drug targets to develop new treatments. The recent outline lists 483 drug targets, which are regarded as solving all the drugs on the market. Knowing all human genes and protein will greatly expand the search for suitable drug targets. Although only a small number of human genes can be used as drug targets, it can be predicted that this number will be above several thousand, and this prospect will lead to the large-scale development of genome research in drug research and development. Some examples can illustrate this point:
⑴ Neurotransmitter (5-HT) mediates rapid excitatory response through chemically gated channels. The previously identified 5-HT3A receptor gene produces functional receptors, but it has much smaller conductance than in vivo. Cross-hybridization experiments and EST analysis failed to reveal other homologues of known receptors.
Recently, however, a putative homologue was identified through a low-demand search of the draft human genome sequence, which was on the long arm of chromosome 11 in a PAC clone. Homologues were expressed in striatum, caudate nucleus and hippocampus, and full-length cDNA was obtained later. This gene encoding amine receptor is named 5-HT3B. When combined with 5-HT3A to form a heterodimer, it appears to be responsible for the large conductance ceramine channel. Given the central role of amine pathway in mental illness and schizophrenia, the discovery of a major new therapeutic target is quite interesting.
⑵ The contractile and inflammatory effects of cysteinyl leukotriene, previously considered as slow reaction substance (SRS-A) of allergic reaction, are mediated by specific receptors. A second similar receptor, CysLT2, was identified by recombination of mouse EST and human genome sequence. This led to the cloning of a gene with 38% amino acid identity with the only other receptor previously identified. This new receptor, showing high affinity and binding of several leukotrienes, is mapped on chromosome 13 related to allergic asthma. This gene is expressed in airway smooth muscle and heart. As an important target in the development of anti-asthma drugs in leukotriene pathway, the discovery of new receptors plays an important role.
(3) Alzheimer's disease has abundant β -amyloid deposits in senile plaques. β -amyloid is produced by proteolysis of precursor protein (APP). One enzyme is β-APP lyase, which is transmembrane aspartic protease. Computer search of draft sequence of human genome recently identified a new homologous sequence of BACE, encoding a protein named BACE2, which has 52% amino acid sequence identity with BACE. It contains two activated protease sites and the necessary Down syndrome region mapped to chromosome 21 like APP. It raises the question whether too many copies of BACE2 and APP contribute to accelerating the deposition of β -amyloid in the brain of patients with Down syndrome.
Given these examples, we systematically identify the collateral homologues of traditional drug target protein in the genome sequence. The target list used identifies 63 entries in the SwissPrott database and has a unique access code.
an example of basic biology
is to solve a mysterious problem that has puzzled researchers for decades: the molecular basis of bitterness. Humans and other animals have different responses to a certain bitter taste (response polymorphism). Recently, researchers mapped this feature to humans and mice, and then searched the relevant regions on the draft human genome sequence of G protein-coupled receptors. These studies soon led to the discovery of a new family of these proteins, which proved that almost all of them were expressed in taste buds. Experiments confirmed that receptors in cultured cells responded to specific bitter substrates.
The human genome map is the property of all mankind, and this research achievement should be shared by all mankind and benefit all mankind, which is the knowledge of scientists from all over the world who participated in the human genome project. It is noteworthy that at present, in the field of human genome research, some private companies are scrambling to apply for patents for their achievements. Celera Gene Company of the United States has said that it wants to apply for a patent for some research results and provide them to pharmaceutical companies for a fee.
Found a number of important genes that dominate human diseases
such as obesity gene and bronchial asthma gene. New discoveries of these genes are reported every year. The discovery of these genes has enhanced people's understanding of many important disease mechanisms, and promoted the whole medical thought to shift from focusing on treatment to focusing on prevention more quickly. For example, Professor Xia Jiahui of Hunan Medical University published on May 28th, 1998 that the pathogenic gene of human nervous high-frequency deafness (GJB3) was cloned, which was the first time cloned in China.
under the impetus of the human genome project, several brand-new disciplines have emerged. Such as genomics and bioinformatics
industrialization of biotechnology. A number of world-class large companies have turned their focus to life science research and biotechnology products. This trend is also closely related to the human genome project.
Progress and Future
On June 26th, 2, scientists from six countries, including the United States, Britain, France, Germany, Japan and China, who participated in the human genome project, announced that the draft of the human genome had been completed. The final map requires that the clones used for sequencing can faithfully represent the genome structure of autosomes, and the sequence error rate is less than one in ten thousand. 95% euchromatin regions were sequenced, and each Gap was less than 15kb. The completed drawing will be completed in 23, two years ahead of schedule.
Complete the human genome sequence map
(1) The completed sequence is generated from the clone generated by the current physical map, covering more than 96% of the euchromatin region of the genome. A completion sequence of about 1Gb has been achieved. The rest has also been sketched, and all clones are expected to reach 8 ~ 1 times coverage, which is about 99.99% correct in the middle of 21.