2019-2020年高中英语必修9Module2Section2Backgroundination.doc

2019-2020年高中英语必修9Module2Section2Backgroundinformation1. How is DNA sequencing done?DNA sequencing, the process of determining the exact order of the 3 billion chemical building blocks (called bases and abbreviated A, T, C, and G) making up the DNA of the 24 different human chromosomes, is the greatest technical challenge in the Human Genome Project. Achieving this goal will help reveal the estimated 100,000 human genes within our DNA as well as the regions controlling them. The resulting DNA sequence maps will be used by21stcentury scientists to explore human biology and other plex phenomena. Meeting Human Genome Project sequencing goals by xx will require continual improvements in sequencing speed, reliability, and costs. Standard methods are based on separating DNA fragments by gel electrophoresis, which is extremely labor intensive and expensive. Total sequencing output in the munity was about 200 Mb for xx. Encouraging progress ranges from enhancements of gel-based technologies and the development of novel, gel-less automatable approaches, such as the use of DNA fragments bound to a solid surface DNA chips, and separation of fragments by mass spectrometry. New gel-based sequencers use multiple tiny (capillary) tubes to run standard electrophoretic separations. These separations are much faster because the tubes dissipate heat well and allow the use of much higher electric fields. See a figure depicting this technology. 2.What is the difference between draft sequence and finished sequence?A new goal (5/99) of the HGP is to generate a scaffold of known DNA sequence across an estimated 90% of the human genome. This working draft sequence will be of lower accuracy than the finished sequence and will not be continuous across the 3 billion bases of the human genome. However, the data will be invaluable to many biomedical scientists as they strive to understand genes important to their own research. Generating the draft will require researchers to sequence each piece of DNA only about 5 times, instead of the usual 10 times used for obtaining the highest quality sequence that is 99.99% plete and allows for only a single error in 10,000 bases. Remaining gaps and errors in the working draft sequence will be corrected over the years to achieve the ultimate goal of the Human Genome project: a plete, high-quality human DNA reference sequence by xx. 3.The normal cell cycleIn most tissues of the body, cells multiply through a process known as the cell cycle. Before cells can multiply and divide into other cells, they have to make exact copies of their DNA. DNA is the genetic code that is in all the cells of our bodies and is exactly the same code in each cell no matter what tissue the cell is from. Chromosomes are made up of the genes of our cells and our genes are made up of strands of DNA. Each cell of our body has two copies of each gene, one inherited from our mother and one from our father. The nucleus of the cell houses our chromosomes and genes.Normally, most cells are not actively growing and dividing and are in the G0 or resting phase of the cell cycle and have a diploid or 2N DNA content. Cells in the G1 phase are actively cycling but like G0 cells have a diploid or 2N DNA content. A small percentage of cells in normal tissues are undergoing DNA synthesis (making a copy of their DNA) and are in the S phase of the cell cycle (have a DNA content between 2N and 4N). A few cells have pleted their DNA synthesis and doubled their amount of DNA and are in the G2 phase of the cell cycle (have a 4N or tetraploid DNA content). After cells double their DNA, they undergo mitosis (M phase) dividing into two daughter cells that are exact genetic copies of each other and have a DNA content of 2N.Nowells hypothesisThere are many events or steps that occur in Barretts esophagus that lead to the development of cancer. A few of these events are known but most are not. Most of the known events appear to occur early, before high-grade dysplasia or cancer actually develops. No one knows what the late events are that give cells the ability to leave their normal growth boundaries and bee a cancer.It is now widely accepted that the development of most cancers is due to something called genomic or genetic instability. This theory was first proposed by Dr. Peter Nowell in 1976. The theory is that for some unknown reason, perhaps due to environmental factors or inherited factors, some cells in the body develop genetic abnormalities that give them the ability to outgrow genetically normal cells. These abnormal cells grow and expand into a clone of cells (a group of cells having the same genetic make-up) and may replace their neighboring normal cells. Eventually one of the abnormal clones may undergo another genetic change that leads to the development of a sub-clonal population with the expansion of this cell line into its own large clone of cells. As multiple genetic abnormalities occur, multiple sub-clones develop or evolve. Eventually, one of these sub-clones may acquire the necessary bination of genetic abnormalities to bee a cancer. Ball diagram of Nowells hypothesisThe green balls represent cells that have developed a genetic abnormality and are expanding or growing into a clone of cells. One of these cells develops a second genetic abnormality, illustrated by a blue ball, seen to expand into its own clone of cells or subclones of the green population. A third genetic mistake is made, illustrated by a dark red ball, with clonal expansion of this cell population. Eventually, another genetic mistake is made in one of the cells of the dark red population that allows that cell to bee a cancer.Cell cycle checkpoint genesIncredibly, genetic mistakes are rarely made in the duplication of a cells DNA. If a genetic mistake is made, for example - caused by exposure of a cell to radiation, there are genes (called cell cycle checkpoint genes) that control the cell cycle and prevent cells from dividing into two daughter cells. These cell cycle checkpoint genes insure that abnormal clones of cells will not be produced by the tissues of our bodies under normal circumstances.Site of p53 action on the cell cycleIf a G1 cell makes a genetic mistake, the protein made by the p53 gene does not allow that cell to enter S phase and copy its DNA. The abnormal G1 cell will usually undergo programmed cell death. This prevents cells with genetic abnormalities from dividing and undergoing clonal expansion and evolution.The p53 geneThe p53 gene was the first cell cycle checkpoint gene to be discovered in humans. It is referred to as a tumor suppressor gene because its normal function is to suppress the development of tumors by detecting genetic mistakes in G1 cells resulting in arrested cell growth (cell cycle arrest) or destruction (programmed cell death) of the cells with the mistake. When genetic abnormalities develop in the p53 gene leading to loss of its normal function, tumors more readily develop because cells with genetic mistakes are allowed to divide and pass the mistake on to daughter cells.p53 gene abnormalities are detected in up to 95% of Barretts associated cancers indicating that loss of function of the p53 gene is a necessary step in the progression to cancer in Barretts esophagus. Loss of function of the p53 gene in Barretts esophagus is one of the earliest known genetic events in the development of cancer and it is closely tied to abnormalities that develop in the cell cycle of Barretts cells. These abnormalities can be detected by a test called flow cytometry (a test that measures the amount of DNA in a cell).