During translation the genetic information present in mRNA directs the order of specific amino acids to form a polypeptide or protein. The mRNA has a series of triplet bases, each triplet forming a codon. The codons pair with anticodons of the tRNA molecule. Each anticodon consists of three free bases.This pairing follows the A U and G C combination. Thus the codon GUC pairs with the anticodon CAG of tRNA.
Thus the series of codons on mRNA determines the series of anticodons of the different tRNA molecules, and hence of the amino acids. Since the triplets of mRNA in turn depend upon the series of bases in DNA, it follows that the DNA molecule determines the sequence of amino acids, and hence the structure of the protein molecule.
The translation process consists of activation of amino acids, transfer of the activated amino acid to tRNA, initiation of polypeptide chain synthesis, chain elongation and chain termination
Showing posts with label GENETICS. Show all posts
Showing posts with label GENETICS. Show all posts
Monday, December 21, 2009
Components of RNA Polymerases of Escherichia Coli and Bacillus Subtilis -
| Subunit | Molecular Weight | Function | |
| E.coli | B.subtilis | ||
| β' (beta') | 160,000 | 160,000 | Binding of RNA polymerase of DNA |
| β (beta) | 150,000 | 150,000 | Binding with sigma factor |
| α (alpha) (2) | 40,000 | 45,000 | Promoter recongnition (?) |
| δ (delta) | -- | 21,000 | -- |
| ω1 ( omega 1 ) | -- | 11,000 | Not essential for normal activity |
| ω2 ( omega 2 ) | -- | 9,500 | Not essential for normal activity |
| σ sigma | 90,000 | 55,000 | Recognition of start signals (initiation) |
Characteristics of Subunits of Different RNA Polyemerases of Calf Thymus -
| RNA Polymerase | Subunits and their molecular weights | ||||||
| AIa MW | SA1 197,000 | SA2 126,000 | -- -- | SA4 44,000 | SA5 25,000 | SA6 16,500 | |
| AIb MW | SA1 197,000 | SA2 126,000 | SA3 51,000 | SA5 44,000 | SA5 25,000 | SA6 16,500 | |
| BI | SB1 | -- | SA2 | SB3 | SA4 | SA5 | SB6 (a+b) |
| MW | 14,000 | 140,000 | 34,000 | 25,000 | 20,000 | 16,500 | |
| BIIa BIIb MW | -- -- | SB2a SB2b 180,000 | SB3 140,000 | SA4 34,000 | SA4 25,000 | SA5' 20,000 | SB6 (a+b) 16,500 |
RNA Polymerases in Eukaryotes
In eukaryotic cells multiple forms of DNA dependent RNA polymerase are responsible for synthesis of cellular RNA. These differ in structure, function and localization. According to one terminology the RNA polymerases are named enzymes I, II and III. According to another terminology, based on sensitivity to amanitin, RNA polymerases are divided into three classes, A, Band C.
Class A polymerases are insensitive to amanitin and arc localized in the nucleoli. They include enzyme AI (RNA polymerase I) and AII (IB). AI has been purified from calf thymus, mouse myeloma and rat liver.
Class B polymerases are sensitive to low concentrations of amanitin(10-9 to 10-8 M), and are synonymous with polymerase II. They have been purified from calf thymus, rat liver, mouse myeloma and chick liver, among other tissues.
Class B polymerases can be resolved into three forms, BO (IIo), BI (IIA) and BII (a+b) (IIB). The BII form can be further resolved into two isoenzymes BIIa and BIIb. Class B polymerases are nucleoplasmic in location.
Class C polymerases are sensitive to high concentrations of amanitin(10-5 to 10-4 M). and have been resolved into CI, CII, CIIIa and CIIIb forms. Mouse myeloma polymerase III has been resolved into two chromatographic forms, IIIA which appears to be nuclear in origin and IIIB which is found mainly in the cytoplasm. Polymerase IIIA is synonymous with CIIIa and polymerase IIIB with CIIIb
Molecular structure. Each RNA polymerase is composed of two high molecular weight subunits or polypeptides and 4-6 smaller ones. Calf thymus RNA polymerases AIa, AIb, BI, BIIa and BIIb have been studied in detail.
Calf thymus RNA polymerase BII exists in two forms, BIIa and BIIb which differ only in their largest subunits (MW 180,000). In BIIa the subunit is SB2a and in BIIb it is SB2b. In class B polymerases the SB6 subunit consists of two isomers, SB6a and SB6b.BI and BII polymerases have additional SB5' subunits. SA3 does not appear to be essential for RNA synthesis on DNA templates.
The localization of class A polymerases (polymerase I) in Q),e nucleolus suggests a role in the synthesis of rRNAs. The involvement of Class C polymerases is not excluded. Class B polymerases (polymerase II) are involved hi the synthesis of heteronuclear RNA (hnRNA), a precursor of messenger RNA (mRNA).
Class C polymerases (polymerase III) appear to be involved in the synthesis of 5S RNA and pre 4S RNAs which are precursors of cytoplasmic tRNAs. Thus in eukaryotes, polymerases I, II and III are involved in the synthesis of rRNA, mRNA and tRNA, respectively. This is in contrast to the condition in prokaryotes where the synthesis of the three types of RNA is controlled by a single RNA polymerase.
Class A polymerases are insensitive to amanitin and arc localized in the nucleoli. They include enzyme AI (RNA polymerase I) and AII (IB). AI has been purified from calf thymus, mouse myeloma and rat liver.
Class B polymerases are sensitive to low concentrations of amanitin(10-9 to 10-8 M), and are synonymous with polymerase II. They have been purified from calf thymus, rat liver, mouse myeloma and chick liver, among other tissues.
Class B polymerases can be resolved into three forms, BO (IIo), BI (IIA) and BII (a+b) (IIB). The BII form can be further resolved into two isoenzymes BIIa and BIIb. Class B polymerases are nucleoplasmic in location.
Class C polymerases are sensitive to high concentrations of amanitin(10-5 to 10-4 M). and have been resolved into CI, CII, CIIIa and CIIIb forms. Mouse myeloma polymerase III has been resolved into two chromatographic forms, IIIA which appears to be nuclear in origin and IIIB which is found mainly in the cytoplasm. Polymerase IIIA is synonymous with CIIIa and polymerase IIIB with CIIIb
Molecular structure. Each RNA polymerase is composed of two high molecular weight subunits or polypeptides and 4-6 smaller ones. Calf thymus RNA polymerases AIa, AIb, BI, BIIa and BIIb have been studied in detail.
Calf thymus RNA polymerase BII exists in two forms, BIIa and BIIb which differ only in their largest subunits (MW 180,000). In BIIa the subunit is SB2a and in BIIb it is SB2b. In class B polymerases the SB6 subunit consists of two isomers, SB6a and SB6b.BI and BII polymerases have additional SB5' subunits. SA3 does not appear to be essential for RNA synthesis on DNA templates.
The localization of class A polymerases (polymerase I) in Q),e nucleolus suggests a role in the synthesis of rRNAs. The involvement of Class C polymerases is not excluded. Class B polymerases (polymerase II) are involved hi the synthesis of heteronuclear RNA (hnRNA), a precursor of messenger RNA (mRNA).
Class C polymerases (polymerase III) appear to be involved in the synthesis of 5S RNA and pre 4S RNAs which are precursors of cytoplasmic tRNAs. Thus in eukaryotes, polymerases I, II and III are involved in the synthesis of rRNA, mRNA and tRNA, respectively. This is in contrast to the condition in prokaryotes where the synthesis of the three types of RNA is controlled by a single RNA polymerase.
Protein Synthesis - History
1941. Caspersson and Brachet showed that nucleic acids are connected with protein synthesis.
1952. Porter described the endoplasmic reticulum.
1953. Palade described the ribosome.
1954. Gamow suggested a minimum genetic code of three nucleotides.
1955. Grunberg-Manago and Ochoa isolated the enzyme which links RNA nucleotides, to from RNA in vitro.
1956. Kornberg reported that in vitro synthesis an enzyme is necessary for DNA synthesis.
1956. Hoagland and co workers showed that separate enzymes catalyse the activation of different amino acids.
1957. Hoagland and others reported the presence of tRNA, and showed that it combines with amino acids before protein synthesis.
1957. Kornberg and co-workers isolated DNA polymerase enzyme of E. coli that could be used for in vitro synthesis of DNA.
1958. Tissieres and Watson isolated 70S E. coli ribosomes and showed that they consist of two subunits, 50S and 30S
1958. Crick proposed the central dogma of molecular biology, that DNA determines the sequence of amino acids in a polypeptide.
1961. Nirenberg and Mathei demonstrated that a particular RNA sequence produces a particular amino acid sequence.
1961. Jacob and Monod postulated the presence and function of mRNA in protein synthesis, and proposed the operon concept.
1961. Brenner, Jacob, and Meselson demonstrated the function of mRNA in protein synthesis.
1961. Crick and others produced direct evidence that the genetic code is a triplet code.
1961. Hall and Spiegelman obtained direct evidence that the mRNA molecule is formed on one DNA template strand.
1963. Temin reported that in certain tumour viruses RNA synthesizes DNA, which in turn codes for proteins (Teminism).
1964. Holley described the nucleotide sequence of alanine tRNA mole cule of yeast.
1964. Nirenberg and Leder showed that tRNA binding on the ribosome depends on mRNA.
1966. Spiegelman and colleagues successfully replicated biologically active viral RNA in test tube.
1967. Kornberg and Sinsheimer synthesized single stranded DNA in ØX174 bacteriophage
1967. Khorana and others showed that DNA ligase is capable of joining short lengths of DNA.
1970. Khorana synthesized an artificial gene from DNA nucleotides.
1952. Porter described the endoplasmic reticulum.
1953. Palade described the ribosome.
1954. Gamow suggested a minimum genetic code of three nucleotides.
1955. Grunberg-Manago and Ochoa isolated the enzyme which links RNA nucleotides, to from RNA in vitro.
1956. Kornberg reported that in vitro synthesis an enzyme is necessary for DNA synthesis.
1956. Hoagland and co workers showed that separate enzymes catalyse the activation of different amino acids.
1957. Hoagland and others reported the presence of tRNA, and showed that it combines with amino acids before protein synthesis.
1957. Kornberg and co-workers isolated DNA polymerase enzyme of E. coli that could be used for in vitro synthesis of DNA.
1958. Tissieres and Watson isolated 70S E. coli ribosomes and showed that they consist of two subunits, 50S and 30S
1958. Crick proposed the central dogma of molecular biology, that DNA determines the sequence of amino acids in a polypeptide.
1961. Nirenberg and Mathei demonstrated that a particular RNA sequence produces a particular amino acid sequence.
1961. Jacob and Monod postulated the presence and function of mRNA in protein synthesis, and proposed the operon concept.
1961. Brenner, Jacob, and Meselson demonstrated the function of mRNA in protein synthesis.
1961. Crick and others produced direct evidence that the genetic code is a triplet code.
1961. Hall and Spiegelman obtained direct evidence that the mRNA molecule is formed on one DNA template strand.
1963. Temin reported that in certain tumour viruses RNA synthesizes DNA, which in turn codes for proteins (Teminism).
1964. Holley described the nucleotide sequence of alanine tRNA mole cule of yeast.
1964. Nirenberg and Leder showed that tRNA binding on the ribosome depends on mRNA.
1966. Spiegelman and colleagues successfully replicated biologically active viral RNA in test tube.
1967. Kornberg and Sinsheimer synthesized single stranded DNA in ØX174 bacteriophage
1967. Khorana and others showed that DNA ligase is capable of joining short lengths of DNA.
1970. Khorana synthesized an artificial gene from DNA nucleotides.
Friday, December 11, 2009
A Short History of Mapping(Reading The Human Blueprint)
"All human disease is genetic in origin," Nobel laureate Paul Berg of Stanford University told a cancer symposium a few years ago. Berg was exaggerating only slightly. It has become increasingly evident that virtually all human afflictions, from cancer to psychological disorders and susceptibility to infection, are rooted in our genes. "What we need to do now is find those genes," claims James Watson, who shared a Nobel Prize for deciphering the structure of DNA and who now directs the National Center for Human Genome Research at the National Institutes of Health.
The necessary guide will be a map fixing each of the estimated 50,000 to 100,000 human genes to its correct location on the chromosomes. "Like the system of interstate highways spanning our country, the map of the human genome will be completed stretch by stretch," Watson says. He expects that this map, the goal of the federally funded Human Genome Project, will provide the key to understanding the nearly 4,000 known genetic disorders and the countless diseases whose origin may be due in part to genetic malfunctions, as well as the astonishing variety of normal human traits.
Such a map has been on the wish lists of molecular explorers for years. Without it, nailing the culprits responsible for genetic diseases requires not only hard work, ingenuity, and determination, but more than a little luck. Although researchers were aided by luck when they found the general location of the gene for Huntington's disease (HD) on chromosome 4 in 1983, for instance, since that time they have spent eight years painstakingly slogging through the target area at the tip of the chromosome and still have no gene in sight.
Yet single-gene diseases such as HD are relatively easy targets. Disorders that seem to be caused by the interplay of several genes, hypertension, atherosclerosis, and most forms of cancer and mental illness, are much more difficult to track down. Having a map of the entire human genome will make it theoretically possible to identify every gene that contributes to them.
A gene map can also lead researchers to new frontiers in drug development. Once all the genes are identified and their bases are sequenced, it will be possible to produce virtually any human protein-valuable natural pharmaceuticals, such as tissue plasminogen activator, interferon, and erythropoietin - as well as new molecules designed specifically to block disease-producing proteins.
The NIH gene-mapping project officially began in October, 1990. But the map of the human genome has been in the making for a good part of the century. It started in 1911, when the gene responsible for red-green color blindness was assigned to the X chromosome following the observation that this disorder was passed on to sons by mothers who saw colors normally. Some other disorders that affect only males were likewise mapped to the X chromosome on the theory that females, who have two X chromosomes, were protected from these disorders by a normal copy of the gene on their second X chromosome unlike males, who have one X and one Y chromosome.
The other 22 pairs of chromosomes remained virtually uncharted until the late 1960s. Then biologists fused human and mouse cells to create uneasy hybrid cells that cast off human chromosomes until only one or a few remained. Any recognizable human proteins in these hybrid cells thus had to be produced by genes located on the remaining human chromosomes. This strategy allowed scientists to assign about 100 genes to specific chromosomes.
Map-making really took off in the early 1970s, when geneticists discovered characteristic light and dark stripes or bands across each chromosome after it was stained with a chemical. These bands, which fluoresced under ultraviolet light, provided the chromosomal equivalent of latitudes. They made it easier to identify individual human chromosomes in hybrid cells and served as rough landmarks on the chromosomes, leading to the assignment of some 1,000 genes to specific chromosomes.
Around the same time, recombinant DNA technology began to revolutionize biology by allowing researchers to snip out pieces of DNA and splice them into bacteria, where they could be grown, or cloned, in large quantities. This led to two new mapping strategies. In one, in situ hybridization, scientists stop the division of human cells in such a way that each chromosome is clearly visible under a light microscope. Then they use probes to find the location of any DNA fragment on these chromosomes. Originally these probes were radioactively labeled, but chemically-tagged probes that can be made to fluoresce have been found to yield far more accurate and rapid results.
The other strategy is to use DNA variations as markers on the human genome, as proposed by Botstein, White, Skolnick, and Davis in 1980. This has resulted in a flood of new markers and an explosion in the knowledge of genes' chromosomal whereabouts. The number of genes mapped grew from 579 in 1981 to 1,879 in 1991. Gene mappers, who used to meet to coordinate their findings every year or so, now update the map every day via electronic databases.
Meanwhile, scientists learned to sequence the genes they isolated. This became possible in the mid-1970s when Frederick Sanger at Cambridge University and Walter Gilbert and Allan Maxam at Harvard University developed efficient new methods for determining the order of bases in a strand of DNA. Automated high-speed sequencing by machine followed in the 1980s. Now, once a new gene has been identified, it is immediately sequenced to understand the nature of the protein it codes for and to identify mutations that are related to disease.
Sequencing the entire genome, however, means sequencing at least 3 billion base pairs of DNA - a chromosome of each type, or half the total number of chromosomes in a human cell. This remains a daunting project.
Generally the most interesting or accessible genes have been located first, creating a disparity among chromosomal maps. While the map of the X chromosome appears to be as densely populated as the New York coast, for instance, chromosome 18 looks as lonesome as central South Dakota.
The Human Genome Project should even out the map by sending explorers into chromosomal terra incognito. "The project really isn't doing anything new. What it's doing is creating order and accountability," says geneticist Eric Lander of the Whitehead Institute.
This orderly process is expected to produce a genetic linkage map in which the positions of genes for specific traits and diseases are superimposed on a grid of evenly spaced markers along the chromosomes. The project's five-year goal is to cover the entire genome with 1,500 genetic markers placed at equal intervals. Scientists will be able to determine any gene's location relative to these markers.
In addition, the project will create a physical map that shows actual distances along the chromosomes in terms of base pairs.
The physical map probably will be constructed of long overlapping stretches of DNA cloned in yeast and known as yeast artificial chromosomes (YACs). Developed in 1987 by Maynard Olson, now an HHMI investigator at Washington University in St. Louis, YACs make it possible to clone and store very large DNA segments - much larger than those that can be cloned in bacteria. The technique has reduced the number of DNA pieces that need to be placed in the right order from about 100,000 to 10,000. Recently, Olson assembled a YAC library of the entire genome and distributed it for the use of gene mappers.
At least two approaches have been developed to unite the genetic linkage map and the physical map so that a researcher can easily move back and forth between the two. One is to dot both maps with a new kind of marker known as sequence-tagged sites, or STSs - long sequences of DNA that generally occur only once in the whole human genome and can be used as common reference points. The other approach is to plot the position of existing genetic markers onto the physical map by means of in situ hybridization.
Meanwhile, new strategies promise to speed up sequencing significantly. Some researchers have reported that it may not be necessary to sequence every base but to sequence certain pivotal regions of DNA and fill in the blanks later. Moreover, automated sequencing and computer software designed specifically for genome analysis are already reducing sequencing time. As the pace of mapping and sequencing quickens, so does the pace of data collection. The Genome Data Base, developed by The Johns Hopkins University in collaboration with HHMI, integrates various kinds of mapping and sequencing data, as well as the constantly evolving genetic linkage map. The Paris-based Centre d'Etude du Polymorphisme Humain collates data from laboratories around the world to develop a series of consensus maps for each chromosome. Another international body, the Human Genome Organisation, is starting to coordinate gene-mapping efforts in 42 nations.
The Genome Project has often been criticized as the intrusion of "Big Science" on the traditionally "small science" of biology. However, "everyone's beginning to realize this isn't at all like putting up a space station or erecting a supercolliding superconductor," says Glen Evans of the Salk Institute in La Jolla, California. "We're not going to undertake large-scale sequencing until new technology makes it cheap to do," explains James Watson.
If a map of the genome and sets of overlapping clones had been available when researchers set out to find the cystic fibrosis gene, their task would have taken only a fraction of the time and cost, points out Thomas Caskey, of the HHMI unit at the Baylor College of Medicine. "The investigators wouldn't have had to clone region after region looking for the gene," he says. "They could have just reached into the freezer and pulled out two markers flanking it. The same would be true for many other diseases. And remember, once we make this map, we will never have to do it again
http://www.accessexcellence.org/RC/AB/IE/Short_History_of_Mapping.php
The necessary guide will be a map fixing each of the estimated 50,000 to 100,000 human genes to its correct location on the chromosomes. "Like the system of interstate highways spanning our country, the map of the human genome will be completed stretch by stretch," Watson says. He expects that this map, the goal of the federally funded Human Genome Project, will provide the key to understanding the nearly 4,000 known genetic disorders and the countless diseases whose origin may be due in part to genetic malfunctions, as well as the astonishing variety of normal human traits. Such a map has been on the wish lists of molecular explorers for years. Without it, nailing the culprits responsible for genetic diseases requires not only hard work, ingenuity, and determination, but more than a little luck. Although researchers were aided by luck when they found the general location of the gene for Huntington's disease (HD) on chromosome 4 in 1983, for instance, since that time they have spent eight years painstakingly slogging through the target area at the tip of the chromosome and still have no gene in sight.
Yet single-gene diseases such as HD are relatively easy targets. Disorders that seem to be caused by the interplay of several genes, hypertension, atherosclerosis, and most forms of cancer and mental illness, are much more difficult to track down. Having a map of the entire human genome will make it theoretically possible to identify every gene that contributes to them.
A gene map can also lead researchers to new frontiers in drug development. Once all the genes are identified and their bases are sequenced, it will be possible to produce virtually any human protein-valuable natural pharmaceuticals, such as tissue plasminogen activator, interferon, and erythropoietin - as well as new molecules designed specifically to block disease-producing proteins.
The NIH gene-mapping project officially began in October, 1990. But the map of the human genome has been in the making for a good part of the century. It started in 1911, when the gene responsible for red-green color blindness was assigned to the X chromosome following the observation that this disorder was passed on to sons by mothers who saw colors normally. Some other disorders that affect only males were likewise mapped to the X chromosome on the theory that females, who have two X chromosomes, were protected from these disorders by a normal copy of the gene on their second X chromosome unlike males, who have one X and one Y chromosome. The other 22 pairs of chromosomes remained virtually uncharted until the late 1960s. Then biologists fused human and mouse cells to create uneasy hybrid cells that cast off human chromosomes until only one or a few remained. Any recognizable human proteins in these hybrid cells thus had to be produced by genes located on the remaining human chromosomes. This strategy allowed scientists to assign about 100 genes to specific chromosomes.
Map-making really took off in the early 1970s, when geneticists discovered characteristic light and dark stripes or bands across each chromosome after it was stained with a chemical. These bands, which fluoresced under ultraviolet light, provided the chromosomal equivalent of latitudes. They made it easier to identify individual human chromosomes in hybrid cells and served as rough landmarks on the chromosomes, leading to the assignment of some 1,000 genes to specific chromosomes.
Around the same time, recombinant DNA technology began to revolutionize biology by allowing researchers to snip out pieces of DNA and splice them into bacteria, where they could be grown, or cloned, in large quantities. This led to two new mapping strategies. In one, in situ hybridization, scientists stop the division of human cells in such a way that each chromosome is clearly visible under a light microscope. Then they use probes to find the location of any DNA fragment on these chromosomes. Originally these probes were radioactively labeled, but chemically-tagged probes that can be made to fluoresce have been found to yield far more accurate and rapid results.
The other strategy is to use DNA variations as markers on the human genome, as proposed by Botstein, White, Skolnick, and Davis in 1980. This has resulted in a flood of new markers and an explosion in the knowledge of genes' chromosomal whereabouts. The number of genes mapped grew from 579 in 1981 to 1,879 in 1991. Gene mappers, who used to meet to coordinate their findings every year or so, now update the map every day via electronic databases.
Meanwhile, scientists learned to sequence the genes they isolated. This became possible in the mid-1970s when Frederick Sanger at Cambridge University and Walter Gilbert and Allan Maxam at Harvard University developed efficient new methods for determining the order of bases in a strand of DNA. Automated high-speed sequencing by machine followed in the 1980s. Now, once a new gene has been identified, it is immediately sequenced to understand the nature of the protein it codes for and to identify mutations that are related to disease.
Sequencing the entire genome, however, means sequencing at least 3 billion base pairs of DNA - a chromosome of each type, or half the total number of chromosomes in a human cell. This remains a daunting project.
Generally the most interesting or accessible genes have been located first, creating a disparity among chromosomal maps. While the map of the X chromosome appears to be as densely populated as the New York coast, for instance, chromosome 18 looks as lonesome as central South Dakota.
The Human Genome Project should even out the map by sending explorers into chromosomal terra incognito. "The project really isn't doing anything new. What it's doing is creating order and accountability," says geneticist Eric Lander of the Whitehead Institute.
This orderly process is expected to produce a genetic linkage map in which the positions of genes for specific traits and diseases are superimposed on a grid of evenly spaced markers along the chromosomes. The project's five-year goal is to cover the entire genome with 1,500 genetic markers placed at equal intervals. Scientists will be able to determine any gene's location relative to these markers.
In addition, the project will create a physical map that shows actual distances along the chromosomes in terms of base pairs.
The physical map probably will be constructed of long overlapping stretches of DNA cloned in yeast and known as yeast artificial chromosomes (YACs). Developed in 1987 by Maynard Olson, now an HHMI investigator at Washington University in St. Louis, YACs make it possible to clone and store very large DNA segments - much larger than those that can be cloned in bacteria. The technique has reduced the number of DNA pieces that need to be placed in the right order from about 100,000 to 10,000. Recently, Olson assembled a YAC library of the entire genome and distributed it for the use of gene mappers.
At least two approaches have been developed to unite the genetic linkage map and the physical map so that a researcher can easily move back and forth between the two. One is to dot both maps with a new kind of marker known as sequence-tagged sites, or STSs - long sequences of DNA that generally occur only once in the whole human genome and can be used as common reference points. The other approach is to plot the position of existing genetic markers onto the physical map by means of in situ hybridization.
Meanwhile, new strategies promise to speed up sequencing significantly. Some researchers have reported that it may not be necessary to sequence every base but to sequence certain pivotal regions of DNA and fill in the blanks later. Moreover, automated sequencing and computer software designed specifically for genome analysis are already reducing sequencing time. As the pace of mapping and sequencing quickens, so does the pace of data collection. The Genome Data Base, developed by The Johns Hopkins University in collaboration with HHMI, integrates various kinds of mapping and sequencing data, as well as the constantly evolving genetic linkage map. The Paris-based Centre d'Etude du Polymorphisme Humain collates data from laboratories around the world to develop a series of consensus maps for each chromosome. Another international body, the Human Genome Organisation, is starting to coordinate gene-mapping efforts in 42 nations.
The Genome Project has often been criticized as the intrusion of "Big Science" on the traditionally "small science" of biology. However, "everyone's beginning to realize this isn't at all like putting up a space station or erecting a supercolliding superconductor," says Glen Evans of the Salk Institute in La Jolla, California. "We're not going to undertake large-scale sequencing until new technology makes it cheap to do," explains James Watson.
If a map of the genome and sets of overlapping clones had been available when researchers set out to find the cystic fibrosis gene, their task would have taken only a fraction of the time and cost, points out Thomas Caskey, of the HHMI unit at the Baylor College of Medicine. "The investigators wouldn't have had to clone region after region looking for the gene," he says. "They could have just reached into the freezer and pulled out two markers flanking it. The same would be true for many other diseases. And remember, once we make this map, we will never have to do it again
http://www.accessexcellence.org/RC/AB/IE/Short_History_of_Mapping.php
Biography of Gregor Mendel (1822-1884)
The theories of heredity attributed to Gregor Mendel, based on his work with pea plants, are well known to students of biology. But his work was so brilliant and unprecedented at the time it appeared that it took thirty-four years for the rest of the scientific community to catch up to it. The short monograph, Experiments with Plant Hybrids, in which Mendel described how traits were inherited, has become one of the most enduring and influential publications in the history of science.
Mendel, the first person to trace the characteristics of successive generations of a living thing, was not a world-renowned scientist of his day. Rather, he was an Augustinian monk who taught natural science to high school students. He was the second child of Anton and Rosine Mendel, farmers in Brunn, Moravia. Mendel's brilliant performance at school as a youngster encouraged his family to support his pursuit of a higher education, but their resources were limited, so Mendel entered an Augustinian monastery, continuing his education and starting his teaching career.Mendel's attraction to research was based on his love of nature. He was not only interested in plants, but also in meteorology and theories of evolution. Mendel often wondered how plants obtained atypical characteristics. On one of his frequent walks around the monastery, he found an atypical variety of an ornamental plant. He took it and planted it next to the typical variety. He grew their progeny side by side to see if there would be any approximation of the traits passed on to the next generation. This experiment was "designed to support or to illustrate Lamarck's views concerning the influence of environment upon plants." He found that the plants' respective offspring retained the essential traits of the parents, and therefore were not influenced by the environment. This simple test gave birth to the idea of heredity.
Mendel's research reflected his personality. Once he crossed peas and mice of different varieties "for the fun of the thing," and the phenomena of dominance and segregation "forced themselves upon notice." He saw that the traits were inherited in certain numerical ratios. He then came up with the idea of dominance and segregation of genes and set out to test it in peas. It took seven years to cross and score the plants to the thousand to prove the laws of inheritance! From his studies, Mendel derived certain basic laws of heredity: hereditary factors do not combine, but are passed intact; each member of the parental generation transmits only half of its hereditary factors to each offspring (with certain factors "dominant" over others); and different offspring of the same parents receive different sets of hereditary factors. Mendel's work became the foundation for modern genetics.
The impact of genetic theory is no longer questioned in anyone's mind. Many diseases are known to be inherited, and pedigrees are typically traced to determine the probability of passing along an hereditary disease. Plants are now designed in laboratories to exhibit desired characteristics. The practical result of Mendel's research is that it not only changed the way we perceive the world, but also the way we live in it.
Subscribe to:
Posts (Atom)
