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Genetics from mendel to Era of microarray classical Genetics
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Genetics from mendel to Era of microarray classical Genetics

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the science of heredity. Genetics is concerned primarily with understandingbiological properties that are transmitted from parent tooffspring. The subject matter of genetics includes hered-ity, the molecular nature of the genetic material, the waysin which genes (which determine the characteristics oforganisms) control life functions, and the distributionand behavior of genes in populations.

Genetics is central to biology because gene activityunderlies all life processes, from cell structure and function to reproduction. Learning what genes are, how genes are transmitted from generation to generationhe principles of heredity were not understood untilthe mid-nineteenth century, when Gregor Mendel ana-lyzed quantitatively the results of crossing pea plants thatvaried in easily observable characteristics. He publishedhis results, but their significance was not realized in hislifetime.

Several years after his death, however, re-searchers realized that Mendel had discovered fundamental principles of heredityThe structure of DNA was first described in 1953, andsince that time genetics has become one of the most excit-ing and ground-breaking sciences. Our understanding ofgene structure and function has progressed rapidly sincemolecular techniques were developed to clone or amplifygenes, and rapid methods for sequencing DNA becameavailable. Research in genetics underwent a revolution in 1972,when Paul Berg constructed the first recombinant DNAmolecule in vitro, and in 1973, when Herbert Boyer andStanley Cohen cloned a recombinant DNA molecule forthe first time.

The development by Kary Mullis in 1986of the polymerase chain reaction (PCR) to amplifyspecific segments of DNA spawned another revolution. Recombinant DNA technology, PCR, and other moleculartechnologies are leading to an ever-increasing number ofexciting discoveries that are furthering our knowledge ofbasic biological functions and will lead to improvementsin the quality of human life. In recent years, the sequencing of the genomes ofa large number of viruses and organisms has changed thescope of experiments performed by geneticists.

For example, we can study a genome’s worth of genes now in oneexperiment, allowing us to obtain a more complete understanding of gene expression. understanding of the abstract nature of genes (fromthe transmission genetics part) with the molecular natureof genes (from the molecular genetics is one of the best approachClassic Principles. classic experiments, a number of which have led to discoveriesThese experiments include:•Griffith’s transformation experiment•Avery and his colleagues’ transformation experiment•Hershey and Chase’s bacteriophage experiment•Meselson and Stahl’s DNA replication experiment•Beadle and Tatum’s one-gene–one-enzyme hypothe-sis experiments•Mendel’s experiments on gene segregation•Thomas Hunt Morgan’s experiments on gene linkage•Seymour Benzer’s experiments on the fine structureof the gene•Jacob and Monod’s experiments on the lac operonThe Subdisciplines of GeneticsGeneticists often divide genetics into four major subdis-ciplines:1.

Transmission genetics (sometimes called classicalgenetics) is the subdiscipline dealing with how genesand genetic traits are transmitted from generation togeneration and how genes recombine (exchange be-tween chromosomes). Analyzing the pattern of traittransmission in a human pedigree or in crosses of ex-perimental organisms is an example of a transmis-sion genetics study. 2.

Molecular genetics is the subdiscipline dealing withthe molecular structure and function of genes. Ana-lyzing the molecular events involved in the genecontrol of cell division, or the regulation of expres-sion of all the genes in a genome, are examples ofmolecular genetics studies. Genomic analysis is partof molecular genetics.

3. Population genetics is the subdiscipline that studiesheredity in groups of individuals for traits that are de-termined by one or only a few genes. Analyzing thefrequency of a disease-causing gene in the human pop-ulation is an example of a population genetics study.

4. Quantitative genetics also considers the heredity oftraits in groups of individuals, but the traits of concernare determined by many genes simultaneously. Analyz-ing the fruit weight and crop yield in agriculturalplants are examples of quantitative genetics studies.

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Single nucleotide polymorphisms (SNPs)practical applicationsAmplify DNA for Cloning (PCR)✓ Amplify DNA for sequencing without cloning (PCR)✓ DNA sequencing reaction (PCR)✓ Mapping genes and regulatory sequences✓ Linkage analysis (identify genes for traits/diseases)✓ Diagnose disease✓ Pathogen screening✓ Sex determination✓ Forensic analysis✓ Paternity/maternity (relatedness)✓ Behavioral ecology studies (relatedness)✓ Molecular systematics and evolution (comparing homologous sequences in different organisms)✓ Population genetics (theoretical and applied)✓ Physiological genetics (studying basis of adaptation)✓ Livestock pedigrees (optimize breeding)✓ Wildlife management (stock identification/assessment)✓ Detection of Genetically Modified Food (GMOs)the Polymerase Chain Reaction (PCR)✓ Ability to generate identical high copy number DNAs made possible in the 1970s by recombinant DNA technology (i.e., cloning).✓ Cloning DNA is time consuming and expensive (>>$15/sample).✓ Probing libraries can be like hunting for a needle in a haystack.✓ PCR, “discovered” in 1983 by Kary Mullis, enables the amplification(or duplication) of millions of copies of any DNA sequence with known flanking sequences. ✓ Requires only simple, inexpensive ingredients and a couple hours.DNA templatePrimers (anneal to flanking sequences)DNA polymerasedNTPsMg2+Buffer✓ Can be performed by hand or in a machine called a thermal cycler.✓ 1993: Nobel Prize for ChemistryHow PCR works:1. 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Next, each reaction mixture is electrophoresed in a separate lane (4 lanes) at high voltage on a polyacrylamide gel. 10.Pattern of bands in each of the four lanes is visualized on X-ray film.11.Location of “bands” in each of the four lanes indicate the size of the fragment terminating with a respective radio-labeled ddNTP.12.DNA sequence is deduced from the pattern of bands in the 4 lanes.Automated Dye-Terminator DNA Sequencing:1. Dideoxy DNA sequencing was time consuming, radioactive, and throughput was low, typically ~300 bp per run.2. Automated DNA sequencing employs the same general procedure, but uses ddNTPs labeled with fluorescent dyes.3. Combine 4 dyes in one reaction tube and electrophores in one lane on a polyacrylamide gel or capillary containing polyacrylamide.4. UV laser detects dyes and reads the sequence.5. Sequence data is displayed as colored peaks (chromatograms) that correspond to the position of each nucleotide in the sequence.6. 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vaccine, suspension of weakened, killed, or fragmented microorganisms or toxins or other biological preparation, such as those consisting of antibodies, lymphocytes, or messenger RNA (mRNA), that is administered primarily to prevent disease.human B cellA vaccine can confer active immunity against a specific harmful agent by stimulating the immune system to attack the agent. Once stimulated by a vaccine, the antibody-producing cells, called B cells (or B lymphocytes), remain sensitized and ready to respond to the agent should it ever gain entry to the body. A vaccine may also confer passive immunity by providing antibodies or lymphocytes already made by an animal or human donor. Vaccines are usually administered by injection (parenteral administration), but some are given orally or even nasally (in the case of flu vaccine). 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They may produce a mild or subclinical form of the disease. Attenuated vaccines include those for measles, mumps, polio (the Sabin vaccine), rubella, and tuberculosis. Inactivated vaccines are those that contain organisms that have been killed or inactivated with heat or chemicals. Inactivated vaccines elicit an immune response, but the response often is less complete than with attenuated vaccines. Because inactivated vaccines are not as effective at fighting infection as those made from attenuated microorganisms, greater quantities of inactivated vaccines are administered. Vaccines against rabies, polio (the Salk vaccine), some forms of influenza, and cholera are made from inactivated microorganisms. Another type of vaccine is a subunit vaccine, which is made from proteins found on the surface of infectious agents. Vaccines for influenza and hepatitis B are of that type. 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Meister survives and later becomes the caretaker of Pasteur’s tomb in Paris.In 1894, Dr Anna Wessels Williams isolates a strain of the diphtheria bacteria that is crucial in the development of an antitoxin for the disease.novel vaccineRecombinant DNA technology has also proven useful in developing vaccines to viruses that cannot be grown successfully or that are inherently dangerous. Genetic material that codes for a desired antigen is inserted into the attenuated form of a large virus, such as the vaccinia virus, which carries the foreign genes “piggyback.” The altered virus is injected into an individual to stimulate antibody production to the foreign proteins and thus confer immunity. The approach potentially enables the vaccinia virus to function as a live vaccine against several diseases, once it has received genes derived from the relevant disease-causing microorganisms. A similar procedure can be followed using a modified bacterium, such as Salmonella typhimurium, as the carrier of a foreign gene.Gardasil human papillomavirus vaccineVaccines against human papillomavirus (HPV) are made from virus like particles (VLPs), which are prepared via recombinant technology. The vaccines do not contain live HPV biological or genetic material and therefore are incapable of causing infection. Two types of HPV vaccines have been developed, including a bivalent HPV vaccine, made using VLPs of HPV types 16 and 18, and a tetravalent vaccine, made with VLPs of HPV types 6, 11, 16, and 18.Another approach, called naked DNA therapy, involves injecting DNA that encodes a foreign protein into muscle cells. The cells produce the foreign antigen, which stimulates an immune response.Vaccines based on RNA have been of particular interest as a means of preventing diseases such as influenza, cytomegalovirus infection, and rabies. Messenger RNA (mRNA) vaccines are advantageous because the way in which they are made allows them to be developed more quickly than vaccines made via other methods. In addition, their production can be standardized, enabling rapid scale-up for the manufacture of large quantities of vaccine. Novel mRNA vaccines are safe and effective; they do not contain live virus, nor does the RNA interact with human DNA.advantage and dis advantageBenefits of vaccinationFind out from Dr. Tina Tan of Northwestern University why adult vaccination against various types of diseases is importantSee all videos for this articleIn addition to the development of memory B cells, which are capable of triggering a secondary immune response upon exposure to the pathogen targeted by a vaccine, vaccination is also beneficial at the population level. When a sufficient number of individuals in a population are immune to a disease, as would occur if a large proportion of a population were vaccinated, herd immunity is achieved. That means that if there is random mixing of individuals within the population, then the pathogen cannot be spread throughout the population. Herd immunity acts by breaking the transmission of infection or by lessening the chances of susceptible individuals coming in contact with a person who is infectious. Herd immunity provides a measure of protection to individuals who are not personally immune to the disease—for instance, individuals who, because of their age or underlying medical conditions, cannot receive vaccines or individuals who received vaccines but remain susceptible. Herd immunity played an important role in the successful eradication of smallpox, and it is vital in preventing the spread of diseases such as polio and measles.Adverse reactionsVaccination carries some risk of reaction, though adverse effects typically are very rare and very mild. The most common reactions to vaccines include redness and soreness around the vaccination site. More severe adverse reactions, such as vomiting, high fever, seizure, brain damage, or death, are possible for some vaccines. Such reactions are exceptionally rare, however—occurring in less than one in a million people for most vaccines. Severe reactions also tend to affect only certain populations, such as persons whose immune systems are compromised by preexisting disease (e.g., HIV/AIDS) or who are undergoing chemotherapy.Claims have been made that vaccines are responsible for certain adverse health conditions, particularly autism, speech disorders, and inflammatory bowel disease. Some of those claims focused on thimerosal, a mercury-containing compound used as a preservative in vaccines. Some people believed that autism was a form of mercury poisoning, caused specifically by thimerosal in childhood vaccines. Those claims have been discredited. Still, misinformation and fear generated by false claims about associations between autism and vaccines had a significant impact on individuals’ perceptions about vaccine safety. In addition, most individuals in countries where vaccination is widespread have never personally experienced vaccine-preventable disease. Thus, the focus of concern for some people shifted from the negative effects of vaccine-preventable disease to the possible negative effects of the vaccines themselves.Complacency about vaccine-preventable diseases, combined with concerns over the effects of vaccination, led to decreasing levels of vaccination coverage in some areas of the world. As a consequence, not only were individuals susceptible to vaccine-preventable diseases, but, at population levels, vaccination rates dropped low enough to cause losses of herd immunity, thereby allowing outbreaks of disease. Such outbreaks brought high costs to societies, especially in terms of health and medical care, disability and economic strain, and loss of life. In the 20th century in Japan, England, and Russia, for example, numbers of children vaccinated against whooping cough dropped sufficiently low so as to enable outbreaks of disease that involved thousands of children and resulted in hundreds of deaths

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medical genetics learn abnormal human variations
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medical genetics learn abnormal human variations

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Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specialty, predictive medicineMedical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research into the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology, intellectual disabilities, autism, mitochondrial disorders, skeletal dysplasia, connective tissue disorders, cancer genetics, and prenatal diagnosis. Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics are revealing etiologies for morphologic, endocrine, cardiovascular, pulmonary, ophthalmologist, renal, psychiatric, and dermatologic conditions. The medical genetics community is increasingly involved with individuals who have undertaken elective genetic and genomic testing.

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