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Genetics is built on a rich tradition of discovery and experimentation. Transmission genetics is genetics is the process by which traits controlled by genes are transmitted through gametes from generation to generation. Mutant strains can be used in genetic crosses to map the location and distance between genes. The Watson-Crick model of DNA structure explain how genetic information is stored and expressed. This is the foundation of molecular genetics. genetics . Recombinant DNA technology revolutionized genetics, and was the foundation for the Human Genome Project , and has generated new fields that combine genetics with information technology. Biotechnology provides genetically modified organisms with uses varying from agriculture to medicine. Model organisms used organisms used in genetics research are now utilized in combination with recombinant DNA technology and genomics to study human diseases. Genetic technology is developing faster than the policies, laws, and conventions that govern its use.
On December 1998 , deCODE Genetics had received a license to create and operate a datebase drawn from the medical records of Iceland’s 270,000 residents. It was a resource for research and was very successful till its end in 2012. deCODE Genetics had picked Iceland because (1) resident’s high level of genetic relations (2) few immigrants brought new genes and (3) Iceland’s health-care system is state-supported. This brings up plenty of ethical questions. More than any other time in the history of science, addressing the ethical questions surrounding an emerging technology is as important as the information gained from that technology.
I. History of Genetics 8000-1000 B.C. Selective breeding of several species Cultivation of plants (5000 B.C.) • •
Golden Age of Greek Culture Hippocratic School of Medicine’s On the Seed argued that “humors” served as bearers of hereditary traits (parts in miniature form) Humors can be altered before passing down to offspring (inheritance of acquired traits) •
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Aristotle proposed male semen contained “vital heat” that producing offspring of the same form as the parent. Vital heat cooked menstrual blood (physical substance) from females
Charles Darwin and Evolution Charles Darwin (1859) Published “On the Origin of Species” •
Existing species arose by descent with modification from ancestral species •
“Theory of Natural Selection” According to Alfred Russel Wallace, populations tend to contain more offspring than the environment can support, leading to a struggle for survival among individuals. Those with heritable traits that allow them to adapt to their environment are able to survive and reproduce better. A new species may result if a population carrying these inherited variations becomes reproductively isolated.
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Lacked an understanding of genetic basis of variation and inheritance
Gregor Jordan Mendel (1866) Showed how traits were passed from generation to generation in pea plants Offered a general model of how traits are inherited Brought to light by Correns, de Vries, and Tschermak around 1900 Closed gap in Darwin’s theory by laying the foundation for the chromosomal theory of inheritance •
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Dawn of Modern Biology (1600 – 1850) William Harvey (1600s) “Theory of Epigenesis” •
An organism develops from a fertilized egg by a succession of developmental events that transform the egg into an adult •
Conflicted with the “Theory of Preformation” Fertilized egg contains complete miniature adult called the homunculus
Schleiden and Theodor Schwann “Cell Theory” •
All organisms are composed of basic units called cells, which are derived from similar preexisting structures •
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Conflicted with the idea of spontaneous generation (disproved by Louis Pasteur)
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II. Advancements in Genetics Mendel’s Transmission of Traits Gregor Mendel Augustinian Monk that conducted decade long series of experiments using peas Each trait in the plant is controlled by a pair of genes and that during gamete formation, members of a gene pair separate from each other Foundation of Genetics (study of heredity and variation) •
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Genetic Variation Drosophilia melanogaster (fruit fly) – a whiteeyed fly was spotted amongst red eyed flies •
Caused by a mutation in of of the genes controlling eye color •
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Mutation – any heritable change in the DNA sequence, source of all genetic variation Allele – alternative forms of a gene Phenotype – observable features Genotype – set of alleles for a given trait
Chemical Nature of Genes Proteins and DNA were the major chemical components of chromosomes, people were not sure what was the carrier of genetic info Avery, MacLeod, McCarty (1944) – DNA was the carrier of genetic information (supported by virus researchers) •
Chromosome Theory of Inheritance Terms Diploid Number (2n) – characteristic o number of chromosomes in most eukaryotes Haploid Number (n) – produced from o meiosis, essential for maintaining 2n Homologous Chromosomes – paired o chromosomes in diploid cells o Mitosis – type of cell division, chromosomes are identical in daughter and parent cell Meiosis – type of cell division, gamete o formation, cells only receive one chromosome from each pair Walter Sutton/Theodor Boveri – Behavior of chromosomes during meiosis is identical to the behavior of genes during gamete formation o Proposed that genes are carried by chromosomes o Chromosome Theory of Inheritance •
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III. Era of Molecular Genetics Structure of DNA and RNA James Watson and Francis Crick (1953) Described the structure of DNA – Nobel Prized (1962) •
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Inherited traits are controlled by genes residing on chromosomes faithfully transmitted through gametes
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Table 1.1. DNA vs RNA DNA Double-helix Deoxyribose sugar Thymine Ladder-like
RNA Single-Stranded Ribose sugar Uracil
Proteins and Biological Function Proteins are the end products of gene expression Proteins are molecules with the potential for enormous structural diversity and serve as the mainstay in biological systems Enzymes (largest category) – biological catalysts Notable proteins other than enzymes o Hemoglobin – oxygen-binding molecule in RBCs o Insulin – pancreatic hormone Collagen – connective tissue molecule o o Actin and Myosin – contractile muscle proteins •
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The central dogma of molecular biology – that DNA is a template for making RNA, which in turn directs the synthesis of proteins – explains how genes control phenotypes
IV. Recombinant DNA Technology Began with the discovery that restriction enzymes used by bacteria to cut the DNA of invading viruses could be used to cut any organisms DNA at specific nucleotide sequences, producing a reproducible set of fragments Researchers found ways o insert these DNA fragments into carrier DNA molecules (vectors) to form recombinant DNA molecules These can be cloned through bacterial reproduction, and these clones can be used to isolate genes (for study) Genome – the complete haploid DNA content of a specific organism Genome libraries – collection of clones that represent an organisms genome •
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V. Expansion in Biotechnology Biotechnology – use of recombinant DNA technology and other molecular techniques to make products Plants, Animals, and Food Supply Transfer of heritable traits across species using recombinant DNA technology creates transgenic organisms Has revolutionized the agriculture industry Dolly the Sheep (1996), cloned by nuclear transfer •
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Genotype to Phenotype Sickle-cell anemia – mutant form of hemoglobin, results from having 1 out of the 146 amino acids in the protein changed •
Mutant B-globin cause RBCs to polymerize when the blood’s oxygen concentration is low, forming long chains of hemoglobin that distort the shape of RBCs (make it fragile), Sickle-shaped blood cells block blood flow in cappiliaries and small blood vessels •
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All symptoms caused by a change in a single nucleotide shows that these two are intrinsically linked
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Genetics and Medicine Every child bearing couple has an approximately 3% risk of having a child with some form of genetic anomaly Biotechnology has allowed a prenatal diagnosis of heritable disorders and to test the parents as “carriers” •
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research [easy to grow, short life cycle, many offspring, analysis is straightforward] Modern Set of Genetic Model Organisms Addition of more model organisms like viruses (T phages and lambda phage) and microorganisms (bacterium Escherichia coli and yeast Sacchaomyces cerevisia) Notable Model Organisms Caenorabditis elegans (nematode) – o simple nervous system o Arabidopsis thaliana (plant) – short life cycle, used in plant biology o Danio rerio (zebrafish) – small, reproduces rapidly, egg, embryo, and larvae are transparent •
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VI. New and Expanding Fields Recombinant DNA technology has prompted scientists to consider sequencing all the clones in a library to derive the nucleotide sequence of an organism’s genome (Human Genome Project, 1990-2003) Several new biological disciplines arose Genomics – study of genomes o Proteomics – identifies the set of o proteins present in a cell under a given set of conditions and studies their functions and interactions o Bioinformatics – to develop hardware and software for processing nucleotide and protein data •
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Uses on Human Diseases What is learned in animals can be used in humans (life has a common origin) We have yet to reach a consensus on how and when some of this technology will be determined to be ethically safe and acceptable •
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VII. Model Organisms Principles of inheritance were of universal significance amongst plants and animals Model organisms – organisms used for the study of basic biological processes Old Generation of Model Organisms o Drosophilia melanogaster (fruit fly) o Mus musculus (mouse) Used because (1) Genetic mechanisms are universal and (2) Suitable for genetic •
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VIII. Age of Genetics Nobel Prizes and Genetics Genetics is well celebrated in the Nobel Prizes •
Thomas Morgan – Chromosome Theory of Inheritance (1933), Unnamed (2002, 2006, 2007), Blackburn, Greider, Szostak (2009), Edwards (2010), Ramakrishnan, Steitz, Yonath (2010)
Genetics and Society Genetics technology is having a profound effect on society, but policies and legislation governing its use are lagging behind the resulting innovations •
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