Understanding the basics of biochemistry, DNA, genetics, disease, drugs and immunity for everyone.
With the thorough background of enzymes and biochemical process, students will have a better understanding of rationale for using various medications in disorders affecting metabolic pathways. Have sufficient exposure to all the high yield concepts and questions for their preparation towards USMLE Step 1 exam and beyond. MBIO Genetics 3 credits Upon successful completion of this course the student will be able to: Understand the molecular mechanisms of how chromosomal abnormalities and genetic mutations lead to aneuploidies, genomic disorders, single gene diseases, and complex disorders.
Understand the strategy and technology used for gene mapping and disease gene identification.
Describe the current approaches for the treatment of genetic disease including gene therapy. Understand the recent advances in prenatal diagnosis, cancer genetics, and pharmacogenetics. Other skills learned by the students will be evaluation of pedigrees, calculating recurrence risk, and using Hardy-Weinberg to determine mutation frequencies in populations.
MBEH Biostatistics and Epidemiology 2 credits Upon successful completion of this course the student will be able to: Understand the basic concepts and principles of epidemiology. Identify the basic strategies for observational and experimental studies. Use the epidemiologic approach to define and measure the occurrence of disease and health in populations.
Identify data needs for calculating standard epidemiological measures. Understand collection of scientific data, appropriate analysis using statistical tests and results interpretation. Distinguish the roles of epidemiology and biostatistics in the prevention of disease and the improvement of health.
MMCR Immunology 2 credits Upon successful completion of this course the student will be able to: Describe the cells and tissues involved with innate and adaptive immunity. Know the molecular and cellular mechanisms employed in innate immune responses, and those used in the humoral and cell-mediated arms of adaptive immunity.
Know the details of antigen processing and presentation by antigen presenting cells and the central role of MHC molecules in this process. Understand the maturation and selection of B and T lymphocytes and how gene rearrangement generates the diverse antigen receptors required for lymphocyte activation. Understand how activated lymphocytes carry out different effector functions and produce memory during a humoral or cell-mediated adaptive response.
Understand the clinical aspects of immunology including tolerance and autoimmunity, transplantation and immunosuppression, immunotherapy strategies against tumors, hypersensitivity reactions, and the consequences of congenital immunodeficiencies. Students must be able to solve clinical problem by explaining underlying pathology. Students must be able to analyze lab reports pertaining to inflammatory diseases.
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- DNA is only one among millions of possible genetic molecules -- ScienceDaily?
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Describe the various types of hemodynamic disorders, identify the structural changes, and explain the underlying pathology. Name various benign, and malignant tumors, understand the differences between benign and malignant tumors, explain the biology of tumors, identify correctly histological features and have an overview of important cancers. Explain the immune basis of primary immune deficiency, and autoimmune disorders, describe various changes seen in the organs affected, and are able to interpret lab reports.
Define, explain, and draw an algorithm to explain various types of anemia. Students should be able to evaluate cases of anemia, and interpret lab reports. Describe various types of reactive conditions associated with white cell abnormalities, discuss the various types of hematological malignancies based on pathogenesis, and be able to interpret lab investigations. Understand the pathogenesis of tumors involving renal, and prostate. Students must be able to identify histological features, interpret investigations, and explain clinical features of renal and prostate tumors.
Identify, and distinguish testicular tumors. Discuss the morphological features, and clinical presentations of major testicular tumors.
Differentiate, and describe various skin disorders of immune, infectious, and neoplastic origin. Define, describe, and identify diseases affecting the CNS. Students should be able to explain the pathogenesis of various developmental, demyelinating, dementia, and tumors affecting the CNS. Evaluate the status of a neurological patient. Perform the neurological exam. Identify problems via neuro imaging techniques.
Discuss site, level, and type of injury. MMCR Microbiology 5 credits Upon successful completion of this course the student will be able to: Identify the common etiologic agents of the disease and be able to determine the causative agent of the particular case from case clues. Classify general characteristics regarding disease or organism, predisposing conditions, epidemiology, mechanism of pathogenicity, and major tests used in identifications.
Describe mechanisms of virulence and pathogenesis for microorganisms. Identify the appropriate therapies, drug mechanism of action and resistance mechanisms for antimicrobials, antivirals, antifungals and antiparasitics. MBEH Behavioral Science 5 credits Upon successful completion of this course the student will be able to: Describe the progression through the life cycle and recognize the major milestones from conception to death.
Understand the biologic principles which govern changes in cells and tissues as a response to abnormal stimuli, and the functional consequences and clinical significance of morphologic changes. Understand how these changes alter during the course of the medical and surgical therapy and the differential diagnosis. Describe various specific changes which occur in specialized organs due to harmful pathogens and other agents.
DNA is only one among millions of possible genetic molecules
Recognize disease at the gross, microscopic and ultrastructural level. Understand the various pathological, molecular and immunologic techniques used to reach the diagnosis. Transcription of the interrupted repeats was also noted for the first time. They identified interrupted repeats in 20 species of microbes as belonging to the same family. Four cas genes cas 1—4 were initially recognized. The first publication  proposing a role of CRISPR-Cas in microbial immunity, by the researchers at the University of Alicante , predicted a role for the RNA transcript of spacers on target recognition in a mechanism that could be analogous to the RNA interference system used by eukaryotic cells.
Koonin and colleagues extended this RNA interference hypothesis by proposing mechanisms of action for the different CRISPR-Cas subtypes according to the predicted function of their proteins. The researchers manipulated the resistance of S. By manipulating the nucleotide sequence of the guide RNA, the artificial Cas9 system could be programmed to target any DNA sequence for cleavage.
CRISPR has been modified to make programmable transcription factors that allow scientists to target and activate or silence specific genes. Liang and Y. The scientists showed that during DNA recombination of the cleaved strand, the homologous endogenous sequence HBD competes with the exogenous donor template. DNA repair in human embryos is much more complicated and particular than in derived stem cells. These differences may give Cas12a some advantages over Cas9. This means there is no disruption to the recognition sequence after repair, and so Cas12a enables multiple rounds of DNA cleavage.
By contrast, since Cas9 cuts only 3 base pairs upstream of the PAM site, the NHEJ pathway results in indel mutations which destroy the recognition sequence, thereby preventing further rounds of cutting. In theory, repeated rounds of DNA cleavage should cause an increased opportunity for the desired genomic editing to occur. Family RF Collectively the 93 cas genes are grouped into 35 families based on sequence similarity of the encoded proteins.
Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose.
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Classification is also based on the complement of cas genes that are present. The phylogeny of Cas1 proteins generally agrees with the classification system. CRISPR-Cas prevents bacteriophage infection, conjugation and natural transformation by degrading foreign nucleic acids that enter the cell. When a microbe is invaded by a bacteriophage , the first stage of the immune response is to capture phage DNA and insert it into a CRISPR locus in the form of a spacer.
Mutation studies confirmed this hypothesis, showing that removal of cas1 or cas2 stopped spacer acquisition, without affecting CRISPR immune response. Multiple Cas1 proteins have been characterised and their structures resolved. In the I-E system of E.
Bioinformatic analysis of regions of phage genomes that were excised as spacers termed protospacers revealed that they were not randomly selected but instead were found adjacent to short 3—5 bp DNA sequences termed protospacer adjacent motifs PAM. New spacers are added to a CRISPR array in a directional manner,  occurring preferentially,      but not exclusively, adjacent   to the leader sequence.
Analysis of the type I-E system from E. That sequence contains a strongly conserved final nucleotide nt adjacent to the first nt of the protospacer. This nt becomes the final base in the first direct repeat.
Genetic testing - Canadian Cancer Society
The mechanism that causes this phenomenon was discovered in the type I-E system of E. A significant enhancement in spacer acquisition was detected where spacers already target the phage, even mismatches to the protospacer. Newly acquired spacers that result from the priming mechanism are always found on the same strand as the priming spacer.
In type I-E and type I-F systems, the proteins Cas6e and Cas6f respectively, recognise stem-loops    created by the pairing of identical repeats that flank the crRNA. Type III systems also use Cas6, however their repeats do not produce stem-loops. Cleavage instead occurs by the longer transcript wrapping around the Cas6 to allow cleavage just upstream of the repeat sequence. Unlike the other two systems the crRNA does not contain the full spacer, which is instead truncated at one end.
CrRNAs associate with Cas proteins to form ribonucleotide complexes that recognize foreign nucleic acids. Type II systems rely on a single multifunctional protein, Cas9 , for the interference step.
The mechanism for distinguishing self from foreign DNA during interference is built into the crRNAs and is therefore likely common to all three systems. Throughout the distinctive maturation process of each major type, all crRNAs contain a spacer sequence and some portion of the repeat at one or both ends. The cas genes in the adaptor and effector modules of the CRISPR-Cas system are believed to have evolved from two different ancestral modules. A transposon-like element called casposon encoding the Cas1-like integrase and potentially other components of the adaptation module was inserted next to the ancestral effector module, which likely functioned as an independent innate immune system.
The basic model of CRISPR evolution is newly incorporated spacers driving phages to mutate their genomes to avoid the bacterial immune response, creating diversity in both the phage and host populations. To resist a phage infection, the sequence of the CRISPR spacer must correspond perfectly to the sequence of the target phage gene. Phages can continue to infect their hosts given point mutations in the spacer.
A study of S.
Genetic testing - Canadian Cancer Society
A comparative genomic analysis showed that E. The latter's strains that diverged thousand years ago still contained the same spacer complement. Similar to the targeted studies of the oral cavity, some showed little evolution over time.
In one week, S. Another S.