Genetics

Course Director: Dr. Shellon Thomas

Course Lecturers:       

• Dr. Mary Maj
•  Dr. Sharmila Upadhya
• Dr. Cris Martin
• Dr. Felicia Ikolo

Content Review:  Ms. Atoum Abdullah      

Course Director Contact Information:  sthoma10@sgu.edu 

Course Lecturer(s) Contact Information: 

• fikolo@sgu.edu
• mmaj@sgu.edu
• shupadhya@sgu.edu 
• cmartin@sgu.edu  
• AAbdulla@sgu.edu

Course Director Office Hours: Posted in the announcements section every week or you can request an appointment by email

Course Lecturer(s) Office Hours: Posted in the announcements section every week or you can request an appointment by email

Course Management tool: Sakia (mycourses), Exemplify (examsoft), TurningPoint App for your smartphone and ZOOM for live lectures, quizzes and office hours

Course Description: Biol 320 Genetics 

This is a basic course in Genetics appropriate for Arts and Science students as well as students of Premedical and Preveterinarian studies. Genetics is presented over 16 weeks as part of the discipline-based curriculum in line with the expectations of the St George’s University School of Medicine, designed to provide a fundamental basis for understanding Human Genetics pertinent to clinical medicine based on the Genetics Learning Objectives published by the American Society of Human Genetics (ASHG). You will be introduced to the language embedded in Medical Genetics and Molecular Biology. These general competencies and specific objectives are described in the ASHG MEDICAL SCHOOL CORE CURRICULUM IN GENETICS. Specifically, this course is designed to introduce you to the fundamental design of DNA leading to the structure and function of the human genome. 

A basic understanding of chemistry, biology and physics will be assumed.

Course Objectives: 

1. Apply knowledge of the basic structure of genes and fundamental processes of life at the molecular, cellular and organismal levels.
2. Apply knowledge of the structure and function of genetic information and how it is related to the health of the human body.
3. To gain an appreciation of how disruption of normal genetic processes may give rise to both developmental problems of an organism  and to a diseased state.

Student Learning Outcomes:

1. Understand the principles of genetic transmission. 
2. Describe the use of model organisms and mutant strains to understand the nature of genes found within chromosomes.
3. Understanding the basics of gene expression
4. Describe how DNA is studied to determine genotype as it relates to human disease.

Program Outcomes Met by This Course:

MCAT Topic Areas Assessed: Content Categories

1. Biomolecules have unique properties that determine how they contribute to the structure and function of cells, and how they participate in the processes necessary to maintain life.
   1. Structure and function of proteins and their constituent amino acids
      1.  Separation techniques: Isoelectric point Electrophoresis
   2. Transmission of genetic information from the gene to the protein
      1. Nucleic Acid Structure and Function
         1. Nucleotides and nucleosides, DNA structure, base pairing specificity
      2. DNA Replication
         1. Mechanism of replication, separation of strands, specific coupling of  free nucleic acid
      3. Transcription
         1. Mechanism of transcription
      4. Translation
         1. Roles of mRNA, tRNA, rRNA, Post-translational modification of proteins, Role and structure of ribosomes
      5. Genetic Code
         1. The triplet code
   3. Transmission of heritable information from generation to generation and the processes that increase genetic  diversity
      1. Meiosis and Other Factors Affecting Genetic Variability 
         1. Important differences between meiosis and mitosis
      2. Mendelian Concepts
         1. Recessiveness, Homozygocity and Heterozygocity    

• Highly-organized assemblies of molecules, cells, and organs interact to carry out the functions of living organisms.

SAS Grading Scale 

Grades will be assigned as follows:

A  = 89.5% or better

B+ = 84.5 - 89.4%

B  = 79.5 - 84.4%

C+ = 74.5 - 79.4%

C = 69.5 - 74.4%

D = 64.5 - 69.4%

F = 64.4% or less 

Course Materials:

Text:

Klug, Cummings, Spencer, Palladino and Killian, 2019, Concepts of Genetics, 12th Edition, Pearson Education Inc. 

ISBN-13: 978-0134604718 

ISBN-10: 013460471

Important pages and chapters to accompany the lectures can be found in the lecture schedule.

Course Requirements and Percent of Grade:

All exams will be computer based using the ExamSoft software. Online quizzes will be computer based within MyCourses Tests & Quizzes application. There will be an ExamSoft Practice Quiz worth 0.2% of your final mark. There will be four other online quizzes worth a total of 4.8% of the final grade. There will be four interactive multiple choice question sessions (iMCQ) based on Special Topic Pre-reading assignment, each worth 1.25% of the final grade. There will be four exams, each worth 22.5% of your final grade. 

The breakdown is as follows:

22.5%	Exam 1 (grade based on performance)
22.5%	Exam 2 (Midterm) (grade based on performance)
22.5%	Exam 3 (grade based on performance)
22.5%	Exam 4 (Final) (grade based on performance)
1.25%	Online Quiz 1 (grade based on performance; you get multiple attempts)
1.25%	Online Quiz 2 (grade based on performance; you get multiple attempts)
1.25%	Online Quiz 3 (grade based on performance; you get multiple attempts)
1.25%	Online Quiz 4 (grade based on performance; you get multiple attempts)
1.25%	Module 1 iMCQ 1 (must get minimum of 50% correct for credit)
1.25%	Module 2 iMCQ 2 (must get minimum of 50% correct for credit)
1.25%	Module 3 iMCQ 3 (must get minimum of 50% correct for credit)
1.25%	Module 4 iMCQ 4 (must get minimum of 50% correct for credit)

Examinations using ExamSoft

Exam questions will consist mainly of simple multiple choice questions with a small percentage of clinical vignette 

• Exam #1 covers: 100% Lecture and DLA content from Module 1
• Exam #2 covers: 95% Lecture and DLA content from Module 2 5% from Module 1 
• Exam #3 covers: L95% Lecture and DLA content from Module 3 5% from Module 2 
• Exam #4 covers: 95% Lecture and DLA content from Module 4 5% from Module 3

Online Quizzes

You will have four online quizzes available through MyCourses under the Tests & Quizzes tab. These exams will be available for about 10 days before the due date and you will have multiple attempts to answer questions. Your grade will be based on the number of question that you get correct.

iMCQ Sessions

A special Topics Reading Assignment will be posted 10 days before the iMCQ session. Students are expected to read the assignment prior to attending the session. Students must correctly answer at least 50% of the questions to earn points. Make up sessions will not be offered and you must join the session on time. The lowest score of 4 will be dropped.  

***Marks are earned through your performance on tests and will not be negotiated

Zoom Classroom Etiquette

1. The sound on cell phones and computers must be switched off during lecture time. 
2. Speaking during the lecture session with your microphone on is very disruptive to students and lecturers alike. Please be respectful. 
3. Mute your microphone when not speaking to the class

Online Etiquette  

Students of St. Georges University, Genetics BIOL320, who create/contribute to social networks, blogs, wikis, or any other type of social media both on and off the sgu.edu domain for school/work/personal purposes WILL NOT post or release proprietary (including all information found on or within databases of any official SGU websites such as SAKAI), confidential, sensitive or personally identifiable information about SGU faculty, administration or employees as well as any faculty intellectual property, to ANY social media websites. In particular, PowerPoint lecture slides, including the figures from “Concepts of Genetics” and practice problems must not be distributed. Failure to abide by this will be considered a violation of professionalism as indicated in the SGU Student Handbook.

Clicker Etiquette

It is the responsibility of each student to register for an individually assigned Turning Point account and download the TurningPoint App to your smart phone for use in every class session and iMCQ session. It is the student’s responsibility to make sure that the clicker/App is registered and in good working order. A student caught in possession of clickers/App not assigned to them is in violation of the Honor Code and subject to Disciplinary action. A student who has given their clicker to a classmate is in violation of the Honor Code and subject to Disciplinary action.

1.1 Recorded DLA: History of Genetics

1. Recall the names of Hippocrates, Aristotle, William Harvey, Matthias Schleiden, Charles Darwin, Alfred Wallace, Gregor Mendel and understand their contribution to the current knowledge of Genetics
2. Discuss how genetics has progressed from Mendel to DNA in Less Than a Century
3. Recall how humans began to understand that traits and diseases are passed from parent to offspring
4. Know the definition of genetic terms presented in this lecture
5. Understand the basic structure and function of DNA, RNA and Proteins

1.2 Live: Introduction and Mitosis  

1. Understand the point distribution for all assessments
2. Understand the "Medical Excuse" system if you are ill during an exam
3. Understand that there will be no "make up" sessions for the iMCQs, you must log in on time for class, and must answer at least 50% correct for full marks
4. Recall that Online Quizzes must be completed before the due date and your mark is based on the number of questions you get correct
5. Compare the structure of eukaryotic vs. prokaryotic cells and describe how this is linked to genetic function
6. Describe why chromosomes exist in Homologous pairs in Diploid organisms
7. Describe the different cell cycle stages for both interphase and mitosis
8. Compare the different structures of DNA during the cell cycle stages
9. Describe the structure of chromosomes in metaphase based on the position of the centromere
10. Know the meaning of the chromosome number and the DNA content (e.g. n & c versus 2n & 2c versus 2n & 4c)

1.3 Recorded: Meiosis

1. Compare and contrast mitosis versus meiosis
2. Describe the significance of crossing over to genetic variation
3. Identify how the development of gametes varies between spermatogenesis versus oogenesis
4. Follow the events leading to the reduction of genetic material through meiosis I and II
5. Define synapsis, tetrad, dyad, monad, crossing over, bivalent, chiasma, centrioles and spindle fibers, polar body
6. Recorded: Mendelian Genetics I   You must watch the recorded DLAs before attending the Live Lecture
7. Recorded: Mendelian Genetics II  You must watch the recorded DLAs before attending the Live Lecture

1.6 Live: Extensions of Mendelian Genetics

1. Discuss pros and cons of some of the various model systems used in genetics and biology
2. Outline Mendel’s laws of inheritance
3. Discuss AR and AD patterns of inheritance and give examples of genetic disorders
4. Define, discuss, and give examples for: null mutation (AR), haploinsufficiency, gain of function, dominant negative, incomplete dominance, pseudodominance, codominance, genetic lethality, and adult onset
5. Discuss sex (X) -linkage 
6. Calculate risk/probabilities for inheritance of AR and AD traits and alleles
7. Define, discuss, and give examples for term used to explain genetic phenomena such as epistasis, hypostasis, sex influenced, sex limited, anticipation, conditional mutation, hemizygous, pleiotropy, Bombay phenotype.

1.7 Recorded: Chromosome Mapping in Eukaryotes

1. Define: complete linkage, independent assortment linkage with crossing over, linkage group
2. Describe how genes linked on the same chromosome will segregate together and how genes far apart on the same chromosome may not segregate together
3. Describe how crossing over serves as the basis for determining the distance between genes in chromosome mapping and as the distance between two genes increases, mapping estimates become more inaccurate
4. Discuss how chromosome mapping is currently performed using D N A markers and annotated computer database
5. Define Lod Score Analysis and Somatic Cell Hybridization which were historically important in creating Human Chromosome Maps
6. Describe the DNA markers: RFLP, microsatellites and SNP

1.8 Module 1 iMCQ: Questions will come from both live lectures and recorded sessions (DLAs) of Module 1

2.1 Live: Sex Determination and the Sex Chromosomes

1. Understand the difference between Heterogametic and homogametic sex determination in different species
2. Outline important features of the Y Chromosome and how it determines maleness in humans 
3. Examine nondisjunction and compare nondisjunction in autosomes vs. sex chromosomes; nondisjunction in meiosis I vs. meiosis II; nondisjunction in male vs. female gametes
4. Describe the genetic disorders resulting from the nondisjunction of sex chromosomes: Klinefelter, Turner, 47, XXX, and 47, XYY
5. Describe Barr Bodies and how female cells undergo dose compensation with the X Chromosome so that most of the genes on the X chromosome are monoallelic in both males and females
6. Dosage Compensation Prevents Excessive Expression of X-Linked Genes in Humans and Other Mammals
7. Describe how Glucose-6-phosphate dehydrogenase deficiency can be seen in some females even though it is X-linked recessive
8. Describe 3 cases where temperature variations can control sex determination

2.2 Recorded: CRISPR and the SRY Gene

1. Define bacteriophage and CRISPR and nuclease
2. Understand the CRISPR locus and define “spacer region” and “repeat region”
3. Describe CRISPR Cas editing method
4. Know the difference between Electroporation, Microinjection and Lipid Nanoparticles E. Describe What is special about Cosmo the calf

2.3 Recorded: Variations in Chromosome Number

1. Describe the steps to generate a karyotype and Giemsa staining
2. What is an ideogram?
3. Compare aneuploidy versus polyploidy
4. Compare and contrast the clinical features of Down, Edward and Patau Syndrome E.      Describe the two theories that lead to mosaicism

2.4 Recorded: Variations in Chromosome Arrangement 

1. Recall the basic structure of a chromosome
2. Describe the different chromosome rearrangements: deletions; duplications; inversions; translocations C. Explain the genetic mechanism and clinical features of Cri du chat, Potocki Lupski Syndrome and Intercalary Curly Calf Syndrome

4. Outline the benefits of gene duplications
5. Describe paracentric vs. pericentric inversions
6. Describe balanced translocations and discuss how carriers are unaffected but how these translocations may affect progeny
7. Outline the genetic mechanisms of Fragile X syndrome and describe clinical manifestations
8. Describe Maternal Serum Screen and the disorders the screen detects I. List the most common defects detected by ultrasound

2.5 Live: Extranuclear Inheritance

1. Define extranuclear inheritance, organelle heredity, infectious heredity, maternal effect, endosymbiotic theory, heteroplasmy, pleiotropy, variable expressivity, reactive oxygen species, mitochondrial proliferation, ragged red fibers
2. Describe the most common source of mtDNA damage
3. Outline the origin of heteroplasmy from the primordial germ cell to mutant load of mature oocytes
4. Describe the clinical features of the following mitochondrial diseases: Leber’s hereditary optic neuropathy, Kearns-Sayre syndrome, MELAS and MERRF syndromes 
5. Outline mitochondrial replacement therapy
6. Compare human nuclear (genomic) DNA to mitochondrial DNA

2.6 Recorded: DNA structure and Analysis

1. Understand the nomenclature of DNA and RNA including 5’ to 3’ directionality, base pairs, phosphodiester bonds, numbering of the pentose sugar carbons, nucleosides vs. nucleotides vs. oligonucleotides vs. polynucleotides
2. Compare the structures of purines to pyrimidines, ribose to deoxyribose
3. Compare and contrast the pair bonding of A-T and C-G  (strength, numbers, type of bond)
4. Describe the evidence that was used to create a model of the double helix: Rosalind Franklin, Raymond Gosling and Erwin Chargaff
5. Compare A-form of DNA to B-form
6. Give example of secondary structures in single stranded RNA
7. Define the 3 classes of RNA in prokaryotes and eukaryotes
8. Describe the RNA molecules which are specific for eukaryotes I. Define melting temperature and electrophoresis

2.7 Module 2 iMCQ: Questions will come from both live lectures and recorded sessions (DLAs) of Module 2

3.1 Live: DNA replication

1. Explain the experiments which led to the conclusion that DNA replication occurs in a semiconservative manner
2. Describe how DNA is synthesized and how synthesis is regulated. 
3. Describe the functions of enzymes involved in DNA synthesis
4. Compare and contrast DNA replication in prokaryotes and eukaryotes.
5. Compare DNA synthesis on the leading and lagging strand of the DNA
6. Explain how topoisomerases modify stress on the DNA double helix during DNA replication
7. Explain that telomeres solve stability and replication problems at eukaryotic chromosome ends H. Explain why recombination is essential for genetic exchange and DNA repair.

3.2 Recorded: DNA Organization in Chromosomes

1. Explain how supercoiling facilitates compaction of the DNA of viral and bacterial chromosomes.
2. Discuss how specialized proteins help in the organization of prokaryotic DNA.
3. Explain how D N A is organized into chromatin in eukaryotes.
4. Explain how chromosome banding differentiates regions along the mitotic chromosome.
5. Distinguish sequence organization characterized by repetitive D N A in eukaryotes.
6. Explain how the vast majority of a eukaryotic genome does not encode functional genes.

3.3 Recorded: Transcription

1. Understand the flow of genetic information from DNA to Protein
2. Compare and contrast DNA synthesis to RNA synthesis
3. Compare the differences between prokaryotic and eukaryotic
4. List the most common types of RNA
5. List the enzymes that synthesize prokaryotic and eukaryotic mRNA 
6. Differentiate between the template and non-template strands of DNA (know all the different terms to describe the same)
7. Describe the three stages of RNA synthesis, Initiation, elongation and termination
8. Discuss the importance of the various consensus sequences described
9. Describe the importance post-transcriptional modifications of eukaryotic mRNA
10. List the importance of post-transcriptional modifications
11. Outline key differences between prokaryotic and eukaryotic Termination of Transcription
12. Define Open reading frame (ORF), polycistronic gene, consensus sequence, Pribnow box, TATA box, promoter, ribosomal binding site, NTP, hairpin loop, regulatory element, short translation window and long translation window

3.4 Recorded: Translation

1. Describe Codon and use of the Genetic Code Dictionary

10. Describe Open Reading Frame
11. Describe the structure of tRNA 
    • Importance of secondary structure, site of amino acid attachment, anticodon

12. Understand how an amino acid is attached to the 3’ end of tRNA
    • Aminoacyl tRNA synthetase with 2 substrate binding sites and one active site

13. Understand the wobble hypothesis and why some amino acids have many codons
14. Know the “S” sizes of prokaryotic and eukaryotic ribosomes and the large and small subunit (not all the rRNA sizes)
15. Remember that ribosomes made of both protein and rRNA 
16. 3 major differences between prokaryotic and eukaryotic translation
17. Describe what binds at the E, P and A sites of a ribosome
18. Identify when the peptide bond is formed in a protein that is being synthesized
19. Outline the steps of peptide synthesis
    • From initiation to release of the polypeptide

3.5 Live: Gene Mutation, Repair and Transposition

1. Describe the different types of mutations and where they can be found
2. Become familiar with the definitions to describe mutation types including allelic heterogeneity
3. Outline the importance of Iceland studies
4. Describe the mechanisms of DNA replication errors: slippage; tautomeric shifts; depurination and deamination; oxidative damage; other mutagenic agents
5. Understand the mechanisms of transposable elements: DNA and RNA transposons
6. Describe the different types of DNA repair: proofreading; mismatch repair; post-replication repair; SOS system repair; photoreactivation repair; base excision repair; and nucleotide excision repair
7. Describe 3 human syndromes that are due to defective nucleotide excision repair: Xeroderma pigmentosa; Cockayne syndrome; and Trichothiodystrophy

3.6 Recorded: Gene Regulation

1. Understand the difference between inducible vs. constitutive genes
2. Compare negative and positive regulation of inducible genes
3. Know the definitions of everything in bold and on Definitions pages
4. Describe promoter and operator and structural genes
5. Understand negative regulation of the lac operon (lactose→allolactose is the inducer)
6. Understand positive regulation of the lac operon (controlled by cAMP levels) G. Memorize on vs. off for expression of the structural genes of the lac operon

3.7 Module 3 iMCQ: Questions will come from both live lectures and recorded sessions (DLAs) of Module 3

4.1 Live: Epigenetic Gene Regulation

1. Describe the molecular alterations to the genome to create the epigenome:
   1. Modifications to DNA to create CpG islands
   2. Modifications to histone proteins to generate heterochromatin
2. Describe the different types of non-coding RNA
3. Compare biallelic gene expression to monoallelic gene expression
4. Describe the mechanism of parent of origin imprinting
5. Describe the heritability of epigenetic traits
6. Understand the mechanism of abnormal epigenetic regulation in Beckwith-Wiedemann Syndrome, describe clinical features
7. Understand hyper vs hypo-methylation events that may lead to cancer

4.2 Recorded: Developmental Genetics

1. Explain the establishment of anterior/posterior polarity in fruit fly embryos. Define the genes and gene families involved.
2. Describe the translational regulatory mechanisms involved in fruit fly pattern formation.
3. Describe the inheritance of maternal effect genes and their associated phenotype.
4. Describe the concept of Lewis Wolperts French Flag model for establishing gene expression domains.
5. Define a homeodomain containing protein, and Hox genes.
6. Summarize the evolutionary conservation of the Hox cluster in vertebrates and their functions.
7. Explain homeotic mutations and their effects in fruit fly and mammals.

4.3 Recorded: Cancer Genetics I     4.4 Live: Cancer Genetics II

1. Identify common characteristics of cancer
2. Explain the clonal origin of tumors with examples
3. Explain the role of cyclins and CDKs in relation to cell cycle and alterations in cancer
4. Explain signal transduction of the growth factor pathway
5. Distinguish oncogenes and tumor suppressor genes
6. Explain the role of ras, myc and abl proteins
7. Explain apoptosis and how mutation in apoptotic genes can result in cancer (Bcl-2)
8. Identify mechanisms that result in activation of an oncogene from a proto-oncogene
9. Explain the functions and roles of tumor suppressor genes using p53 and Rb as examples. Explain the terms ‘two hit hypothesis’ and ‘loss of heterozygosity’ in relation to tumor suppressor genes
10. Differentiate sporadic and familial cancer in relation to tumor suppressor genes
11. Identify the role of viruses and environmental agents that contribute to the development of cancer

4.5 Recorded: Population Genetics Part A

1. Explain how the Hardy Weinberg equilibrium can describe allele distribution in populations 
2. Explain how to calculate allele frequencies
3. If given the incidence rate of an autosomal recessive trait, be able to calculate ‘q’ the recessive allele frequency
4. If given the incidence rate of an autosomal recessive trait, be able to calculate carrier frequency
5. Discuss why rare deleterious recessive alleles can never be eliminated from a population
6. Describe why most rare deleterious recessive alleles are “hidden” in heterozygous carriers (who do not have the phenotype) 
7. Explain how when 2 different populations (same species) meet and randomly mate, only 1 generation is needed to achieve a new Hardy Weinberg equilibrium for all alleles, and all loci

4.6 Recorded: Population Genetics Part B

1. Describe the assumptions of the Hardy Weinberg equilibrium
2. Explain factors that might cause a deviation from the Hardy Weinberg equilibrium
3. Differentiate between selection, heterozygote advantage, genetic drift, founder effect, genetic bottleneck, and consanguinity
4. Explain how when 2 different populations (same species) meet and randomly mate, only 1 generation is needed to achieve a new Hardy Weinberg equilibrium for all alleles, and all loci

4.7 Recorded: Threshold Traits and Multifactorial Inheritance

1. Discuss why the majority of the disease load in human populations is controlled by multifactorial inheritance
2. Describe how multifactorial traits can be explained with the threshold model of inheritance
3. Discuss how risk changes when one individual in a family has a multifactorial disorder D. Explain how most cancers are multifactorial in nature
4. Describe twin studies

4.8 Recorded: Quantitative Traits and Multifactorial Inheritance

1. Describe quantitative trait loci (QTLs) and how additive alleles can contribute to measurable traits
2. Derive from the Punnet square and classic Mendelian ratios how quantitative traits can produce distinct phenotypic classes
3. Explain how the curve of measured values is smoothened by many contributing alleles, and environmental influences
4. Describe the Gaussian distribution
5. Discuss how central tendency is estimated
6. Discuss how distribution from central tendency is estimated

4.9 Module 4 iMCQ: Questions will come from both live lectures and recorded sessions (DLAs) of Module 4