Intro Genome Bio 2013

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BIOL 105. Introduction to Genome Biology (Fall 2013)
Instructor: Dr Weigang Qiu, Associate Professor of Biology
Room: C104 Hunter North (a Computer Lab)
Hours: Tuesdays, 12:45-3:15PM
Office Hours: Room 839 HN; Tuesday 5-7pm or by appointment. Phone: 212-772-5296.
Email: weigang@genectr.hunter.cuny.edu (I will advise students before and after the class as well as during office hours. Emails will be answered only in special situations.)

General Information

Content Diagram

Course Description

  • Background: A genome is the total genetic content of an organism. Driven by breakthroughs such as the decoding of the first human genome and rapid DNA-sequencing technologies, biomedical sciences are undergoing a rapid and profound transformation into a highly data-intensive field, which requires familiarity with concepts in both biology and computer science. Genome information is revolutionizing virtually all aspects of biology and medicine and will lead to major advances such as more efficient production of renewable energy, better cures for cancers, and longer and healthier life expectancy.
  • Contents: This course will introduce genome-sequencing technologies, explore genome projects online, and discuss both the benefits and challenges (e.g., ethical and legal) of the genomic revolution to society. Each session will consist of lecture instructions and computer-based laboratory practices.
  • Learning Goals
    • Human Genome: Knowing the basic content and structure of the human genome
    • Central Dogma: Understanding the Central Dogma and how genes are regulated (i.e., turned on/off)
    • Genome diversity: Knowing the three major divisions of life, the use of DNA/protein sequences to classify organisms, and mechanisms of genome evolution
    • Bioinformatics: Understanding the importance of computation and statistics in producing, analyzing, and disseminating genome information
  • Learning Outcomes
    • Be able to describe the structure and function of the human genome
    • Be able to find chromosomal location, function, disease-association, and variability of a human gene using scientific databases
    • Be able to identify and classify organisms based on their DNA sequences
    • Be able to describe the processes of genome evolution, including mutation, duplication, recombination, horizontal gene transfer, genetic drift, and natural selection
  • Textbook: Arthur Lesk (2012). Introduction to Genomics (2nd Edition). Oxford University Press. Amazon Link
  • Academic Honesty: Hunter College regards acts of academic dishonesty (e.g., plagiarism, cheating on examinations, obtaining unfair advantage, and falsification of records and official documents) as serious offenses against the values of intellectual honesty. The College is committed to enforcing the CUNY Policy on Academic Integrity and will pursue cases of academic dishonesty according to the Hunter College Academic Integrity Procedures.

Grading Policy

  • Treat assignments as take-home exams. Student performance will be evaluated by weekly assignments and three exams. While students are allowed to work in groups for assignments (and answers to some questions are available on the textbook website), students are expected to compose the final answers independently. Writings that are virtually exact copies to each other or to the web answers will be considered plagiarism. Zero points will be given to ALL involved individuals if the instructor considers there is enough evidence for plagiarism. To avoid being investigated for plagiarism, Do NOT copy or let others copy your work.
  • Submit assignments in Printed Hard Copies. Email attachments will NOT be accepted. Each assignment will be graded based on timeliness (20%), effort (40%), and correctness (40%).
  • Since each session will consist of a web-based practical session, attendance is required and part of the grade.
  • Composition of your final grade
    • Assignments: weekly assignments, totaling 100 pts
    • Mid-term and Final Comprehensive Exams: 3 mid-terms X 50 points each = 150 pts
    • Attendance and active classroom participation (50 pts): 1 unexcused absences = 40 pts; 2 absences = 30pts; More than 2 = 0. Points will be deducted for lack of participation in computer-lab exercises.

Weekly Schedule (All Tuesdays)

September 3. Introduction to Genomics (1)

  1. Lecture Slides:
    File:BIOL105-Intro-Genomics.pptx
  2. Course Overview
  3. Contents of the human genome (Chapter 1, pg. 3-10)
  4. Genome organization (Chapter 1, pg. 10-17)
  5. Assignment 1 (15 pts, due 9/10) [Finalized on 9/5, 7pm]
    1. (2 pts) (Note: modified from the textbook) Exercise 1.1. (a) Make a very rough estimate of the average density (e.g., number of genes per million base pairs) of protein-coding genes in the human genome, assuming total genome size ~ 3 x 10^6 bp and total number of genes ~ 3 X 10^4 genes. 
      Answer: 3x10^4 (genes)/3x10^9 (bp; typo in the original question)=1 gene every 10,000 bp
      (b) Further assuming that the average gene length is 1000 bp, what is the proportion of bases that code for proteins? 
      Answer: 3x10^4x10,000 (bp in genes)/3x10^9 (bp, total)=1x10^-2, or 1% of the total bases code for genes
    2. (4 pts) Exercise 1.3. For the standard genetic code (see lecture slides), give an example of a pair of codons related by a synonymous single-site substitution (a) at the third position and (b) at the first position. (c) Give an example of a pair of codons related by a non-synonymous single-site substitution at the third position. (d) Can a change in the second position of a codon ever produce a synonymous mutation? 
      Answer to (d): No. All 2nd position changes are non-synonymous. Stop codons are not "synonymous" amino acids.
    3. (4 pts) Exercise 1.4. (a) Is it possible to convert Phe to Tyr by a single base change? If so, what would be possible wild-type and mutant codons? 
      Answer: Yes. Either TTT (Wild Type, WT) to TAT (Mutant, MU), or TTC (WT) to TAC (MU). Both are changes at the 2nd codon position.
      (b) Is it possible to convert Ser to Arg by a single base change? If so, what would be possible wild-type and mutant codons? 
      Answer: Yes. Either AGT (Wild Type, WT) to CGT (Mutant, MU), or AGC (WT) to CGC (MU). Both are changes at the 1st codon position.
      (c) What is the minimum number of base substitutions that would convert Cys to Glu? 
      Answer: Three. Cys codons are either TGT or TGC, and Glu codons are either GAA or GAG. These two amino acids don't share the first, second, or the third codon positions.
      (d) In the evolution off an essential protein encoded by a single gene, a Trp is converted to a Gln by two successive single-base changes. What is the intermediate codon?
      Answer: TGG (Trp) through CGG (Arg, 1st position change) to CAG (Gln, 2nd position change). The other possibility is highly unlikely since it goes through a stop codon: TGG through TAG (Stop, 2nd position change) to CAG (Gln, 1st position change)
    4. (5 pts) Weblem: Use the NCBI Human Genome Resource webpage to identify diseases associated with heamoglobin alpha-1 (HBA1). Summarize its association with the disease "alpha-thalassemia". Include key references and a discussion on why this is a case against "genetic determinism". 
      Answer: [http://www.omim.org/entry/141800 Online Mendelian Inheritance in Man database Entry 141800] lists 5 diseases associated with HBA1 mutations. See [http://www.omim.org/entry/604131 See OMIM Record #604131] for information on alpha-thalassemia. The key reference is Weatherall (2001), which concludes that heritability of alpha-thalassemia is low and environmental factors influences the disease outcome. Mutations at HBA1 locus alone is not a sufficient predictor of the disease, an argument against "genetic determinism" (At the least, it's not a single-gene genetic disease).

September 10. Introduction to Genomics (2)

  1. Lecture Slides:
    File:Session-2-intro-to-genomics-part-2.pptx
  2. Assignment 2 (Finalized on 9/11 @11pm)
    1. (2 pts) (Modified from Exercise 1.8). Using the NCBI human genome browser, find out which of the following bands of human chromosome 16 are gene-rich: p13.3, q22.1, or q11.2? 
      Answer: According to the NCBI Human Genome Resource page (at the 1/100 zoom level and using "recenter"), the q22.1 has 32 genes, q11.2 has 0 genes, and p13.3 has 74 genes. So q13.3 and q22.1 (both light-colored) are gene-rich, while q11.2 (darker-colored) is gene-poor.
    2. (4 pts) (Modified from Exercise 1.11). Make a printout of the GenBank file with the Accession "V00488" (print ONLY the part with the DNA sequence). Mark the following sequence regions with highlighters: (a) all introns, (b) all exons, (c) 5'-UTR and 3'-UTR, (d) start and stop codons. (Hint: Use the "Graphics" view with zooming.) 
      Answer: Using the Graphics view and zoom in at the nucleotide level, you will find the following coordinates: Primary transcript: 98-929, Exon 1: 98-230 (most likely 98-229), Exon 2: 348-551 (should be 347-551), Exon 3: 692-929, Intron 1: 231-347 (should be 230-346, starting with GT and ending in AG), Intron 2: 552-691, 5, Start Codon: 135-137, Stop Codon: 818-820, 5'-UTR: 98-134, 3'-UTR: 821-929
    3. (4 pts) (Modified from Exercise 1.12). On a separate printout of the GenBank file with the Accession "V00488" (print ONLY the part with the amino-acid sequence). Mark the following regions with highlighters: (a) amino acids coded for by exon 1, (b) by exon 2, (c) by exon 3. (Hint: Use the "Graphics" view with zooming). (D) Is it possible that a single codon is split by an intron (e.g., 1st codon position on exon 1 and 2nd & 3rd nucleotides on exon 2) ?
  • Answer key for 1.11

    Answer key for 1.11

  • Answer key for 1.12

    Answer key for 1.12

September 17. Introduction to Genomics (3)

  1. Lecture Slides:
    File:Session-3.pptx
  2. Genome database (Chapter 1, pg.24-30)
  3. Cancer genomics: The Cancer Genome Atlas (TCGA) Project
  4. Genome evolution (Chapter 1. pg.30-35)
  5. Assignment 3 (Finalized on 9/18, Thursday, 11:55pm)
    1. (6 pts). Problem 1.6 (on page 38). Instructor's Note: (1) Mark your answers on a printout or copy of Figure 1.17(a); (2) for part (d), show your work. A simple choice without reasoning or explanation will NOT get full credits.
    2. (4 pts). Read/Watch the following links and extract one example to describe how genome sequencing helps health care.
      1. HapMap benefits
      2. Impact of cancer genomics
      3. Link between cancer genomics and personalized therapy

September 24. First Mid-term Exam

October 1. Genome Structure and Function (1)

  1. Lecture Slides:
    File:Session-4.pptx
    (updated)
  2. Classic Genetics (Chapter 3, pg.80-82)
  3. Structure of DNA (Chapter 3, pg. 90-93)
  4. DNA replication and PCR (Chapter 3, pg 93-95)
  5. Assignment 4 (Tentative)
    1. (5 pts). Two alleles (T and t) are segregating at a single genetic locus In a population of diploid individuals. "T" is the dominant allele and "t" is recessive for a phenotype (e.g., "Taster" and "Non-taster"). If two parents are both heterozygotes at this locus, what is the expected Mendelian ratio of genotypes of their offspring? Mendelian ratio of the phenotypes? Show your work.
    2. (5 pts) Answer the following questions about the Polymerase Chain Reaction (PCR):
      1. Describe the three steps in each round of PCR, including the approximate temperature and the reaction occurring at each step
      2. What are the key chemical ingredients required for amplifying a DNA region using PCR?
      3. Starting from a single DNA molecule (note: double-stranded), what is the total number of copies of DNA after 20 rounds of PCR amplification? Show your work.
    3. (5 pts) Fill in Table 1 on Slide #12 based on the gel picture. Explain the basis of your counts and frequencies.

October 8. Genome Structure and Function (2)

  1. Lecture Slides
  2. Linkage Map (Chapter 3, pg.82-85)
  3. Chromosomal Translocation (Chapter 3, pg.85-87)
  4. Automated Sequencing (Chapter 3, pg 97-104)
  5. Assignment 5.

October 15. No Class (Monday Schedule)

October 22. Genome Variation (1)

October 29. Genome Variation (2)

November 5. 2nd Mid-term Exam

November 12. Genome Evolution (1)

November 19. Genome Evolution (2)

November 26. Genome Evolution (3)

December 10. Review

December 17. Final Exam

Links

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