Genes and Genetics

Course Aims

“What are we?” “Where do we come from?” These questions are as old as time itself, fundamental and universal in nature and traceable back to the days of Ancient Rome and Greece. The primary target of the medical sciences that we pursue is human disease, but the ultimate goals of our studies are to learn and elucidate what we humans are made of at the molecular level and how diseases compromise molecular structures and interactions that are precisely organized.

Based on the knowledge acquired in biochemistry, this course aims to answer questions like, “What are genetics?”, “What are genes?”, “How is gene expression controlled?”, and “What is happening in genetic diseases?”

With the completion of the Human Genome Project in 2003, the genes that constitute our bodies have been identified. However, the entire DNA sequence has yet to be fully decoded. No one is sure which regions of the genome are transcribed at which developmental stage in which cell types or tissues in order to perform functions assigned to the encoded molecules. In this course “Genes and Genetics”, we will learn about the regulatory mechanisms of gene expressions and their aberrations, both of which are still being intensively investigated. In addition, the genetic bases that make humans as diverse –sometimes changing the way one is susceptible to a particular disease - as we are.

Key Features

De novo sequencing of novel species – like the Human Genome Project – is becoming more and more active, and with the advent of high-throughput sequencing machines, it will not be long before the entire genome is sequenced on a personal level. While at this moment the majority of nucleotide sequences that constitute our genome are nothing more than a mind-boggling array of code which hardly make any sense, functional characterizations of coded molecules, as well as regulations of gene expressions, are advancing. Moreover and hopefully, research will soon involve the functional characterization of non-coding regions that make up 98% of the human genome. In both medical research and clinical medicine, I believe that the knowledge of cytogenetics, molecular genetics, and molecular bases of monogenic and multifactorial diseases will become more important and more essential in the future.

By using videos and introducing a genetic perspective of the latest news in the lectures, I hope to make the topics easier to understand. On the other hand, as cutting-edge genetic research does not require the translated Japanese words, English words are mostly presented in the lectures. It is rather tough, but it is my wish that, some of the students will, having acquired knowledge of leading-edge research in the field of genetics through this course, one day grow up to be world leaders in this newly rising field of medicine.

Contents

1. Introduction: inheritance, genetics, genetic disorders, monogenic disorders, multi-factorial disorders
2. Structure of Chromosomes and Genes: histone, DNA, chromatin, nucleosome, centrosome, telomere, eukaryotes, prokaryotes
3. Genomes and Genetics: exon, intron, spacer, repetitive sequence, pseudogene
4. Genetics: dominant inheritance, recessive inheritance, sex-linked inheritance
5. Synthesis, Replication, and Repair of DNA: DNA polymerase, DNA fork, Okazaki fragment, primiase, DNA ligase, mismatch repair, exonuclease, xeroderma pigmentosum
6. Transcription and Translation of Genetic Information: central dogma, RNA polymerase, splicing, spliceosome, snRNA, codon
7. Regulation of Gene Expression Control and Disorders of Genetic Information : control of cis-elements and trans-factors, promoter, enhancer, silencer, TATA box, CAAT box, GC box, Zn finger, leucine zipper, helix turn, homeodomain
8. Cell Cycles and Cell Fission: cell cycles, diploidy, quandriploidy, mitosis, meiosis, kinetocore
9. Basics of Gene Manipulation Methods: restriction enzyme, plasmid, nucleotide sequencing, blotting, cloning, gene expression, library, PCR, Taq polymerase, denaturation, annealing, extension, primer, template DNA, RT-PCR, recombinant protein, transgenic animals, gene targeting
10. Genome Analysis: gene translocation, point mutation, SNP, microsatellite, RFLP
11. Linkage Analysis of Monogenic Disorders, Association Study of Multifactorial Disorders, and Genetic Counseling

Textbooks

The following books are recommended for this course:

• Bruce Alberts. Molecular Biology of the Cell, 5th. Ed. Garland Publishing Inc.
• Harvey Lodish et al. Molecular Cell Biology, 6th. Ed. W. H. Freeman & Co.

Both books can be viewed free of charge at http://www.ncbi.nlm.nih.gov/books.

Instructor in Charge

Kinji OHNO, Neurogenetics

Related Resources

The following books are recommended for study:

• B. Alberts et al. Essential Cell Biology, Garland Publishing Inc.
• Harvey Lodish et al. Molecular Cell Biology, 6th. Ed. W. H. Freeman & Co.

Assignments

This Course, ‘Genes and Genetics’ is composed mostly of lectures, leaving no time for active participation of the students (student presentations, for example). The following are sample questions from the 2007 year examinations. The questions may offer a glimpse of what we expect the students to acquire in the course.

1. Consider a case in which two phenotypes do not follow the Mendel's second law of inheritance. Explain why.
2. Explain the mechanisms that cause recombination in meiosis.
3. Calculate the percentage of type-O phenotype of the ABO blood type under the following conditions: type-A allele 30%, type-B allele 10%, type-O allele 60%
4. Explain the following terms: phenotypes and genotypes, homozygotes and heterozygote, dominant inheritance and recessive inheritance
5. Describe the structure of nucleosomes.
6. In evolutionary terms, what does the existence of synteny in humans and mice imply? Explain.
7. Describe the difference between the physical map and the recombination map (include the definition of centiMorgan in your explanation)
8. Describe the human genome in size, number of genes, and constituents.
9. Explain the following: LINEs, SINEs, minisatellites, microsatellites
10. Draw a diagram of the human gene. Be sure to show the following tags and add explanations: promoter region, 5'UTR region, 3'UTR, and open reading frame
11. Write the English name, 3-letter code, and 1-letter code for each of the 20 amino acids.
12. Describe the differences between the following groups of terms: missence mutations, nonsense mutations, splice site mutations, inframe DNA arrangement, frameshift DNA arrangement
13. Explain the difference between dominant and recessive genetic disorders from the viewpoint of their effects on a cellular and protein level. Be sure to explain the following terms as well: dominant negative effect, haploinsufficiency, gain of function, loss of function.
14. Describe the mechanism of X-inactivation using XIST and XIC. Also describe 3 examples of X-inactivation.
15. Explain the following terms: mRNA, rRNA, tRNA, snRNA, and snoRNA
16. Describe the transcription initiation mechanism of the eukaryotic RNA polymerase II.
17. Describe the mechanisms of ‘mRNA capping’ and ‘poly A addition’ in eukaryotic mRNA. Also explain why this mechanism is necessary for mRNA.
18. Describe cis-elements that are recognized by U1 snRNA, U2 snRNA, U2AF65, and U2AF35 that are trans-factors involved in pre-RNA splicing.
19. Describe the roles of A, P, and E sites of ribosomes. Also describe the protein synthesis mechanism within ribosomes.
20. Describe the mechanism involved in the translation termination process.

Course Schedule

Session	Contents	Lecturer
1	Introduction: Genes and Genetics, Genetic Diseases	Kinji OHNO
2	Structure of Genes and Chromosomes	Kinji OHNO
3	Genomes and Genes	Kinji OHNO
4	Genetics: Dominant, Recessive, and linked inheritance	Kinji OHNO
5	DNA Synthesis, Replication and Repair	Motoshi SUZUKI
6
7	Regulation of Gene Expression and Genetic Disorders: Promoters, Enhancers, Transcription Factors	Takashi OKAMOTO
8
9	Transcription and Translation of Genetic Information: the Central Dogma, Transcription and Translation, Splicing	Kinji OHNO
10
11	Cell Cycles and Cell Fission	Takeshi URANO
12
13	Basic Genetic Manipulation Methods	Takeshi SENGA
14	Genome Medicine	Takeshi SENGA
15	Extra Session reserved for make-up lessons
16	Clinical Genetics, Genetic Counseling	Norio OZAKI

Lecture Handouts

Note: All files are in Japanese.

• Excerpts from Power Point Slides used in the lecture , Neuro-Information Genetics, Kinji OHNO
• Genome Map , Created by the Department of Biostudies and Society, Graduate School of Biostudies, Kyoto University

Grading

Evaluation will be based on attendance and the end-of-term examination. A 50% attendance rate or better is necessary to earn credit.

---