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Last update: doc. RNDr. Dana Holá, Ph.D. (09.06.2023)
DUE TO MANY TOPICS THIS LECTURE COVERS AND MANY NEW CONCEPTS AND TERMS, STUDENTS ARE MOSTLY RECOMMENDED TO REGISTER FOR THIS LECTURE DURING THE 2ND YEAR OF THEIR BACHELOR´S STUDY. Be aware that this lecture is in the Czech language only! |
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Last update: doc. RNDr. Dana Holá, Ph.D. (09.06.2023)
The presentations from individual topics, together with mp3 audio recordings are available to the students signed for this subject at the Moodle server http://dl2.cuni.cz/ (the word key necessary for the login into this course at Moodle is given to students during the first lecture). For more details see the information directly available at the respective Moodle course.
Snustad D.P., Simmons M.J.: Principles of Genetics. John Wiley and Sons, Inc., USA. Klug W.S. et al.: Concepts of Genetics. Pearson Education, Inc. Russell P.J.: i-Genetics: A Mendelian Approach. Pearson Education, Inc., and Benjamin Cummings.
Pollard T.D. et al: Cell Biology. Elsevier, Inc. Alberts B. et al.: Molecular Biology of the Cell, W.W. Norton & Company Passarge E.: Color Atlas of Genetics. Georg Thieme Verlag KG. Nussbaum, McInnes, Willard: Thompson and Thompson Genetics in Medicine. Elsevier, Inc.
Students seriously interested in pursuing further studies in genetics and molecular biology are also recommended to follow journals publishing reviews on these topics in the series Nature Reviews …, Current Opinion in …, Annual Review of …, Trends in …, Frontiers in … and also the BioEssays journal. |
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Last update: doc. RNDr. Dana Holá, Ph.D. (08.09.2023)
Examination is based on the WRITTEN test. Only the second reparation term after the repeated registration of the subject is a combined exam (written test + verbal examination) in the presence of a committee (the commitee in this case usually consists of other lecturers of genetics at the Bachelor´s study level from the Faculty of Science). The knowledge regarding individual topics included in this subject, that is necessary for the successful passing of the exam, is always stated at the end of the presentations from individual topics which are available to the students signed for this subject at the Moodle server http://dl2.cuni.cz/ (the word key necessary for the login into this course at Moodle is given to students during the first lecture). At the end of the winter term, additional information and useful aids for students for their exam preparation will be available directly at the Moodle course. The examination test is based on 18 questions; students have to write their answers, not only tick off possible good/bad answers. Each individual test contains 12 questions per 2 marks and 6 questions per 1 mark; student can thus get 30 marks for the whole test. According to the final number of marks, students are classified using the following system: 25 and more marks - classification 1; 20-24.75 marks - classification 2; 15-19.75 marks - classification 3; less than 15 marks - exam was not successfully passed (classification 4). The time available for completing the test is 145 min. Each question represents a different topic / area of genetics from the whole lecture. The individual areas correspond to the following numbers of presentations/topics stated in the Syllabus (sometimes a question can even combine mutually related things from two separate areas):
The majority of examination terms occurs during January/February; a sufficient number of places is always available in a timely manner according to the study rules. Students should register for exam during this time period. In addition to this, there are usually three other exam terms from March to June and one last term in September; these terms should by used mostly for repeats of previously unsuccessful tries. DO NOT PROCRASTINATE - DO NOT TAKE YOUR FIRST TRY FOR THE EXAM AT THE END OF FEBRUARY OR DURING THE SUMMER TERM !!! |
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Last update: doc. RNDr. Dana Holá, Ph.D. (09.06.2023)
1. Introduction into Genetics The general scope of genetics, genomics and their branches. The main genetic models and their properties. 2. Applications of Genetics in Everyday Life Plant and animal breeding. Transgenic plants, animals and other organisms and their utilization in agriculture, food industry, pharmaceutics and other fields of human occupation. Genetics in medicine: biopharmaceutics, drug development, pharmacogenetics/genomics, nutrigenetics/genomics, gene therapy (possibilities, advantages and problems) and gene doping, genetic counselling (including the basic information on non-invasive and invasive methods of prenatal diagnostics, karyotype analysis and DNA diagnostics). DNA profiling and forensic genetics (including its various branches – paternity searching, criminal science; identification of victims of natural and other disasters; history/archeology/paleothology; genetic genealogy; other utilization of DNA profiles). 3. From Genotype to Phenotype 1a or What Exactly is the Gene? (the Classical Genetics – Principal Terms and Mendel Postulates) The main rules of inheritance (Johann Gregor Mendel a his postulates), their implications for phenotype expression in progeny generations. The „branching method“ and its utilization in the analysis of genotypic or phenotypic ratios. The main terms of „classical“ genetics, genetic nomenclature. 4. From Genotype to Phenotype 1b or What Exactly is the Gene? (the Classical Genetics – Expansion of Mendel Postulates and Their Limitations) The validity and limitations of Mendel postulates in specific situations: intragenic interactions (incomplete dominance, codominance); multiple allelism; lethality; genocopies, phenocopies, pleiotropy; intergenic interactions (epistasis, inhibition/suppression, complementarity, gene redundancy, polymorphic interactions, cumulative duplicity); penetrance, variable expressivity; effects of environment on phenotype expression, genetic anticipation; maternal effect. 5. From Genotype to Phenotype 2 or What Exactly is the Gene? (Chromosomal Genetics Within the Context of Heredity Rules) Chromosomal basis of the heredity. Main landmarks in the history of cytogenetics, chromosomal theory of heredity and its experimental proofs. Sex-linked, sex-limited and sex-influenced traits and their inheritance. Gene linkage and the violation of the rule of independent segregation of alleles. Uniparental and biparental non-Mendelistic inheritance associated with the existence of extranuclear DNA in eukaryotes. 6. From Genotype to Phenotype 3a or What Exactly is the Gene? (Molecular Genetics - DNA as the Genetic Material) DNA and RNA as the genetic material (the discovery of nucleic acids, their chemical composition and structure, experimental proofs of their role as the genetic material). 7. From Genotype to Phenotype 3b or What Exactly is the Gene? (Molecular Genetics – Central Dogma or How to Get from DNA to Polypeoptide) The evolving definition of the gene during the first half of the 20th century (1 gene = 1 enzyme, 1 protein, 1 polypeptide). tRNA and mRNA as mediators between DNA and polypeptide. The genetic code, how it was broken and what are its properties. The central dogma of molecular genetics and its subsequent modifications. 8. From Genotype to Phenotype 3c or What Exactly is the Gene? (Molecular Genetics – Problems with Gene Definition at the Molecular Level) Why it is not possible to unambiguously define a gene at the physical/molecular level? Gene loci and associated complications (overlapping genes, genes inside other genes, gene segments, scrambled genes, moving genes). Transcriptional definition of gene and associated complications (the main structure of gene and its regulatory regions, operons, alternative start and end sites of transcription and translation, alternative and trans splicing of transcripts, RNA editing, alternative reading frames, codon reassignment, recoding, translational bypass, less common aminoacids, trans translation, protein splicing, polyproteins, modifications of polypeptide ends, other amino acid modification, non-coding RNA). 9. From Genotype to Phenotype 4 or What Can Also Affect the Inheritance and Phenotype Expression (Epigenetics) The epigenetic inheritance (its definition, the main mechanisms and characteristics). The principal non-Mendelistic phenomenons associated with the epigenetic inheritance: X chromosome inactivation in mammals, parental imprinting, paramutation, positional effect, transcriptional and posttranscriptional gene silencing due to transgenes, environmental induction of heritable changes of gene expression, phenotypes associated with prions. 10. From Phenotype to Genotype/Gene 1a or How Is It Done (What Can Be Deduced from Hybridization: the First Steps of the Forward Genetic Analysis) The forward and the reverse genetic analysis. Random and non-random mutagenesis; genetic screening and selection. Testing of genetic hypotheses based on the hybridization results (chi-squared test). Principles and limitations of the complementation and epistatic analyses and the suppressor/enhancer analysis. 11. From Phenotype to Genotype/Gene 1b or How Is It Done (Linkage Genetic Mapping - and Some Extras) Genetic mapping based on recombination (main terms and fundamentals of the procedure, two-point and three-point tests for the determination of gene distance and order on a chromosome, linkage interference, mapping functions, linkage mapping using DNA markers, genetic polymorphisms (main types, their properties and utilization during mapping), restriction endonucleases and their utilization in genetic mapping). 12. From Phenotype to Genotype/Gene 1c or How Is It Done (Special Methods of Forward Genetic Analysis in Humans) Pedigree symbols. Main types of monogenic inheritance and their recognition from genetic pedigrees. Problems and limitations of pedigree analysis. Genetic mapping in humans based on recombination (linkage and association mapping). 13. From Phenotype to Genotype/Gene 2 or How Is It Done (Cytogenetic Analysis) The general scope of cytogenetics. Functional structures of eukaryotic mitotic (metaphasic) chromosome that are visible under microscope, morphological types of metaphasic chromosomes; karyotype, karyogram and ideogram. The main steps in the preparation of cytogenetic specimens. Homogenic and selective staining of eukaryotic chromosomes (including various types of chromosome banding). Cytogenetic nomenclature. Fluorescence in situ hybridization (its main principle, probe types, utilization for various purposes; mFISH, SKY, mBAND; GISH). Comparative genomic hybridization (CGH) and its utilization. MLPA and its utilization. 14. From Phenotype to Genotype/Gene 2 or How Is It Done (DNA Sequencing) Sample preparation before DNA sequencing (basic principles). DNA amplification (basic principles of DNA cloning and PCR, methods of DNA amplification used by the current sequencing technologies). Sequencing technologies of the 1st, 2nd and 3rd generation, their principles, advantages and limitations (Sanger/dideoxy sequencing, pyrosequencing, pH sequencing, sequencing using cyclic reverzible terminators, ligation sequencing, real-time sequencing, nanopore sequencing). Assembly and annotation of whole genome DNA sequence. Reference genomes and their main databases. 15. Genome Characteristics, Structure and Organization 1 (Genome Definition and Main Characteristics) The main data used for genome description (size; GC content; gene density, gene types and properties; repeat and regulatory sequences, ...). Sequence homology (the main types of gene homologs, gene families). Comparison of genomes among various organisms. Genome diversity within species. Genome dynamics. Pangenomes. 16. Genome Characteristics, Structure and Organization 2 (Genomes of Viruses and Related Biological Entities) Various types of viral genomes and their characterization (size; type of nucleic acid; segmented and multipartite genomes, recombination; informational content – coding and non-coding component; typical properties of viral genes and their organization...). Virophages and subviral agens (satelites and viroids) and their genetic information. 17. Genome Characteristics, Structure and Organization 3 (Genomes of Bacteria and Archaea) Characterization of bacterial and archeal genomes: size; type of nucleic acid; various components; ploidy; informational content – coding and non-coding component; typical properties of bacterial genes and their regions; gene organization within the genome; various types of repeat sequences and their potential biological roles. Structure and organization of bacterial / archaeal chromosome (DNA and protein components, DNA spiralization and superspiralization (and how to expres their type and degree), NAPs and their function, histones of archaea, various levels of chromosome organization from loops to macrodomains or compartments). Bacterial plasmides, their various types and properties, their utilization as cloning vectors. 18. Genome Characteristics, Structure and Organization 4a (Eukaryotic Nuclear Genome – Its Main Characteristics) Characterization of the eukaryotic nuclear genome: size; chromosome numbers; informational content – coding and non-coding component; typical properties of eukaryotic genes and their regions; gene organization within the genome; various types of repeat sequences (main structural types, their localization and potential biological roles) ... 19. Genome Characteristics, Structure and Organization 4b (Eukaryotic Nuclear Genome – Main Components of Chromatin) The basic structure of chromatin (nucleosome, chromatosome). DNA and protein components of eukaryotic chromatin (histones and their chaperones, HMG and SMC proteins, histone modifications and DNA methylation writers and erasers, readers of these modifications, ATP-dependent chromatin remodelling proteins). Consequences of chromatin modifications for its organization and gene expression. 20. Genome Characteristics, Structure and Organization 4c (Eukaryotic Nuclear Genome – Structure and Organization During Interphase) Original and current models of chromatin organization into higher-order structures. Chromatin loops, topologically associated domains, chromosomal compartments. Chromatin association with various nuclear structures (LADs, NADs; MARs/SARs). Chromosomal territories. 21. Genome Characteristics, Structure and Organization 4d (Eukaryotic Extranuclear Genomes) Eukaryotic semi-autonomous organelles (mitochondria, plastids, MLO, apicoplast) end the endosymbiotic theory of their origin. The transfer of genetic information among nucleus, plastids and mitochondria. Genomes of semi-autonomous organelles (size; type of nucleic acid; informational content, typical properties of genes and their organization; ploidy; variability within and among species / organisms ...). Heteroplasmy, homoplasmy. Genome of nucleomorph. Cytoplasmic plasmids of some fungi. 22. Genomes During the Cell Cycle 1a (DNA Replication – Its Basic Course) The main phases of cell cycles of eukaryotes, bacteria and archaea and their main checkpoints. Bidirectional DNA replication and its main mechanisms (replication origins; the course of initiation, elongation and termination; the components of replication apparatus necessary for these processes; common characteristics and differences among various organisms; DNA replication in the context of eukaryotic chromatin; how to keep replicated DNA molecules together). 23. Genomes During the Cell Cycle 1b (DNA Replication – Specific Types) Replication of telomeric DNA. Various mechanisms of unidirectional DNA replication (displacement loop/strand displacement, rolling circle, rolling hairpin) of some organellar, plasmid and viral genomes. DNA replication utilizing recombination. DNA and RNA replication with the involvement of transcription and reverse transcription in some viruses. 24. Genomes During the Cell Cycle 2a (Chromosome Segregation – Main Components of This Process) Chromosome segregation in bacteria and archaea. Eukaryotic karyokinesis: structure and function of various components of mitotic apparatus (kinetochor, MTOC and mitotic spindle, molecular motor proteins); mechanisms of chromosome condensation in the M-phase of cell cycle. 25. Genomes During the Cell Cycle 2b (Chromosome Segregation – the Course of Karyokinesis) The individual phases of mitosis and the associated changes of structure and organization of chromosomes and mitotic spindle; The M (spindle) checkpoint of cell cycle. 26. Genetic Variation 1a (Sexual Reproduction and Sex Determination) The main sources of genetic variation. Sexual reproductions – the main terms and characteristics, advantages and disadvantages. Mating types in unicellular eukaryotes. Genetic and non-genetic sex determination in multicellular eukaryotes – sex chromosome independent systems (environmental sex determination, haplodiploidy and pseudohaplodiploidy, cytoplasmic sex determination). Sex chromosome dependent systems of genetic sex determination (types and examples including the basic information on the molecular level – particularly in vertebrates, Drosophila melanogaster and Caenorhabditis elegans). Sex chromosome evolution. Polygenic sex determination. The theory of gene balance and sex chromosome dosage compensation (including its main molecular mechanisms). 27. Genetic Variation 1b (Meiosis and Recombination) Alternation between haploid and diploid state in various organisms, meiosis during the life cycles, gametogenesis. Meiosis (terminology, individual meiotic phases (with a particular focus on the prophase of the I. meiotic division) and the associated changes of structure and organization of chromosomes; specific properties of the I. and II. meiotic divisions). Homologic recombination of DNA during meiosis, its course, mechanisms and possible results (dHJ resolution, disolution, SDSA; the origin of crossing-over and non-crossing over based on these processes). Genetic consequences of crossing-over in heterozygotes and their progeny. Crossing-over interference. Meiotic gene conversion. Meiotic drive. 28. Genetic Variation 2 (Horizontal Gene Transfer) The horizontal transfer of genetic information and its main mechanisms in bacteria and archaea (transformation, transduction, capsduction, conjugation, vesiduction, etc.). Utilization of some of these processes for genetic mapping in bacteria. The horizontal transfer of genetic information between bacteria/archaea and eukaryotes, and among various eukaryotes. The possible consequences of the horizontal gene transfer at the phenotype level. 29. Genetic Variation 3a (Changes of DNA Sequence; the Origin of DNA Breaks and Other DNA Damage) Heritable and non-heritable changes of DNA sequence. Mutation rate/frequency. Spontanneous, induced and adaptive mutations. Main mechanisms leading to the spontaneous changes of DNA sequence (base tautomery, base deamination, depurination/depyrimidination, DNA polymerase slippage). Dynamic mutations and their associated phenotypes. Oxidative DNA damage. Main types of physical and chemical mutagenes and mechanisms of their action (ionizing and non-ionizing radiation, base analogues, intercalating agens, alkylation, deamination and hydroxylation agens, etc.). Mutagenicity tests. Biological mutagenes (only a brief mention). 30. Genetic Variation 3b (Cell Response to DNA Damage) The main steps in cell response to DNA damage in eukaryotes. SOS response in bacteria. Various systems of direct and indirect repair of single- or double strand DNA damage and the principles of their mechanisms (proofreading activity of DNA polymerase, fotoreactivation reparation, DNA alkyl transferases; base excision repair, nucleotide excision repair, mismatch repair; DSB repair based on the homologic recombination and non-homologous end-joining, other mechansims of DSB repair). The main systems of DNA damage tolerance and the principles of their mechanisms (TLS, template switching). 31. Genetic Variation 3c (Mitotic Recombination) Mitotic recombination and its possible genetic consequences (equal or unequal sister chromatid exchange, exchange between hmologous or nonhomologous chromosomes, gene conversion; loss of heterozygosity). Programmed mitotic recombination (mating type switching in yeasts, V(D)J recombination and class switch recombination in immunoglobuline or T-cell receptor genes). 32. Genetic Variation 4a (Mutations on a Small Scale) Classification of mutations according to various points of view. Point/gene mutations and their main types (substitutions, insertions, deletions; frameshift mutations; their effect on DNA or polypeptide sequence and general consequences). Splicing, regulatory and polar mutations, their main types and consequences. Silent and neutral mutations. 33. Genetic Variation 4b (Transposable Elements) The discovery of transposeble elements, their main types and groups in bacteria and eukaryotes, various mechanisms of their transposition. The consequences of mutations due to transposable elements. 34. Genetic Variation 4c (Mutations on a Large Scale: Structural Aberrations of Chromosomes) Chromosomal rearrangements: inversion, translocation, chromosome fusion, compound chromosomes, isochromosomes, ring chromosomes, deletions and microdeletions, duplications. Mechanisms of their origin and possible consequences on the phenotypic level (including their role in cancerogenesis). 35. Genetic Variation 4d (Mutations on a Large Scale: Changes of Chromosome Numbers) Changes of chromosome number: aneuploidy and its various types (nullisomy, monosomy, trisomy ...), euploidy and its various types (monoploidy / polyploidy, orthoploidy / anorthoploidy, paleopolyploidy / neopolyploidy, autopolyploidy / allopolyploidy, amfidiploidy). Mechanisms of their origin and possible consequences on the phenotypic level (including their role in cancerogenesis), their evolutionary significance. Tissue-specific polyploidy, endopolyploidy. Genetic mosaics and chimeras (including chromosomal ones). Supernumerary chromosomes (marker chromosomes, B chromosomes). Programmed elimination of chromosomes of whole chromosome sets. 36. Genetic Variation 5 (Classification of Mutations According to Other Aspects) Gametic and somatic mutations, their main characteristics and consequences. Gain-of-function and loss-of-function mutations and their various types (hypermorphic, neomorphic, hypomorphic, amorphic, antimorphic). Protooncogenes, oncogenes, tumor-supressor genes, mutator genes (some main examples and basic mechanisms of their function). Lethal, conditionally lethal and conditional mutations. Direct and reverse mutations. Back and suppressor mutations, their various types and consequences. Enhancer mutations 37. The Basics of Population Genetics 1 (Main Terms and Basic Principles) The main terms of population genetics. Description of population genetic structure, diversity and variation (frequency of alleles and genotypes, population polymorphism and heterozygosity). Hardy-Weinberg law of the relationship between allelic and genotype frequencies in a population, HW equilibrium (HWE), its conditions and the testing of its existence in a population. The extension of HWE to polyploid organisms, multiallelic loci and sex-linked loci. 38. The Basics of Population Genetics 2 (Deviations from HWE 1) Violations of HWE and its consequences for allelic and genotype frequencies in a population: nonrandom mating (assortative mating, inbreeding, etc.) in a population; genetic drift (the bottleneck effect, the founder effect, fragmentation of a population into subpopulations / merging of subpopulations; effective size of population, Wahlund principle and effect). 38. The Basics of Population Genetics 3 (Deviations from HWE 2) Violations of HWE and its consequences for allelic and genotype frequencies in a population: migration; tion přírodní selection (directional, balancing and disruptive); genetic draft. Linkage equilibrium and disequilibrium in a population. Dynamic equilibrium in a population. 40. The Basics of Quantitative Genetics Continuous and discontinuous variation; meristic and treshhold traits. Multifactorial hypothesis od the inheritance of quantitatice traits. Main statistical parameters utilized by quantitative genetics. Components of phenotypic variation of yuantitative traits and basic methods of their estimation. Heritability of quantitative traits, basic methods of its estimation a utilization in artificial selection/breeding. QTL and their identification (all methods of quantitative traits analysis and QTL only at the most basal level). |