CLINICAL GENETICS DEPARTMENT
CLASSES IN HUMAN GENETICS, 2018/19
AM, TW, AR, CH BIS
1. Introduction to human genetics. DNA and RNA.
The structure of genetic material. DNA, RNA and chromatin nucleoproteins structure. The structure of genomes (bacteria, bacteriophages, yeast, viruses, mitochondria, higher eukaryotic cells). The structure of genes. simple and composed genes. Gene families, sets and clusters.
2. DNA Replication. (Quiz 1)
Definition of replicon, replication fork and origin. Different aspects of replication in prokaryotic and eukaryotic DNA (replicon size, origin numbers, termination, etc). Mechanisms of replication (D-loop, rolling circles, problem of linear replicons, etc). Prokaryotic and Eukaryotic DNA polymerases and their role in DNA replication. Semidiscontinous replication, leading and lagging strand, Okazaki fragments. Role of SSB proteins. The accuracy of replication.
3. Transcription and Translation. (Quiz 2)
Definition of coding strand, template, start point, terminator, transcription unit. Stages of transcription (template recognition, initiation, elongation and termination). RNA polymerase and its subunits. Sigma factor and its role in template recognition. Definition of closed binary complex, open binary complex, ternary complex, abortive initiation. Consensus sequences and promoter recognition. Operons, repressors, co-repressors, inducers. Positive and negative control of operon. Catabolite repression. Eukaryotic RNA polymerases and their general factors. Regulation of transcription - main aspects. mRNA splicing. tRNA structure. Bacterial and mammalian ribosomes. The stages of protein synthesis. Genetic code and its features. Codon - anticodon recognition. Mutagenesis. Definition of mutation, different types of mutation (deletion, insertion etc.), mechanisms leading to induction of different mutation. Types of mutagens (chemical etc.). Recombination and repair.
4. Chromosomes. (Quiz 3)
Mitosis and meiosis. Chromosome structure and classification, chromosome analysis (karyotyping, banding techniques, FISH), Numerical chromosome abnormalities (aneuploidy, euploidy, meiotic nondisjunction, anaphase lag, mosaicism), Structural chromosome abnormalities (deletions, duplications, inversions, translocations, isochromosome. Robertsonian translocation, balanced/unbalanced aberrations), marker chromosomes.
5. Chromosomal disorders. (Quiz 4)
Mendel law’s. Types of inheritance. Sex determination, sex chromosomes, sex-chromatin body. Sex-chromosome anomalies (Turner syndrome, Klinefelter syndrome), autosomal aberrations (Down syndrome, translocation Down syndrome, Patau syndrome, Edward's syndrome, cat's cry syndrome, fragile X syndrome), microdeletions (Prader-Willi syndrome, Angelman syndrome) Indications for karyotype examination.
6. Single gene alterations I. (Quiz 5)
Autosomal dominant disorders: achondroplasia, Apert syndrome, Huntington disease, neurofibromatosis (NF-1, NF-2), Marfan syndrome, osteogenesis imperfecta,
Autosomal recessive disorders: albinism, cystic fibrosis, galactosemia, Gaucher disease, haemochromatosis, mucopolisaccharidoses, phenylketonuria, sickle-cell anemia, Tay-Sachs disease, the thalassemias
7. Single gene alterations Il/multifactorial diseases. (Quiz 6)
Sex-linked disorders: Ehlers-Danlos syndrome, glucose-6-phosphate dehydrogenase deficiency (G6PD), hemophilia A, hemophilia B, Duchenne muscular dystrophy, Becker muscular dystrophy. Multifactorial diseases: Atherosclerosis, autism, diabetes mellitus, epilepsy, hypertension, neuronal tube defects, myocardial infarction, multiple sclerosis, schizophrenia, spina bifida, stroke
8. Immunogenetics. (Quiz 7)
The humoral and cellular immune systems. Immunoglobulin molecules and genes. The genetic basis of antibody diversity. The ABO and Rh blood groups. The major histocompatibility complex. Immunodeficiency diseases: primary (X-linked agammaglobulinemia, SCID, Wiskott-Aldrich syndrome, Ataxia teleangiectasia, Di George'a anomaly), secondary ( AIDS syndrome)
9. Oncogenesis. (Quiz 8)
Cell cycle and its phases. Cycle progression, check points and regulation of cycle progression (cdk, cyclins). Association between p53 protein and cell cycle progression. Definition of proto-oncogene and oncogene, immortalization, transformation, metastasis, growth factors. The main aspects of signal transduction. Receptors - different structure and localization. Protein tyrosine kinases and protein serine/threonine kinases and their role in signal transduction. The Ras/MAPK pathway. Oncogenes products as a part of signal transduction cascades Proto-oncogenes activation by means of insertion, translocation or amplification. Retroviruses and their role in oncogenesis. Tumor suppressor genes (P53, Rb, APC, BRCA1, BRCA2). Association between pRb and cell cycle. The role of different oncogenes and tumor suppressors in oncogenesis (colon cancer, retinoblastoma, Li-Fraumeni syndrome, breast cancer etc.). The main aspects of apoptosis.
10. Laboratory practice. (Quiz 9)
11. Laboratory practice. (Lab Quiz 1)
12. Genetic imprinting. Mitochondrial diseases. (Lab Quiz 2)
Genetic imprinting in human diseases. Mitochondrial DNA and mitochondrial inheritance. Mitochondrial diseases: Kearns-Sayre syndrome, Pearson syndrome, MERRF, MELAS, NARP, Leigh disease, LHOH.
13. Genetic and environmental basis of human anomalies. (Quiz 10; from topic 12)
Genetic and environmental basis of human anomalies: causes, nomenclature, etiology
and pathogenesis, types of anomalies, anthropometry, prenatal diagnosis, implications of the child with malformations for the family and society.
14. Genetics counseling. Population genetics.
Definition, genetics counselor, timing, preparation of the genetics counseling session. Genetics counseling cases (pedigree analysis). Population genetics. Hardy-Weinberg Law.
15. Laboratory practice III.