Cytogenetics and cytogenomics

Course unit title

Scientific direction

Scientific code

Faculty

Department (s)

Cytogenetics and cytogenomics

Biology N 010

Life Sciences Center

Institute of Biosciences

Total number of credits

Mode of studies

Number of credits

Lectures, self-study, consultations, seminars (optional)

8

Aims of course

To provide knowledge of chromosome structure, their functions, changes during the cell cycle and under the influence of environmental factors. To provide understand of the significance of changes in chromosomal structure for the development and diseases of the individual.

Main topics

1. Classical and modern cytogenetic methods. Differential staining of chromosomes, types of chromosome banding, banding types; nomenclature of banded chromosomes. In situ hybridization, its applications, different types of FISH (Rx-FISH, MCB, COBRA-FISH, Cas-FISH, Oligopaint-FISH). Comparative genomic hybridization (CGH, aCGH, SNP-CGH). Comparison of classical and molecular methods of cytogenetics, their advantages and disadvantages, scopes and principles of choice. Other methods of chromosome analysis (flow cytometry, chromosomal microdisection, immunofluorescence)

2. Morphology of eukaryotic chromosomes. Karyotype, its species’ specificity, number, size and shape of chromosomes. Normal human karyotype; nomenclature of a normal and abnormal karyotype.

3. Chromosomoes of specific structure. Polytenic chromosomes, thei DNA replication and mechanisms of polytenization. „Lampbrush“ chromosomes, their structure. B chromosomes.

4. Changes of chromosome numbers and structure. Chromosome-type aberrations, mechanisms of their formation and analysis in metaphase chromosomes. Aneuploidy, mechanisms of its formation. Dependency of the frequency of aneuploidies on centromere structure. Consequencies of aneuploidies at genome, transcriptome and proteo,e levels. Human genetic diseases caused by deletions. Microdeletions and microduplications. Genetic disorders caused by balanced translocations, Robertsonian translocations and inversions; pecularities of gametogenesis in individuals with translocations and inversions. Numerical chromosome abnormalities. Karyptypic pecularities of cancer cells, effects of chromosomal rearrangements on the expression of oncogenes and tumour suppressor genes. Karyotypic instability in cancer cells: cycle „breakage-fusion-bridge“, chromothripsis, chromoplexy, chromoanasynthesis. Relation between chromothripsis and telomeric instability, aneuplody and formation of micronuclei.

5. Centromeres. Structure of centromeres; formation of centromeres as epigenetic process. Struture and pecularities of centromeric DNA and chromatin. Structure of kinetochore. Models of centromere structure.

6. Telomeres. Telomeric repeats, G overhangs, D and T loops. Shelterin complex and its functions. Telomerase. Reasons and consequences of telomeric dysfunction.

7. 3D chromatin structure. Methods of analysis of 3D chromatin. Hi-C method. Topologically associating domains (TAD), mainproteins participating in their formation (CTCF, cohesin); loop extrusion. Hierarchical structure of chromatin. Relation of 3D chromatin structure with functional chromatin types. 3D chromatin dynamics during the cell cycle

8. Spatial structure of chromosoes and diseases. Chromosomal structural variability that does not change TAD boundaries. Chromosome structural changes that disrupt TAD boundaries. Structural variability of chromosomes shifting TAD boundaries. Changes in the 3D genome in cancer cells. Hierarchical genome structure and diseases

9. Structure of chromosomes in the nucleus. Lamina Associating Domains (LAD); interaction of chromatin with the nucleus; PcG bodies, their formation and structure; Integration of various methods (imaging, sequencing, modelling) for the analysis of chromatin structure in living cell nuclei. Modern models of chromatin structure.

Main literature

• Lazutka J.R., Slapšytė G. Eukariotų chromosomų struktūra. Kaunas: Technologija, 2008.
• Sumner A.T. Chromosomes: Organization and Function. Oxford,  Blackwell Publ., 2008
• Vogel and Motulsky’s Human Genetics. Problems and approaches. 4th edition (Eds.: M.R. Speicher, S.E. Antonarakis, A.G. Motulsky). Springer-Verlag Berlin Heidelberg, 2010.
• Cancer Cytogenetics. Methods and Protocols. (2nd edition. (Ed. L.J. Campbell). Humana Press, 2011

Assessment strategy

Assessment criteria

Exam

or

written report and seminar presentation

During the exam, the candidate answers three open questions. Alternatively, candidates may prepare written report on selected topics and present it during the seminar.

Knowledge and skills are evaluated with points from 1 to 10. 10 (excellent) - excellent, exceptional knowledge and abilities; 9 (very good) - very good knowledge and abilities; 8 (good) - knowledge and abilities are above average (a student independently, reasonably, clearly states the essence of the given question, is well acquainted with the terminology of the taught subject); 7 (average) - average knowledge and abilities; there are few not essential mistakes (a student independently but incoherently and without justification sets out the essence of the question, uses the basic definitions of the subject); 6 (satisfactory) - knowledge and abilities are below average, there are mistakes (a student independently, but inconsistently, superficially, unclearly presents the essence of the question, understands the main definitions of the subject); 5 (weak) - knowledge and abilities meet the minimum requirements (a student independently but vaguely, without analysis, inconsistently presents the essence of the question, partially understands the basic definitions of the subject); 4,3,2,1 (insufficient) - the minimum requirements are not met.

Juozas Lazutka

prof.

Veronika Dedonytė

Approved by the Council of Doctoral School of Life Sciences Center No (4.10)600000-KT-… on the 14th of October 2021

Chairman dr. Daiva Baltriukienė