Veidlapa Nr. M-3 (8)
Study Course Description
Medical Applications of Genomics
Course Code
BUMK_071
Branch of Science
Biological sciences; Environmental biotechnology; Genetics; Medical biotechnology
ECTS
3.00
Target Audience
Biology; Life Science; Medicine
LQF
Level 7
Study Type And Form
Full-Time
Study Course Implementer
Course Supervisor
Baiba Vilne
Structure Unit Manager
Juta Kroiča
Structural Unit
Department of Biology and Microbiology
Contacts
Riga, 16 Dzirciema Street, +371 67061542
About Study Course
Objective
Learn the molecular pathomechanisms of diseases, learn next-generation sequencing technologies, identify the most widely used databases for functional and clinical interpretation of genetic variation, using specific case studies, to perform practical work with databases, for the interpretation of genetic variation, using knowledge of gene, transcript and protein structure and functional association with clinical symptoms. At the successful finishing the course, one will be able to independently prepare a clinical interpretation for genetic variations.
Preliminary Knowledge
Basic knowledge in molecular biology is required, with a focus on the human genome, transcriptome and proteome: a basic understanding of gene structure and expression, its regulation, splicing and alternative splicing, genetic variations, their types and possible effects on gene expression. Prior knowledge in biostatistics and bioinformatics and prior knowledge in clinical medicine is optional but highly desirable.
Learning Outcomes
Knowledge
1.Learners will gain knowledge about genomics, the most important databases in genetics used for the clinical interpretation of genetic variants, the main principles of data acquisition and processing methods.
Skills
1.To search, select, classify and analyze big data from next generation sequencing using different digital tools and technologies in order to classify and perform clinical interpretation for genetic variants.
Competences
1.1. Creates solutions to complex problems by independently classifying genetic variants and interpreting them clinically using next-generation sequencing data (big data), browses, searches and selects data, information and digital content using various digital tools and technologies such as software tools (e.g. These tools and digital tools, such as software tools (e.g. FASTQC, VcfTools, VariantInterpreter, SEQR) and different databases (e.g. Ensembl/GENCODE, UniProt, gnomAD) to find solutions to ill-defined complex problems such as genetic variant classification and clinical interpretation for molecular diagnosis. 2. Understands the process of acquisition and interpretation of next generation sequencing data (laboratory and bioinformatics processing steps) and is able to identify potential sources of error and propose ways to overcome them, thus making creative use of digital technologies. 3. Able to educate and guide other medical colleagues (geneticists and laboratory physicians) in the creative use of digital technologies for the analysis and interpretation of genetic variants.
Assessment
Individual work
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Title
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% from total grade
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Grade
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1.
Individual work |
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In each practical class is planned to have practical work using the knowledge gained in the lecture with other examples will be asked for students till next class to prepare the homework that is discussed in next class. The topics of homework are:
1. Nomenclature of genetic variants.
2. Using databases to find out the type of disease associated with gene changes.
3. clinical interpretation of genetic variants using The American College of Medical Genetics and Genomics (ACMG) and other guidelines - criteria related to the description of the variant in publications (criteria PP5 and BO6), interpretation of the frequency of the variant (BA1, BS1, BS2, PM2 PS4).
4. Detailed explanation for the interpretation of genetic variants using prediction tools – PVS1, PS1, PM1 PM5, PP2, BP1 differences in the interpretation of amino acid changes, nucleotide changes without amino acid changes, splice links, indels.
5. Detailed explanation for the interpretation of genetic variants based on disease symptoms (criteria PP4), functional data of the variant (criteria BS3, PS3), use of in silico tools (criteria PP3 and BP4), segregation of variants in the family (criteria BS4, PP1), variants in cis or in a trans state (criteria BP2, PM3); existence of an alternative phenotype (criterion BP5).
6. Visualization of variants with IGV, interpretation of exome data.
7. Interpretation of CNV.
8. Classification of specific genetic variants, evaluation of reporting. Evaluation of clonality, its importance in clinical decision-making.
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Examination
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Title
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% from total grade
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Grade
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1.
Examination |
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2.
Examination |
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or each lesson (except the first), the learner has prepared a homework on the topic of the previous lesson, which is evaluated in a point system. All practical classes must be attended and all homework must be submitted for the overall assessment. At the end of course students should pass exam, that is evaluated with points. In order to evaluate the quality of the study course as a whole, the student must fill out the study course evaluation questionnaire on the Student Portal.
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Study Course Theme Plan
FULL-TIME
Part 1
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Lecture
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Auditorium
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2
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Topics
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Type of genetic variations, their nomenclature. Gene expression (transcriptome). Protein types and their structure.
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-
Class/Seminar
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Computer room
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2
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Topics
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Type of genetic variations, their nomenclature. Gene expression (transcriptome). Protein types and their structure.
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-
Lecture
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Auditorium
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2
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Topics
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Disease molecular pathomechanism. Gene-disorder association.
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Class/Seminar
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Computer room
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2
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Topics
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Disease molecular pathomechanism. Gene-disorder association.
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Lecture
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Auditorium
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2
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Topics
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Genetic variant clinical interpretation. ACMG guidelines and provided changes by ClinGen and ACGS. Most important databases.
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-
Lecture
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
|
Auditorium
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2
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Topics
|
Genetic variant clinical interpretation. ACMG guidelines and provided changes by ClinGen and ACGS. Most important databases.
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-
Lecture
|
Modality
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Location
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Contact hours
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|---|---|---|
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On site
|
Auditorium
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2
|
Topics
|
Genetic variant clinical interpretation. ACMG guidelines and provided changes by ClinGen and ACGS. Most important databases.
|
-
Class/Seminar
|
Modality
|
Location
|
Contact hours
|
|---|---|---|
|
On site
|
Computer room
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2
|
Topics
|
Genetic variant clinical interpretation. ACMG guidelines and provided changes by ClinGen and ACGS. Most important databases.
|
-
Class/Seminar
|
Modality
|
Location
|
Contact hours
|
|---|---|---|
|
On site
|
Computer room
|
2
|
Topics
|
Genetic variant clinical interpretation. ACMG guidelines and provided changes by ClinGen and ACGS. Most important databases.
|
-
Class/Seminar
|
Modality
|
Location
|
Contact hours
|
|---|---|---|
|
On site
|
Computer room
|
2
|
Topics
|
Genetic variant clinical interpretation. ACMG guidelines and provided changes by ClinGen and ACGS. Most important databases.
|
-
Lecture
|
Modality
|
Location
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Contact hours
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|---|---|---|
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On site
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Auditorium
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2
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Topics
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Main methods of next generation sequencing, specifics of bioinformatic analysis
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-
Class/Seminar
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Computer room
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2
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Topics
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Main methods of next generation sequencing, specifics of bioinformatic analysis
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-
Lecture
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Auditorium
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2
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Topics
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Copy number variations, methods of their detection and interpretation.
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Class/Seminar
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Computer room
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2
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Topics
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Copy number variations, methods of their detection and interpretation.
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Lecture
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Auditorium
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2
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Topics
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Detection, interpretation of somatic variants. Their clinical meaning and specifics in reporting.
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-
Class/Seminar
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Modality
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Location
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Contact hours
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|---|---|---|
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On site
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Computer room
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2
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Topics
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Detection, interpretation of somatic variants. Their clinical meaning and specifics in reporting.
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Total ECTS (Creditpoints):
3.00
Contact hours:
32 Academic Hours
Final Examination:
Exam
Bibliography
Required Reading
1.
Alberts Bruce, et al. Molecular Biology of the Cell. 7th ed. W. W. Norton & Company, 2022.
4.
Posey JE., Harel T., Liu P., Rosenfeld JA., James RA., et al. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. N Engl J Med. 2017 Jan 5;376(1):21-31. doi: 10.1056/NEJMoa1516767
5.
Schubert J., Wu J., Li MM., Cao K. Best Practice for Clinical Somatic Variant Interpretation and Reporting. Clin Lab Med. 2022 Sep;42(3):423-434. doi: 10.1016/j.cll.2022.04.006. Epub 2022 Aug 22. PMID: 36150821.
6.
Li MM., Cottrell CE., Pullambhatla M., Roy S., et al. Assessments of Somatic Variant Classification Using the Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists Guidelines: A Report from the Association for Molecular Pathology. J Mol Diagn. 2023 Feb;25(2):69-86. doi: 10.1016/j.jmoldx.2022.11.002. Epub 2022 Dec 9. PMID: 36503149.