BMB815: Human Molecular Genetics - Molecular Pathology and Diagnostic Methods (5 ECTS)

STADS: 01013001

Level
Master's level course

Teaching period
The course is offered in the autumn semester.

Teacher responsible
Email: bragea@bmb.sdu.dk

Timetable
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Prerequisites:
A Bachelor’s degree in Biochemistry and molecular biology or Biomedicine or equivalent.

Academic preconditions:
Students taking the course are expected to:

• Have knowledge of theories and experimental methods from the field of Molecular Biology and Biomedicine. 
• Be able to analyze theoretical and practical problems and use relevant models for problem solving and to make and argue for scientific decisions.
• Be able to describe, formulate and convey problems and themes from the area of Molecular biology and Biomedicine.

Course introduction
The purpose of the course is to give the student an insight into and skills to perform and apply the development of molecular-genetic diagnostic methods, their use in research, and how these methods can be modified and optimized for highly reliable routine use in the diagnosis and monitoring of diseases.

The other important purpose is to convey to the students knowledge about the principles of medical genetics, the classical modes of inheritance and other clinically important patterns of inheritance, such as for instance epigentic inheritance and inheritance which exhibit anticipation. The molecular pathology of and therapies for representative inherited diseases will also be covered by this course.

This course builds on knowledge gained in courses from the bachelor education in BMB or Biomedicine, in particular the BMB508 course. It provides the theoretical basis for further studies into projects in human molecular genetics in the master project and it also enables the student to include human molecular genetic analyses and theories in master projects where such themes are relevant and needed.

In relation to the competence profile of the degree it is the explicit focus of the course to ensure that the student will obtain knowledge about the fundamental principles of a number of modern molecular-genetic diagnostic methods and their use in disease research. Finally, the student will obtain knowledge about the requirements for implementing a molecular-genetic diagnostic method in a hospital environment for routine investigation of patients.

Through laboratory exercises, examinatoriums and demonstrations by specialists, the student will acquire knowledge on how sophisticated molecular-genetic diagnostic methods are organised, implemented and quality controlled. The student will obtain skills to perform selected representative methods and analyses. Thus, the students achieve - through practical examples – a stronger theoretical knowledge on the molecular genetic methods, and furthermore they obtain an understanding of the fundamental principles of reliable diagnosis.

Finally, the students will through hands-on experience obtain knowledge on the basic principles for treatment of selected inherited diseases by use of antisense oligonucleotides.

Expected learning outcome
The learning objectives of the course are that the student demonstrates the ability to:

• Critically read, interpret and communicate original research literature in molecular diagnostics.
• Explain selected techniques used in molecular diagnostics.
• Explain the classical modes of inheritance and other clinically important patterns of inheritance and explain the molecular pathology of representative inherited diseases.
• Account for - and apply in practice – the principles and methods used in genetic diagnosis of heritable diseases.
• Possess knowledge of the ethical aspects in relation to genetic counselling in families and in relation to screening of a population.
• Account for the main stages in the development of a molecular-genetic diagnostic method.
• Outline the theoretical and experimental criteria and limitations for a defined molecular-genetic diagnostic problem.
• Chose the optimal method for a defined molecular-genetic diagnostic problem.
• Formulate new questions and investigations based on obtained results.
• Define overall quality criteria for the clinical use of molecular-genetic diagnostics.
• Possess knowledge on the use of computer-based analysis tools and selected databases.
• Interpret data from selected molecular-genetic diagnostic tests.
• Participate in interdisciplinary collaboration with the health sector/ health industry on the development of molecular-genetic disease diagnostics.
• Explain the basic principles underlying use of therapeutic antisense oligonucleotides in treatment of selected inherited diseases.

Subject overview
The following main topics are contained in the course: Human Genetics and Molecular Biology. More specifically:

• Molecular genetics for diagnosis of inherited disease (The use of PCR in mutation-specific and general mutation scanning assays). DNA sequencing.
• Diagnostic applications of Next Generation Sequencing for mutation detection and characterization of gene-expression.
• Analysis of chromosomal aberrations (Microscopy and molecular cytogenetics).
• Methods for characterization of gene-expression (micro-arrays, RNA-seq and quantitative PCR).
• Quality assurance, validation, sources of variation and errors in molecular genetic diagnostic testing.
• Use of bioinformatic analysis tools for evaluation of the potential pathogenic effects of sequence variations and mutations and their distribution and frequencies in a population. Searches in sequence-, variation/mutation- and disease-databases.
• Ethical issues regarding genetic consulting of families and genetic screening in populations.
• New molecular therapeutic approaches for inherited diseases.

Literature

• Peter Turnpenny and Sian Ellard. Churchill Livingstone/Elsevier: Emery’s elements of medical genetics, 14th edition – 2012,ISBN: 9780702040436.
• • Herudover udvalgte artikler og øvelsemanual.

Website
This course uses e-learn (blackboard).

Prerequisites for participating in the exam

1. Participation in lab. work is a prerequisite for exam part a. Pass/fail, internal marking by teacher.
2. Active participation in examinatoriums (80 % presence) is a prerequisite for exam part b. Pass/fail, internal marking by teacher.

Assessment and marking:

1. Report on lab work, pass/fail, internal marking. All exam aids allowed. 2 ECTS
2. Project assignment, Danish 7-mark scale, internal marking. All exam aids allowed. 3 ECTS

Reexamination in the same exam period or immediately thereafter.

Expected working hours
The teaching method is based on three phase model.
Intro phase: 18 hours
Skills training phase: 37 hours, hereof:
 - Tutorials: 21 hours
 - Laboratory exercises: 16 hours

Educational activities

Educational form
The intro-phase consists of lectures. The lectures provide an introduction to the different course topics, which are covered by the text book and primary literature such as scientific articles.  In order to achieve the competences in the topics covered the course it is necessary that the students read the text book and literature.

In the training-phase competences in the central parts of the course are trained. This includes   – pedigree analysis for the most common inheritance patterns and risc calculation. Competences in how to select the correct genetic diagnostic approach and how to analyze results is also trained. An understanding of the most frequent molecular pathologic mechanisms and suitable therapies thereto are also trained. Methods for genetic analysis at the population level and for association studies are trained. There is much emphasis on training an understanding and capability to interprete whole genome/transcriptome based analyses, for instance next generation sequencing. The examinatoriums are based on team work in solving genetic problems. In the laboratory exercises the student work in teams performing hands-on experiments with diagnostic methods and treatment of an inherited disease at the molecular level.

In the study-phase it is expected that the students individually study the textbook and work with problem-solving of theoretical exercises in genetics which are uploaded to blackboard. Moreover, preparation of oral presentations for the examinatoriums and a report on the practical laboratory exercises are central components of the study-phase.  The students will receive feedback from the lecturers on these parts. The students are also expected to spend part of the study-phase on preparing for laboratory work and preparing a project assignment, which is part of the final examination of the course.

Language
This course is taught in English, if international students participate. Otherwise the course is taught in Danish.

Course enrollment
See deadline of enrolment.

Tuition fees for single courses
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