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2022/2023

Molecular Pathology

Code: 100949 ECTS Credits: 6
Degree Type Year Semester
2500253 Biotechnology OT 4 2

Contact

Name:
Assumpció Bosch Merino
Email:
assumpcio.bosch@uab.cat

Use of Languages

Principal working language:
catalan (cat)
Some groups entirely in English:
No
Some groups entirely in Catalan:
No
Some groups entirely in Spanish:
No

Teachers

Anna Maria Bassols Teixido
Maria Fátima Bosch Tubert

Prerequisites

There are no official prerequisites, but it is assumed that the student has previously acquired enough solid knowledge on subjects of first courses: Biochemistry, Biology, Molecular Genetics, Genetics and  Basic and Advanced Instrumental Techniques.

You must qualify for the safety in laboratories test. The test can be answered in the corresponding space on the intranet and the information you need to check is in the Communication area of the Degree in Biotechnology.

Objectives and Contextualisation

Provide a general knowledge about the molecular bases of the development of genetic diseases and deepen in the application of biochemical and molecular biology techniques for their study, diagnosis and therapeutics. In order to integrate this information, some selected examples of genetic diseases will be described at the molecular level.

Competences

  • Act with ethical responsibility and respect for fundamental rights and duties, diversity and democratic values.
  • Apply the principal techniques for the use of biological systems: recombinant DNA and cloning, cell cultures, manipulation of viruses, bacteria and animal and plant cells, immunological techniques, microscopy techniques, recombinant proteins and methods of separation and characterisation of biomolecules.
  • Describe the molecular, cellular and physiological bases of the organisation, functioning and integration of living organisms in the framework of their application to biotechnological processes.
  • Design continuation experiments for problem solving.
  • Interpret experimental results and identify consistent and inconsistent elements.
  • Introduce changes in the methods and processes of the field of knowledge to provide innovative responses to the needs and demands of society.
  • Learn new knowledge and techniques autonomously.
  • Make an oral, written and visual presentation of one's work to a professional or non-professional audience in English or in one's own language.
  • Read specialised texts both in English and one's own language.
  • Reason in a critical manner
  • Search for and manage information from various sources.
  • Search for, obtain and interpret information from the principal databases on biology, bibliography and patents and use basic bioinformatic tools.
  • Take account of social, economic and environmental impacts when operating within one's own area of knowledge.
  • Take sex- or gender-based inequalities into consideration when operating within one's own area of knowledge.
  • Think in an integrated manner and approach problems from different perspectives.
  • Use ICT for communication, information searching, data processing and calculations.
  • Work individually and in teams

Learning Outcomes

  1. Act with ethical responsibility and respect for fundamental rights and duties, diversity and democratic values.
  2. Analyse and interpret the published data relating to studies on genetic linkage and positional cloning in order to identify genes associated with genetic diseases.
  3. Describe and use techniques from biochemistry and molecular biology for detecting mutations responsible for genetic diseases in different types of samples and for prenatal diagnosis.
  4. Describe the methodologies for generating animal models of human diseases and their limitations, and general applications of molecular therapy and gene therapy.
  5. Describe the molecular bases of genetic diseases in their different mechanisms, and provide examples of each type of mechanism, their functional repercussions and therapeutic approaches.
  6. Design continuation experiments for problem solving.
  7. Explain the molecular bases of such phenomena as loss and gain of function, incomplete penetrance, anticipation, variable expressivity, genetic impression and inactivation of the X-chromosome.
  8. Interpret and integrate the data from the principal biochemical analyses and from molecular genetic diagnosis, and correlate these with the clinical data.
  9. Interpret experimental results and identify consistent and inconsistent elements.
  10. Introduce changes in the methods and processes of the field of knowledge to provide innovative responses to the needs and demands of society.
  11. Learn new knowledge and techniques autonomously.
  12. Make an oral, written and visual presentation of one's work to a professional or non-professional audience in English or in one's own language.
  13. Read specialised texts both in English and one's own language.
  14. Reason in a critical manner
  15. Relate the different types of DNA mutations to their effects on gene expression.
  16. Search for and manage information from various sources.
  17. Submit a basic query to databases on genes and genetic diseases and interpret the results.
  18. Take account of social, economic and environmental impacts when operating within one's own area of knowledge.
  19. Take sex- or gender-based inequalities into consideration when operating within one's own area of knowledge.
  20. Think in an integrated manner and approach problems from different perspectives.
  21. Use ICT for communication, information searching, data processing and calculations.
  22. Work individually and in teams

Content

THEORY

1. Introduction to genetic diseases. Definition of health and disease. Definition of genetic disease. Garrod’s contribution: Inborn errors of metabolism. Data bases of genetic diseases. Monogenic, polygenic and multifactorial diseases. Mendelian inheritance. Incidence and prevalence of genetic diseases in the population.

2. Mutations in DNA as a cause of genetic diseases.  Definition of mutation. Mutation rate. Types of molecular mutations and their effect on gene expression. Haemoglobinopathies. Enzymopathies: Blocking a metabolic pathway. Glucose-6-phosphatase, galactosemia and phenylketonuria deficiencies.

3. Molecular genetics diagnosis. Type and origin of analyzed samples. Prenatal and carrier diagnostics. Non-invasive techniques. Methods for detection of point mutations (SNPs), dynamic mutations, deletions and chromosomal rearrangements. Microarrays.

4. Molecular bases of inheritance and genetic diseases. Loss of function. Recessivity. Dominance. Haploinsufficiency. Negative dominant effect. Gain of function. Variable expressivity. Incomplete penetrance. Epigenetics. Genomic imprinting. Prader-Willi and Angleman syndromes. Chromosome X inactivation. Functional hemizygosity. Mosaic females. XIST gene and chromosome X inactivation center (XIC).

5. Identification of disease-associated genes.  Strategies. Functional cloning. Positional cloning. Genetic and physical maps. Linkage analysis. LOD score. Zoo blots. CG isles. Exon trapping. Exon prediction. Chromosome jumping. Candidate genes.

6. Monogenic diseases:Cystic fibrosis. Alteration on chloride ion transport. Identification of the associated gene. Structure and function of the cystic fibrosis transmembrane regulator (CFTR). Effects of ∆F508 and other mutations. Compound heterozygous. Therapeutic approaches.

7. Diseases caused by dynamic mutations. Classification. Proposed mechanism. General characteristics: Incomplete penetrance, anticipation, premutation. X-fragile syndrome. Effect of trinuclotide CGG expansion. Function of FMR1 gene.

8. Polygenic diseases: Alzheimer’s disease. Types of lesions. Candidate and susceptibility genes. Amyloid protein precursor (APP). Role of secretases in APP processing. Presenilins. Drugs: Acetylcholinesterase inhibitors. Additional therapeutic approaches.

9. Chromosomal diseases: Down síndrome (Trisomy 21). Effect of maternal age. Phenotype. Causes. Gene dosage effect. Candidate genes. Down syndrome critical region. Animal models. Prenatal diagnosis.

10. Diseases of amino acid metabolism.  Phenylketonuria and other hyperphenylalaninemias. Phenylalanine hydroxylase deficiency. Structure and effect of mutations. Neonatal diagnosis and prevention.

11. Diseases of lipid metabolism. Familiar hypercholesterolemia. Cholesterol metabolism and LDL. Associated loci. Structure and function of LDL receptor. Effect of mutations.

12. Diseases of carbohydrate metabolism. Glycogen storage diseases. Galactosemias.

13. Diabetes mellitus. Type 1 diabetes. Type 2 diabetes.

14. Diseases of collagen biosynthesis and structure. Osteogenesis imperfecta. Ehlers-Danlos syndrome. Alport syndrome.

15. Muscular dystrophies. Duchenne muscular dystrophy. Becker muscular dystrophy. Limb-girdle musculardystrophy. Structure of dystrophin and dystrophin-dystroglycan complex.

16. Biochemistry and molecular biology of cancer (I). Cancer as a multicausal process. Cancer epidemiology and risk factors. Fundamental alterations in cancer cells.

17. Biochemistry and molecular biology of cancer (II). Oncogenes and protooncogenes: Activation mechanisms, membrane, cytoplasmatic and nuclear oncoproteins. Tumor suppressor genes: Molecular bases and their relationship with hereditary cancers. Cancer and apoptosis.

18. Biochemistry and molecular biology of cancer (III). Molecular bases of invasion and metastasis. Therapeutic approaches.

19. Molecular biology techniques to study disease mechanisms (I). Introduction to transgenesis techniques in animals. DNA microinjection into fertilized oocytes.

20. Molecular biology techniques to study disease mechanisms (II).  Introduction to techniques for targeted genomic alterations: Obtaining knock-out and knock-in animals using classical and CRISPR / Cas9 techniques.

21. Introduction to gene therapy. Types of vectors. Development of strategies for gene transfer into specific cells and tissues.

 

SEMINARS

Suggested topics:
										
											
										
											    Pigmentary retinosis
										
											    Charcot-Marie-Tooth's disease
										
											    Parkinson's disease
										
											    Colorectal cancer
										
											    Lesch-Nyhan Syndrome
										
											    Amyotrophic lateral sclerosis
										
											    Adrenoleukodystrophy
										
											    Rett syndrome
										
											    Gaucher's disease
										
											    Malignanthyperthermia
										
											    Marfan Syndrome
										
											    Friedreich's Atlas
										
											    Neurofibromatosis
										
											    Colorectal cancer
										
											    Mitochondrial diseases
										
											    Immunodeficiencies
										
											    Narcolepsy
										
											    Schizophrenia
										
											    Alcoholism
										
											    Pharmacogenomics and toxicogenomics

Methodology

Material available on the Intranet of the subject

Teaching guide

Calendar of teaching activities (lectures, tutorials, assessments, deliveries ...)

Visual material used by teachers in the lectures

Self-learning topics (Seminars)

Short questions, clinical cases, statements of problems

Collection test questions as an exam model

The training activities include: theory classes, seminars and laboratory practices, each of them with their specific methodology. These activities will be complemented by a series of tutorial sessions that will be additionally scheduled and a collection of deliveries for continuous evaluation.

Lectures

The content of different subjects will be explained with the support of visual material that will be available to students through the Intranet of the subject. This visual material will be written in Catalan, Spanish or English. Lecture sessions will be the most important part of the theory section.

 

Seminars

Knowledge of some parts chosen from the contentof the different subjects will have to be searched through autonomous learning by students. It will evaluated as oral presentations in the Seminar sessions and it will also be uploaded as a study material on the Intranet for all students to have access. Oral presentations in English will be positively valued.

The group will be divided into two subgroups (maximum 30 students per subgroup), whose lists will be made public at the beginning of the course. There will be 10 sessions of seminars during the course where students will prepare an oral presentation for a chosen self-study (see seminar contents). Presentations in PowerPoint format and a summary of a maximum half-page will have to be sent to the teacher a week before. She/He may suggest changes or modifications during that week that must be included in the presentation.

The oral presentation of the seminar will have a maximum duration of 20 min., with the following scheme:

• Inheritance and epidemiology,

• Clinical (symptomatology),

• Molecular genetics (chromosomal location and gene identification),

• Biochemistry (mutations / allelic variants and genotype-phenotype correlation),

• Diagnosis and therapeutics.

The rest of the time will be devoted to solving doubts, answering questions, raising a debate, etc., where all those attending the seminar will be able to participate.

The oral presentation will be shared among the members of the group (2 students), so that everyone has the opportunity to speak al least for 10 min.

Attendance and accomplishing oral presentations at the Seminars are mandatory for all students, except in cases where there is a documented justification. Active participation of the students in the seminars will be rated, so that it will have an impact on the seminar grade. Lack of attendance will discount a percentage of the seminar mark.

Delivery of clinical cases, short questions or problems

Every 10-12 theory topics a collection of questions that may contain clinical cases, short questions or problems will be delivered through the intranet tool and that will have to be answered back within a short period of time, that will be determined when the questions proposed. Questions will be related to concepts explained in the lectures but also to self-learning topics that must be searched and studied through autonomous learning by the students.

Tutorials

Tutorials will be carried out s requested by students. If the number of requirements is extremely high, especially for midterm exams or the resolution of clinical cases or short questions, up to 2 classroom tutorials would be scheduled and they will be announced on a timely basis through the intranet. The objective of these sessions will be to resolve doubts, review basic concepts, solve problems or clinical cases proposed through intranet short questions, guide on the consulted sources of information and carry out debates on the topics for which there are planned autonomous learning or that have been proposed by the teachers. These sessions will not be lectures nor will be treated new topics from the official content of subjects, but will be sessions of debate and discussion.

Laboratory practices

Three sessions of 4 hours each will be programmed. The hours and laboratories could be checked sufficiently in advance on the intranet of the course and on the website of the BioScience School.

The subject will be taught in small groups of students, in the practice laboratory.

Students will have a Practices Manual before the start of the practical sessions and, where appropriate, a questionnaire that will available on the intranet.

In each practical session, it is mandatory that the student wears: his own gown, lab glasses and the Practices Manual. You also have to bring a notebook, where each student will write down the observations made as well as a permanent marker.

To carry out the laboratory practices, students will work in pairs under the supervision of the professor in charge. At the beginning of each session, the teacher will make a brief theoretical explanation of the content of the practice and the experiences to be carried out by the students.

In order to achieve good performance and acquire the competences corresponding to this subject, it is essential that the student will comprehensively read the Practices Manual, familiarize with the practices that will be carried out in each session, as well as the methodology that will need to be applyied in each case.

 

Annotation: Within the schedule set by the centre or degree programme, 15 minutes of one class will be reserved for students to evaluate their lecturers and their courses or modules through questionnaires.

Activities

Title Hours ECTS Learning Outcomes
Type: Directed      
Laboratory practice 12 0.48 11, 2, 21, 3, 5, 4, 6, 7, 12, 8, 9, 20, 14, 17, 15, 22
Theory lectures 30 1.2 1, 19, 18, 2, 16, 3, 5, 4, 7, 8, 10, 13, 20, 14, 15
Type: Supervised      
Delivery of clinical cases, short questions and problem solving, through the Intranet 3 0.12 2, 21, 16, 3, 5, 4, 6, 7, 12, 8, 9, 20, 14, 17, 15, 22
Seminars 10 0.4 1, 19, 18, 11, 2, 21, 16, 3, 5, 4, 7, 12, 8, 10, 13, 20, 14, 17, 15, 22
Tutorials 5 0.2 2, 21, 16, 3, 5, 4, 7, 8, 9, 13, 20, 14, 17, 15
Type: Autonomous      
Delivery of clinical cases, short questions and problem solving, through the Intranet 12 0.48 11, 2, 21, 16, 3, 5, 4, 6, 7, 8, 9, 13, 20, 14, 17, 15
Preparation of seminars 24 0.96 11, 2, 21, 16, 3, 5, 4, 7, 8, 9, 13, 20, 17, 15, 22
Study 48 1.92 11, 2, 21, 16, 3, 5, 4, 7, 8, 9, 13, 20, 14, 15

Assessment

The evaluation of this course will have the format of continous assessment with a recovery final test. The objective of the continuous assessment is to encourage the students' effort throughout the semester, allowing them to monitor their degree of follow-up and understanding of the subject. The final test of recovery is used to verify that the student has reached the necessary degree of integration of knowledge of the course.

Theory (6/10)

Individual assessment through:

• Two midterm tests with short questions.

• A final proof of re-assessment that will have the same format as the midterm exams and will cover the entire subject of the course. This exam is intended for students who have not previously passed midterm tests. To be eligible for the retake process, the student should have been previously evaluated in a set of activities equaling at least two thirds of the final score of the course or module. Thus, the student will be graded as "No Avaluable" if the weighthin of all conducted evaluation activities is less than 67% of the final score.

The date, time, place of the tests can be consulted sufficiently in advance on the Intrnanet of the course or on the website of the BioSciences School.

 

Delivery of answers for clinical cases, problems and continuous assessment tests through the intranet (1/10)

There will be a maximum 2 deliveries

Seminars (1.5/10)

Assessmentof teamwork:

The obtained mark will be the same for all the members of the team, as long as all of them have prepared and exhibited in an equivalent manner. The involvement of the different members of the team will be verified through a small individual and confidential survey. Seminars presentation in English will recieve an extra point in the final seminar's mark.The participation (questions, interventions, debate, etc.) of the students attending the seminars will be positively valued. The presentation of the seminars in English will receive 1.5 extra points in the seminar mark. There will be a question about the content of the seminars in the 2nd midterm test as well as in the final proof of re-assessment.

Evaluation of individual learning:

The two sections (Theory and Seminars) are inseparable, so that the student must participate, and be evaluated, in both to overcome the matter. Therefore, participation in the seminars is mandatory, both on the day of the oral presentation and the attendance at the other seminars of the peers. Students missing more than 40% of programmed sessions will be graded as "No Avaluable". The active participation of the students in the seminars will have an impact on the seminar grade. A selection of seminars, which are also part of the contents of the subject, will be evaluated with a question to the examination of the 2nd midterm exam, and will contribute in a proportional way to the mark of this exam. The recovery exam will also include a seminar question. 

Laboratory practices (1.5/10)

Attendance to laboratory practice sessions is mandatory. Any delay or lack of assistance must be documentally justified. In order to be abletopass the course, at least 80% of the scheduled sessions are required.

Students must write a report where they will present and discuss the results obtained during the practical sessions. This work will represent 75% of the practice mark. The date of delivery of the dossier will be fixed by the teacher. In addition, the practical ability of each group of students will be evaluated taking into account the results obtained, which will represent 25% of the practical note.

The assessment will be based not only on the elaboration of the practices dossier but also on the attitude and aptitude of the student during the sessions.

Students who do not have a practical grade score of 5 or more can not pass the course.

In the case of not passing the course and from the second enrollment, the repeating students with a practice mark equal to or greater than 5, will not have to attend the sessions of practices nor theyhave to evaluated of practices. This exemption will be maintained for a period of two additional tuition fees.


Requirements to pass the course

It is necessary to obtain a final grade equal to or greater than 5 to pass the course, either through midterm or through the final re-assessment test. In order to be able to do the average between midterm tests, without going to the final re-assessment test, the student will have to obtain in the two midterm exams a qualification equal or higher than 4.5. The topics corresponding to the partial theory tests with a qualification of less than 4.5 will be evaluated in the final re-assessment test, where it will be also necessary to obtain a qualification equal or higher that 4.5 of each midterm topics to be able to average with the scores of the rest of the activities. However, those students who have passed the partial tests of theory and want to improve their qualification may choose to attend to the final test of re-assessment for the totality of the subject or only one of the midterm exams. The student who is attending a re-assessment exam is resigning the partial/s scores.

The students from a second enrollement of the course will not have to carry out the educational activities or the evaluations of those activities passed with a score higher than 5, like the seminars and the delivery of questions of continous assessment.

The student will obtain the "No avaluable " qualification if any of the two assumptions are given: 1) The number of assessment activities carried out has been less than 67% of those programmed for the course. 2) The evaluation of all the assessment activities carried out does not allow to achieve the global rating of 5 in the event that it had obtained the maximum grade in all of them.

 

 

 

 

Assessment Activities

Title Weighting Hours ECTS Learning Outcomes
Attendance, attitude, aptitude and laboratory work dossier 15% 0 0 11, 2, 21, 3, 5, 4, 6, 7, 12, 8, 9, 20, 17, 15, 22
Delivery of clinical cases, short questions and problem solving, through the Intranet 10% 1 0.04 11, 2, 21, 16, 3, 5, 4, 6, 7, 8, 9, 13, 20, 14, 17, 15
Oral presentation and participation in seminars 15% 1 0.04 1, 19, 18, 11, 2, 21, 16, 3, 5, 4, 6, 7, 12, 8, 9, 10, 13, 20, 14, 17, 15, 22
Theory midterm individual exams 60% 4 0.16 1, 19, 18, 11, 2, 16, 3, 5, 4, 7, 8, 9, 10, 13, 20, 14, 15, 22

Bibliography

Basic Bibliography

Oliva, R. Genética Médica. 3ª ed. Universitat de Barcelona. Barcelona, 2004.

Valle, D. L., Antonarakis, S., Ballabio, S., Beaudet, S.L., Mitchell, G.A. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, Inc. New York, 2019.

Strachan T, Goodhip J, Chinnery P. Genetics and Genomics in Medicine. Garland Science, Taylor & Francis Group. NY & London, 2015.

Strachan, T., Read, A.P. Human Molecular Genetics 5th Edition. Garland Science, Taylor & Francis Group. London, 2019.

Sudbery, P. Genética molecular humana. 2ª ed. Pearson Educación, Madrid, 2004. Spanish version of Human molecular genetics, 2nd ed. Pearson Education, 2002.

Complementary Bibliography

Amstrong L. Epigenetics. Garland Science. New York. 2014.

Jorde, L.B., Carey, J.C., Bamshad, M.J., White, R.L. Genética Médica. 3ª ed. Elsevier. Madrid, 2005.

Lewin, B. Genes VIII. Pearson Prentice Hall. Upper Saddle River, 2004.

Matthes, D.J. Problems and solutions for Strachan & Read'sHuman Molecular Genetics2. Bios Scientific Publishers.Oxford, 2001.

Nussbaum, R.L., McInnes, R.R., Willard, H.F. Thompson & Thompson Genetics in Medicine with clinical case studies. 6th ed. W.B. Saunders. Philadelphia, 2004.

Weinberg, R.A. The Biology of Cancer. 2nd ed. Garland Science. New York. 2014.

Internet addresses

On-line Mendelian Inheritance in Man (OMIM). http://www.ncbi.nlm.nih.gov/Omim/

Molecular Medicine MedPulse®http://www.medscape.com/px/splash

Medline Plus®http://www.nlm.nih.gov/medlineplus/

Genes and Disease. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=gnd.TOC&depth=2

Software

None.