Medical practice is increasingly oriented towards personalized medicine, where the genetic characteristics of every patient are key. Therefore, a solid knowledge of Genetics is essential for the future professionals of Medicine.



The subject of Medical Genetics aims to increase the student's understanding of how genes contribute to human physiology and pathology. In this subject, we deal with the mechanisms that contribute to the development of diseases directly caused by genetic alterations (monogenic or chromosomal), as well as the mode of transmission of these diseases. Other more complex diseases, such as cancer, in which Genetics plays a relevant role, are also studied. During the course, reference is made to the different medical specialties where the knowledge of Genetics is applied. In particular, the genetic aspects of several clinical cases of diseases related to different specialties are discussed.



Genetics can facilitate the integration of knowledge from different areas, and thus, the subject of Medical Genetics is directly related to other subjects of the Degree in Medicine. For example, 3rd year students should have acquired (in 1st and 2nd year subjects, such as Cell Biology, Genetics, and Biochemistry) a basic knowledge of the models of inheritance and transmission of characters, the structure and function of genes, or the regulation of gene expression, which will be reinforced, expanded and contextualized by studying the subject of Medical Genetics. On the other hand, Medical

Genetics is related to other 3rd year subjects, such as Pharmacology (through Pharmacogenetics), as well as to subjects of later years, such as Pathology and Pediatrics (genetic basis of many human pathologies, many of which affect children).



Relationship between the subject of Medical Genetics and professional practice: By observing the total disease burden in the population, an increase in the proportion of genetic diseases can be noted. This is due, on one hand, to our increasing knowledge on the genetic basis of many diseases and, on the other hand, to the fact that the advances in Medicine during the last century have reduced the impact of other types of pathologies. In addition, technological advances make possible

an accurate diagnosis of many diseases based on DNA analysis, and it is expected that gene therapy or replacement of defective genetic material will be a reality in the coming years.



At a time when prevention is one of the primary objectives of current medical practice, Genetics is an indispensable tool to better understand the basis of the pathological process, and therefore to devise useful prevention strategies. Furthermore, personalized medicine seeks to find the best treatment for each patient and, to this end, it is necessary to take into account the individual characteristics of each person, including the genes involved in their disease. The doctor of the

future will work in this complex scenario, where Genetics and Genomics will be of paramount importance. The subject of Medical Genetics provides the fundamental tools to the students, so that they can deepen in the diseases specific to each of the professional specialties of Medicine.

COMPETENCIES (MODULE)

To draw and interpret pedigrees; to calculate the risk of recurrence and to recognize human phenotypical features: to understand the structure and regulation of the human genome; to understand the molecular basis of human genetic diseases, as well as the origin and consequences of chromosomal alterations; to set up the experimental approaches required for the analysis or genetic diagnosis of a pathology; to know how to use the tools for the analysis of human genetic variability.



COMPETENCIES (TRANSVERSAL)

CT1. Instrumental. Analysis and synthesis capability; organization and planning capability; oral communication; problem solving.

CT2. Personal. Self learning. Use of databases with information relevant in the field of Medical Genetics.

CT3. Systemic. Team work capability. Work ethics, motivation, self-demand.



LEARNING OUTCOMES (LO)

LO1. To adequately solve complex problems related to the inheritance of diseases as represented in pedigrees.

LO2. To establish the relationships between human genome alterations and human pathologies, in order to use such alterations as markers for diagnosis, prognosis and targeted treatment.

LO3. To select, in a well-argued manner, the cytogenetic or molecular techniques best suited for the diagnosis of different genetic pathologies.

LO4. To explain the features and consequences of a genetic disease, in a manner that is both correct and understandable for either health professionals or patients.

Topic 1: Medical Genetics in the context of health: medical dimension of the advances in Human Genetics.



Theoretical-practical content:

Genetics as an integrative element in the training of a physician. The importance of genetics in the medical profession.

The effects of Genetics on human health at different stages of life. Relationship of Genetics with other Medical specialties.

Genetics in personalized medicine. New genetic technologies in clinical practice.



Topic 2: Use of molecular tools and techniques in the clinical diagnosis of genetic diseases.



Theoretical-practical content:

Informatics tools for use in Medical Genetics. Obtaining genomic information. Genomic browsers (Ensembl) and databases (OMIM, GeneReviews, Genetic Testing Registry).

PCR: polymerase chain reaction. Design of primers for PCR (exercise). Techniques for mutation analysis: hybridization,

Sanger sequencing, NGS (next generation sequencing).

Techniques for the analysis of gene expression at the level of RNA (RT-PCR, expression microarrays) and protein (immunoblot, immunohistochemistry).



Topic 3: Pedigree drawing and Population Genetics: Genes in families and populations. Monogenic and multifactorial inheritance. Pedigree analysis and calculation of the risk of recurrence. Allelic and genotypic frequencies.



Theoretical -practical content:

General organization of the human nuclear and mitochondrial genome.

Genes: structure, expression and regulation. Protein-coding genes and non-coding RNA.

Repetitive DNA. Alu Sequences, microsatellites.

Epigenetics: Histone modifications and DNA methylation. Methods to study DNA methylation.

Importance of the family history in medicine. The pedigree as a fundamental tool for the study of family history. Inheritance patterns of monogenic diseases. Rules, tools and procedures to calculate the risk of recurrence. Limitations and problems.

Population Genetics. Allelic and genotypic frequencies. Hardy-Weinberg Law. The Importance of Population Genetics in Medicine: carrier frequency, human groups with high prevalence of genetic disease.



Topic 4: Effect of chromosomal and genetic alterations on genetic diseases: study of human chromosomal abnormalities. Models of molecular alterations that cause disease. Genotype-phenotype correlation.



Theoretical-practical content:

The human chromosomes and their analysis. Karyotype and ideogram. Classical and molecular cytogenetic techniques (FISH, CGH and MLPA). Origins and clinical consequences of numerical and structural chromosomal abnormalities.

Molecular pathology: classification of mutations and clinical consequences. Loss and gain of function. Cancer and congenital errors of metabolism.

Specific nomenclature in Molecular pathology and Cytogenetics.



Topic 5: Applications of Genetics in Clinical Practice: Genetic counselling. Fundamentals and applications of Pharmacogenetics and Gene Therapy.



Theoretical-practical content:

Criteria for requesting a genetic test, interpretation of results and communication to the patient. The process of Genetic counseling.

Pharmacogenetics: genetic variability and drug metabolism.

Gene therapy. History, objectives and challenges. Methodological basis: vectors and procedures in vivo or ex vivo.

Achievements and problems.

Topic 1: Medical Genetics in the context of health: medical dimension of the advances in Human Genetics.



Methodology and teaching modalities:

Master class (Lecture). (1 hour)

Conferences by professionals of Genetics in the health field. (2h)



Topic 2: Use of molecular tools and techniques in the clinical diagnosis of genetic diseases.



Methodology and teaching modalities:

Master classes (Lectures). (6h)

Laboratory Practice: DNA extraction and PCR amplification. (4h)

Computer Practices: Practical exercise: design of PCR primers. (4h)

Genomic databases: genes and diseases (4h)

Classroom Practices (Problem solving): Diagnosis by Molecular Techniques (6h)

Problem-based learning: Seminars: (1h) Management of a family with a genetic disease - i) search for information



Topic 3: Pedigree drawing and Population Genetics of: Genes in families and populations. Monogenic and multifactorial inheritance. Analysis of pedigrees and calculation of the risk of recurrence. Allelic and genotypic frequencies.



Methodology and teaching modalities:

Master Class (Lecture). (1 hour)

Classroom Practices (Problem solving): Pedigree Analysis and Disease Inheritance (6h)

Problem-based learning: Seminars: (1h)

Management of a family with a genetic disease - ii) pedigree analysis and risk calculation



Topic 4: Effect of chromosomal and genetic alterations on genetic diseases: study of human chromosomal abnormalities. Models of molecular alterations that cause disease. Genotype-phenotype correlation.



Methodology and teaching modalities:

Master Classes (Lectures). (6h)

Classroom practices: Use of nomenclature (2h)

Guided discussion of clinical cases (2h)

Classroom practices (Problem solving): Results of molecular and cytogenetic techniques (6h)

Laboratory practice: Preparation and observation of human karyotype. (4h)

Problem-based learning: Seminars: (1h)

Management of a family with a genetic disease - iii) relationship between the genetic alteration and the clinical consequences



Topic 5: Applications of Genetics in Clinical Practice: Genetic counselling. Fundamentals and applications of Pharmacogenetics and Gene Therapy.



Methodology and teaching modalities:

Master Classes (Lectures). (6h)

Classroom Practice: Ethics and Genetics -Reading and discussion of articles (2h)

Preparation and presentation of seminars

Problem-based learning: Seminars: (2h)

Management of a family with a genetic disease - iv) presentation of the case to the group and communication to the family (therapeutic options and genetic counseling)

• Continuous Assessment System
• Final Assessment System
• Tools and qualification percentages:
  • Written test to be taken (%): 45
  • Realization of Practical Work (exercises, cases or problems) (%): 15
  • Team projects (problem solving, project design)) (%): 30
  • Exhibition of works, readings ... (%): 10

It is mandatory to perform all the tests, and obtain a mark of at least 50% in each one of them.



1.- Theoretical evaluation (written test)



Criteria: The student correctly answers theoretical questions and adequately solves practical problems(pedigree analysis, interpretation of genetic diagnostic techniques and chromosomal analyses). He/she properly uses professional terminology (including nomenclatures for mutations and chromosomal alterations).



Tools: written test: Three theory questions and two problems / practical exercises.



2.- Practical evaluation (Realization of practices - exercises, cases or problems)



Criteria: The student correctly performs laboratory practices, properly manages experimental equipment and materials, and is capable of interpreting the results. He/she is able to extract relevant information using computer tools and Genetics databases.



Tools: Supervision of laboratory practical sessions. Report of computer practice sessions.



3.- Continual assessment (teamwork, problem solving and project design, presentation of works, paper discussion...)



Criteria: The student attends to classes and participates actively. He/she works autonomously, and addresses the problems raised in previous classes. He/she makes contributions to during teamwork exercises (seminars and group exercises). He/she asks questions and makes interesting comments in the classroom. He/she collaborates in the learning of his/her classmates. The seminar presentation (both preliminary rehearsals and the final presentation) contains all the relevant information and

it is presented in a correct and interesting manner. The slides are well designed. In his/her presentation, the student integrates and contextualizes correctly the concepts explained in theoretical sessions, and he/she respond correctly to questions posed by the teacher or his/her classmates. The student uses the terminology appropriate to each situation (colleagues and patients).



Tools: Observation of the student's attitude in the classroom and the dynamics of work during the preparation of the seminar and in tutorial sessions.



Deliverables: seminar summaries, solved exercises and problems raised in class to

evaluate autonomous work. Tutorial sessions (at least 3), report and public presentation (10 min) of a seminar on a genetic disease prepared during the course.



Students who wish to be evaluated through a final evaluation system must communicate their renounce to continual assessment by writing to the lecturer responsible for the subject. This communication should be made within 9 weeks after the beginning of the semester, in accordance with the official calendar of the Center.



The final evaluation will consist on a written test in which all the learning outcomes of the subject will be evaluated. Not sitting the written test will imply refusing the exam call, and it will be officially recorded as not taken, or "No presentado", for students subject to both continuous or final evaluation.



During the evaluation tests, the use of books, notes, as well as telephones, electronic equipment, computers or other devices is strictly forbidden. Only a calculator is allowed. In case of dishonest or fraudulent practice, the provisions of the protocol on academic ethics and prevention of dishonest or fraudulent practices in the evaluation tests and academic works at the UPV / EHU will be applied.



Not sitting the written test will imply refusing the exam call, and it will be officially recorded as not taken, or "No presentado", for students subject to both continuous or final evaluation.

The extraordinary examination call will be carried out through a final evaluation system. It will consist on a written test in which all the learning outcomes of the subject will be evaluated. The mark in the test will determine 100% of the final mark.



During the evaluation tests, the use of books, notes, as well as telephones, electronic equipment, computers or other devices is strictly forbidden. Only a calculator is allowed. In case of dishonest or fraudulent practice, the provisions of the protocol on academic ethics and prevention of dishonest or fraudulent practices in the evaluation tests and academic works at the UPV / EHU will be applied.



Not sitting the written test will imply refusing the exam call, and it will be officially recorded as not taken, or "No presentado", for students subject to both continuous or final evaluation.

Basic bibliography

-New Clinical Genetics 4th Ed Andrew Read and Dian Donnai ed Scion 2021 ISBN 9781911510703

-Genetics in Medicine. 8thEd. W.B.Nussbaum, R.L., McInnes, F.R. & Willard, H.F. 2015. Elsevier. ISBN 9781416030805

- Human Molecular Genetics 4th Ed. Tom Strachan & Andrew P. Read. 2011. Garland Science. ISBN 9780815341499

In-depth bibliography

- Lewis, R.2003. Human Genetics. Concepts and Applications. 5th ed. McGraw Hill. Boston. ISBN 007246268-X
- Jorde, Carey, Bamshad & White. 2010. 4th ed Medical Genetics 3rd edition. Mosby. ISBN: 0323020259
- Turpenny P, Allard S. 2012 Emery's Elements of Medical Genetics 14th ed.
-Pierce, B.A. Genetics Essentials: Concepts and Connections. 2015 (3rd Ed.). W. H. Freeman and Co. ISBN:1464190755

Journals

-Nature Genetics Reviews
-Current opinion genetics

Web addresses

- On any mendelian phenotype:
http://www.ncbi.nlm.nih.gov/omim/
http://www.geneclinics.org/
- Specific for cytogenetics and chromosomal abnormalitites:
http://www.slh.wisc.edu/cytogenetics/index.php