PD:Malalties Genètiques Mendelianes i Complexes

Teaching plan for the course unit

General information

Course unit name: Mendelian and Complex Genetic Diseases

Course unit code: 568777

Academic year: 2021-2022

Coordinator: Roser Corominas Castiñeira

Department: Department of Genetics, Microbiology and Statistics

Credits: 5

Single program: S

Estimated learning time

Total number of hours 125

Face-to-face and/or online activities

- Lecture	Face-to-face	11
- Problem-solving class	Face-to-face	4
- IT-based class	Face-to-face	6
- Seminar	Face-to-face	10

Supervised project

Independent learning

Competences to be gained during study

Basic competences
CB6 - Possess and understand knowledge that provides a basis or opportunity to be original in the development and / or application of ideas, often in a research context.

CB7 - That students know how to apply the knowledge acquired and their ability to solve problems in new or little-known environments within broader (or multidisciplinary) contexts related to their area of study.

CB8 - That students are able to integrate knowledge and face the complexity of making judgments based on information that, being incomplete or limited, takes into account social and ethical responsibilities linked to the application of their knowledge and judgments.

CB9 - That students know how to communicate their conclusions and the knowledge support them to specialized and non-specialized audiences in a clear and unambiguous way.

CB10 - That students possess the learning skills that allow them to continue studying in a way that will largely be self-directed and autonomous.

General / transversal competences

CG1 - Ability to think critically, logically and creatively. Ability to analyze and synthesize.

CG3 - Ability to work in groups and collaborate with other researchers.

CG4 - In a more academic and generic field, the Master aims to acquire the habit and ability to read and critically interpret scientific publications related to the subject and be able to design, write and defend a research project.

Specific competences

• Understanding the genetic basis of Mendelian and complex disorders, to characterize them properly.

• Capacity to apply the concept of heritability to human traits and diseases.

• Knowledge of and capacity to employ the experimental and analytical approaches (statistical and bioinformatics) used in the study of genetic disorders.

• Awareness and understanding of the open questions on the genetic basis of human diseases.

Learning objectives

Referring to knowledge

For many years, the study of human genetic diseases has focused on chromosomal abnormalities and monogenic disorders, which are rare among the general population. Recently, the study of common disorders, caused by the interaction of multiple genetic and environmental factors, has expanded thanks to the advents in the field of genetic epidemiology, the development of novel tecnologies (genotyping and massive genome sequencing techniques) and of appropriate statistical methods (along with large increases in computing power). The master’s degree in Genetics and Genomics, through the module of Human Genetics, provides a course dedicated to the study of these disorders – a growing field of increasing importance within the health system – and to new experimental approaches to the study of Mendelian diseases.

General Objectives
The main objective of this subject is to provide a general and state of the art vision of the study of genetic disorders, with an emphasis on the most prevalent pathologies among the general population. The course focuses on the genetic basis, the structure (and interactions) and the environmental factors involved in both monogenic and complex disorders. Topics include discussion on basic analytical tools as recombination and association studies. It also reviews new experimental approaches derived from the development of high throughput technologies for large-scale genetic/genomic/transcriptomic analysis. Finally, in a computer session, students will performa a simulation of the genetic study of complex diseases using appropriate bioinformatic tools.

In order to provide a more integrated knowledge in the Human Genetic Specialty, the courses ‘Genetic Diseases, Mendelian and Complex’ and ‘Genetic Diagnose’ have been coordinated, programmed to be performed simultaneously and organized in weekly units that focus on the same topic.

As far as possible, the gender perspective will be incorporated into the development and activities of the subject.

Teaching blocks

1. Week 1: Leveling

* Monogenic diseases. Pedigrees and types of inheritance patterns. Linkage. Mosaicism, penetrance and expressivity, imprinting, anticipation, and other complications to mendelian patterns. Complex diseases. Application examples.

2. Week 2: Rare disorders and Next Generation Sequencing (NGS)

* Strategies to identify genes responsible for Mendelian diseases (including exome/genome/transcriptome sequencing) and molecular pathology. Identifying the disease gene. Positional cloning. Model organisms. Candidate genes. Exome Sequencing for the identification of Mendelian disease genes. DNA and RNA high throughput analyses technologies. Molecular pathology. Functional studies.

3. Week 3: Structural variations (SV)

* Genomic SV. Mechanismes to generate SV. Detection SV. Structural variations and disease. Uniparental Disomies. Mosaicism.

4. Week 4: Genome Wide Association Studies (GWAS)

* Association studies. GWAS. Genotype imputation. Meta-analyses. Intermediate phenotypes. Biomarker, Surrogate endpoint, Intermediate endpoint, and Endophenotype.

5. Week 5: Quantitative genetics

* Family studies of complex traits. Multifactorial, heritability, Polygenic theory. Risk ratio. Twin studies. Complex Segregation Analyses.

Association studies and linkage analysis of complex traits. Linkage. Non-parametric methods of linkage. Affected sib pairs (ASP) analysis.

Evolution and genetic diseases.

6. Week 6: NGS in complex disorders. Precision medicine

* Functional annotation of variants outside gene regions. Single variant association test. Collapsing methods. Common functions/pathways.

7. Practicals

* Computational methods in genome-wide association studies (GWAS) on PLINK: samples quality control, analysis of population stratification based on principal component analysis (PCA), GWAS association study, Manhattan plot and secondary analysis of GWAS results on FUMA (Functional Mapping and Annotation of GWAS)

8. Seminars

* Articles presentations and genetic counselling case study discussion.

9. Symposium on Rare Disorders

* The symposium is focused on the genetic bases of rare disorders. It includes talks from four prestigious researchers focused on the discovery of diseases genetic basis, the past and present genetic diagnose, research studies, including therapeutic approaches and animal models, as well as genetic counseling. At the end there is a round table discussion session. The student will have a complete overview of the state of the art of the particular topic.

Teaching methods and general organization

Face-to-face learning activities

They consist of theory classes, seminars and practical computer classes. It also includes talks by visiting lecturers, specialized in the field.

Independent learning activities

They comprise recommended and further reading, in order to ensure full understanding of the concepts presented in class. A series of problem-solving exercises related to specific case studies must also be completed.

Tutorial sessions

Teachers are available for consultation on any doubts or questions related to the subject, both in person during office hours or at any time via email.

Official assessment of learning outcomes

• 60% Multiple choice and short questions exam.

Exam evaluating the basic concepts explained in class, including questions on the content of lectures given by guest lecturers and the articles presented by other students. The students must have at least 4/10 in this part to pass the course.

• 40% Presentation and discussion on a scientific paper related to one of the course topics.

Reading and study resources

Consulteu la disponibilitat a CERCABIB

Book

Human Molecular Genetics 5th Edition.2019

Tom Strachan and Andrew Read

ISBN: 9780815345893

Human Molecular Genetics 5th Edition.2019