2010-2011 academic year

Clinical Genetics (20424)



Qualification/course: bachelor's degree in Human Biology

Year: third

Term: first

Number of ECTS credits: 4 credits

Student commitment: 100 hours

Teaching language or languages: Spanish/Catalan

Teaching staff: the subject coordinator is Dr. Luis Pérez Jurado. Drs Victoria Campuzano, Xavier Estivill and Miguel del Campo will also participate in the teaching, and Olaya Villa, Ivon Cuscó and Clara Serra will be involved in the practical sessions.



1. Introduction to the subject

Genetics forms part of virtually all the fields of biology; it is in a phase of rapid growth and presents numerous implications and applications. In medicine, genetics is the basis for understanding the inheritance of certain diseases, providing counselling for families, and for undertaking scientific research aimed at an understanding if the molecular mechanisms of diseases that enables the development of new diagnostic methods and therapeutic approaches. The biotechnology industry is growing very quickly, using genetic tools to develop pharmaceutical and diagnostic products, among others. Genetics is also routinely applied for forensic purposes, in the identification of individuals or to determine very low levels of contamination in organisms.

Individual genetic variations are responsible for molecular and biochemical variability in individuals. This variability is partly due the variable composition of the DNA sequence and its chemical modifications. These mutations contribute to this variability, but not all mutations are biologically significant. Some may be harmful, others may be neutral and others can provide evolutionary advantages. Without variation and without any mutations, there would be no diversity and consequently no evolution. The variable phenotype in human beings is the result of interaction between genes and the environment, which vary in its degree and over time. Variations have a molecular expression in the sequence, structure and function of regulating proteins and nucleic acids. They are also responsible for disease, which from this point of view involves an imbalance in the normal homeostatic relationship between the genome and the environment.

This course is an opportunity for students to come into contact with the field of genetics, focusing on its application in the study of human physiology and pathology. As is the case in professional practice, the subject will be integrated and coordinated with related areas. Genetics and genome studies are vital for defining solid scientific foundations for health professionals.



2. Competences to be acquired

Students should:

1. Understand the genetic basis of human pathology and variability, and be aware of the terminology.

2. Understand the medical relevance of genetic examination and the family history, and the psychological and social importance of genetic data.

3. Be aware of interactions between genes and the atmosphere in susceptibility to disease.

4. Be aware of the ethical, legal and social aspects, risks and benefits of research and medicial application of genetic technology.

5. Be able to work with the various sources of written and telematic information for an in-depth study of specific aspects of genetics.

6. Be able to integrate the concepts of genetics with the other biomedical disciplines.

7. Be able to apply the knowledge acquired to their professional work in the future and to genetic diagnosis, prediction of empirical risk and genetic counselling of families, and to biomedical research.



3. Contents

Theory classes

Subject 1

Introduction to genetic medicine. Morbidity and mortality of genetic diseases. Mendelian inheritance in man. Construction of genealogies. Segregation analysis. Bayes theorem.

Subject 2

Non-Mendelian inheritance. Somatic and germinal mosaicism. Cytoplasmatic inheritance. Gametic imprinting. Genetic anticipation. Biology of gemelarity. Diagnosis of zygosity.

Subject 3

Examination in medical genetics. Dysmorphology. Patients with congenital disorders.

Subject 4

The human genome and its complexity. Genes and chromosomes. Functional elements and repetitive sequences. The Genome Project. Mapping human genes. Genome analysis.

Subject 5

Genetic recombination and linkage analysis. The "lod score". Production of genetic maps. Linkage imbalance and transmission imbalance. Quantitative trait loci (QTLs). Parametric and non-parametric analysis, association.

Subject 6

Identification and isolation of genes responsible for diseases. Functional cloning. Positional cloning / Positional candidate. New technologies and genomic strategies.

Subject 7

Molecular basis of monogenic diseases: autosomal recessive, dominant and X-linked. Dominance mechanisms. Examples of various models. 

Subject 8

Genetic heterogeneity in monogenic diseases. Locus heterogeneity. Allelic heterogeneity. Neurosensory diseases.

Subject 9

Molecular basis of genetic anticipation. Clinical relevance and molecular mechanisms. Fragile X syndrome, Huntington's chorea and spinococerebral ataxia.

Subject 10

Mitochondrial inheritance and its disorders. Homoplasmy and heteroplasmy. Mitochondrial encephalomyopathies Ageing and mitochondrial DNA.

Subject 11

Cytogenetics I. Chromosome alterations and cytogenetic nomenclature. Diseases with a chromosomal basis. Autonomous and gonosomal aneuploidies. Structural alterations: reciprocal and Robertsonian translocations. Production and segregation mechanisms.

Subject 12

Cytogenetics II. Structural alterations: Insertions, duplications, deletions, uniparental disomies. Recurring genomic mutations. Segmental duplications. Genomic imprinting. Regulation and pathology.

Subject 13

Genetic bases of the human sexual determination and differentiation and its pathology. Genetic control of sexual determination.

Subject 14

Genetic bases of complex diseases. Multifactorial diseases. Biological basis for conduct. Genetic psychiatry.

Subject 15

Genetic bases of the response to medicines and drugs. Individual susceptibility. Pharmacogenetics and pharmacogenomics.

Subject 16

Genetics of cancer. Cancer as a genetic somatic disease. DNA repair genes, oncogenes and suppressor genes. Cytogenetics of cancer. Familial cancer.

Subject 17

Genetic diagnosis. Direct diagnosis and indirect diagnostic. Pre-symptomatic diagnosis and predisposition. Mass screening.

Subject 18

Genetic counselling. Prenatal diagnosis. Pre-implantation diagnosis with assisted reproduction.

Subject 19

Treatment of genetic diseases. Development of specific drugs. Gene and cell therapy.

Subject 20

Genomic medicine and predictive medicine. Personalised medicine. The present and the future.



Problem-solving and seminars

PRO1. Genealogies and genetic linkage (2 h)

PRO2. Empirical risk. Counselling. Bayes theorem (2 h)

PRO3. Cytogenetics and molecular cytogenetics (2 h)

PRO4. Molecular genetics, cancer diagnosis (2 h)

SEM1. Ethical aspects of research and diagnostic and therapeutic applications of genetic technology (2 h)


Programme of practical sessions

PRA1. Karyotyping and molecular cytogenetics (4 h)

PRA2. (Computing) Experimental design in diagnostic genetics. Computer resources (2 h)

PRA3. Indirect molecular diagnosis. Genetic linkage (4 h)

PRA4. Direct molecular diagnosis (4 h)


4. Assessment

The main system of assessment will be by means of a written examination, which will consist exclusively of multiple choice questions on theoretical subjects and practical activities, including solving genetic problems. This examination will account for 60% of the final mark, and a partial mark of over 4/10 must be obtained for the other assessments to be taken into consideration.

25% will come from the continuing assessment in problem-solving seminars and assessment of the practical session notebook, while the remaining 15% will depend on the individual practical exercise.


5. Bibliography and teaching resources

5.1. Basic bibliography

There is no ideal single textbook that over the entire programme of the subject exactly. Summaries of the content of each subject, and the problems to be solved (and subsequently their solutions) will be provided in the Campus Global.

1. STRACHAN T, READ AP (2004) Human molecular genetics 3. Garland Science, New York.

2. RIMOIN DL, CONNOR JM, PYERITZ RE, KORF BR (ed.) (2002) Emery and Rimoin s principles and practice of medical genetics, 4th ed. Churchill Livingstone, London.

3. JORDE, LB; CAREY, JC; BAMSHAD, MJ; WHITE, RL (2005) Medical Genetics. 3rd ed. Mosby.

5.2. Complementary bibliography

HESLOP-HARRISON JS, FLAVELL RB (1993) The Chromosome. Bios Scientific Publishers.

LACADENA JR (1996) Citogenética. Editorial Complutense. Madrid.

WAGNER RP, MAGUIRE MP, STALLINGS RL (1993) Chromosomes. A synthesis. Wiley-Liss.

VISERAS, E (1998) Cuestiones y problemas resueltos de Genética. Pub. University of Granada, Granada.

5.3. Teaching resources

Compenium of resources produced by the library:

http://www.upf.edu/bibtic/bio/biogene.html

Teaching resources on the human genome, cytogenetics and medical genetics:

http://www.genome.gov/Education/

http://www.tokyo-med.ac.jp/genet/mfi-e.htm

http://medgen.genetics.utah.edu

http://www.nchpeg.org/

Register / encyclopedia of genetic diseases and molecular information:

OMIM: http://www.ncbi.nlm.nih.gov/OMIM

ORPHANET: http://www.orpha.net

Societies

Spanish Human Genetics Association: http://www.aegh.org/

American Society of Human Genetics: http://www.ashg.org/

European Society of Human Genetics: http://www.eshg.org/



6. Methodology

The course consists of a theoretical syllabus that includes twenty areas covering medical genetics. To provide the maximum encouragement for students' active learning, weekly genetics problems related to the subject will be posed, based on models used in the theory classes. These problems should be solved individually or in groups and they will subsequently be debated in class discussions.    

There is also a programme of practical sessions which covers experimental and design aspects of the various areas of genetics in order to consolidate the knowledge gained in theory classes. Practical sessions take place in groups of fifteen students. Each practical session will take place over two weeks during which each group will do the session on one day, so that all the groups will carry out the practical session at the same time, which will coincide with the theory classes. As well as completing the practical session script which contains specific questions, students must also complete an independent individual practical exercise.


7. Programme of activities

Theory classes: twenty lectures lasting 45-50 minutes each.

Problem-solving and seminars: five 2-hour sessions, 1 hour of group work and 1 supervised hour to complete the solution.

Practical session programme: three laboratory practical sessions of 4 hours each and one 2-hour biocomputing practical session.