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DiagnÒstic genÈtic (GENETICS AND NEUROSCIENCES) 2.5 Credits

Objectives: This module tries to give an in-depth view on the biological implications of genome variation, mainly focusing on neurosciences and specifically in neurological disorders. It will give a fresh view to many aspects of present biology and biomedicine, including genetic bases for complex diseases, evolutionary medicine, functional analysis, pharmacology, structural biology, systems biology, comparative genomics and many others.

LECTURES

Genome structure and variation

1. From genes to genomes: organization from DNA sequences to chromosomes. The gross structure of the genome. Coupling chromosomal and sequence organization and evolution. Eukaryotic and prokaryotic chromosomes. Isochores, CG content and distribution of genes.

2. Genome variation: SNPs, Indels, STRs, copy number, segmental duplications and chromosome variation. The measure of the genetic variation at the DNA level: polymorphisms, heterozygosity, number of segregating sites, nucleotide diversity, ? estimators.

3. The meaning and measure of the genetic differences between populations. Measure and representation of genetic variation. Partioning FST (AMOVA), trees and 2D representations.

Dynamics of variation

4. Genetic variation dynamics in populations. The general framework of population genetics. Hardy-Weinberg equilibrium. Factors that alter the equilibrium: mutation, selection, drift and migrations

5. The biological meaning of mutation. Mutation and disease. Evolutionary changes in nucleotide sequences. Estimating the number of nucleotide substitutions between DNA sequences. Rates and patterns of nucleotide substitution.

6. Genetic drift and its effects. Effective population size. Examples of drift in humans and other organisms. The Wrigth-Fisher model.

7. Selection. Types of selection: purifying, balancing and positive selection. The neutral theory of molecular evolution.

8. Gene genealogy and coalescent theory. Departures from neutrality: basic tests from sequence data. Detecting natural selection from polymorphism and divergence data.

9. Recombination and linkage disequilibrium: concept and measures. Haplotypes and their estimation. Recombination hotspots.

10. Linkage disequilibrium and the genetics of complex traits. Power. TagSNPs, informativeness and portability. Whole genome scans: promises and pitfalls.

Applications for the genetic analysis of complex disease

11. The genetic bases of diseases. Family aggregation and linkage analysis.

12. The genetics of common diseases. The common variant common disease hypothesis. Use of haplotypes and of functional networks. Application of Gene Ontology.

13. Applications to linkage mapping and association studies. Whole Genome Scans and the present and future of the study of the genetic bases for common diseases. The CeGen as a service platform.

14. Genetic diagnosis and gene therapy. Genetic counseling. Genetic screening in populations.

15. The Human Genome Project as a paradigm of sequencing genomes. Resequencing projects. The HapMap and ENCODE projects. Private initiatives: Perlegen, Celera, Gennaissance, DeCode Genetics. Biobanks and P3G. Ethical aspects

SEMINARS (36 hours)

These are additional lectures with subjects related to the main topics. Some of them could be new topics and others are in depth views of the lectures.
Some lectures, including problems, use of software and paper discussion is directly related to human genetics and its relationship to neurological diseases, including:

1.- The genetic and clinical implications of trinucleotide repeat expansions

2.- The analysis of mendelian disorders. Lod scores and the use of Whole Genome Scans

3.- The analysis of complex diseases: the case of Alzheimer disease

4.- The analysis of complex traits: the case of psychiatric disorders.

5.- The genetic analysis of neuronal functions: adaptation, novelty and conservation.

- Specific software for genetic analysis of mendelian disorders

- There are many papers relevant in this area, to be chosen

- Cinema debate: comments on a selected film
These could include:
- GATACA

6.- Bioinformatic applications, including:
- Sequence databases, BLAST and standard procedures
- PHASE
- SNPator
- Linkage and other fundamental programs
- Others….

LECTURERS

Unitat de Biologia Evolutiva: Jaume Bertranpetit, David Comas, Francesc Calafell, Arcadi Navarro, Elena Bosch