03553 - Medical Genetics

Learning outcomes

At the end of the course, the student possesses the knowledge and methodological tools for studying human genetic diseases; knowledge of hereditary mechanisms in humans; issues related to the diagnosis of genetic diseases; basic notions of some molecular and cellular analysis techniques; the ability to acquire specific skills regarding their selection and applicability to biomedical problems; understanding the significance of studying modern genetics and knowledge on fundamental analysis tools within the professional skills characterizing the profession.

 

Course contents

Introduction to the course: medical genetics and its scope – glossary and definitions – structure and function, operational concepts – definition and relationship between genotype and phenotype – wild-type allele and mutant allele – dominant transmission and recessive transmission of traits. Reconstitution of pedigrees and risk assessment. Symbolism of pedigrees, product vesrus sum rule for transmission probability calculations.

Genetic diseases: classical transmission modes – autosomal recessive transmission and examples (cystic fibrosis) – autosomal dominant transmission and examples (achondroplasia) – X-linked transmission and examples (Duchenne muscular dystrophy). Exceptions to Mendelian inheritance: concepts of clinical heterogeneity and genetic heterogeneity. Triplet repeat diseases and examples: Huntington's disease – concepts of anticipation, premutation; Fragile X syndrome – role of methylation and X inactivation. Non-canonical modes of transmission. Examples and concepts of imprinting, uniparental disomy, and epigenetics (Angelman syndrome and Prader-Willi syndrome) – Mitochondrial inheritance: maternal heredity, polyploidy (heteroplasmy and homoplasmy), threshold effect – Concepts of penetrance and variable expressivity with examples.

Chromosomal pathology: structural and numerical aberrations of chromosomes with clinical examples. Trisomies and monosomies of autosomes and sex chromosomes. Balanced and unbalanced translocations: reproductive outcomes of carriers of balanced translocation. Robertsonian translocations: mechanisms and reproductive issues. Classical and molecular cytogenetic techniques. FISH and its applications. Comparative genomic hybridization (CGH) techniques, technical aspects, and its applications in diagnostics.

Multifactorial diseases, empirical risk calculation. The role of polymorphisms. Studies on twin cohorts (concordance and discordance).

Approaches to disease gene research. Association studies. Polymorphic genetic markers. Next-generation sequencing. Variants prioritization

Post-consultation genetic tests: diagnostic, presymptomatic, predictive, and prenatal.

Brief overview of DNA analysis techniques and mutational screening: PCR, Real-Time PCR. Post-PCR analysis: restriction enzymes, Sanger sequencing. Basics of next-generation sequencing - exome sequencing. Concept of gene panel analysis. Microsatellite analysis. Use of genetic and non-genetic databases: NCBI, Pubmed, OMIM, gnomAD, Ensembl. Bioinformatic tools for predicting protein variant pathogenicity: polyphen2. Bioinformatic tools for designing and validating primers: primer3. Genomic browsers: Ensembl and UCSC.

 

Readings/Bibliography

Thompson & Thompson - Genetics in Medicine. Idelson-Gnocchi publisher.

Tobias, Connor, Ferguson-Smith - Fundamentals of Medical Genetics. Pearson publisher.

Read A. Donnai D. - Clinical Genetics. 2007 Publisher: UTET MEDICAL SCIENCES

The use of the text is optional.

 

Teaching methods

Face-to-face lectures with PowerPoint presentations.

 

Assessment methods

Written exam with 18 multiple-choice questions, including:

8 questions with a score of 1.5

4 questions on methodology in medical genetics with a score of 2.0

6 exercises with a score of 3.0

Maximum overall score: 38 points

Only one correct answer. Penalty -0.5 points for each wrong answer. 22 points required to pass the exam.

The use of a calculator is not allowed.

In the case of an online exam, if there is a connection failure during the test, the exam will be converted to an oral exam.

 

Teaching tools

Students will be provided with electronic format presentations used during the lectures after each lesson.

 

Office hours

See the website of Ivana Kurelac