HUMAN MOLECULAR GENETICS
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- Versione italiana
- Academic year
- 2022/2023
- Teacher
- CHIARA SCAPOLI
- Credits
- 6
- Didactic period
- Primo Semestre
- SSD
- BIO/18
Training objectives
- The Human Molecular Genetics course, which is taught in the first semester of the 3rd year of the degree in Biological science, has been designed to introduce fundamental concepts and technological advances in the study of human molecular genetics with emphasis on molecular aspects. Students will understand: the structure, function, and transmission of genes in human, the interactions both among genes and between genes and the environment, and the role of genetic factors in health and disease. The main study designs for genetic analysis of Mendelian and complex traits in humans will be explained, the impact of new knowledge of the human genome on methods for mapping genes on human chromosomes will also be presented. The basic concepts of population genetics and cancer genetics will also be provided.
Knowledge and understanding:
By the end of the course, the student will have learned the main tools of human genome analysis and the molecular basis of genetic diseases. In particular, the student will know the main approaches for genetic analysis of Mendelian and complex traits (linkage analysis, allelic association also extended to the whole genome, GWAS), elements of molecular pathology and the main bioinformatics tools for the analysis of d human genome. The student will acquire the knowledge of the basic laboratory techniques for the analysis of DNA and its polymorphisms.
Applying knowledge and understanding:
The main methodologies used in human genetic analysis will be acquired, particularly the ability to (a) determine the mode of inheritance of simple or complex Mendelian traits through family- or population-based approaches; (b) estimate the probability of parent-child transmission of a trait; and (c) assess the genetic link between genes or alleles through population- or family-based studies. The following skills will also be acquired: (a) use of major statistical tests to test the significance of experimental data; (b) population-level genetic analysis; and (c) basic methodologies for characterizing DNA polymorphisms..
Making judgements:
Acquisition of critical skills in analysing and interpreting experimental results of genetic tests. Understanding of the probabilistic nature of predictions in the transmission of traits to the offspring. Awareness of the complex relationship between genotype and phenotype and of the evolutionary importance of genetic variability. Critical interpretation of statistical tests to verify the significance and the inference derived from the analysis of experimental data.
Communication skills:
Ability to express genetic concepts and data through proper scientific terminology. Ability to communicate and explain, even to non-specialists, issues concerning heredity, the relationship between genotype and phenotype and the molecular basis of genetic diseases in humans.
Learning skills:
Acquisition of fundamental knowledge for advanced studies in human molecular genetics and a better understanding of biological phenomena, also through the development of capabilities in the connection between the various biological/genetic processes and the other disciplines. Prerequisites
- Although there are no prerequisites, the student should have a good knowledge of basic concepts of general biology and genetics, with particular care of Mendel's laws and their extensions, cytogenetics, molecular biology and biochemistry.
Course programme
- The course provides an overview of the basics of human molecular genetics: from Mendelian principles to genomic medicine. Upon completion of the course, the student should have a clear understanding of the following concepts:
Population genetics (8 hours)
The Hardy-Weinberg law for autosomal and X-linked loci and its application. Factors affecting genetic variation: mutation, migration, genetic drift, natural selection. Mendelian population and gene pool. Hardy-Weinberg law: definition, calculation of allelic and genotypic frequencies, examples and problems. Evolutionary factors involved in H-W equilibrium: genetic drift, founder and bottleneck effect, genetic isolation, inbreeding, mutation, selection, migration, heterozygote advantage. Mutation-selection balance.
The human genetic variability (6 hours).
DNA markers: RFLP, VNTR, STR, STS, EST. Rare and common variants (polymorphisms). Molecular pathology: understanding the functional effect of genetic variants; functional effects of point mutations. Dynamic mutations and triplet repeat expansion disease (TRED). Submicroscopic structural variants: copy number variations (CNVs) and their pathological effects; unequal crossing over as a mechanism that generates structural variants.
Inheritance of simple Mendelian diseases in humans (10 hours).
- Genetic analysis of human pedigrees. Main transmission patterns in genealogical trees of Mendelian characters (autosomal dominant, recessive, X-linked). The genetic mapping of Mendelian characters. Role of recombination in gene mapping. Calculation of the overall likelihood of a pedigree: informative meiosis, estimate of LOD scores and threshold.
Genetic dissection of complex or multifactorial diseases (10 hours).
- Strategies for the identification of genetic factors involved in complex diseases. Non-parametric linkage analysis, case-control association studies, association studies extended to the whole genome (GWAS). Wide genome scanning. Identification of susceptibility genes through Linkage Disequilibrium analysis. Strategies in identifying and cloning disease genes: relative risk and odds ratio (OR). Significance levels and multiple tests.
- Quantitative Trait Loci. Polygenic model. Multifactorial threshold model (discontinuous characters). Heritability: basic concept, familial aggregation and twin studies to estimate heritability.
Linkage disequilibrium analysis and HapMap project (6 hours).
The limits of the association studies for the identification of susceptibility to complex diseases. "Common disease-common variant" model and the role of multiple rare variants in complex diseases. Structure and molecular analysis of the human genome. Next generation sequencing: general characteristics. Exome sequencing and its application.
Guided experimental activities on the main features of major genomic browsers (NCBI, Ensembl, UCSC, etc).and pubblic genomic databases (dbSNPs, gnomAD, etc.) will be performed (8 hours). Didactic methods
- The course, with a total duration of 48 hours (6 CFU), is structured in lectures and exercises concerning the analysis and resolution of virtual experiments (for 40 hours). As part of the course, labs on querying major genomic browsers (NCBI, Ensembl, UCSC, etc.) and genomic databases (dbSNPs, gnomAD, etc.) are provided to supplement individual preparation (8 hours).
Lectures are held weekly in the classroom and exposure is through the use of power-point slides and, for better understanding of some topics, also the classic blackboard. Learning assessment procedures
- The aim of the exam is to test the level of knowledge and deepening of the topics of the course program and the reasoning skills developed by the student on issues related to human molecular genetics.
Depending on how the COVID-19 emergency will evolve, the exam can take place in the following two ways (the choice will depend on the pandemic conditions in December and on the decisions of the Academic governance).
Under current arrangements, the examination is conducted in the presence: the exam is written, and consists of 7 multi-choice questions and 4 open questions on all the main topics of the course. To each multiple-choice response value can score up to 2 (-0.5 penalty for wrong answer). Each open response value can score up to 4.5. The assessment is expressed in thirtieths (minimum grade 18/30) and it is obtained by the total score achieved in the test. In any case, the exam is not considered passed whether the student scores =2 in two or more questions. The test will last 2 hour.
In the event that the examination cannot be held in person (due to worsening health conditions and on the University's instructions), the examination will be conducted via on-line platform: it will consist of 20 questions, 18 of which multiple choice (for each one will be assigned a score of 2 with a penalty of 0.25 in case of wrong answer), the last two questions will be open and will be worth 5 points a. The exam will be passed with a score equal to or higher than 26, the honors will be obtained with scores higher than 44. The test will have a total duration of 50 minutes.
In both modalities the scores will be expressed in thirtieths and results from the overall score obtained in the test, the minimum score necessary to consider the exam passed is 18/30.
Compensation arrangements will be provided for students with special needs and the procedures of the examination will be evaluated individually. Reference texts
- Recommended Books:
- Strachan T., Read A.P.. Human Molecular Genetics (5th edition, 2019) Taylor & Francis group.
- RL Nussbaum, RR Mclness, HF Williard - Titolo: "Thompson e Thompson Genetics in Medicine" 8th edition (2015) Elsevier
