Medical Genetics - HUMAN GENETICS (2019/2020)

Course code
Name of lecturer
Giovanni Malerba
Number of ECTS credits allocated
Academic sector
Language of instruction
II semestre dal Mar 2, 2020 al Jun 12, 2020.

To show the organization of the course that includes this module, follow this link * Course organization

Lesson timetable

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Learning outcomes

The course aims at providing the fundamentals of human and molecular genetics, organisation of the human genome at different resolution levels, from chromosome to single nucleotide, and of occurence and transmission of human biological variation in single individuals, families or populations. To refine the student's ability to apply the acquired knowledge in real situations, practical exercises and problems will be proposed in the field of diagnostic and / or research in human molecular and medical genetics.
At the end of the course, the students will have knowledge and tools necessary for the understanding of principles and molecular mechanisms responsible for the transmission of normal and abnormal characters in humans, the mode of occurrence of hereditary biological variation and to recognise when this variation can be likely pathological, as well as to derive disease gene and allele frequency in populations and for the genetic risk estimation.
The Human Genetics unit is propaedeutic for the comprehension of Fundamentals of Medical Genetics.


- Cytogenetics: human chomosomes, normal karyotype. Chromosomal abnormalities, numerical and structural. Chromosomal polymorphisms and CNV.
- Medical cytogenetics. Chromosomic syndromes and Genome disorders of autosomes and sexual chromosomes (ex. Of Down, Turner and Kleenefekter S.). Uniparental disomy (UPD).
- Bases of human genetics. Human genome organization, gene order on human chromosomes. Structure of eukaryotic genes. Repetitive DNA.
- Fundamentals of classical genetics. Genetic diseases and hereditary diseases. Mendelian inheritance and atypical inheritance patterns: Mitocondrial inheritance, heteroplasmy and mitochondrial diseases, reduced penetrance, varable expressivity; digenic and triallelic inheritance, incomplete dominance, etc. Somatic and Germinal Mosaicism. Pedigree construction and analysis.
- Epigenetics and regulation of gene expression. DNA metilation. Chromatine remodeling. X chromosome inactivation.
- Parent-of-origin effects: Non-equivalence of male and female genomes. Imprinting and diseases due to genomic imprinting defect. Uniparental diploidy: hydatiform moles and ovarian teratomas.
- Molecular genetics in medicine. Gene mutations, mutation nomenclature. Mutagenesis and DNA repair. Molecular pathology of the gene: biological relevance and effect on the phenotype of mutations, gain and loss of function mutations, dominance and recessiveness; genotype-phenotype correlation. Criteria for mutation classification as disease-causing.
- Diseases due to expansion of unstable repeat sequences (dynamic mutations). Unstable repeat expansion, premutation and full mutation, Sherman's paradox, anticipation.
- Functional non coding RNA. Housekeeping and regulatory RNAs. Functional and patological role.
- Genetic variation in individuals and populations. Mutation and polymorphism. The Hardy-Weinberg law, allele and genotype frequency calculation. Inbreeding and relatedness. Effect of mutation, natural selection, migration and genetic drift; geographic isolate.
- DNA polymorphisms: RFLP, SNP, VNTR, minisatellites, microsatellites. Allelic Identity by State (IBS) or by Descendant (IBD).
- Application of genetic polymorphism analysis: Individual identification, paternity testing. Total and partial chimerism after bone marrow transplantation. Diagnosis by linkage analysis.
- Genetic risks and risk estimation. Bayesian analysis. Consanguinity and genetic risk.

The teaching will be delivered in English, through frontal sessions covering the whole exam program and aimed at achieving the learning outcomes (12 lessons). The Human Genetics unit is propaedeutic for the unit of Fundamentals of Medical Genetics.
To successfully address the course, rudimentary knowledge of biology and formal genetics fundamentals may be helpful. To this purpose the first lessons of this unit will be dedicated to briefly recap this basic concepts and, moreover, the teacher is available to provide additional didactic materials or didactic support to help students lacking parts or all of these basic knowledge.
Besides the reference texts, oral explanations will be coadiuvated by PowerPoint presentations. Summaries of these presentations, other additional didactic materials and possible updatings and communications, from both units, will be made available to students, in pdf format for download, through a dedicated homepage on the University e-Learning platform, troughout the course.
During the whole Academic Year, students may request personal reception to the teacher, by phone or e-mail.

Reference books
Author Title Publisher Year ISBN Note
Strachan, Goodship, Chinnery Genetics and Genomics in Medicine (Edizione 1) Garland Science - Taylor and Francis Group 2014
Strachan T. and Read A. Human Molecular Genetics (Edizione 5) Garland Science (CRC press) 2018

Assessment methods and criteria

The exam consists in a single oral discussion on the topics listed in the syllabus of both the units, and can be taken in one of the four available sessions, scheduled as follow: 2 in the Summer Session at the end of the teaching, 1 in Autumn Session, 1 in Extraordinary Session in Winter.
The student will have to demonstrate to possess an advanced comprehension of the teaching contents allowing the critic analysis and reprocessing of the studied notions and to know how to apply the acquired knowledge to distinguish the various types of inheritance, interpret pedigree and genetic data, interpret genomic and sequencing data, recognise the different mutations and genetic factors involved in genetic disease development, determine and analyse genetic frequencies in a population, determine the recurrence genetic risk, solving proposed exercises and exposing their arguments accurately, with clarity and using the appropriate scientific language.
At the end of the interview, a single global evaluation, expressed as a score out of 30, will be made considering the student's overall preparation on both units. A final mark of 18/30 is needed to pass the exam. All students will be tested for the same skills: content of the exam will be the same for attending and non-attending students.