Module I: Human Genetics and Genomics

Degree course: 
Corso di Second cycle degree in BIOMEDICAL SCIENCES
Academyc year when starting the degree: 
Academyc year when helding the course: 
Course type: 
Compulsory subjects, characteristic of the class
Second semester
Standard lectures hours: 
Detail of lecture’s hours: 
Lesson (48 hours)

To follow this course, the student must have a basic molecular genetics background, as well as biochemical, physiological and cellular/molecular biology basic notions.A good knowledge of English will be important to read and understand texts and publications that will be provided to the students as teaching material.

At the end of the course, students will undergo an oral examination. During the exam, the acquired knowledge will be evaluated by asking the student to answer and further discuss at least three different topics selected from the syllabus. For each student, the final judgement will consider the quality and precision of the answers (70%), the ability to motivate statements (20%) and the communication skills (10%). The scheduled time for each exam will be about 20-25 minutes and the exam will be considered passed with a final mark equal or higher than a 18/30 threshold. The latter method for finalk mark definition will be applied only to students attenting the Double Degree Master of Science. By contrast, for those students attending this module in the context of the integrated course of ADVANCED AND QUANTITATIVE GENETICS (Basic and Applied Biomedical Sciences) the final mark will be the weighted mean of the marks obtained for both modules.

Voto Finale

The purpose of the course in Advanced and Quantitative Genetics – Module of Human Genetics and Genomics- is to provide the students with a detailed knowledge in the most recent topics and achievements in the field of genetics and genomics applied to the human genome. Modern approaches within these fields will be described and discussed in this course. Moreover, the module will provide a comprehensive picture of the recent field of human genome science. The topics of the course have been selected focusing on the conceptual and methodological current approaches in genome science, with a special attention on both the relevant potentials and pitfalls in these areas. This course thus aims to provide the knowledge and abilities needed for the understanding the structural and functional content of the human genome, with frequent references to the genetic mechanisms underlying biological processes in normal and pathological conditions in humans.
The expected learning outcomes for this course will be the following:
• A detailed knowledge of the principles of genomic sciences and both the experimental approaches and main achievements in the field of genomics.
• The ability to carry out bibliography searches and to synthesize the retrieved informations in oral and/or visual representation.
• The ability to achieve an informed judgment, adequate expertise and communication skills in relation to both the experimental approaches and main scientific achievements in genome sciences.
• The ability to develop a critic awareness and ability to analyze and discuss issues related to the course contents and the comprehension skills required to develop and maintain issues related to the acquired knowledge, by means of critical reasoning and problem-solving attitudes

• From Genetics to Genomics: introduction to the theoretical issues and the main technological achievements leading to the birth of genomic science (2 hours)

• Genome project, part 1: Rationale, aims and planning. Polymorphic genetic markers and genetic maps. Assembly of the first genomic maps for the human and animal models genomes. Theoretical basis of linkage analysis in humans. The concepts of disease gene and positional cloning. Calculation of LOD scores and recombination fraction in the human genome. Autozygosity and linkage disequilibrium mapping approaches for human Mendelian disorders. The path form disease gene mapping to disease gene identification (10 hours)

• Genome project, part 2: Introduction to the physical maps of a genome. Somatic cell and radiation hybrids. Physical maps based on FISH assays. Genomic libraries and assembly of recombinant clone contigs by fingerprinting or STS-content mapping. Transcription maps of the genome: the EST project. The concept of positional candidate cloning (8 hours)

• Genome project, part 3: Theoretical issues concerning genome sequencing. The first complete non-human genome sequences. Human genome sequencing: the “clone-by-clone” e “whole genome shotgun” approaches. The public and private human genome projects. Validation and implementation of the human genome sequence assembly (8 hours)

• The post-genomic era: Preliminary comparison of public and Celera human genome assemblies. Anatomy of the human genome. Genome “paradoxes” and their resolution. Gene number and biological complexity: toward a new definition of “gene”. Genome annotation approaches. The informational content of the human genome. The GeneOntology and EnCODE projects Comparative genomics approaches to genome annotation. The human chromosome Y as a paradigm of genome evolution. (8 hours)

• Functional Genomics: Forward and reverse genomics approaches in the most widely used model organisms (3 hours)

• Genomic approaches for the genetic dissection of complex diseases: Theoretical bases. Linkage analysis approaches for complex diseases: study of families showing Mendelian segregation of a complex disease and Sib Pair analysis. The concept of Linkage disequilibrium mapping. The advent of SNP markers and the HapMap project. Genome-wide association studies: potentials and limitations. The concept of missing heritability (GWAS) (6 hours)

• Introduction to personal genomics. Approaches for next generation sequencing. Modern approaches to identify genes underlying monogenic disorders: exome sequencing The first personal genomes. The 1000 genome project. Personal Genomics: potentials and limitations. (3 hours)

All arguments will include an explanation of different experimental approaches aimed at demonstrating the current evidence. The students will thus review the main molecular techniques used in modern genome science

The teaching material is updated regularly and will be provided to all students in the e-learning online platform as Powerpoint or Pdf files, short notes, animation files and articles from scientific literature on selected issues related to the course’s topics..

Recommended textbook:
• T Strachan & A. Read – “Human Molecular Genetics” (Garland Science Publ.)
• T Strachan, J Goodship & P Chinnery – “Genetics and Genomics in Medicine” (Garland Science Publ.)

6 CFUs of oral class lectures, as reported in the course content section. Class lessons will be held with the aid of slide presentation sessions, possibly coupled to projection of didactic movies when required.

Prof. Francesco Acquati will receive students upon appointment by e-mail (