AIMS AND CONTENT

LEARNING OUTCOMES

In-depth knowledge about inheritance as it occurs in human beings, and comprehension of the main molecular and cellular mechanisms related to the pathogenesis of inherited and acquired diseases.

AIMS AND LEARNING OUTCOMES

The course aims at deepening into the main genetic laws of inheritance, and corresponding exceptions to standard genetic transmission (dynamic mutations imprinting, etc), such as: mapping of either simple or complex genetic traits, population genetics and the effects of the inbreeding, in addition to the human genome organization, the molecular basis of the inherited diseases, the genotype-phenotype correlation, and the most recent identification of new disease genes through the next generation sequencing (NGS) approach.

At the end of the course the student will be able to interpret and evaluate data of recurrence of genetic disorders both within families and inside population.

TEACHING METHODS

The course is organized in frontal lessons held in English. The topics included in the syllabus will be explained by the professor through PowerPoint presentation, also using examples from scientific papers. Students will be stimulated to ask questions and formulate answers using interactive modalities.

SYLLABUS/CONTENT

• Inheritance in Men: physiological and pathological phenotypes
• Mendelian Inheritance

                Autosomal dominant disorders

                Autosomal recessive disorders

                Chromosome X inactivation and X-linked disorders

• Deviation from Mendelian Inheritance

                Incomplete penetrance and variable expressivity

                Lethal alleles

                De novo mutations, germline and somatic mosaicisms

                Mitochondrial inheritance

                Imprinting disorders and parent-of-origin gene expression

                Disease anticipation and dynamic mutations

                Other atypical modes of inheritance (X-linked limited to female)

• Chromosomal disorders and Cytogenetics

                Human Karyotype          

                Numerical and structural chromosomal abnormalities: types and mechanisms

                Abnormalities of Sex chromosomes

                Copy number variants (CNVs)

                Experimental approaches to the study of chromosomal abnormalities   

• Genetic Mapping of phenotypic traits

                Polymorphisms

                Family-base studies (parametric linkage analsysis)          

                Homozygosity mapping

                Genome/Exome Sequencing

• Complex inheritance

                Polygenic Theory            

                Heritability, relative risk ratio, concordance in MZ twins.             

                Linkage disequilibrium

• Mapping of complex traits

                Non-parametric linkage analysis

                            Affected sib-pairs

                            Association studies

                            Family-based association studies: transmission disequilibrium (TDT) test

                Sequencing studies and Gene Burden test

• Mutations

                Classification of mutations         

                Pathogenic mechanisms

                            Gain- and loss-of function mutations

                            Mutations affecting splicing

                            Nonsense mediated mRNA decay

                            RNA foci

                            Trinucleotide expansion

                            Epigenetic mutations

• Population Genetics

                Assessment of allele and genotype frequencies

                Hardy-Weinberg equilibrium

                Factors influencing H.W. equilibrium (selection, migration, population size)

• Bioinformatics in human genetics

                Mapping of sequencing reads

                Call, annotation and filtering of variants

                Functional analysis of variants  

                Exome/Genome Sequencing

                Use of genetic Databases

RECOMMENDED READING/BIBLIOGRAPHY

Lecture notes and reviews covering the whole course will be available for the students in Aulaweb. In addition, students will be provided with files containing genetic problems with solutions

Recommended reference textbook:

• Strachan & Read: Human Molecular Genetics. Bios Scientific Publisher

TEACHERS AND EXAM BOARD

Exam Board

CLAUDIA CANTONI (President)

NICOLA TRAVERSO (President)

FEDERICO ZARA (President)

RENATA BOCCIARDI

ALDAMARIA PULITI

LESSONS

LESSONS START

II semester, March 2020

Class schedule

HUMAN GENETICS AND LABORATORY

EXAMS

EXAM DESCRIPTION

The exam is carried out as oral test in English or in Italian, as preferred by the student. The final vote is expressed out of 30.

ASSESSMENT METHODS

The oral exam, in English or Italian, will allow to test students on most of the content of the course, by assessing their knowledge on human genetics, as well as the acquired ability to connect different topics and to eventually solve genetic problems.

Proficiency in English language, if opted by the student, will not be evaluated, but it must be sufficient to show the student’s knowledge of the subjects, with an adequate level of expertise.

Exam schedule