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.
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.
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.
Autosomal dominant disorders
Autosomal recessive disorders
Chromosome X inactivation and X-linked disorders
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)
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
Polymorphisms
Family-base studies (parametric linkage analsysis)
Homozygosity mapping
Genome/Exome Sequencing
Polygenic Theory
Heritability, relative risk ratio, concordance in MZ twins.
Linkage disequilibrium
Non-parametric linkage analysis
Affected sib-pairs
Association studies
Family-based association studies: transmission disequilibrium (TDT) test
Sequencing studies and Gene Burden test
Classification of mutations
Pathogenic mechanisms
Gain- and loss-of function mutations
Mutations affecting splicing
Nonsense mediated mRNA decay
RNA foci
Trinucleotide expansion
Epigenetic mutations
Assessment of allele and genotype frequencies
Hardy-Weinberg equilibrium
Factors influencing H.W. equilibrium (selection, migration, population size)
Mapping of sequencing reads
Call, annotation and filtering of variants
Functional analysis of variants
Exome/Genome Sequencing
Use of genetic Databases
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:
Ricevimento: For appointment please write to: federico.zara@unige.it
CLAUDIA CANTONI (President)
NICOLA TRAVERSO (President)
FEDERICO ZARA (President)
RENATA BOCCIARDI
ALDAMARIA PULITI
II semester, March 2020
HUMAN GENETICS AND LABORATORY
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.
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.
