Human molecular genetics

A.Y. 2019/2020
Overall hours
BIO/13 MED/03
Learning objectives
The main objective of the course is to provide advanced information on the genetic basis of human disease, to understand the impact of new knowledge on the genome in the study of human molecular genetics and to acquire knowledges on fundamentals of vertebrate developmental biology and the main signaling pathways that, if altered, lead to defects in tissue and organ formation
Expected learning outcomes
After completing the course, the student will have knowledges on specific issues related to the analysis of the human genome, the basics of the developmental biology and the molecular basis of genetic diseases . In particular, the student should know: the fundamentals of molecular pathology, the main steps of the embryo development, the signaling pathway involved in the development, the most commonly used techniques in molecular diagnosis of genetic diseases, and the main approaches for the genetic analysis of Mendelian and complex characters.
Course syllabus and organization

Single session

Lesson period
Second semester
Course syllabus
Molecular analysis of the human genome. The Human Genome Project. Mapping and genome sequencing
Human genome organization. Multigene families and pseudogenes. Human repeated sequences. Organization, distribution and function of RNA genes in humans
Mendelian inheritance. Autosomal dominant and recessive inheritance. Complications of the patterns of inheritance: genetic heterogeneity, incomplete penetrance, variable expressivity, late onset , anticipation, somatic and germline mosaicism
Atypical pattern of inheritance, mitochondrial inheritance; imprinting and uniparental disomy ,
Sex-linked inheritance. X and Y linked genes; chromosome inactivation X; functional mosaicism resulting from the X chromosome inactivation, Determination and sex differentiation.
Structure and function of chromosomes. Human karyotype: morphology and classification of human chromosomes; Kariotyping and chromosome banding; prenatal and postnatal chromosome analysis. Molecular cytogenetic techniques applications.
Chromosomal abnormalities. Numerical chromosomal abnormalities and their effects (polyploidy, aneuploidy); meiotic and mitotic non-disjunction. Main human aneuploidy of autosomes and sex chromosomes. Structural chromosomal abnormalities and their effects; Balanced and unbalanced rearrangements; Mosaicism.
Mutations and genome instability. Classes and molecular mechanisms of mutations. Genetic polymorphisms. Main types of DNA polymorphisms used as genetic markers (RFLP, microsatellites, SNPs). Molecular pathology: mutation for loss or gain of function in relation to dominance-recessiveness. Submicroscopic structural variants: copy number variants (CNVs) and their pathological effects; unequal crossing over as a mechanism that generates structural variant. Repeat instability
Mechanisms and classification of dynamic mutations. Fragile X Syndrome, Myotonic Dystrophy , Huntington disease
Molecular pathology. Methods for the identification of point mutations: methods to identify new mutations. Genetic markers, recombination frequency and construction of genetic maps. Complex or multifactorial diseases: continuous and discontinuous characters; interaction with the environment; characters with threshold effect. Concept of heritability. Twins studies. 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). Study of linkage disequilibrium and HapMap project.

Identification and characterization of candidate genes for inherited diseases.

The genetics of hereditary cancers. The tumor suppressor genes and the two-hit mechanism.

Developmental Biology
Brief history of developmental biology: cytoplasmic determinants, mosaic model, induction, differential expression, specification and determination. Fertilization, gametes and gametogenesis, prevention of polyspermy.
Segmentation and maternal genes: the example of Drosophila
Gastrulation: examples in Xenopus, chicken and human. Human body axes formation: Speeman organizer, Niewkop center, dorsalizing signals, WNT and Nodal pathways, mesoderm and neural palte induction, ventralizing signals, BMP pathway.
Neurulation: neural plate and neural tube.
Somitogenesis: clock and wavefront, Notch pathway, somites metamerization
Antero-posterior axis: HOX genes. Studies in Drosophila and human.
Central Nervous system regionalization.
Organogenesis: limb development in vertebrates, Hh pathway, FGF pathway.
Prerequisites for admission
Students must have fulfilled all the prerequisite requirements indicated in the study plan: Molecular biology, Techniques in molecular and cellular biology.
Teaching methods
Teaching methods: Lectures
Educational material (ppt presentations) will be uploaded on the Ariel website.
Attendance required.
Teaching Resources
Tom Strachan Judit Goodship Patrick Chinnery, "Genetica & Genomica nelle scienze mediche", 2016 Ed. Zanichelli
Tom Strachan, Andrew Read, "Human Molecular Genetics", 2018 5a Ed. Garland Science,
Wolpert, "Biologia dello sviluppo"2017 Ed. Zanichelli
Gilbert, Barresi "Biologia dello sviluppo"2018 Ed. Zanichelli
Assessment methods and Criteria
The assessment method includes an oral exam.
The oral test is a discussion with each of the teachers involved in the course, aimed to ascertain the knowledges and the ability to understand and integrate all the topics of the course. The ability to organize acquired knowledge, the critical reasoning as well as the efficacious communication of the information will be assessed.
Assessment: final mark (/30) based on the results of the discussion
BIO/13 - EXPERIMENTAL BIOLOGY - University credits: 0
MED/03 - MEDICAL GENETICS - University credits: 0
Lessons: 48 hours