B5844 - GENETICA GENERALE

Course contents

Mendel: basic principles of heredity.Experimental and analytical approach of Mendel's experiments; Mendel's fundamental principles; concepts of gene and allele; methods for calculating genotypic and phenotypic ratios.
Statistical analysis of genetic data: probabilities and the chi-square test. Transmission of hereditary traits in humans: analysis of family trees.

Cell division and chromosome inheritance
Cell cycle in eukaryotic organisms, karyotype and the structure and number of eukaryotic chromosomes; concepts of somatic line and germ line
Mitosis and meiosis: behavior of chromosomes in gamete formation; Mendel's laws as a consequence of chromosome dynamics at meiosis.

X linked inheritance, gene dosage compensation and sex determination.
Inheritance of X-linked loci in Drosophila (e.g., white locus); evidence for chromosomal theory of inheritance (Bridges' non-disjunction experiments).
Chromosomal sex determination
Gene dosage compensation in mammals.

Mendelian genetics in humans
Pedigree analysis, Mendelian segregation models (autosomal dominant inheritance, autosomal recessive inheritance, X linked)

The molecular function of alleles
The molecular nature of alleles. Functional consequences of mutations (loss of function, gain of function). Concepts of haploinsufficiency, negative dominant effect

Extensions of Mendelian genetics.
Changes in dominance relationships (incomplete dominance, codominance); multiple alleles; the ABO blood group system; lethal genes
Interaction between genes and environment; penetrance and expressiveness; sex-influenced traits
Different genes influencing a phenotype: gene interaction; epistasis and modified Mendelian relationships; complementation analysis; genetic heterogeneity.
Continuous variation and multifactorial inheritance. Explanation of how Mendelian principles can explain continuous variation. Polygenic theory. Multifactorial traits, threshold multifactorial traits.

Recombination, Linkage, and genetic maps.
Independent assortment and linkage of genes; recombination as a consequence of crossing-over; genetic maps based on recombination frequency; linkage analysis by test-cross
Relationship between crossing over and map units; effect of multiple crossing-overs; map constructions by three-point crosses; coincidence and interference coefficient; map functions; comparison between genetic maps and physical maps

Genetic variability
Mutations and genetic variability; types of mutations and their consequences; spontaneous and induced mutations; experiments showing that spontaneous mutations are random; examples of physical and chemical mutagenic agents and their mechanism of action.
Basic concepts of DNA repair mechanisms

Mutations and gene function.
Analysis of nutritional mutants in Neurospora crassa and the "one gene-one enzyme" hypothesis of Beadle & Tatum
Effects of genetic variants on gene function and phenotype

Chromosomal rearrangements and structural variants
Variations in chromosome number and structure: overview. Karyotype analysis, FISH, array-CGH.
Aneuploidies and chromosomal disorders in humans; consequences in chromosome segregation at meiosis
Structural variants: mechanisms of occurrence and their consequences.

Molecular analysis of genes and genomes
Basic concepts on the main techniques of genome analysis; cloning and construction of genomic libraries; physical and genetic maps of the genome; DNA sequencing (Sanger's method); genome sequencing, Human Genome Project

Analysis of genetic variability and identification of disease genes
Genotyping of SNPs and CNVs by microarray
Linkage analysis in human pedigrees, lod score calculation
Positional cloning of disease-causing genes
Linkage analysis for diagnostic or predictive purposes

Population genetics
Genetic variability in populations; allele and genotype frequencies. Hardy-Weinberg equilibrium.
Evolutionary mechanisms that alter allele and genotype frequencies in populations (mutation, selection, genetic drift, migration, non-random inbreeding and inbreeding); balance between evolutionary forces.

Introduction to quantitative and complex trait genetics.
Quantitative traits, concept of heritability
Association mapping for the study of complex characters; linkage disequilibrium mapping and GWAS

Readings/Bibliography

• Michael L. Goldberg, Janice A. Fisher, Leroy Hood, and Leland H. Hartwell GENETICA: Dall'analisi formale alla genomica. 3 ed. Mc Graw Hill

• Benjamin Pierce "GENETICA" Zanichelli

• Griffiths A,J.F. et al. "Genetica. Principi di analisi formale." Zanichelli
• Peter J. Russell . “ GENETICA Un approccio molecolare ” Edit. Pearson
• Snusdat D.P. – Simmons M.J. – PRINCIPI DI GENETICA. V Edizione. Edit. EdiSES
• Brooker R.J. "Principi di Genetica" McGraw-Hill

Teaching methods

The course provides Integrative Digital Didactic (DDI) instruments to support learning activities and exam preparation. On the Moodle Virtuale Platform, students will have access to:
- lecture slides, articles and links to web pages, made available prior to the lecture and subdivided for each topic in the syllabus
- links to videos and animations, as extra support to better understand the concepts illustrated in the lecture.
- A series of problems with solutions, divided by topic
- self-assessment quizzes, made available at the end of each course topic
- To stimulate students' interest and involvement, interactive activities are provided during the lessons (Wooclap platform)

Assessment methods

Final written exam including multiple choice questions, questions with open answers and problem solving

Teaching tools

- Slide presentations

- Additional materials, exercises, and web links available through the Moodle platform virtuale.unibo.it

Access is restricted to University of Bologna students who are enlisted to the course

Office hours

See the website of Elena Maestrini