00451 - Genetics

Learning outcomes

Main purpose of this course is to provide some basic knowledges of genetic methods and to explain necessary elements for understanding advanced genetic problems.

Course contents

DNA as Genetic Material:

• Griffith's experiments, Avery-MacLeod-McCarty experiments, and Hershey and Chase experiments.

• Three-dimensional structure of DNA and RNA (Watson, Crick, Franklin, Wilkins).

Semiconservative Replication of DNA:

• The Meselson and Stahl experiment.

• Replication of circular DNA.

• DNA replication in eukaryotes.

• Mitosis and meiosis.

• Organization of DNA in chromosomes, chromatin structure.

Overview of RNA Transcription Mechanisms

The Genetic Code:

• Demonstration that the genetic code is a triplet code.

• Deciphering of the genetic code: experiments by Nirenberg and Ochoa.

• Characteristics of the genetic code.

Overview of mRNA Translation Mechanisms

Mendelian Genetics:

• Monohybrid crosses, dihybrid crosses, chi-square test.

The Chromosomal Theory of Inheritance:

• Experiments by Morgan and Bridges.

• Sex-linked inheritance, sex determination, analysis of sex reversal mutants in humans, dosage compensation (Barr, Lyon).

Extensions of Mendelian Genetic Analysis:

• Modifications of dominance relationships (incomplete dominance, codominance),

• Multiple alleles (ABO blood group system),

• Pleiotropy, lethal alleles, gene interactions, dominant epistasis, recessive epistasis,

• Sex-influenced inheritance, environment and gene expression,

• Penetrance and expressivity, temperature-sensitive alleles,

• Maternal effect inheritance.

Mendelian Genetics in Humans:

• Pedigree analysis.

Association, Recombination, and Mapping of Eukaryotic Genes:

• (in Drosophila melanogaster, Saccharomyces cerevisiae).

Three-Point Cross:

• Coincidence and interference.

Gene Mutations:

• Functional consequences of mutations (loss of function, gain of function).

• Concepts of haploinsufficiency, dominant negative.

Detection of New Mutations:

• Mutagenesis and mutational mechanisms.

• DNA repair mechanisms (BER, NER, Mismatch Repair, HDR, NHEJ).

• Examples of hereditary diseases linked to mutations in genes coding for DNA repair factors.

Ames Test

Chromosomal Mutations:

• Variations in chromosome structure and number.

• Genetic diseases related to changes in chromosome number (Turner, Klinefelter, Triple X, XYY trisomy, Trisomy 21, Trisomy 18, consequences of chromosome nondisjunction in meiosis).

• Genetic diseases (chronic myeloid leukemia, Burkitt’s lymphoma, neuroblastoma, lipoma) related to chromosomal structural alterations: duplications, deletions, amplifications, translocations (balanced and unbalanced), paracentric and pericentric inversions, ring chromosomes, acentric chromosomes, Robertsonian translocations.

Complementation and Its Exceptions

Delbrück-Luria Fluctuation Test and Its Implications for Evolutionary Theory

Population Genetics:

• Hardy-Weinberg equilibrium.

Laboratory:

• Activities involving recombinant DNA technology: DNA cloning, restriction enzymes, agarose gel electrophoresis, restriction mapping, PCR, application of selection and screening concepts.

Readings/Bibliography

Any textbook of Genetics pulished after 2020.

 

Reading and analyses of the following scientific articles

he Significance of Pneumococcal Types. [https://pubmed.ncbi.nlm.nih.gov/20474956/]Griffith F.J Hyg (Lond). 1928 Jan;27(2):113-59

STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES : INDUCTION OF TRANSFORMATION BY A DESOXYRIBONUCLEIC ACID FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III. [https://pubmed.ncbi.nlm.nih.gov/19871359/]Avery OT, Macleod CM, McCarty M.J Exp Med. 1944 Feb 1;79(2):137-58

Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. [https://pubmed.ncbi.nlm.nih.gov/13054692/]WATSON JD, CRICK FH.Nature. 1953 Apr 25;171(4356):737-8.

THE REPLICATION OF DNA IN ESCHERICHIA COLI. [https://pubmed.ncbi.nlm.nih.gov/16590258/]Meselson M, Stahl FW.Proc Natl Acad Sci U S A. 1958 Jul 15;44(7):671-82.

Gene action in the X-chromosome of the mouse (Mus musculus L.). [https://pubmed.ncbi.nlm.nih.gov/13764598/]LYON MF.Nature. 1961 Apr 22;190:372-3.

Teaching methods

lectures with ppt slides and paper reading 

Assessment methods

oral exam preceded by a brief written test with two genetic problems to be solved

Teaching tools

power point slides

Office hours

See the website of Giovanni Perini