Il “Dogma Centrale” della Biologia

Cromosomi umani condensati

Bandeggio cromosomico

Genes and Diseases 1902, A. Garrod proposes the “one gene one enzyme ” hypothesis (upon Bateson’s suggestion) Garrod, A. E. The incidence of alkaptonuria: a study in chemical individuality. Lancet II: 1616-1620, 1902.

The Genetic Basis of Diseases: Chromosomal Aberrations 1956 Human karyotype is defined (Tjio J.H & Levan A. 1956. The chromosome number of man. Hereditas 42, 1-6) 1970s chromosome banding techniques Many known pathological aberrations aneuploidies (e.g., Down syndrome) Translocations (e.g., leukemias) Deletions (e.g., Prader-Willis syndrome, del 15q11-13)

The Genetic Basis of Diseases: Single Gene Mutations Pathogenic Mutation: any change in the DNA sequence leading to a disease Aa changes (e.g., cystic fibrosis) Non-sense changes Splicing mutations Deletions/insertions (affecting or not the ORF): e.g., DMD

The Genetic Basis of Diseases: Somatic Mutations and Cancer Mutations in ‘tumour suppressor genes’ (Rb, BRCA1 e 2 etc.) Mutations in oncogenes (Myc, Src) Activating mutations Chromosomal aberrations (e.g., CML). Mutations in genes involved in DNA repair mechanisms (e.g., colon cancer).

The Genetic Basis of Infectious Diseases Genetic material introduced into the host (DNA or RNA) Expression of exogenous genes (including oncogenes, e.g., HPV16-E6) Can integrate in the host genome (e.g., HIV) Many polymorphisms are known to either increas or decrease susceptibility to infectious disease (e.g., HIV-protective CC chemokine receptor 5-Δ32/Δ32)