Phenotypic variation and genetic models. Consequences of meiosis: segregation, independent assortment, crossing-over. Normal and pathologic human karyotype. Mutagenesis and cancerogenesis. Overview of molecular genetic tools. Human genome organization. Genetic polymorphisms. Genetic linkage and gene mapping. Predictive and presymptomatic genetic tests. Prenatal diagnosis. Gene therapy. Poligenic and multi-factorial traits: heritability, familial aggregation. Population genetics and evolution.
Human Heredity: Principles & Issues, 8th Edition, by M.R. Cummings. Brooks/Cole, 2009.
Understand the mechanisms of transmission and expression of genetic information at the molecular, cellular, organismic, and population level. Appreciate phenotypic variation and recognize the genetic model that best fits it.
40 hours of traditional lectureship
Type of Assessment
oral exam, final mark (18-30 out of 30)
Module I (3 credits)
Size and complexity of the human genome. Structural genes and the organization of the eukaryotic gene. Gene families. Pseudogenes. Non-coding RNAs.
Mitosis and meiosis. Differences between oogenesis and spermatogenesis.
Mendelian analysis. Concepts of locus, allele, dominance, recessiveness, genotype, phenotype.
Mendelian genetics in humans. Distribution in families. Pedigrees.
Autosomal and X-linked, dominant and recessive inheritance.
X inactivation: basic principles, cytological evidence, phenotypic consequences.
Mitochondrial DNA and matrilineal inheritance.
The eukaryotic chromosome. Mitotic chromosome and interphase chromatin.
The normal human karyotype. Criteria for classification of chromosomes and cytogenetic nomenclature. Chromosome heteromorphisms.
Numerical and structural chromosomal abnormalities: genesis and effects.
Methods of recombinant DNA: cloning vectors, selection and screening of recombinant clones; genomic and cDNA libraries; hybridization assays with DNA probes.
PCR and DNA sequencing.
Genetic polymorphisms: single nucleotide polymorphisms (SNPs), restriction fragment length polymorphisms (RFLPs), variable number of tandem repeats (VNTRs or minisatellites), short tandem repeats (STRs or microsatellites), copy number variation (CNV).
Linkage. Informative matings. Transmission of linked genes vs. independent assortment. Crossing over and recombination. Constructing genetic maps. Relationship between genetic maps and physical maps. Linkage disequilibrium.
Strategies for identifying disease genes: positional cloning and candidate gene approach.
Genetic testing: pre-symptomatic diagnosis, predictive testing.
Gene therapy, methods of gene transfer (viral and macromolecular vectors, artificial chromosomes).
Prenatal diagnosis and medicine. Reproductive technology and other prospects for prenatal diagnosis (preimplantation diagnosis).
Regenerative medicine (tissue and organ transplantation, stem cells).
Module II (3 credits)
Genes and populations. Panmissia. Population stratification. Gene and genotype frequencies. Hardy-Weinberg proportions. Mutation rate. Natural selection and reproductive fitness. Relations between mutation and selection. Heterozygote advantage and balanced polymorphism. Gene flow. Inbreeding. Population size and stochastic effects: random drift, founder effect, bottleneck effect.
Spontaneous mutations. Mutations induced by chemical and physical agents. Missense, nonsense, splice-site mutations. Deletions, insertions, duplications, unstable triplet repeat. Somatic mutations and neoplastic transformation
Mechanisms for maintaining genomic integrity. Base excision repair; nucleotide excision repair; mismatch repair.
Cellular proto-oncogenes. Activation of proto-oncogenes: chromosomal translocations, point mutations, gene amplification.
Tumor suppressor genes. Hereditary tumors: Knudson's two-hit theory and the model of retinoblastoma.
Irregularities in the transmission of Mendelian traits. Defective penetrance. Modifier genes. Diseases due to unstable sequences. Genomic imprinting, uniparental disomy.
Quantitative traits. Continuous phenotypic variability: frequency distribution and normal approximation. Partitioning phenotypic variability. Heritability, regression and correlation.
Semiquantitative traits. Genetic susceptibility. The “threshold" model. Twin studies. Familial aggregation.
Strategies for identifying genes contributing to complex diseases. Common confoundings: incomplete penetrance, phenocopies, epistasis, genetic heterogeneity.