-> First part

1. The human genome, genes, and chromosomes

Chromatin, heterochromatin, dose compensation, chromosomes in mitosis and meiosis. Genes structure and the human genome.

2. Gametogenesis and zygote

Zygote generation, chromosomal determination of sex

3. Cytogenetics

Human karyotype, mitotic chromosomes,  banding techniques, meiotic chromosomes

4. Chromosomal disorders

Mutations, number and structure abnormalities, sex chromosomes, X chromosome inactivation, X female abnormalities, sex chromosome abnormalities in males

5. Study of family trees

Monogenic disorders, autosomal dominant inheritance, recessive and sex-related

6. Exceptions to Mendelian inheritance

6.1 Issues related to the interpretation of family trees.

6.2 Variable expressivity and incomplete penetrance (Ex: Holoprosencephaly).

6.3 Genetic heterogeneity (Ex: deafness).

6.4 Late-onset diseases and anticipation (Ex: Huntington's disease).

6.5 Unbalanced X chromosome inactivation and X / autosomal translocations.

6.6 Germinal and somatic mosaicism.

6.7 Mitochondrial inheritance (examples of mitochondrial diseases).

6.8 Imprinting.

7. Molecular epidemiology and susceptibility to multifactorial diseases

Polygenic diseases: Quantitative and semi-quantitative characters. Evaluation of the genetic component in complex genetic diseases. Strategies for the identification of susceptibility genes.

8. Developmental genetics

Mono-dizygotic twins, control of sexual development, genetic defects of embryonic development: Homeobox and Hedgehog genes, Defects in limb development.

9. Disorders of sexual development

Determination of gonadal sex and differentiation of phenotypic sex

10. Genetic testing and genetic counseling

Genetic counseling and diagnostic tests with different utilities and applications: prenatal, postnatal, screening, presymptomatic and susceptibility. The genetic report, diagnostic pathways 

11. Prenatal diagnosis

Chorionic villus sampling. Amniocentesis. Cordocentesis. Cytogenetic analysis, Molecular analysis. Preimplantation, genetic diagnosis. Future developments: non-invasive prenatal diagnosis

12. Diagnostic techniques

PCR, Real-Time PCR, Sequencing

-> Second part

13. Genetically determined Human diseases.

13.1 Biological and genetic bases of diseases.

13.2 Placement within diagnostic pathways.

13.3 Gene therapy.

13.4 Practical and interpretative exercises, risk calculation, drafting of a genetic report.

14. Introduction to genomics and post-genomics.

14.1 IT services and tools in genetic diseases.

14.2 Database of pathologies and variants.

14.3 Interpretation of variants based on computer databases and scientific literature.

14.4 Identification of disease genes: Functional cloning and positional cloning, the candidate-by-position gene approach.

14.5 The Human Genome Project and the use of the human genome sequence for the identification of disease genes.

14.6 . Next generation sequencing and its clinical applications. International databases

15. Chromosomal syndromes and genomic disorders

Main chromosomal aberration syndromes: Trisomy 13, trisomy 18, trisomy 21. Cry-du-chat syndrome. Wolf syndrome. Turner and Klinefelter syndrome. CGH arrays and cryptic chromosomal rearrangements. Diagnostic approach to intellectual disability. Abnormalities of sex chromosomes

17. Diseases caused by genomic imprinting

Angelman syndrome. Prader-Willi syndrome. Genomic imprinting and medically assisted procreation

18. The most common genetic disorders

Cystic fibrosis and pathologies related to the CFTR gene, Thalassemia and Hemoglobinopathies, Hemochromatosis,

19. Diseases caused by dynamic mutations

Fragile X chromosome syndrome. Myotonic dystrophy. Huntington's disease. Kennedy's disease. Friedreich's ataxia. Autosomal dominant spinocerebellar ataxia.

20. Neurological and neurodegenerative disorders and complex phenotypes

Movement disorders: Spastic paraplegies, Parkinsonisms, Ataxias, Dystonia. Genetically-determined dementias: Alzheimer's, frontotemporal dementias. Neuromuscular diseases: Spinal muscular atrophy, Amyotrophic lateral sclerosis (ALS), Muscular dystrophy, Hereditary peripheral neuropathies

21. Cardiological diseases

Hereditary primary cardiomyopathies. Hypertrophic cardiomyopathy. Left ventricular non-compaction. Dilated cardiomyopathy. Arrhythmogenic cardiopathies

22. Eye diseases

Retinitis Pigmentosa, Usher Syndrome, Stargar's Disease, Retinal Macular Degeneration

23. Rare diseases

Orphan drugs and the complexity of the genetic component. Applications of the clinical exome.

24. Functional assays

Bioinformatics, Minigene assay, Generation IPS cells

25. Gene therapy

25.1 Methods and clinical trials concerning the pathologies addressed. Outline of Gene Transfer, Targeting of transgenes, RNA interference, CRISPR and gene editing.

25.2 Main applications of gene therapy in hereditary diseases (Cystic fibrosis; Hereditary coagulopathies). Specific aspects of tumor gene therapy

26. Cancer Genetics

Hereditary tumor syndromes, somatic mutations, oncogenes and tumor suppressors

27. Forensic Genetics

The study of inter-individual variability, Molecular typing, Interpretation of profiles,  biostatistic calculation

28. Microbiome

Involvement of the microbiome in the pathophysiology of human disease

-> Third part

29. Has the time come for genotype-based nutrition decisions?

Nutrigenetics or nutrigenomics?

30. Genetic nutrition in practice:

Genetic syndromes that tend to respond well to nutrition interventions, genetic variants that increase health risks unless dietary intake is adjusted, how down syndrome affects nutritional needs

31. Where nutrigenetic differences come from

When our ancestors could still make their own vitamins, recent evolution of genetic differences, mechanisms of evolutionary adaptation, genetic variants linked to lactase persistence in populations around the world

32. The genetics of taste and smell

Genes and ligands related to bitter taste

33. Gender differences

Polymorphisms in estrogen-responsive genes, male-specific polymorphisms

34. How nutrients are affected by genetics

34.1 Inborn errors of metabolism versus common genetic variants

34.2 Newborn metabolic testing, urea cycle defects, phenylketonuria, pku treatment, cystinuria, cystinuria treatment, hartnup disease, maple syrup urine disease, fat intake and utilization, sterols, phytosterolemia, cholesterol hyperresponders, carbohydrates,  carbohydrate digestion, alcohols

34.3 Major ethanol-metabolizing alcohol dehydrogenases, minerals, vitamins

35. How does nutrigenetics influence long-term health?

Preconceptual and prenatal nutrition, nutrigenetics of birth defect risks, prenatal nutrition, boosting cognitive development of infants

36. Cancer, nutrition, and genetic predisposition

Nutrition-related risk of developing type 2 diabetes mellitus,  lipoprotein response to lipid intake, thromboembolism, the obesity epidemic, appetite regulation, fatty liver disease

37. Tools for nutrigenetic research and practice

In vitro and animal models, genetic manipulation of cultured cells, animal cross breeding, nutrigenetic studies in humans, genotype versus allele frequency, twin studies, family studies, association studies, case-control studies, prospective cohort studies, mendelian randomization,  nutritional pharmacogenetics

The teaching material prepared by the lecturer in addition to recommended textbooks (such as for instance slides, lecture notes, exercises, bibliography) and communications from the lecturer specific to the course can be found inside the Moodle platform › blended.uniurb.it