Learning objectives

Referring to knowledge Describe the genetic and physiopathological bases of monogenic diseases due to occasional mutations, dynamic mutations and large rearrangement of genetic material. Genomic, chromosomal and imprinting diseases. Multifactorial diseases. Pathologies of the mitochondrial genome. The gender perspective will be incorporated into the development and activities of the subject whenever possible.

 

 

Teaching blocks

 

1. Introduction

*  Introduction; development of the concept of congenital disease; types of congenital diseases; strategies for the study and diagnosis of genetic diseases; programs used to detect and screen genetic diseases at the prenatal, neonatal and adult stages; strategies for the treatment of genetic diseases; animal models for the study of genetic diseases

2. Autosomal recessive diseases

*  Autosomal recessive diseases and loss of function; cystic fibrosis; phenylketonuria; galactosemia; Tay-Sachs disease

 

3. Autosomal dominant diseases

*  Autosomal dominant diseases and loss of function: familial hypercholesterolemia, GLUT1 deficiency; dominance due to gain of function: familial amyloidotic polyneuropathy; dominance due to dominant-negative mutants: generalised thyroid hormone resistance syndrome; Osteogenesis imperfecta

4. Mitochondrial genome diseases

*  Specific concepts: heteroplasmy; diseases caused by point mutations (LHON, MERRF, MELAS); diseases caused by deletion (Kearns-Sayre syndrome, CPEO); mitochondrial DNA depletion syndromes; mitochondrial pathologies with Mendelian basis

 

5. X-linked disorders (recessive)

*  Duchenne muscular dystrophy; gene identification; allelic and clinical heterogeneity; the dystrophin protein and the DPC complex; molecular diagnosis; therapy

6. X-linked diseases (dominant)

*  Fragile X syndrome; presentation in women; the FMRP protein; trinucleotide repeat diseases; Huntington’s disease

7. Genetic heterogeneity

*  The example of hearing loss; monogenic forms: dominant or recessive, autosomal and X-linked

8. Chromosomal diseases

*  Chromosomal aberrations; Down syndrome; Down syndrome critical region (DSCR); other chromosomopathies

9. Genomic diseases

*  The 22q11.2 deletion syndrome; other contiguous gene syndromes; low copy repeats (LCR); diagnosis

10. Imprinting

*  Concept; imprinting and human pathologies; Prader-Willi and Angelman syndromes; molecular mechanisms.

 

11. Complex diseases I

*  Genetics of complex diseases; polygenic inheritance; genetic and environmental factors; polygenic risk score

12. Complex diseases II

*  Genetic bases of common diseases in adults; association analysis; genome-wide association (GWA)

13. Multigenic and multifactorial diseases of metabolism

*  Genetic bases of obesity and type 2 diabetes; gene-environment interaction in the multigenic diseases of the metabolism

 

 

Teaching methods and general organization

 

The methodology of the course consists of the following activities: — Lectures and specific seminars on the contents of the programme. — Interactive activities: practical training in the use of databases for genetic diseases. — Discussion of articles and clinical cases, and presentations by students.

 

 

Official assessment of learning outcomes

 

Students are assessed on the basis of the following activities: — Continuous assessment activities (40% of the final grade): a) a self-assessment test on the contents, mid-semester; b) a test to assess the ability to follow a scientific conference on a specific topic of the course; c) a questionnaire on the use of the OMIM database on hereditary diseases; d) a questionnaire and a discussion session on direct-to-consumer testing; e) seminars consisting of the critical analysis (individually or in groups) of a related scientific publication, and an oral presentation or written assignment. — Written examination including theory and seminars (60% of the final grade).   Examination-based assessment Written examination including theory and seminars (100% of the final grade).

Reading and study resources

Check availability in Cercabib

Book

READ, A.P.; DONNAI, D. New clinical genetics. 3rd ed. Banbury : Scion, 2015

Human molecular genetics. Fifth edition. 2019. Tom Strachan and Andrew Read

https://cataleg.ub.edu/search~S1*cat?/Xhuman+molecular+genetics&searchscope=1&SORT=D/Xhuman+molecular+genetics&searchscope=1&SORT=D&extended=0&SUBKEY=human+molecular+genetics/1%2C376%2C376%2CB/frameset&FF=Xhuman+molecular+genetics&searchscope=1&SORT=D&1%2C1%2C  

STRACHAN, T. and LUCASSEN, A., 2023. Genetics and genomics in medicine. Second edition. Boca Raton: CRC Press Taylor & Francis Group. ISBN 9780367490812.

https://cercabib.ub.edu/permalink/34CSUC_UB/acbrpu/alma991013062109406708  

Web page

OMIM (On-line Mendelian Inheritance in Man)

https://www.ncbi.nlm.nih.gov/omim/