The course will focus on the study of the molecular mechanisms whose alterations are the basis of human metabolic diseases. The course will also address the molecular techniques of genome typing for both the diagnosis of genetic diseases and the assessment of the genetic predisposition to metabolic diseases will be considered.

Topics.

1.  Introduction.

The biochemical genetics. The WTO definition of health. Disease, disorder, condition, syndrome. The inherited metabolic diseases. The multifactorial metabolic diseases. The endocrine-metabolic diseases.

2.  The metabolism in humans.

Bioenergetics Enzymatic catalysis. Isozymes, allozymes, and genetic variants of enzymes. Nutrition in brief

3.  Anatomy of the human genome.

Genome packaging in eukaryotes. The modification of nucleosomes. Satellite DNA. Alphoid probes. The centromere. Eukaryotic chromosome structure. Transposons. Barbara McClintock's controlling elements. Retrotransposons. LINEs and SINEs repeats. The Alu family. Gene and gene-related sequences in the human genome. Gene family. α- and β-globin loci. Pseudogenes. Ribosomal DNA (rDNA). Nucleolus organizer region.

4.  Molecular basis of antibody diversity.

The human MHC locus. The human IG light-chain loci. The human IG heavy-chain loci. Molecular mechanism of somatic recombination. Allelic exclusion.

5.  Mutations that cause inherited metabolic diseases.

The molecular basis of mutations. Point mutations. Replication slippage. Chromosomic mutations. Hemoglobinopathies and Thalassemias. Karyotype aberrations.

6.  Genetics of metabolic disorders

Inheritance of monogenic diseases. Effects of the mutant allele. Haploinsufficiency. Overdominance. Effects of a mutation in structural genes. Achondroplasia. Autosomal dominant single-gene diseases: incomplete penetrance, variable expressivity. Waardenburg syndrome. Autosomal recessive single-gene diseases: pleiotropy, complementation. X-linked disorders. Genetic heterogeneity.

7.  Genome typing.

Simple sequence length polymorphism. Minisatellites. Paternity test. Microsatellites. Short tandem repeats (STRs) and genetic fingerprinting. The CODIS database. Single nucleotide polymorphisms (SNPs). RFLP techniques. Next-generation sequencing. dbSNP database. SNPs and Alzheimer's disease.

8.  Regulation of gene expression

Core promoter. Assembly of the transcription preinitiation complex. Mediator. Promoter-proximal and long-range regulatory elements.

9.  Signal-transduction.

Intracellular receptors. G protein-coupled receptors. G proteins and their effectors. Receptor-tyrosine kinases. SH2 domain and adapter proteins Mechanism of NF-κB action. STAT activation. RAS pathways.

10.   Inborn errors of metabolism.

Single-gene metabolic disorders. Measures of disease frequency: incidence and prevalence. Genetic disorders of carbohydrates, amino acids, and purine metabolism.

11.   Hyperlipidemias.

Plasma lipid transport. Apolipoproteins. Chylomicrons. VLDL, IDL, and LDL. HDL. The Fredrickson classification of familial hyperlipidemias. Familial hypercholesterolemia, familial dysbetalipoproteinemia, and lipoprotein lipase deficiency.

12.   Hyperglycaemias.

Maintenance of blood glucose homeostasis. Role of insulin: biosynthesis and mechanisms of action. Glucagon's functions. Adrenaline and cortisol. Type 1 diabetes and metabolic implications. Type 2 diabetes and insulin resistance.

List of metabolic diseases.

Carbohydrate metabolism:

• VON GIERKE DISEASE
• POMPE DISEASE
• FORBES DISEASE / CORI DISEASE
• ANDERSEN DISEASE
• MCARDLE DISEASE
• HERS DISEASE
• GALACTOSEMIA I
• GALACTOSEMIA II
• GALACTOSEMIA III
• ANEMIA, DUE TO G6PD DEFICIENCY
• TYPE 1 DIABETES
• TYPE 2 DIABETES

Amino acid metabolism:

• PHENYLKETONURIA
• HYPERPHENYLALANINEMIA, BH4-DEFICIENT, C
• ALKAPTONURIA

Purine metabolism:

• LESCH-NYHAN SYNDROME
• SCID DUE TO ADA DEFICIENCY

Hyperlipidemias:

• HYPERLIPOPROTEINEMIA, TYPE I
• HYPERCHOLESTEROLEMIA, FAMILIAL, 1
• HYPERLIPIDEMIA, FAMILIAL COMBINED, 3
• HYPERLIPOPROTEINEMIA, TYPE IV
• HYPERLIPOPROTEINEMIA, TYPE III

The student will demonstrate to have acquired the mastery of knowledge on metabolic diseases covered in the course (knowledge and understanding). The student will demonstrate to be able to elaborate independently the acquired notions to identify the molecular mechanisms responsible for the biochemical or metabolic diseases as well as their etiology (making judgments). The student will demonstrate the ability to integrate and update his knowledge using the main bioinformatics tools (applying knowledge and understanding). The student must also show the ability to clearly communicate the knowledge acquired (communication skills) and the logical conclusions arising from the study of the discipline (learning skills).

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

Anonymous self-assessment tests consisting of closed-ended questions. The tests will be done during the lessons and will not be evaluated for the final exam.

Teaching

Classroom lessons.

Course books

Suggested books:
DR Ferrier "Le basi della biochimica" 2015 Zanichelli;
DL Nelson, MM Cox "Introduzione alla biochimica di Lehninger" 2015 Zanichelli.

Assessment

At the end of the course, the student will have to write a short essay dealing with a metabolic disease assigned by the teacher and discuss it through an electronic presentation. The short article must be written following the structure showed in class and published on institutional websites (link_wd) (link_pp). This examination test will weigh 50% on the final evaluation. The assessment ends with an oral exam of two topics (25% - 25%) chosen from those carried out during the lessons. The evaluation will be aimed at verifying the student's synthesis skills and communicative and expressive skills as well as the acquisition of appropriate scientific terminology.

Disability and Specific Learning Disorders (SLD)

Students who have registered their disability certification or SLD certification with the Inclusion and Right to Study Office can request to use conceptual maps (for keywords) during exams.

To this end, it is necessary to send the maps, two weeks before the exam date, to the course instructor, who will verify their compliance with the university guidelines and may request modifications.