Medical Genetics

Code:

CB4002

Acronym:

CB4002

Keywords
Classification	Keyword
OFICIAL	Biological Sciences

Instance: 2016/2017 - 2S

Active?	Yes
Responsible unit:	Molecular Pahology and Immunology
Course/CS Responsible:	Master in Biochemistry

Cycles of Study/Courses

Acronym	No. of Students	Study Plan	Curricular Years	Credits UCN	Credits ECTS	Contact hours	Total Time
M:BQ	20	Plano de Estudos do MBIOQ_2013-2014	1	-	6	56	162

Teaching language

Suitable for English-speaking students

Objectives

1. ATTITUDES: genetic disease as an extreme of human variability; we are all cariers of deleterious mutations; the only particularity of asymptomatic mutation carriers is that they have been detected; our responsibility towards the relatives of a proband with a hereditary disease; sharing all medical and genetic information so that consultands can make informed life decisions; help patients in their decision-making process, without influencing them with our personal believes, and respect their choices; acknowledge the limitations of our current knowledge and interventions; feel the need of constant self-learning in a rapidly evolving field.

2. SKILLS: to collect, register and interpret in a correct manner a family history; to determine the hereditary nature of a disease and its mode of inheritance; to evaluate simple genetic risks; to recognize the social and psychological consequences of the status of being at risk for a genetic disease; to recognize the psychosocial impact of a hereditary disease upon the whole family; to know how and where to get the relevant information; to develop a genetic thinking of medical problems; to recognize the main chromosomal syndromes, congenital malformations and the most frequent hereditary diseases; to know the main indications and the limitations of genetic (cytogenetic, biochemical or molecular) testing, interpret its results and know its limitations; to understand the need for referral of apropriate cases to a genetics clinic.

3. CONCEPTS: the individuality of each human being and human normal variation; genetic, congenital, familial and hereditary; the various concepts of gene; types of polymorphisms; types of mutations; role of genes in health and disease; synteny, linkage and genetic mapping; haplotype, linkage disequilibrium and association; structure and classification of chromosomes; the normal karyotype; most frequent chromosomal anomalies; causes of repeated miscarriages and infertility; chromosomal aberrations in cancer; mutagenesis, teratogenesis and carcinogenesis; the various levels and concepts of sex and gender; sexual determination and differentiation; phenotypical consequences of the inactivation of X-linked genes (Lyonization); phenotypical consequences of balanced translocations (position effect); maternal and paternal age effects on the appearance of genetic diseases; modes of inheritance; main features of Mendelian inheritance; consanguinity and gene frequency in the appearance of recessive diseases; gene-gene interactions and the environment; sex influence and sex limitation; incomplete penetrance and variable expressivity; age-dependant penetrance and anticipation of age-of-onset; epitasis and modifier genes; genetic heterogeneity and phenocopies; de novo mutations and germinal mosaicism; methylation of genes and parental origin effects; genomic imprinting; uniparental disomy; dynamic mutations caused by triplet repeat expansions; mitochondrial inheritance; the multifactorial threshold model; estimation of allelic and genotypic frequencies; main techniques for molecular diagnosis of genetic diseases; semiology of the face and syndromology; pleiotropy and Mendelian, chromosomal and environmental syndromes; frequency, karyotype and phenotypic features of the major chromosomal syndromes; indications to request a karyotype; Mendelian diseases and syndromes, as examples of basic genetic principles; main congenital anomalies and factors causing them; intersex and its causes; genetic factors in cancer; genetics of common (complex) diseases; susceptibility genes; empirical risks and Bayesian estimation of complex genetic risks; genetic registries; screening, treatment and prevention of genetic diseases; prenatal and preimplantation genetic diagnosis (PGD); principles and techniques of genetic counselling; most frequent genetic diseases and services and programs available in the country; the ethical, legal and social issues (ELSI) of genetic diseases.

Learning outcomes and competences

To acquire "genetic thinking" about health conditions.

To recognize the role of genes, the envirnment and other factors in health and illness.

To collect, register and interpret a family history, determine the hereditary nature of a disease and its mode of inheritance; to evaluate genetic risks in simple cases; to recognize the social and psychological consequences of status of being at-risk; to recognize the psychosocial impact of a hereditary disease on all family members; to know how and where to get the relevant information; to develop genetic thinking of medical problems, recognize the main chromosomal syndromes, congenital malformations and the most frequent hereditary diseases; to know the indications and the limitations of genetic tests (cytogenetic, biochemical or molecular) and interpret its results; to understand the need and time of appropriate referral to a genetics clinic or service.

Working method

Presencial

Pre-requirements (prior knowledge) and co-requirements (common knowledge)

Population genetics

Har­dy-Weinberg law. Estimation of gene frequencies and tets for H&W equilibrium. Mutation, selection and evolution. Panmixy and assortative mating. Con­cept of genetic lethal. Lethal equivalent and genetic load. Genetic fitness and selection coefficient. Heterozygous advantage. Compensatory dominance, genetic complementation and meiotic drift. Balanced, transitory and neutral polymorphisms. Genetic flow. Migration.

Population isolates and stratification. Genetic drift and founder effect. Consanguinity. Endogamy coefficient.

Men­delism. Locus(i) and size variation with ploidy. Alleles and poliallellism. Dominance and recessiveness. Homozygosity, heterozygosity and hemi­zygo­sity. Dou­ble hete­ro­zygo­te and compound heterozygote. Genetic linkage and recombination.

Molecular genetics

DNA and bacterial transformation. Semi-conservative replication of DNA. Com­­po­­si­tion and structure of DNA. Genetic code and protein synthesis. Transcription of RNA and RNA trans­criptase. Endonucleases and li­ga­ses. Vectors. Plas­mids. Cos­mids. Molecular clone. Genetic library. Reverse trans­crip­tase.

Organization of the human genome. Structure of eukaryote genes, introns and exons. Structural genes. Pseu­dogenes. Gene families. Mytho­chon­drial DNA. Types of molecular mutations. Repairing me­chanisms of DNA. Single sequence and repetitive DNA.

The Jacob and Monod model. Regulator ge­nes and ope­­ra­tors. Regulation me­cha­nis­ms of gene expression on trans­­cri­ption and translation. Post-translational modification of pro­teins.

Restriction enzymes. DNA polymorphisms. RFLPs, VNTRs, mycrosa­telytes and SNPs. Southern blotting. Genetic probes. Amplifica­tion of DNA by PCR. DNA sequencing.

Histology and embryology

Basic notions of embryology. Normal development processes, growth, differentiation and morphogenetic movements. Fecundation, zygote and cleavage. Blastome­res, morula and blastocyst. Endoderm, ec­to­der­m and meso­derm. De­rivatives of the primitive embryonary tissues.

The embryoblast and orga­nogenesis. Embryological calendar. De­velopment of the central nervous system. Wolf and Muller systems. Foetal mem­bra­nes.

Cell biology

Structure of chromatin. DNA and histo­nes. Nu­cleosomes. Eu­chro­­matin and hete­ro­­chromatin. Satellyte DNA. Constitutive hete­rochromatin.

Autosomes and heterosomes. Ploidy. Diploid, haploid and polyploide. Cell cycle division. Cell division and differentiation. Mitosis and meiosis. Quias­­­ms, crossingover and recombination. Spermatogenesis and oogenesis.

Immunology

Erythrocyte and plasmatic blood groups. ABO, Rh, MNS, se­cre­tor and Lewis systems. Haptoglobins.

Genetics of the immune system and its de­fi­ciencies. Major his­to­com­patibility complex (MHC). HLA system and linkage disequilibrium, association of chronic diseases and sus­ceptibility genes.

Diversity of immunoglobulins. Immunoglobulin genes superfamily.

Program

The various concepts of ‘gene’. The human condition in medical genetics. The individuality of the human being. Genetic regulation of the human development, metabolism and homeostasis. Genetic variability and individual susceptibilities. Concepts of “normal” and “healthy”. Recombinant DNA technologies. Synteny and genetic linkage. Physical and genetic mapping. Cell cycle, mitosis and meiosis. Structural and functional aspects of chromatin and chromosomes. Principles and methodologies of classical and molecular cytogenetics. Molecular biology of heterochromatin. Epigenetics. DNA methylation (5-mC). Chromatin modulation. Sex chromosomes. Numerical and structural chromosomal anomalies. Fragile sites. Molecular aspects of chromosomal anomalies. Cell proliferation and chromosomal instability. Mitochondrial DNA. Development genetics. Experimental embryology. Anomalies of human development. Twins in Medical Genetics. Sexual determination and differentiation. Lyonization. Mutagenesis. Cancer genetics and tumour cytogenetics. Modes of inheritance. Classical Mendelian genetics and “deviations”. From the gene to the phenotype. Genetics and eugenics. Methods for collection and registry of family history. Quantitative genetics. Population genetics in Medicine. Genetics and evolution. Genetic anthropology. Molecular diagnosis of genetic diseases Clinical embryology Semiology of genetic syndromes. The karyotype in medical genetics. Chromosomal syndromes. Genetics of reproduction. Mendelian diseases and syndromes, as examples of genetic principles. Mendelian syndromes and dysmorphology. Congenital anomalies. Intersex. Susceptibility genes and common (complex) diseases. Prevention and treatment of genetic diseases. Prenatal diagnosis and preimplantation genetic diagnosis. Principles and techniques of genetic counselling. Gene and cell therapy. Genetic registries. Diseases and genetic services in Portugal. Medical genetics and Ethics.
[See list of all teorethical and practical classes under "CONTENTS" ->  "Documents" -> "GERAL"]

Bibliography:

- Jorge Sequeiros, Beatriz Porto, Carolina Lemos, Manuel Teixeira: Handouts of the slides presented in theorical and practical classes, 2016/17

- Jorge Sequeiros: Apontamentos de Genética Médica, ICBAS, 2016

- Beatriz Porto: Manual de Citogenética, ICBAS, 2016


Addional bibliography:

- Robert L. Nussbaum, Roderick R. McInnes & Huntington F. Willard: Thompson & Thompson - Genetics in Medicine. 8th ed., 2016. Elsevier, Philadelphia, PA. ISBN: 978-1-4377-0696-3

- Andrew Read & Dian Donnai: New Clinical Genetics, 3rd ed., 2015. Scion Publ. Ldt., Banbury. ISBN: 978-1-907904-67-7

Mandatory literature

-; -

Comments from the literature

General and specific bibliography indicated in the "DOCUMENTS" folder "GERAL"

Teaching methods and learning activities

Theoretical and practical classes.

Self-learning.

keywords

Health sciences > Medical sciences > Medicine > Human teratology
Health sciences > Medical sciences > Medicine > Rare deseases
Health sciences > Ethics in health sciences
Health sciences > Medical sciences > Medicine > General pathology
Social sciences > Psychological sciences > Psychology > Social psychology
Natural sciences > Biological sciences > Biology > Genetics
Health sciences > Medical sciences > Medicine > Social medicine
Health sciences > Medical sciences > Medicine > Chronic diseases

Evaluation Type

Evaluation with final exam

Assessment Components

Designation	Weight (%)
Exame	90,00
Participação presencial	10,00
Total:	100,00

Amount of time allocated to each course unit

Designation	Time (hours)
Estudo autónomo	114,00
Frequência das aulas	48,00
Total:	162,00

Eligibility for exams

Minimum frequency of 75% of practical classes.

Calculation formula of final grade

Final examination valued 0 though 20 marks (possible small bonus, only for positive results in the final examination, according to the results of continuous evalutation and presence and interest in both teorethical and practical classes).

Examinations or Special Assignments

Optional.

Internship work/project

NA

Special assessment (TE, DA, ...)

Final examination, according to the general rules at ICBAS

Classification improvement

Final examination, according to the general rules at ICBAS.

Observations

There will be no obligatory works or mid-term examinations.
Participation at both the theoretical (with separate themes) and practical classes is considered esencial.
The handouts of the powerpoints will be made available (before the classes, whenever possible).
With the attentive and participative presence at all classes, together with the other resources made available online, students are expected to do well in the final examinaton.