College aantekeningen Genetics And Public Health (AB_1025)

Lectures Genetics and Public Health

Lecture 1: Meet and Greet Mendel
- Explain the principles of monogenetic (Mendelian) inheritance and illustrate them with examples
- Draw a family tree using information about a family and calculate the risks of suffering from or
passing on an inherited disorder
o Autosomal Dominant Inheritance Pattern (assume heterozygous)
 Homozygous dominant rare
 All children affected
 Characteristics
 Several generations affected
 On average 50% of children of affected parents are also affected
 Inheritance from man to woman, from man to man, from woman to
man and from woman to woman
 Examples
 Huntington disease 100% penetrant always get the disease
 BRCA1 &2 60-80% penetrant
 Lynch syndrome
 Achondroplasia (dwerggroei)
o Autosomal Recessive Inheritance Pattern
 Characteristics
 On average, if both parents are carrier, a quarter of their children are
affected
o Families in which none of the children are affected, but both
parents are carrier, are not observed
 Sometimes parents are consanguineous higher incidence
 Usually just 1 generation
 Examples
 Cystic Fibrosis
 Hemoglobinopathies sickle cell anemia/thalassemia
 Phenylketonuria (PKU)
o X-linked recessive transmission
 Characteristics
 Sons are affected
 Women are (usually) not affected carrier pass on predisposition
 No inheritance from man to man (pass on y-chromosome)
 Examples
 Duchenne Muscular Dystophy
 Hemophilia A & B impaired blood clotting
 Color blindness

Lecture 2: Genes and Diseases
- Explain what is meant by genetic variation




- Describe the following classification of genetic diseases using an example
o Chromosomal disorders
 Numerical or structural changes (0.6% live born)
 Mostly affect autosome
 In general
 Loss of chromosomal material is more dangerous than gain
 Abnormalities of sex chromosome is better tolerated than autosomal

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,  Usually origin de novo
 Examples
 Down syndrome trisomy 21
 Klinefelter XXY (extra X)
o Monogenic disorders
 Most follow Mendelian pattern of inheritance single genes
 Some exceptions HC4 More than Mendel
 Mechanisms of single gene disorders
 Enzyme defects inborn errors of metabolism
o Material to be degraded builds up in certain cells in the body
causes problems
o Example Tay-Sachs Disease
 Defect in membrane receptors/transport systems
o Example Familial Hypercholesterolemia
 Alterations in structure, function, or quantity or non-enzyme proteins
o Example Marfan syndrome
 Genetic variants leading to unusual drug reactions
o Example Cytochrome P450 enzymes
o Mendelian subsets of common diseases
o Multifactorial and complex disorders
 Frequent ±10% lifetime risk
 Most common disorders are multifactorial asthma/arthritis/dementia
 Multi- or polygenic >1, each convey low risk
 And environmental factors
 Complex interactions between gene & environment

Lecture 3: Public Health and Genetics
- Explain the definition of public health genomics
o The responsible and effective translation of genome-based knowledge and technologies
into public policy and health services for the benefit of population health
o Sometimes conflicting principles best health outcome vs freedom to choose
o Difference genetics and genomics
 Genetics study of genes and their roles in inheritance: the way that certain
traits or conditions are passed down from one generation to another
 Genomics study of all of a person’s genes (genome), including interactions of
those genes with each other and with the person’s environment
o In 2000 first genome sequenced
 Knowledge available
 Important moment in political terms
o Cost of the genome dropped most costs now in the analyzing of the genome
o Future prevention advice?
 Stratify per risk group not yet




o Bench or bedside?

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,  Much knowledge in the lab, but patients don’t always profit from it
 Translation is needed scientific findings to health care
- Explain how the benefit of the individual plays a role in public health genomics, clinical genetics
and community genetics
o Genetics in medicine
 Individualism & autonomy insurance payment
 Goal empower counselees
 Outcome informed choice/personal control
 Primary care
 GPs/midwives/child health centers
 Get most (simple) questions
 However
o Genetic knowledge relevant for primary care not adequate
o Fast developments
o Often not “core business”
 Clinical genetics
 Medical specialty
 Diagnosis/prognosis/recurrence risk?
o Cancer in family, young age, often same type
o Counselee has (hereditary) disorder
o Child does not develop adequately (physical
abnormalities/intellectual disability)
 Involves few people
 Complex decisions eg:
o Have (more) children or not?
o Prenatal diagnosis and selective abortion?
o Have both breasts removed?
 Helping people make a choice that suits their moral considerations
and/or what they consider important in life informed decision making
 Genetic testing guidelines
 Counseling, support
 Psychological consequences of testing
 Family issues
 Issues of genetic discrimination
 Usually genetic counseling with testing, but number of tests is
increasing
o Result of large-scale genomic research
 From single gene (Mendelian) conditions to common
complex conditions
 Extending scope of testing in health care
o From reproductive tests to predictive testing
o From reproductive decision making to personal risk reduction
o From rare monogenic to common complex diseases
o From families to large sections of healthy populations
o Public health
 Collectivism & paternalism government funding
 Goal promote health and prevent disease
 Outcome uptake/compliance/decrease number affected/economic benefits
 The focus in on populations > individual
 Human diseases result from gene-environment interaction possibilities for
disease prevention
 Translating research into practice and services  close the gap
- Explain optimistic visions on genomic medicine and give arguments against optimism


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