(422 E2) genomics & life course Flashcards
eugenics
the scientifically inaccurate theory that humans can be improved through selective breeding of populations
the implementation of eugenics practices has caused widespread harm, particularly to populations that are being marginalized
eugenicists believed in
a prejudiced and incorrect understanding of Mendelian genetics that claimed abstract human qualities (e.g., intelligence and social behaviors) were inherited in a simple fashion. Similarly, they believed complex diseases and disorders were solely the outcome of genetic inheritance.
eugenic present day concerns
we are advancing in genetic screening technologies and people may feel pressured to terminate a pregnancy that isn’t “normal” d/t genetic disorders
health equity in the context of genomics
requires an understanding of how health is influenced by biological and non-biological determinants of health in all populations
Creating equal, effective, and affordable access to genomic advances in health care for all
A commitment to health equity will require funders, researchers, health providers, and others to work together to
1) close existing evidence gaps among diverse and underserved populations;
2) ensure that genomic medicine applications, once implemented, are unbiased and equitably accessible; and
3) build the workforce and infrastructure to make widespread adoption of these strategies possible.
types of protected genetic information
-family medical history
-carrier testing (cystic fibrosis, sickle cell, ect)
-prenatal genetic testing
-pre symptomatic and predisposition testing
-analysis of tumors or other assessments of genes, mutations or chromosomal changes
GINA restrictions: employers may not
-Request, require, or purchase genetic information about employees or their family members
-Use a person’s genetic information in decisions about hiring, firing, job assignments, compensation, or promotions
GINA restrictions: health insurers may not
-use a person’s genetic information to set eligibility requirements or establish premium or contribution amounts
-request or require that a person undergo a genetic test
what GINA does not do
-Protect information about current health status or disease simply because it is genetic, if the disease is already manifested and diagnosed
-Apply to life, disability, or long-term-care insurers
if you have the BRCA1 or 2 or Alzheimer’s genes it may be more difficult to get life insurance.
-Apply to TRICARE (military, federal, and VA)
-Protect certain groups, including:
Employees in organizations with fewer than 15 employees
members of the United States military;
veterans obtaining health care through the Veteran’s Administration;
individuals using the Indian Health Service; or
federal employees enrolled in the Federal Employees Health Benefits program (FEHB).
-Apply to sectors outside of employment and health insurance, such as:
Education – Chadham’s middle school case
Housing
Health care??
genetics
The study of heredity and the transmission of characteristics from across generations.
gene
The most basic physical and functional units of heredity. Genes are specific sequences of nucleotide bases that encode instructions for how to make proteins
genome
Total genetic makeup of an organism
-Includes non-coding regions of DNA (~98% of the genome)
~20,000- 25,000 genes in a genome, which is about 5% of the total DNA.
Epigenomics
study of molecular signals that tell the genome how to behave and their relationship to health
Exposomics
study of how all the exposures of an organism alter its health (Exposures can be chemical, biological, psychosocial, and other environmental stimuli that alter the expression of genes, often through epigenetic mechanisms)
epigenetics
non genetic influences on gene expression
-serves as an on/off switch for gene expression/protein coding
-how exposures get “under the skin”
-mechanisms include: DNA methylation, histone modification, transcriptional silencing, telomere shortening
Allostasis
the body’s adaptation to predictable and unpredictable changes in the environment (acute and shorter periods of exposure
Allostatic load
is defined as the cost of chronic exposure to elevated or fluctuating endocrine or neural responses resulting from chronic or repeated challenges that the individual experiences as stressful
what can we do about present day eugenics
-national human genome research institute developed the Ethical Legal Social Implications (ELSI), investigates ethics ares genetics and genomics and the technology associated with it
-addressing structural racism and other issues that foster eugenics based ideas
-understanding and engaging w/ this history in order to create more inclusive and humane future
genomics history
historically, genetics research was conducted w/ large populations of European descent
our genetic knowledge and technologies are based on one specific population -> create technologies that are not as applicable or effective in other populations
-historical misuse of DNA (henrietta lacks & fake vaccines to get DNA)
when we refer to ancestry and ancestry informative genetic markers, what are we not talking about
race
race is
a social construct
not a biological one so there are no racier markers or distinctions genetics
when we create genetic technologies, it is costly and only available in certain areas -> so when we look at how is excluded in the research and receiving the benefits, what is it largely impacted by
the social determinants of health
ethical concerns for consumer genetic testing (23 and Me)
Consider implications of surprising findings are reveal liked paternity or adoption, life limiting diseases that have no treatment are discovered or when data is used to suspects from a crime
Health insurers refusing insurance to people with genes linked to disease (ex: breast cancer)
Employers refusing to hire people who genes linked to mental health disorders
GINA purpose
Prevent discrimination by health insurers based on genetic information
Prevents employers from collecting genetic information about employees or their family members and/or using that information to make decisions
Prevents employers from requesting or requiring genetic tests are changing premiums/co pays/coverage based on genetic info
genetic information protected under GINA
Family medical history
Carrier testing (CF, sickle cell, spinal muscular atrophy)
Prenatal genetic testing (amniocentesis, chorionic villus sampling)
Presymptomatic and predispositional testing ( BRCA, huntington, colon cancer)
Analysis of tumors or other assessments of genes, mutations or chromosomal changes
GINA limitations
Does not prevent anyone from acting based on diseases that are already symptomatic
Does not prevent discrimination from non-medical insurance such as life insurance
Does not prevent discrimination by the government itself (ex: Tricare [military, federal & VA] is not included and neither is education, housing or health care
Chadham’s middle school case
child kicked out of school bc teacher disclosed he had CF to other parents
DNA
double stranded structure that contains all information for development and functioning of an organism
nucleotides
the subunit that comprises DNA
adenine (A)
thymine (T)
Cytosine (C)
Guanine (G)
Base pairs: A&T ; C&G
Single nucleotide polymorphism (SNP)
a single base substitution in DNA
occur ~once every 300 base pairs, meaning there are 10 million SNPs in the entire genome SO to be classified as a SNP, the substitution must occur in 1% of the population
most occur outside of the genes and therefore have no effect on genes or the protein products of genes
If they fall in the gene, they are classified as coding or noncoding
SNP: coding
change the protein product of the gene
SNP: noncoding
affect how much protein is produced from the affect gene
DNA Methylation
Occurs when methyl molecules attach to the nucleotides that the RNA binds to, to begin the transcription process and prevents transcription from occurring
No protein means the gene is not expressed in the body thus the phenotype will vary between methylated and unmethylated genes even though the genotype remains the same
Genotype
Ancestral inheritance or mutation causes differences between individuals:
A single nucleotide
Number of copies of a coding sequence
Number of chromosomes
o Expressed via production of proteins
Phenotype
the observable characteristics of an organism (the presentation of DNA)
Based on genotype but can also be altered by the environment through epigenetic modifications, lack of protein binding sites or carriers, lack of amino acids to code certain proteins, misfolding of proteins
life course dimension
health risk and impact assessment are based specific external environment (diet, tobacco use, PA), general external environment (climate, green spaces, urban environment, social capital) and internal environment (biological factors like metabolic, gut microflora, inflammation, oxidative stress)
these 3 things affect the phenotype
the exposome
the exposures that influence health and disease risk that contribute to a specific phenotype expressed by each individual
complex disease
phenotype occurs through a combination of individual:
-genetic susceptibility (genotype)
-exposures (environment)
-epigenetic modifications (interactions between environments and genes)
most epigenetic markers are
inherited (almost entirely from mother)
referred to as “non genetic inheritance” bc the DNA sequence of the gene does not change
main function of epigenetics is to
cause some genes to be silent (dormant) and others to be active (expressed)
nature
epigenetics are inherited just after fertilization -> allows cellular specialization (what makes a stem cell become optic nerve cells instead of liver cells)
nurture
exposures can cause epigenetic modifications to allow organisms to adapt to their environment (a survival mechanism)
-nutrition, pollution, social stressors, metabolism, sleep hygiene, exercise habits, poverty, violence, discrimination, ect
how can public health address genetic susceptibility
-assess/determine/identify relationships between genetics & environmental factors
-inform people of their risk and ways to mitigate them
-minize negative exposures
-support healthy behaviors
-precision medicine targeting specific genetic risk factors
the dutch hunter winter effect on pregnant women and their offsprings
-babies who were in second or third trimester during the winter were low birthweight
-babied exposed only during 1st trimester were normal birthweight but had worse rates of adult disease
-exposed babies had higher rates of adult obesity, CVD, and cognitive decline than those born before or after the war
stressed (positive or tolerable stress)
increased CO
increased available glucose
enhanced immune functions
growth of neurons in hippocampus & prefrontal cortex
stressed out (toxic stress)
-HTN & CVD
-glucose intolerance & insulin resistance
-infection & inflammation
-atrophy & death of neurons in hippocampus and prefrontal cortex
three domains of stress response
positive stress: contributes to growth
tolerable stress: short lived, no long term harm
toxic stress: severe or chronic stress response that leads to toxic effects on the brain, altered behavior, and maladaptive responses (often result of ACEs or poverty
the complex disease phenotype pathway pyramid
[top]
-disease
-epigenome (epigenetic modification)
-exposome (totality of exposure)
-genetic susceptibility (overlapping risk facts for complex disease)
