genomics and life course theory Flashcards
eugenics
scientifically inaccurate theory - early 20th century
planned breeding, scientific racism, erroneous, immoral
humans can be improved and perfected through selective breeding
prejudiced and incorrect understanding of menedlian genetics: abstract human quality inherited in simple fashion, complex diseases and disorders are solely outcomes of genetic inheritance
eugenics: biological determinism
human behavior directly controlled by genes
some groups are inherently better -> involuntary sterilization, segregation, social exclusion, slavery
caused widespread harm -> especially marginalized pops
eugenics: present day
not fringe movement -> effects still seen today
started in late 1800s -> racist and xenophobic
still exists today
big concern as genetic screening tech advances and actions are taken as result (terminate preg): IVF, preimplantation genetic dx, prenatal screen
involuntary sterilization, forced institutionalization, social ostracization, stigma
eugenics: present day - prevent
address structural racism and other issues
understand and engage with history to create more inclusive and humane future
ELSI research program -> ethical, legal, social issues
health equity in genomics
hx conducted with european descent -> may not be effective in other pops (SDOH limit)
not race, no racial markers -> SNPs from those with similar geographic ancestry
hx misuse of DNA: HELA cells, fake vax for DNA in pakistan (osama)
SDOH and genetic tech: access, cost, medical mistrust
need to correct wrongs of past to improve future
health equity in genomics: moving forward
health influenced by bio and non bio factors in all pops
need equal, effective, affordable access to genomic advancements for everyone
health equity in genomics: moving forward - requirements
need funders, researchers, providers, and others to…
close evidence gaps among diverse and underserved pops and research
ensure genomic med apllications are unbiased and equitably accessible
build workforce and infrastructure to make widespread adoption of these strategies possible
ELSI
ethical, social, legal implications
pop culture and for profit genetics
open access science, crowd sources from surverys combo with genetic info
public data, research findings, internal data
interesting findings, limited clinical significance
pop culture and for profit genetics: ethics
catch 22: no tm for what you may find, whereas some testing like newborn screening provides clear benefit
DNA and crime scenes, children given up, questionable lab and privacy practices
own your personal data -> unregulated data, cant control what happens to yours
23 and me
10 genetic risk rests
fun facts of how DNA influences appearance, pref, phys responses
health predispositions and carrier status
ancestry/genealogy (general location)
ancestry.com
more comprehensive ancestry/background and genealogy
historic references about migration: likely origin and path
health risk summary not FDA approved
genetic info non discrimination act
protections might ease concerns of some
protect against use of genetic info to discriminate in health insurance and employment
some states have more protections
genetic info non discrimination act: types of protected genetic info
fam med history
carrier testing, prenatal, presymptomatic and predispositional, analysis of tumors or other assessments of gene mutations or chromosomal changes
genetic info non discrimination act: restricted practices - employers
cannot:
request or require genetic tests
purchase genetic info about employees or fam
use genetic info in decisions of hire, fire, job assignments, compensation, promotion
genetic info non discrimination act: restricted practices - insurers
cannot:
set eligibility req or est premium or contribution amounts
request or require genetic test
genetic info non discrimination act: limitations
does not:
protect info about current health status or disease if already manifested and diagnosed
apply to life, disability, long term care insurers: BRCA 1/2, AD genes -> may be harder to get life insurance
apply to TRICARE (military, fed, VA)
protect certain groups: employes in organization w <15, US military, vets with healthcare through VA, those using Indian health services, fed employees in FEHB
apply to sectors outside of employment and health insurance: education, housing, healthcare (access or standard of care)
genomics in nursing practice
becoming increasingly important in healthcare
1962: genomics nursing education priority
1998: genetics/genomics part of scope of practice
2003: human genome project
precision health era
direct to consumer genetic testing
clinical genetic testing: oncology, pain manage/anesthesia, psych and MH, reproductive health, OB
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.
DNA
instruction manual
DeoxyriboNucleic Acid (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)
Single Nucleotide Polymorphism
(SNP)
A single base substitution in
DNA.
* ~10 million SNPs in the entire genome
* Some SNPs can change what protein is
produced by the gene; others can
affect how much protein is produced
by the gene.
genotype
the molecular structure of an
organism (one individual’s DNA)
* Ancestral inheritance or mutation
causes differences between
individuals:
* A single nucleotide
* Number of copies of a coding
sequence
* Number of chromosomes
* Expressed via the production of
proteins
phenotype
The observable characteristics of an
organism (the presentation of DNA)
* Based on the 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
- omics
study of how specific components of genome function and interact or how external influences alter the function of the genome
epigenomics
study of molecular signals that tell the genome how to behave and their relationships to health
exposomes
study of how all exposures of an organism alter its health
exposures = chm, bio, phys, env -> alter gene expression via epigenetic mechanisms
exposome
external env general: urban env, climate, social capital, systemic racism
specific external env: containment, diet, phys, activity, tobacco, infections
internal env: met, gut micro, inflam, oxidative stress
complex disease phenotype pathway
combo of:
genotype -> genetic susceptibility at DNA level, DNA does not = destiny, but big factor
exposures -> expsome, environment
epigenetic modification -> interactions btw env and genes
disease
epigenetics
non genetic influences on gene expression
on/off switch for gene expression/protein coding
get under skin
mechanisms of epigenetics
DNA methylation: methyl blocks transcription, not protein, phenotype differs even though genotype same
histone modification (coiled tightness)
transcriptional silencing
telomere shortening
most epigenetic markers inherited
non genetic inheritance: mech through which patterns of disease run through fam; shortly after fertilization, mostly from mom
env exposures can alter markers: on/off to increase survival, gene therapies, meds, decrease exposures may interrupt disease pathways
epigenetics: keep some genes silent and others expressed
nature: epigenetics from mom, allows cellular specialization
nurture: exposures can cause epigenetic modification to allow adaptation to env
how can public health address susceptibility
assess/determine/identity relationships btw genetic and env factors
inform people of their risks and ways to mitigate
decrease negative exposures (smoke free laws)
support healthy behaviors (policies and env)
precisions med targeting specific genetic info
lifecourse theory
attempt to explain how life contexts shape health, behavior, dev (stages v cumulative)
experiences and exposures cumulative -> holistic
early life contexts, including fetal, may cause profound shifts in bio and behavior into old age
risk and protections transmitted across gen and pop
multidisciplinary paradigm
barker hypothesis
fetal origins of health and disease
adverse fetal life context = increased r/o adult disease
early programming impacts gene expression through epigenetic changes
grandchildren also affects -> F eggs
why? -> prioritize immediate survival in womb over long term health
why are grandchildren also affected?
intergenerational transmission: blame women, increased exposure to toxins
placental function controls every aspect of fetal exposure and can prime or program fetal tissues to adapt to perceived extra uterine env
role of public health in lifecourse theory
increase health of childbearing persons
recognize and intervene in pops at elevated risk
interventions for lbw or those exposed to low nutrition in early preg
what about stress
stress = body’s response to changing factors in self or env
stressor = internal or external
responses to acute (short term) can be adaptive and increase survival
allostasis = adapt to predictable and unpredictable change in env, acute;
chronic stress: wear and tear on regulatory systems, >6 mo
cumulative stress leads to weathering, gradual degradation in health: explains social patterning of health and disease, inequality gets under skin
allostatic load: prioritize survival over long term care, cost of chronic exposure to elevated or fluctuating endocrine or neural responses resulting from chronic or repeated challenges that individual experiences as stressful
lifecourse health dev
comprehensive model of trajectory of health dev across life course
accounts for genetic, bio, phys, social contexts
stressed v very stressed
increased CO, gluc, enhanced immune, growth or neurons in hippocampus and prefrontal cortex
stressed out: htn, cvd, insulin intol, insulin resist, infection and inflam, atrophy and death of neurons in hippocampus and prefrontal cortex
toxic stress
poverty and adverse childhood events
ecobiodev model
domains of stress response:
+ -> contributes to growth
tolerable -> short lived, no long term harm
toxic -> severe or chronic response, l/t toxic effects on brain, altered behavior, maladaptive responses, often result of adverse childhood events or poverty
ACE
, not severity or freq, no focus on buffers to decrease toxicity
traumatic experience, <18, remember
score, 10 Q’s
lasting effects: health, behaviors, life potential
coping with: maladaptive, their solution is actually a problem to others, dismissing coping devices as bad habits or self destructive misses their origin source, look into this to treat
ACE: intervene
prevent! -> policies
replace maladaotive, ehacne social support, address sources of trauma - therapy
decrease stigma -> shame increases escalation and use of behavior
ACE: life outcomes
dose response: increased exposure = increased adverse outcomes
group aggregates, dont speak to individual destiny
dont have to dictate life story: protective factors (buffers) build resilience -> decrease R
buffers: nurturing adult, positive relationships, counseling, mindfulness
ACE: public health - foster understanding as PH crisis
s of adverse env, intergenerational trauma
edu, social support, trauma informed care -> build resiliency and buffers
ACE: public health - build support for addressing ACE through hc
need to edu hc workforce about SDOH and ACE impacts
CTIPP -> promote policies and programs informed by science of ACEs and trauma
ACE: public health - increase system capacity
need trauma informed care and prevention
ACE: public health - create policies to foster cross sector care coordination
decrease burden and trauma, tell story over and over
ACE: public health - collab and alignment across sectors and systems
isolated communication have to piecemeal solutions even when we have evidence of what works
need for a roadmap, helps vulnerable comm align across sectors and systems
