walk in that bitch get ethical

prenatal testing

any test used during pregnancy to gain information about the status of the fetus

ultrasound/sonography

screening

blood tests

screening, hormone and protein tests that indicate offs of spina bifida and aneuploidies

direct sampling of fetal DNA

screening and diagnostic

screening

non-invasive, affordable, establishes risk/odds, less accurate

diagnostic

invasive, more expensive, identifies and confirms a condition, more accurate

NIPT/NIPS

blood draw from pregnant person to analyze fetal DNA in their bloodstream, if positive, diagnostic amnio or CVS still recommended (diagnostic)

amniocentisis

transabdominal to get skin cells from amniotic fluid and test for genetic conditions

chorionic villus sampling (CVS)

transabdominal or transcervical, pulls cells from placenta out to test

social model of disability

interaction of disabled people and environment looking at what the person needs

medical model of disability

views impairment as solely pathological looking at what is “wrong” with the person

historical eugenics

population level, mass societal eugenic practices

contemporary eugenics

family/individual level

relational autonomy

how social domination, oppression, stigma, and injustice thwart individual autonomy

disability determinism

suffering, disadvantages, and failure are destiny for people with disability

NBS ethical framework

benefits, economic costs/benefits, equity, psychological impacts, consent

patients in waiting

NBS cases with lab values in ambiguous range (ex. MCAD) resulting in prolonged periods of uncertainty between living normal and sick

why are males affected by x-linked conditions

only need one X to have the condition, females have other X to compensate

blood spot storage

in CA, blood spots stored indefinitely, doctors encouraged to document phenotypic information since data isn’t stored

NBS 1960-2000

low hanging fruit, opt in as default, little controversy

NBS 2001-2010: MS/MS

dramatic treatments, more equitable (developing countries excluded), inexpensive, prolonged false positive lead to patients in waiting, implied consent accepted by most

NBS 2010-2026: PCR

dramatic cures for some but not all, cheap testing but expensive therapies, VUKs biased towards non-Europeans, public starts questioning CA biobank, ex. Hunter and XALD

NBS future: genome

inadequate provider knowledge, expensive, psych consequences expected, biobank issues, consent for family disclosure, ex. Baby Seq

RUSP

recommended uniform screening panel, ended because of $$

tandem mass spec (ms/ms)

detects small compounds/phenotypes, shows secondary conditions, reduces false positive

PKU

deficiency in PAH leads to neurotoxic phenylalanine levels, first condition on NBS (1960s), can lead normal lives with dietary restriction

sickle cell

pain crises in hands and feet, treat with pain meds, antibiotic, gene therapy (2023)

galactosemia

inability to tolerate galactose and lactose, leads to cataracts, liver failure, early death

secondary conditions

getting results other than originally intended, asymptomatic in vast majority

Hunter syndrome

swelling of tissues and developmental regression

embryonic stem cells

pluripotent, can become any cell type

adult/somatic stem cells

multipotent, can become several cell types in organisms

hESC isolation

sperm and egg join → embryo develops 5-7 days → remove inner cell mass of blastocyst → grow in dish → change culture conditions to grow into different cell types

SCNT: makes embryo for the purpose of getting embryonic stem cells

isolate cells from patient → remove nucleus from a donated egg cell → transfer nucleus from patient’s cell to egg → stimulate the cell to begin dividing until blastocyst → isolate inner cell mass and grow in dish → culture cell type of interest and transplant back to patient

iPSCs: makes pluripotent stem cells from somatic cells

isolate skin or fibroblasts from patient → force expression of stem cell regulatory genes with viral vector → wait a few weeks → de-differentiated now to pluripotent → change culture conditions to cell type of interest and transplant back to patient

Dickey-Wicker

illegal to use federal funding for research to create or destroy stem cell lines from embryos

autologous

from same individual being used for

allogeneic

from donor = risk of immune rejection (ESCs)

phase 1 of research

safety focus, small group of health volunteers

phase 2

safety and effectiveness, small group with condition

phase 3

safety and effectiveness, larger more diverse group of people with condition

phase 4

focus on specific populations or safety monitoring (after FDA approval)

hard impacts

direct, measurable outcomes or financial effects of research/technology/interventions

soft impacts

indirect effects of research etc. on social structure, psychology, and mortality (often difficult to quantify or measure)

GxE

people with different genotypes having different effects on phenotype or disease risk from an environmental exposure

types of GxE

no interaction, non-crossover, crossover

drug response as GxE

different genotypes have different responses to same dose (bell curve)

truck

foreign chemical (xenobiotic) that is lipophilic, not charged, not water soluble, poorly excreted

hitch

Phase 1 enzymes that turn it into possibly reactive, are poorly excreted, catalyzed by P450s

trailer

Phase II enzymes that turn into biomolecules, not lipophilic, usually not reactive, water soluble, excretable, catalyzed by transferases

sun exposure and gingers

MC1R activity boosts production of eumelanin = less active in redhead = can’t tan, make pheomelanin → less protective, its degradation product after absorbing UV is genotoxic

Riggs epigenetics

study of changes in gene function that are heritable and don’t entail DNA sequence change

Waddington’s Landscape

causal interactions between genes and their products which bring phenotype into being → explains differentiation

DNA methylation

adds methyl group to 5th base, functions: transcriptional silencing, protecting gene from transposition, genomic imprint, X inactivation, tissue specific gene expression

environmental factors that may induce epigenetic effects

nutrition, behavior, toxins, stress, stochasticity (random)

Dutch Famine example

DNA methylation patterns still changed years later from hungry mothers, showing that events during critical periods of development affect health later in life

ADME

adsorption, distribution, metabolism, excretion

return of results

notifying participants if genetic result that may affect care is found

duty to warn

ethical/legal obligation to inform at-risk family members about patient’s relevant condition, US does not require!!

GINA

prohibits genetic discrimination in health insurance and employment

CAL GINA

expands protection to housing, education, public accommodations, and state funded programs (but still no life, disability, or long-term care insurance

PRSs and EHR issues

psychological labeling, clinicians may not be adequately trained to interpret probabilistic genomic risk, data follows patients for life

STRs in DNA fingerprinting

Analyze highly variable repeated DNA sequences at specific genome locations, using PCR to amplify these markers then gel electrophoresis

CODIS

Combined DNA Index System, established through DNA identification act, administered by FBI

what does CODIS store?

highly polymorphic STRs, mtDNA, and Y-STRs

why are multiple STR loci used for inclusion? are results absolute?

increase the power of discrimination to narrow it down, inclusion is probabilistic

golden state killer

used SNPs to find, identified kin = ethical issues of invasion of privacy, intrusive to innocent people, psychological

Romanov family

STR markers used to determine that five skeletons were related, mtDNA used to compare to living relatives

arrestee state

DNA collected upon arrest (CA, NM, TX, VA, LA

Jesse Gelsinger

OTC deficiency → received adenovirus with OTC gene injected into liver → issues of informed consent and conflicts of interest

in vivo

vector injected directly into bloodstream

in situ

vector placed directly into affected tissues

ex vivo

cells removed from body, incubated with vector, and gene-engineered cells returned to body (usually done with blood cells)

David Vetter

boy in bubble, questions of keeping him healthy vs. is that anyway to live life

SCID

retroviral vectors used, insertion into an unintended location caused leukemia-like syndrome

which has most promise?

AAV → not associated with human disease, small genome easy to manipulate, infects dividing and non-dividing cell, high efficiency of transduction

somatic gene editing

target genes in specific types of cells, no other cells affected, highly regulated

germline gene editing

made early in development so any change is copied to all new cells + passed to future generations, newer

off target effects

acts on unexpected sites on the genome

on target

location correct, consequence is not, can lead to larger unintended edits

velvet eugenics

eugenics enforced by commercialism that seem like common sense by hiding violence behind autonomy and consent

historical bias for surgery in infants: Money

believed gender was malleable until ~18 months justified genital surgeries

sex diversity in non-humans

clownfish, elk/deer, hyenas

Turner syndrome

XO, variable condition = chromosomes aren’t everything

Androgen insensitivity (AIS)

XY, undescended testes, external like F = chromosomes aren’t everything

Congenital Adrenal Hyperplasia (CAH)

seen in both XX and XY, higher than average T levels, variable onset and experiences = hormones aren’t everything