Exam 2 Flashcards

Question

Treacher Collins

Answer 1

-1/50000 -lower jaw and cheekbones smaller than normal, lower eyelid coloboma (notch), downward sloping eyes -outer ear abnormalities (microtia, ear tags, ear pits, atresia), CHL, rarely SNHL -cleft palate about 30% of cases -about 60% cases are sporadic (advanced paternal age) -AD -100% penetrance, variable expressivity -TCOF1 gene on 5q32, treacle protein (directly affects RNA polymerase activity) -P53 is a tumor suppressor gene -stablization of p53 causes the high degree of neuroepithelial apoptosis- loss of neural crest cells -mouse studies of antioxidant supplementation show a degree of reversal

Answer 2

-x-linked recessive 80% of cases, AD, AR -1/5000 -kidney function-hematuria- in early childhood -progressive HL, eye involvement (except AD) -rare aneursyms in males -bilateral HF SNHL in late childhood -about 50% of male patients with x-linked Alport syndrome SNHL by 25 -about 90% of cases are deaf by 40 -less severe progress and outcomes in females -highly variable -COL4A3, COL4A4, COL4A5

Answer 3

-fistulas and cysts associated with 2nd brachial arch -pits, tags, pinna abnormalities, ME and inner ear structural abnormalities, may be unilateral -may have small or abnormal kidney(s), absent kidney, ultimately end stage renal disease possible -may not be identified -often confused with Alport -about 1/40000 -HL in 95.4% of cases -malformed auricles in about 86.8% of cases -second branchial cleft anomalies in 86.5% of cases -preauricular sinus in 87% of cases -renal anomalies in 58.3% of cases

Answer 4

-youngest presentation around 5 but usually occurs in the 3rd decade -0.2-1% prevalence in European studies -AD based on pedigrees -decreased penetrance (25-40%) -multifactorial (bone, endocrine, inflammation, immune) -may be mixed over time -genes: loci identified but do not know what the genes do: OTSC1-OTSC10 -very little progress -also COL1A1, TDF-beta (transforming growth factor)

Answer 5

-may cause DFNB2, DFNA11 and Usher I -11q13.5, about 48 exons (some alternatively spliced), 559 pathogenic mutations -Usher affects hearing, vestibular system and pigmentosa retinitis -progression possible -DFNB2 a precursor to Usher? -low frequency SNHL is some cases affects- stereocilia in hair cells and retinal pigmented cells

Answer 6

-AR, 7q22.3 -gene: SLC26A4 (majority), some evidence for digenic -21 exons, 780 amino acid transmembrane anion transporter protein pendrin -found in thyroid, inner ear and kidney -localizes to apical membrane of cells in the spiral prominence and outer sulcus cells in cochlea; transitional cells of the cristae ampullaris, utriculi and sacculi, cells in the endolymphatic sac -hearing loss, EVA and with syndrome sometimes Mondini -syndrome 1896, 2 sisters with goiter and HL

Answer 7

-fluctuating or progressive SNHL with EVA -pre, peri or even postlingual onset, may pass NBHS -severity, laterality, age of onset of SNHL variable -ABG at low frequencies (3rd window) -incomplete penetrance -highly variable in severity and frequency -abnormal testing frequent in patients but without subjective dizziness: carolis, rotational chair testing, cVEMP, vHIT -vestib findings are not correlated with degree of HL -pathophys: anion exchanger, loss of function, cytoplasmic accumulation; progression may be associated with changes in intracranial pressure

Answer 8

-same gene as Pendred syndrome -hundreds of variants -mostly missense but an be deletions and duplications -can be digenic -likely additional genetic heterogenic

Answer 9

-spectrum for both: often congential, bilateral SNHL often mild to profound but can be mild to moderate, may be progressive or fluctuating, may have vesibular dysfunction, EVA -pendred only: incompletely penetrant euthyroid goiter usually developing teens to 20s, often Mondini dysplasia

Answer 10

-protein called Cadherin 23 (stereocilia interactome) -major cause of HL in some populations -nonsyndromic mostly- bilateral moderate to profound progressive SNHL, prelingual (20+ mutations) -SNHL, retinitis pigmentosa and vestibular dysfunction in Usher (30+ mutations) -do well with CI

Answer 11

-prelingual moderate to severe to profound SNHL -product is transmembrane protein localized to stereocilia channel complex -common cause of recessive deafness in consanguineous Indian, Pakistani, Turkish and Tunisian families -can be progressive

Answer 12

-transmembrane protease -progressive bilateral -variable onset ages and progression rates -sloping audio eventually becomes flat

Answer 13

-DFNB9 -otoferlin, vesicle membrane fusion (IHC) -2p23-24 -3-4% of NSSNHL -ANSDE or profound HL -correlates with ribbon synapses -temperature sensitive allele in humans -truncating mutation may cause severe to profound flat or gently sloping -missense may cause moderate, flat to steeply sloping and is associated with ANSD

Answer 14

-DFNB59 2q31.2 -pejvakin (function related to gene at DFNA5 7q18.3) -AR -pre or post lingual mild-profound HL -ANSD -expressed in spiral ganglion neurons -truncating mutation will cause profound SNHL and vestibular hypofunction

Answer 15

-most common peripheral neurological syndrome'-2 main forms, much genetic heterogeniety- genes usually affect axon function, often myelination -GJB1 Xq13.1 affects hearing (x-linked dominant)

Answer 16

-DFNA12, DFNB21 -alpha-tectorin- non-collagenous extracellular matrix -11q23.3 4% of prelingual HL in Iran, about 4% ADNSHL -most frequently: prelingual, often mid-frequency loss, may be severe to profound, heterozygous less severe -less frequently HF SNHL or postlingual or progressive (missense) -expressed weeks 12-20 -tectorial membrane core is collagen embedded in striated sheet of tectorin -otoconial membrane -pathophysiology: interaction between basal membrane and tectorial membrane traveling wave may affect spatial extent and timing of OHC excitation -audiologic measures: loudness growth curves normal, suprathresholds normal, DPOAEs present at higher stimulus levels, more like CHL than SN

Answer 17

-dominant and varied -mid frequency, progressive, sometimes HF -mutations in the zona pellucida domain would cause mid frequency U-shaped HL -mutations in the zonadhesin-like domain may cause HF HL

Answer 18

-recessive -stable prelingual HL -moderate to severe across all frequencies -more pronounced in the mid frequency range

Answer 19

-otogelin, glycoprotein -moderate SNHL similar to TECTA -not thought to be progressive -DFNB18B -AR -11q15.1 -may have vestib (unlike TECTA)- anchors otoconia -normal imaging likely

Answer 20

-1p34, KCNNQ4 -potassium voltage gated channel, KQT like subfamily, member 4 -regulates K+ current (excitability) -isoforms -complete penetrance -present in hair cells -nonsyndromic, symmetric, progressive predominantly HF SNHL -may be identified through school screenings but likely congenital, most aware by teens, can be as late as 40s -clinical testing available

Answer 21

-4q16.1, wolframin -also syndrome, very rare nonsymdromic recessive -heterozygous for missense mutations -transmembrane protein, 8 exons, expressed highly in the brain and the heart -progressive low frequency SNHL, good speech unless ARHL -often not identified until early childhood -no profound HL -referrals: should be checked out for optic atrophy -testing available

Answer 22

-neurodegenerative spectrum disorder -4p16, 8 exons: wolframin, transmembrane glycoprotein -pathophysiology: post translational protein folding ER -progressive -onset of diabetes mellitus and optic atrophy by age 16 -HL often low frequency, variable, can be profound -diabetes insipidus -neurologic and psychiatric abnormalities -may be initially diagnosis with diabetes type 1 -high morbidity and early mortality -AR

Answer 23

-6p21 -nonsyndromic postlingual HL -may be mid or low frequency -progressive HL beginning in the second to fourth decades

Answer 24

-traditional Usher type -severe to profound SNHL at birth or within 1st year -vestibular areflexia (may not sit by 6 mo, average age of walking around 20 mo, may be described as clumsy, swimming underwater potentially dangerous) -night blindness and RP in late childhood- legal blindness by age 30 -associated with higher risk of poor QoL -ERG testing may not be abnormal for several years

Answer 25

-non-mendelian inheritance -clefting and syndromes involving craniofacial -ARHL -mitochondrial -NIHL -speech/language -genes + environment

Answer 26

-very large numbers -meaningful definitions -consistent and appropriate phenotyping

Answer 27

-catalase: breakdown of superoxide anions -glutathione S-transferase (GST) enzymes: catalyse the conjugation of glutathione with xenobiotics, compounds foreign to human metabolism -N-acetyltransferases (NAT): detoxify harmful substances -Sirt3 (mitochondrial): promotes glutathione-mediated mitochondrial antioxidant defense system in mice, activated in calorie reduction

Answer 28

-16569 base pairs, no histones -well characterized genes: oxidative phosphorylation, rRNA and tRNA mutations -requires nuclear genome products -maternal inheritance or de novo -10-20 times more prone to mutation -pleiotropic effects -penetrance, tissue specificity -regular screening of newborns for most common mutations in China -ethnicity important for specific mutation, prevalence

Answer 29

-variable: penetrance, onset and severity -less than 1% of congenital HL, 5% of post lingual -nonsyndromic: MTRNR1 (1555A>G), MTTS1 -syndromic (metabolic): MELAS, MERFF, MIDD, Leber hereditary optic neuropathy (LHON) no HL -always SNHL -usually progressive -usually symmetrical -often high freq

Answer 30

-lactic acidosis -stroke-like episodes -diagnosis after childhood -progressive disorder -high morbidity and mortality -psychosis

Answer 31

-ragged red fibers- rare

Answer 32

-mid adulthood -HL precedes other symptoms -3243 A to G transition in MTTL1 -2-6% of individuals with diabetes mellitus in Japan

Answer 33

-12S rRNA -interacts with aminoglycosides -HL only (nonsyndromic) -1555A>G, 1494C>T, 961delTins(C)n -epidemiology: 20% in Spanish deaf, 0.7% in German deaf -40% have HL by age 30 -HL is variable age of onset and severity of HL, ranging from profound bilateral HL to WNL, more severe at HF -progressive- over 3 years hearing gets worse -C1494T also AMG susceptability -mutation makes the 12S ribosomes more like the bacterial 12S so it binds aminoglycosides more easily -may affect ability to make proteins for oxidative phosphorylation -affects amount of ATP generates in the cell (if too little it can increase ROS therefore apoptosis) -associated with ototoxicity -high risk in variant in Asian and African populations -huge issue in poorer countries where use AMG more -resistant to TB -HL after a single exposure, more severe than what develops without AMG

Answer 34

-tRNAser -variants make the tRNA for serine either ineffective or less effective -mostly hearing, some neurological, skin -nonsyndromic -HL is childhood onset, variable, mild to severe, progressive -prevalence is about 1% -7445A>G associated with palmoplantar keratoderma (scaling, hyperkertosis, and honeycomb appearance)

Answer 35

disease treatment and prevention based on individual variation in genetics, environment and experiences

Answer 36

-100+ nonsyndromic genes identified (excluding MT and miRNAs) (hereditary HL homepage) -knowledge base is incomplete for populations-basis for panels -massive parallel sequencing/NGS permit WES and WGS -0.01% of the human genome (targeted gene enrichment increases by at least 1000 fold) -capacity of MPS/NGS sequencers- can do DNA from more than one individual

Answer 37

-cCMV: real time PCR of saliva, urine or both within the first 3 weeks or if later, blood spot analysis -imaging

Answer 38

-testing of a symptomatic individual

Answer 39

-testing of a symptomatic individual that is used to establish the diagnosis of a specific genetic disorder when the clinical findings are equivocal

Answer 40

-testing of an asymptomatic individual with a family history of a genetic disorder who is at risk of developing the disorder

Answer 41

-when strong genotype-phenotype correlations exist -establishing the genotype of a symptomatic individual in order to determine the probability that certain phenotypic features will appear over time

Answer 42

-testing performed during pregnancy to determine if a fetus is affected with a particular disorder

Answer 43

-testing one cell removed from an early embryo conceived by IVF for a mutation(s) for which it is specifically at increased risk -embryos that do not have the mutation in question are then transferred to the mothers uterus

Answer 44

-karyotype -FISH

Answer 45

-GWAS -mutation analysis, haplotypes (Soundgene, 23 and me) -sequencing -gene chip, SNP chip -NGS, MPS, WES, WGS -CNV -mitochondrial -epigenetics

Answer 46

-Sanger -NGS (WES and WGS) -Special PCR protocols

Answer 47

-MLPA (multiplex ligation probe assay)- exon sized -FISH not just number but localization

Answer 48

-CGH comparative genomic hybridization -MLPA -algorthisms applied to NGS data -SNP chip scan

Answer 49

-genes related to a particular disease or phenotype (may include mito) -hypothesis driven -limited by what is known and population -must be updated as research progresses -may need to retest if negative -sequences or SNPs

Answer 50

-the protein coding exome -1-5% of total genome -much less to be analyzed -accounts for about 85% of known disease causing variants

Answer 51

-in theory it tests all 3 billion base pairs

Answer 52

-lot of data that takes a lot of computing and professional judgement to be meaningful -not hypothesis driven -may not provide an answer until research advances -may still need some specialized testing for CNV -VUS and unexpected findings are considered a problem

Answer 53

-percent of bases in a sample sequenced at least 1 time, 30 times etc -related to accuracy and reliability

Answer 54

-number of times a nucleotide at a location has been read -more reads = more reliable, more likely to pick up rare variants -need to recognize/account for misreads -30x more common for cheap WES/WGS, panels can be 100x -need very deep depth/coverage for rare variants

Answer 55

-WES and WGS and panels result in millions of reads that are than aligned to the human reference genome -reads go both forward and back so there are two sets -depth indicates the number of reads at a particular base in the reference genome -may apply filters to remove variants ex. synonymous variants -FASTQ panel is the summary

Answer 56

-variants that result in the same AA -a base change that does not change the amino acid because of redundancy

Answer 57

-function --gene function --pattern of expression: right tissue, right time --part of a known pathway? --animal studies: pathways, knock in, knock out

Answer 58

-2%< -may miss regulatory areas -technical issues -cheaper and less analysis needed

Answer 59

-most complete -expensive and harder to analyze -more issues in sharing info -more than 1000$

Answer 60

-potentially lower cost (500 to 3900) -better coverage -must include the gene but can add in candidate genes and low frequency variants

Answer 61

alter the amino acid sequence

Answer 62

-perception of more value to family -unknown (to the researcher) family history, imaging results, comorbid conditions -effect of poor documentation -habit of not bringing it up -identified barriers (physicians lack of knowledge, long wait times, lack of understanding of usefulness, lost to followup, logistical delays, lack of family support)

Answer 63

-must relate to phenotype -knowledge is power -effort to systematize

Answer 64

-determine cause of HL -reduce or eliminate the need for other invasive and costly medical tests -provide info about a patients future hearing and other potential medical complications -answer questions patients may have -prognosis useful for management/rehab -allow estimate of chance of having another child with HL -minimally invasive -promote and benefit from increasingly reliable genotype-phenotype correlations -increases our knowledge about the auditory system -patients needs and desires -patients education, provider education

Answer 65

-MYO7A -DIAPH -COL4A5 -TMPRSS3 -OTOGL -TMC1 -MYO15A

Answer 66

-vestibular migraines: no biological marker so it has to be a clinical diagnosis, consistent with AD, decreased penetrance when family history is present -meniere: about 10% familial, AD, AR, mitochondrial, autoimmine -SSCD -EVA -VS

Answer 67

-unique disease risks and treatments -individualized prediction/management/treatment

Answer 68

-most likely under neurology or ENT care -neuropathies- usually childhood onset, AR -if adult onset, cerebellar (not vestibular): AD, X-linked pattern, rarely late onset AR (Friedrich ataxia) -symptoms: lack of coordination, slurred speech, trouble eating and swallowing, deterioration of fine motor skills, difficulty walking, gait abnormalities, eye movement abnormalities, tremors and heart problems

Answer 69

-gene with significant vestibular effects also causes significant HL -COCH (coagulation factor C homology, cochlin) -extracellular matrix protein, 550 amino acids cleaved into 2 pieces -14q12-13 -AD but two rare loss of function AR -effects usually late onset (20-30): HL can progress to profound by 40-50 -variety of variants including missense mutation and two in-frame deletions: essentially only HL, HL and bilateral vestibular dysfunction, disabling vertigo

Answer 70

-age to sit -age to walk -PTA -parental concern for gross motor development

Answer 71

-can help kids who are at risk of delayed gross motor development, falls, poor visual acuity -early identification has lead to good outcomes from patient

Answer 72

-dopamine (p300) -cholinergic receptor gene (attention) -serotonin transporter studies (auditory hallucinations, P300)

Answer 73

-many chromosomal associations, some candidate gene and family linkage studies -FOXP2: first gene identified with speech and language effects (motor function) -stuttering: connectivity with the corpus callosum, energy use?, dopamine?, 12q23.3 GNPTAB (lysosomal storage-reduced by FOXP2) -little molecular data -dyslexia -specific reading impairment -SLI -ADHD -fragile X

Answer 74

-forkhead box protein -identified by pedigree Mendelian AD -transcription regulator -primary effect in the brain and kidney -active in embryogenesis -part of FOX superfamily (cancer, diabetes) -highly conserved

Answer 75

-gene expression: neuronal and supporting cells -cell migration -axon extension and guidance -synapse development and pruning: cell adhesion (CAM) and scaffolding and synaptic signaling-associated proteins -critical periods

Answer 76

-genetically and clinically complex but speech/language dysfunction almost always present -some pathways/functions consistently identified: chromatin remodeling genes, synaptic development and plasticity and other transcriptional

Answer 77

-overlap with other genes associated with neurodevelopmental disorders -but 26% rate rate, de novo high -possibility of precision medicine

Answer 78

-SNP based -not all speech language correlates with IQ -identified genome-wide significant association for word reading at chromosome 1 (candidates DOCK7, ATG4C, ANGPTL3, USP1)

Answer 79

-difficulty of a complex behavioral phenotype -identified genes, mostly brain development or immune system -large numbers of genetic abnormalities found in families with at least one autistic individual -multiple genes if abnormal in an individual can bring small increments of risk to that individual -de novo mutations -lots of different kinds of genetic changes especially CNV -parental age, including fathers (increase of 2 de novo mutations a year) -AUTS2: autism susceptibility gene but there are many phenotypes

Answer 80

-greater than 100 loci -multiple variants all with small influence -point mutations, microdeletions and duplications, CNVs -balanced chromosomal abnormalities -epigenetic changes -overlap with genes related to neurodevelopmental disorders -one approach: look at families with 2+ females on the spectrum -function: synaptic proteins, fragile x mental retardation which is associated with proteins FMR1, regulators of chromatin modification

Answer 81

-almost all females -about 1 in 10,000 -about 25% have HL -infancy (6-18 months) has normal development then the child will start to miss milestones -de novo MECP2 duplication on X chromosome -slowed growth, microcephaly -neurological: affects speech, movement, language, learning -repetitive hand motions characteristic early stages

Answer 82

-FXS -intellectual disability, behavioral challenges, learning challenges and various physical characteristics -mostly affects males -the most common form of inherited intellectual disability -can look like ASD -FMR1, Xq27.3 -FMR1 gene may cause decreased expression of FMRP: affects mRNA and protein synthesis which may shuttle mRNA, translation of autism related proteins -part of the gene (CGG) is repeated- the more repeats, have hypermethylation of the CpG island proximal to the repeats which silents the promoter -6 to 44 is normal -45-54 is intermediate -55-200 is premutation (protein is still made) -greater than 200 will result in FXS; unstable, no protein -ABR found males WNL -usually have more OM before the age of 5

Answer 83

-intellectual disability -speech and language delay -large ears -long face -soft skin -macroorchidism -connective tissue problems: ear infections, flat feet, high arched palate, hyperflexible joints -ADD/ADHD -ASD -social anxiety -hand biting/flapping -poor eye contact -sensory integration problems -aggression

Answer 84

-intellectual disability (milder form than males) -physical features are less prominent -emotional and mental health concerns -a small percentage of females with a full FXS mutation might show no symptoms at all

Answer 85

-ethical, legal, social issues -psychological benefits/burdens -family health data, parentage -privacy issues -implications for employment, insurance and relationships -choices imply responsibility and moral accountability -definitions important: probability, risk, susceptibility

Answer 86

-autonomy (right to make own decisions) -beneficence (duty to assist) -nonmaleficence (do no harm) -justice (equal treatment and allocation of resources)

Answer 87

-define the problem -determine facts/assumptions -list alternatives/options -evaluate how well solutions are supported by ethical principles

Answer 88

-its creation had good intentions (wanted to increase the prevalence of desirable traits) -negative eugenics prevents bad genes from being transmitted -positive eugenics encourages the 'best' to have children

Answer 89

-person chooses not to be helped (autonomy) but not in the patients interests (beneficence) -patient makes a decision for a child (capable informed parents) -Alzheimers- who decides? -very low birthweight infants

Answer 90

-top down? apply principles to cases or policy issues -bottom up? each case/policy different -middle way? case/policy to principles, moral compromise

Answer 91

-list of serious conditions and enforce it (paternalism, different societal or religious norms) -hands off, anything goes -society does not interfere with choices after counseling but discourages some practices

Answer 92

-SNP based risk -mutlifactorial, complex diseases -estimates genetic predisposition -individual is compared to a population (GWAS data) -number of variants multiplied by their effect size = overall risk of developing a disease -often scores as a percentage -sensitivity highly variable and typically pretty low

Answer 93

-genetic information nondiscrimination act -applies to the legality of genetic testing including: analysis of human DNA< RNA, chromosomes, proteins, or metabolites that detects genotypes, mutations or chromosomal changes not metabolites

Answer 94

-protects individuals from genetic discrimination in health insurance and employment -illegal for a health insurer to use family health history and genetic test results as a reason to deny health insurance or determine cost of coverage -illegal for an employer to use family health history and genetic test results in making decisions related to employment

Answer 95

-information about an individuals genetic tests or the genetic tests of the individuals family members, and the manifestation of a disease or disorder in the individuals family members -also, the request or receipt of genetic services or participation in clinical research that includes genetic services, for both the individual and the individuals family members -an individuals sex or age is NOT protected genetic information under GINA and GINA does not protect disease manifestation in an individual

Answer 96

-provided protection for pre-existing conditions

Answer 97

-nondiscrimination in employment -prohibits use of genetic information in making decisions regarding hiring, promotion, terms, privileges, compensation or termination -prohibits limiting, segregating or classifying of an employee on the basis of genetic information -prohibits request, requirement or purchase of genetic information of an individual or a family member of the individual except in rare cases -prohibits failure or refusal to refer an individual for employment on the basis of genetic information, or causing an employer to discriminate against an individual on the basis of genetic information -prohibits use of genetic information to make decisions about admission to or employment -prohibits in any program for apprenticeship or training

Answer 98

-provide protections from genetic discrimination in life, disability or long term care insurance -cover employers with fewer than 15 employees -apply to those in the military and some other groups -cover an individuals manifested disease or condition (does protect information about manifested disease in an individuals family members -pre-empt state law (if more protective)

Answer 99

-HIPAA provisions apply to genetic information -privacy rule: covered entity need not obtain consent or authorization from the individual for uses and disclosures of protected health information for treatment, payment or healthcare operations -minimum necessary -may be deidentified but genetic information can be reidentified -HIPAA does not apply to consumer genetics

Answer 100

-concealing ones secrets is less relevant than being in control of the distribution and use by others of the data people generate in the course of seeking healthcare, conducting consumer transactions and going about their lives -privacy policies vary widely -are very complex

Answer 101

-incidental findings -intellectual property -translational medicine -genebanking -concepts of identity -genetics and national character/ethnicity -conduct of genetic research -understanding of traits and behaviors -direct to consumer testing -germline vs. somatic -modification vs. selection

Answer 102

-education: FERPA, IDEA, ADA; concerns for discrimination in admissions, educational placement, discipline but no evidence genetic info used now -criminal justice: concern for genetic reductionism/determinism; HIPAA can release PHI to law enforcement without a warrant, subpoena or any other legal process; inferences about facial features, eye color -occupational/environmental risk assessment: exposure limits, nondiscrimination statutes, autonomy vs. paternalism

Answer 103

-BRCA gene litigation: BRCA1 was patented in the 90s but legal issues have since come up with it -2013, ruling that human genes cannot be patented, DNA is a product of nature so there is no intellectual property -can patent complementary DNA (cDNA)

Answer 104

-been rival suits about the original inventor and the first to file the patent -in many countries the inventors are seen as the owners but in the US the first to file the patent (not the inventors) own it

Answer 105

-many countries have no policy -gene editing case in 2018 saw someone use CRISPR to gene edit in utero to make children resistant to HIV infection -scientific community has called for a 5 year moratorium

Answer 106

-informed consent -uncertainty: not all positive tests result in the phenotype, a negative never means that there is a no genetic component -there are risks and benefits with every genetic test like empowerment, relief, can affect family relationships, basis for discrimination, psychologically harmful/beneficial -education- provider and patient/consumer