genetic screening Flashcards
genetic testin
1) changes in DNA
2) changes in chromosome
3) measure genetic changes, RNA analysis as an output of gene expression
4) biochemical analysis to measure protein output
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tests available for more than 2000 genetic conditions
history of genetic testing
1 )1950s, counting chromosomes per cell
- trisomy 21
- monosomy x
2) 70s stain chromosome banding to analyzed chromosome structure
- structural arrangements
3) present, analyze cytogenetics, molecular genetics and genomics
- changes at levels of individual genes, or even SNPs
DCT genetic tests
1) direct to consumer
2) info about medical and non medical traits
3) ancestry, responses to medication, risk for developing conditions
4) cannot determine if you will get a disease
- should not be used alone to determine medical care
reasons for genetic testing
1) learn whether you have a genetic condition that runs in your family
2) learn about chances a child will have it
3) diagnose a condition if you or child has symptoms
4) understand and guide cancer prevention
5) do not do it if it is NOT relevant to you
categories of genetic tests
1) single gene testin
2) panel testing
3) large scale genetic or genomic testing
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no single test can detect all genetic conditions
single gene testing
1) changes in one gene
- duchene muscular dystrophy
- sickle cell
panel testing
1) changes in many genes in one test
- breast cancer
- colon cancer
large scale genetic testing
1) exon sequencing external icon
- whole exome or just genes related to medical conditions
1) genome sequencing external icon
- all person’s DNA
for complex medical histories
types of genetic testing
1) cell free fetal DNA
- non invasive for fetus
- Down syndrome
2) newborn screening
- can identify genetic disorders to treat early in life
- congenital hypothyroidism
- must test for at least 21 disorders
3) diagnostic testing
- rule out a specific condition
- carrier testing
- cystic fibrosis
4) preimplantation genetic diagnosis
- human embryos prior to implantation as part of in vitro fertilization
5) prenatal diagnosis
- detect changes in fetus before birth
predictive and presymptomatic genetic testing
1) test gene mutations that appear after birth
2) predictive testing identify mutations that increase changes of developing disorders
- cancers
- BRCA1 => 65% of breast cancer
3) presymptomatic testing can determine disorder before signs and symptoms occur
- hemochromatosis
4) half of men and 1/3 women will develop cancer in their lifetime
5) certain genetic variants can make risk of cancer higher than average
pharmacogenomics
1) influence o genetic variation on drug response
- examine genetic makeup to determine what medicine and dosage is safest
2) 11 million SNPS in genomes in human
- response to certain drugs can be found in them
non diagnostic testing
1) forensic testing
- DNA sequencing to identify individual
2) paternity testing
- DNA markers to identify inheritance patterns
3) genealogical DNA test
- genetic genealogy to determine ancestry
4) research testing
- to find unknown genes and how they work
estonia
1) all residents offered genome wide genotyping
- personalized reports
2) healthier lifestyles and preventative drugs
united states
1) genetic information nondiscrimination act
- cannot deny health coverage on the basis of genetic predisposition to developing a disease in the future
2) bars employers from using individuals genetic information for job decisions
3) passed by Goerge W Bush and US senate
prenatal diagnosis
1) couples at high risk had to choose between taking risk, abortion, sterilization, adoption, or donor insemination
2) in 1960s, fetal medicine
- perform karyotype on unborn child
- detect abnormalities in fetus
3) 150,000 born in each year with birth defect in US
prenatal testing can involve
1) blood tests
2) imaging
3) chromosome analysis
4) other genetic testing to assess health of mother and baby
prenatal genetic screening and testing
1) Noninvasive
2) invasive
noninvasive
- maternal serum
- cell free fetal DNA
- ultrasonography
- fetal MRI
- fetal echocardiography
invasive
- amniocentesis (fluid, cells)
- chorionic villus sampling
-fetoscopy (Blood, liver, skin, visual)
maternal serum sreening
1) 16w of pregnancy
2) NTD, down syndrome, invorrect gestation age, fetal bleeding, multiple pregnancy, miscarriage, etc
3) biochemical markers
- down syndrome triple test: down AFP, down unconjugated estriol, up hCG
- quad test includes inhibin A
cell free fetal DNA
1 )6-7w of pregnancy
- fetal sec by Y chromosome detection
- X linked recessive disorders
2) chromosomal aberrations, rhesus (Rh) blood type
3) assess from maternal circulation
ultrasound
1) noninvasive
2) identify gestations age, growth, baby number, placental structure, blood flow, PHYSICAL EXAMINATION
ultrasonography
1) 2D, 3D
2) 4D which allows image that is continuously updated, like a moving image
fetal MRI
1) magnetic field to create pictures for evaluation
2) 2nd and 3rd trimesters
3) can supplement ultrasound, more info on fetal brain, other fetal anatomic structures
fetal echiocardiogram
1) ultrasound looking at unborn baby heart structure and function
2)help plan and prepare for infant delivery and special interventions
3) determine treatment and fetal therapy
radiography
1) 10 weeks onwards
2) inherited skeletal dysplasia diagnosis
3) useful on occasion
amniocentesis
1) after 15th weeks of gestation
2) thin needle guided to mother’s abdominal wall into pocket of amniotic fluid
3) 10-20 ml
4) fluid
- NTD (alphafetoprotein)
5) cells
- chromosomal abnormalities, metabolic disorders, molecular defects
6) -0.5-1% risk of miscarriage
- if result is abnormal ,woman may do 3rd trimester termination of pregnancy
chorionic villus sampling
1) 10-13th week of pregnancy
2) needle through cervix or abdomen using small catheter
3) small amount of placental tissue is removed for evaluation of chromosomes or genetic test
4) chromosomal abnormalities, metabolic disorders, molecular defects
fetal blood sampling (chordocentesis)
1) medications can be administered and blood transfusions performed when needed
2) from around 20 weeks gestation
2) management of rhesus iso-immunization, and nonimmune fetal hydrops
4) chromosome analysis may help resolve issues in mosaicism in CN or amniocentesis samples
genetic counseling
1) individuals at risk of congenital abnormalities
2) risk of disease with genetic component in etiology
3) know partner is affected or there is a adverse outcome running in his or her family
requirement for genetic counseling
1) correct diagnosis
2) accurate family history
3) medical history
4) physical exam
5) lab test
6) relationship to affected individuals
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based on etiology of specific disease
- environmental - risk = prevalence in general population
- monogenic - AD, AR, XR, XD
-MF
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recommendation
- genetic testing, prenatal diagnosis, prevention
1st degree relatives
1) sharing 50% genes
2) siblings, parents, children
2nd degree relatives
1) sharing 25% genes
2) grandparents
3) grandchildren
4) uncles and aunts
5) nephews and nieces
3rd degree relatives
1) sharing 12.5% of genes
2) first cousins
3) great grandchildren
amniotic band syndrome
1) 1/15,000
2) recurrent risk for
- 1st degree (low, same as birth)
- 2nd degree is same
- 3rd degree is same
3) because it is environmental, non genetic
cleft lip and palate
1) 1/1000 birth (multifactorial)
2) RR
- 1st degree (square root of population incidence 3%)
- 2nd degree (half of RR of 1st degree 1.5%)
- 3rd degreed (half of 2nd 0.75%)
amelogenesis imperfecta
1) monogenetic (AD in most cases)
2) 1/14000
3) RR
- 1st degree relatives (1 in 2 or 50%)
- 2nd degree - (1 in 4 or 25%)
- 3rd degree (1 in 8 or 12.5%)
ethical and legal issues
1) autonomy
- incorporating respect for individual, consent, confidentiality
2) beneficence
- seeking to do good
3) non maleficence
- seeking not to harm
4) justice
- incorporating
autonomy
1) patients should take decision
2) patient should make decisions that have to be made
3) may seek guidance, requiring judgement of the counselor
4) can be comfortable to opt out freely at any stage of the process
informed choice
1) full information about all options available in a given situation
2) including the option of not participating
informed consent
1) entitled to an honest and full explanation of any procedure or test
2) risks, limitations, implications, and possible outcomes of each intervention
3) some form of signed consent is being obtained for every action that exposes the patient - access to medical records, clinical photography, genetic testing, and storage of DNA
informed consent
1) aims and methods
2) selection criteria
3) duration
4) benefits and risks
5) compensation
6) withdrawal
participating in research
1) voluntary
2) informed consent
3) an attending physician is also the researcher
4) tissue samples or other biological specimens provided for clinical use are also intended for research
5) intention to store the tissue should be specified and consented
6 )children
- informed consent is signed by parents and guardians
confidentiality
1) code number, unlimited access, omitting identification, safeguard of data, limitation
2) right to complete confidentiality
3) stigmatization and guilt may still accompany the concept of hereditary illness
4) ONLY breach under extreme circumstances
- deem that individual may harm self or others
5) difficult area of sharing info between regional genetic services
- require patient consent is the norm
beneficence
1) patient should receive highest priority and benefits
non maleficence
1) protect patient from any kinds of harm
justice
1) should be treated with fairness and benefits and burdens of healthcare distributed equally
ethical dilemmas related to genetics
1) confidentiality
2) prenatal dx
3) predictive testing in childhood
4) implications for the immediate family
5) implications of extended family - XR disorders
6) informed consent in genetic research
7) secondary, or incidental findings
implications for immediate family
1) positive test can have implications or close relatives that may not want to be informed of disease
- ex. huntingtons
2) affects confidentiality and disclosure to third parties
3) can be diagnostic but also predictive
4) DTC, falling cost of genome sequencing, new technologies, is a concern for clinical genetics
