HG exam 3 pgs 1-5

Genetic Testing & Diagnosis 

Test fall into 3 basic categories 

  • Tests before conception: discover what gene an adult has & how it can be passed to their children and discovering what disease gene an embryo may have 

  • After conception: discover genetic diseases in developing fetus 

  • After Birth: diagnosing person who has symptoms 

Types of tests 

  • Predictive / presymptomatic screening 

  • Used to detect gene mutation causing disorders after birth or later in life 

  • Can determine chances of developing certain cancers, typically only tells you your risk 

  • Can predict genetic disorder before symptoms develop 

  • Allows patient to help make decisions about future medical care

  • Types:

  • 1)

  • Presymptomatic_____________ Testing = positive result means you will develop symptoms of

disease at some time in your life (Huntington’s Disease)

  • 2)

  • _____Predisposition____________ Testing = positive result means you are more likely to develop

  • symptoms of disease, but it is not definite (BRCA and breast cancer)

  • Preimplantation screening 

  • Specific technique for ____reducing the risk____________ of having a child with a particular genetic or chromosomal disorder

  • _____specifically detect______________ genetic changes in embryos for IVF

  • Small number of cells taken from embryo and tested, occurs before ___implanation___________

  • Candidates, tests over 100 genetic conditions

- Sex linked disorders

- Single gene disorders

- Women over 35

- Recurrent pregnancy loss 

- Prenatal screening 

- Detects changes in fetus genes or chromosomes ___before birth_______

- Typically offered during pregnancy if there is increased risk

- Cannot cover all inherited disorders/birth defects (there are 4,000 that we know of)

- Only lessens parent’s uncertainty or help them make decisions

- Includes:

- 1)____non invasive _________ procedures = (after 8 weeks) Cell free fetal DNA analysis from maternal blood, can reveal sex of fetus & specific genetic abnormalities

- 2)__invasive ________ procedures = chorionic villus sampling (after 10 weeks) & amniocentesis (after 15 weeks)

  • Newborn screening 

  • Testing ____automatically__________ done _____just after birth__________ to identify genetic disorders

  • Most are for conditions that are serious if treatment not started early in life

  • 32 core conditions every state screens for = most are inborn errors of metabolism __________________________

  • Varies from state to state (Tennessee screens 70 different conditions) 

  • Amino acid disorders = PKU

  • Endocrine disorders = adrenal dysfunction too much androgen

  • Fatty acid oxidation disorders = body cannot break down fatty acids

Hemoglobin disorders = sickle cell

  • Lysosomal storage disorder = lysosomes cannot break down fats

  • Organic acid disorders = metabolic condition where acids build up in blood & urine

  • Other = CF, SCID, Critical Congenital Heart Disease

  • Diagnostic screening 

  • To ___identify or rule_____________out a specific genetic or chromosomal condition

  • Used to confirm_____ a diagnosis when signs & symptoms indicated it

  • Can be performed at ___any stage _______ before or after birth

  • Influences patients choices about health care and management

  • Carrier screening 

  • Typically done for those with a family history of a genetic disorder or certain ethnic groups that have an increased risk of a genetic condition

  • 1) targeted____ carrier screening = based on your ethnicity or family history

  • 2) ___expanded_______ carrier screening = tests 100 genes for specific disease that severely affect quality of life, not based on ethnicity or family history

  • Identifies those who carry ___1 copy ____ of a gene that when present in 2 copies causes a genetic disorder (thus only one of the couple needs to be tested)

  • Provides information for a couple that are planning on having a child in the future

  • Will tell the risk of having a child with that particular genetic condition

  • Forensic screening 

  • Identify person for legal purposes__________

  • not used_______for mutations associated with disease (no real medical application)

  • Good for:

- Identify or exonerate a person involved in a

- crime/investigation

- Victims of catastrophe

- Establish biological relationships (paternity)

- Direct to direct consumer tests 

(+) Provides information without ________involving doctor or insurance _____________________

(+) Easy: Collect sample at home (buccal swab or blood draw) → mail to laboratory

(-) Can be misled by _____unproven tests__________or person providing skewed results

(-) ___genetic privacy_____________

(-) May need someone to interpret or help make decision

- Cannot tell you

1. If ___you will show_____________________of a disorder

2. ___how severe________ the symptoms will be

3. How the disorder will ____progress over time____________

- More direct to direct consumer tests 

23 & Me =

(+) genetic information & ancestral background

(-) genetic mining & pharmaceutical collaborations (Google, Johnson & Johnson)

- Color Genomics = Google, Twitter, Stanford, MIT, Berkely

- fully automated laboratory, analyzes 19 genes of breast & ovarian cancer

- $249/test and provides genetic counselor

- Counsyl = genetic screening service for chromosome conditions, inherited cancers

- Gene by Gene = Whole genome & exome sequencing & mitochondrial testing

- LabCorp of America = diagnostic testing, predictive analysis, personalized medicine

- Myriad Genetics 

- Cornered the market in three areas

1. Predictive medicine ( asses risk)

2. Personalized medicine (response to a drug)

3. Measurement of disease activity

- Discovery of BRCA genes

- BRACAnalysis = test for hereditary breast & ovarian cancer

- COLARIS =  test for hereditary colorectal and uterine cancer

- MELARIS = test for hereditary melanoma

- TheraGuide 5-FU = personalized medicine for toxicity test to chemotherapy

- Panexia =  test for hereditary pancreatic cancer

- Vectra DA = blood test for rheumatoid arthritis

- Supreme court ruling = tried to patent the BRCA gene

 

- Immune system: overview 

Immune system composed of:

- 1.Immune cells (duh!)

- 2.The___molecules________ immune cells secrete

- 3.The____organs/tissues________ where immune cells are made/stored

- The effectiveness of your immune system is to be able to recognize 

- 1. Self vs. non-self cells

- 2. Between healthy vs compromised SELF CELLS (viral infected or cancer cells)

- 3. Between healthy vs pathogenic NON -SELF CELLS (lots of beneficial microbes)

- ***can tell the difference between self vs non-self by cell surface Antigens _____

- immune cell surface molecules 

- Chromosome 6 = encodes Major Histocompatibility Complex (MHC) that encode Human Leukocyte Antigens (HLA)

- 1. MHC I = encode HLA - present ____self peptides_______to cell surface

- = present on all nucleated________ cells

- = tells immune system ______________

- 2. MHC II = encode HLA – present ____anitgens___________ to cell surface

- = present on _______antigen presenting cell_________________

- = tells immune system ____something is wrong____________

- 3. MHC III = encode ___blood proteins___________

- = provides non - specific immune function

- Your HLA “type” – transplants, 6 types, 2 in 20,000, must match 4 of 6 for transplant

  • Human leukocyte antigen genetics 

  • HLA is encoded on Chromosome 6 _________________

  • Cluster of 200 genes

  • Encode surface glycoproteins

  • Importance in:

- 1) Infectious disease

- 2) Transplants

- 3) Autoimmunity

- 4) Cancer

- Antigen processing cells

- APCs

- 1. ____macrophages______ 

- 2. ___dendrtic cells_______ 

- 3. ___b - cells_______ 

- Steps in antigen processing

  1. Phagocytose invader

  2. Digest invader, attach to MHC

      3. Move MHC+antigen to cell surface

      4. Present MHC+antigen to _____APCs (antigen presenting cells)____

- Immune system overview

- Lines of immune defense

- 1. Physical barriers = skin, mucus, cilia, stomach acid

- 2. Innate System = rapid & non - specific

- 3. Adaptive System = slow & specific & memory

- Mutations can

- 1. ___inhibit________ immune function

- 2. Cause immune ___dysfunction________

- 3. Cause ____autoimmune__________ disorders

- 4. Cause increased infection_______

- 5. Cause ____decreased immune cells_______

- * Mutations can work in positive and negative manners

- immune system - innate 

- Rapid, broad defense

- Inflammation = central to this system = creates hostile environment

- Plasma accumulates, area becomes warm, signals immune cells to gather at site

- 3 proteins associated with Innate system (if mutated more susceptible to inf.)

- A.___complement________ = plasma proteins, assist other defenses, MAC punches holes

- B.___collections________ = recognize pathogen pattern sequences, activate phagocytosis

- C.____cytokines_______ = help both innate & adaptive immunity (secreted molecules)

  • 1.___interferon________ alerts immune system to viral infected cells

  • 2.___interleukins________ causes fever = higher body temp = kills bacteria/viruses

  • 3._____tumor necrosis factor______________ = destroys bacterial toxins, attacks cancer cells

- Immune system - adaptive 

- Slower, more specific

- 3 characteristics

- 1.__diverse______ = fights many types of pathogens

- 2. specific______ = distinguish between harmful/helpful

- 3. ___rembers________ = reacts faster upon next infection

- 2 types

- 1. ____humoral______ adaptive immunity (B & T cells) = antibody response

- 2. ____cellular______ adaptive immunity (T - cells) = helper & cytotoxic response

- immune system - adaptive - cellular response 

- Differs from Humoral Response because T cells travel to where they act rather than _____secerting antibodies_____________ as B cells do

- The life of a T cell

- 1.Comes from ____bone marrow_____________

- 2. Travels to thymus_____ to learn “self vs non self”

- 3. Those that learn survive & go out to the body

- 4. Those that do not learn are destroyed

- 5. Job of T cell is to secrete ____cytokines_______ and ___activate_____ other immune cells

- Types of T - cells

- 1.____helper_____T- cells = recognize foreign antigens, stimulate B cells to make antibodies, secrete cytokines, activate cytotoxic T cells

- 2._____cytotoxic______ T - cells = attack virally infected & cancerous host cells. Touches infected cell, releases perforin to destroy host cell

- 3. ____regulatory_______ T-cells = work to control immune response, avoid autoimmune destruction