Cell and Molecular Biology Lecture 30 and 31: Genetic Tests, Gene Therapy, and Prospects in Molecular Medicine I and II

What is defined as the analysis of chromosomes, genes, and/or gene products to determine whether a genetic alteration related to a specific disease or condition is present?

Genetic testing

True or False: All genetic conditions are inherited

False

What are the classifications of genetic testing?

Newborn screening, carrier screening, prenatal testing, diagnostic testing, predictive testing

What is newborn screening designed to do?

Detect conditions prior to the onset of symptoms

What types of diseases/disorders does newborn screening cover?

Only disorders where treatment is available

What does carrier screening cover?

Recessive disorders, ethnicity-based disorders, universal carrier screening

What are some ethnicity-based carrier screenings?

Hemoglobin electrophoresis, Ashkenazi Jewish panel, cystic fibrosis

True or False: Carrier screenings are not always informative

True

Do negative results always exclude carrier status?

No

What are the two examples of prenatal testing?

Prenatal screening and prenatal diagnosis

What are examples of prenatal screening?

Composite first trimester screening, prenatal cell-free DNA screening, quad screen

What are examples of prenatal diagnosis?

Chorionic villus sampling, amniocentesis

What are indications of prenatal testing?

Familial pathogenic variants, aneuploidy, abnormal ultrasound findings

Where is diagnostic testing used?

Symptomatic individuals

What is diagnostic testing used for?

To confirm or rule out a diagnosis

What example would predictive testing be used for?

Hereditary cancer syndromes

What are the types of genetic testing?

Biochemical testing, chromosomal testing, DNA studies

What is the primary target of biochemical testing?

Enzymes

What is biochemical testing usually performed on?

Blood, urine, spinal fluid, tissue

What are some examples of chromosomal genetic testing?

Karyotype, FISH, microarray

What does a karyotype genetic testing tell us?

Number and struture of chromosomes

What does FISH tell us?

Number of chromosomes

What does microarray genetic testing tell us?

Number of chromosomes, microdeletions/microduplications

What is the highest resolution chromosomal genetic test?

Microarray

Does microarray detect single gene disorders?

No

What are the two methods of DNA studies?

Direct, indirect

What are the methods of direct DNA study?

Sequencing, PCR, deletion/duplication analysis, whole exome sequencing

How is indirect testing done?

Linkage analysis

What are the issues related with genetic testing?

Cost, accessibility/availability, eduction, uncertain results, ethical principles, legal/social concerns

What are the four medical ethical principles?

Beneficence, justice, autonomy, non-maleficence

What is the Genetic Information Non-discrimination Act (GINA)?

Protects from discrimination based on genetic information and health insurance

What does GINA not apply to?

Life insurance, long term care/disability insurance

What is the vector for the first case of gene therapy?

Virus

What was the disease treated in the first case of gene therapy?

Adenosine deaminase deficiency

What was the outcome of the first case of gene therapy?

Improved immune function and quality of life

What was Jesse Gelsinger's deficiency?

Ornithine transcarbamylase

What were Jesse Gelsinger's symptoms after being injected with adenovirus?

Multi-system failure

True or False: Cystic fibrosis gene therapy has worked in humans using the Ivacaftor therapy

True

What are some issues with gene therapy?

Inconsistent outcomes, ethical concerns, vector determination is complicated, and target for delivery needs to be determined

What is the study of how each individual's genetic makeup affects drug response?

Pharmacogenomics

What are examples of when pharmacogenomics have been used?

Warfarin, chemotherapy, antivirals

What is the quantification of cell-free fetal DNA in maternal circulation?

Prenatal cell free DNA screening

What are the pros of prenatal cell free DNA screening?

Highest detection rate, lowest false positive rate, highest accuracy, low cost, high accessibility

What are the cons of prenatal cell free DNA screening?

Inability to detect rare conditions, not diagnostic, difficulty interpreting results

What are the concerns with whole genome sequencing?

High volume of data, variants, unintended results, interpretation is subject to current understanding of genetic disease/genomics

What panel utilizes next-generation sequencing and simultaneously analyzes many genes?

Hereditary cancer panels

How are hereditary cancer panels designed?

Based on indication

What are considerations for hereditary cancer panels?

Which genes are included in the lab, cost, insurance access, availability

What depends on the accurate transmission of complex and predictive information and the understanding of how to act on that information?

Success of genetic medicine

Genetic medicine offers the opportunity to detect increased susceptibility to disease and ___________, ____________, and _____________

Alter lifestyle, take preventitive medical measures, provide autonomy

What is the utility of genetic testing?

Predictive power and ability to intervene in a disease process and affect outcome

What is the predictive power of genetic testing limited by?

Penetrance and expressivity in genetic diseases

What are symptoms of hypohidrotic ectodermal dysplasia?

Hypotrichosis, hypohidrosis, hypodontia

What is cleidocranial dysplasia characterized by?

Delayed closure of cranial sutures, midface hypoplasia, hypoplastic/aplastic clavicles, abnormal dentition, hand abnormalities

What is Treacher Collins syndrome characterized by?

Hypoplasia of zygomatic bones and mandible, external/internal ear abnormalities, cleft palate, micrognathia, coloboma of lower eyelid, sparse/absent eyelashes

What is Prader-Willi syndrome characterized by?

Low muscle tone, feeding issues in infancy to obsessive overeating, behavioral issues, short stature, small hands/feet, hypogonadism, soft tooth enamel, thick saliva, grinding

What is Williams syndrome characterized by?

Cardiovascular disease, distinct facial features, connective tissue abnormalities, intellectual disability, growth/endocrine abnormalities

What is Gardner syndrome characterized by?

Benign growths, supernumerary teeth, unerupted teeth, increased risk for colon cancer

Gardner syndrome is a subtype of what?

Familial adenomatous polyposis

What is Gorlin syndrome characterized by?

Jaw keratocysts, basal cell carcinoma, medullloblastoma, facial appearance, skeletal abnormalities

Gorlin syndrome is what type of syndrome?

Nevoid basal cell carcinoma syndrome

What is the general theme of concerns for genetic testing?

Many implications, not universally positive