159 Questions
What is the cost of screening for hundreds of genetic conditions using the VCGS lab?
$975 per couple
What is the purpose of Mackenzie's Mission?
To investigate the best way to provide a national screening program in Australia
Why are ethnicity-specific screening panels available?
Because carrier status for some genetic conditions varies with ethnic background
What is the purpose of prenatal testing of an existing pregnancy for carrier couples?
To prepare for the birth of an affected baby
What is the role of other genes in cystic fibrosis?
They modify the severity of cystic fibrosis
What is the correlation between causative LP/P CFTR variants and certain features of cystic fibrosis?
No correlation with lung function, neonatal intestinal obstruction, diabetes, and growth parameters
What percentage of eligible relatives underwent genetic testing to find out if they are carriers of CF?
12%
What is the purpose of cascade testing in CF?
To identify carriers who are relatives of a diagnosed individual
What is the result of a sweat test that is indicative of CF?
Elevated NaCl in sweat
What type of genetic testing is used to identify LP / P variants in CF?
Gene panel / clinical exome sequencing
What is the benefit of Medicare funding for carrier screening in CF?
It is available for all individuals who want to undergo carrier screening
What is the term for a heterozygote who has one variant identified?
Carrier
What is the primary goal of conducting genome wide association studies in CF research?
To establish causality between genetic variants and disease phenotype
What is a limitation of genome wide association studies when examining genes with low penetrance?
The need for a large sample size
What is the primary advantage of conducting transcriptomic, proteomic, and metabolomic analyses in human tissues and animal models?
To elucidate specific mechanisms underlying disease aspects
What is the main difference between genetic modifiers and environmental modifiers?
Genetic modifiers are inherited, while environmental modifiers are acquired
What is the ultimate goal of CF research using genome wide association studies and other approaches?
To demonstrate causality between genetic variants and disease phenotype
What proportion of disease variation in CF can be attributed to stochastic/environmental factors?
The exact proportion is unknown
What is the primary function of the CFTR protein in the cell?
To regulate mucociliary clearance and anion transport
What is the name of the family of membrane transporters that the CFTR protein belongs to?
ABCC
What is the mechanism by which the CFTR protein is activated?
Phosphorylation by cAMP-dependent protein kinase A
What is the name of the molecular cloning technique used to identify the CFTR gene?
Positional cloning
What is the approximate size of the CFTR protein?
170 kD
What is the function of the nucleotide binding domains (NBDs) in the CFTR protein?
To bind and hydrolyze ATP
What is the name of the process that occurs when the CFTR channel is activated and allows chloride ions to flow?
Gating
What is the name of the subdomains within the nucleotide binding domains (NBDs) that are involved in ATP binding?
Walker A and B motifs
What is the term used to describe the brief periods of channel closure that occur between bursts of channel opening?
Interburst closed events
What is the region of the CFTR protein that is anchored to the cytoskeleton?
C-terminus
What percentage of CF patients are pancreatic sufficient?
15%
What is the predicted severity of CFTR mutations categorized by?
PIP score
What is the percentage of CF patients affected by pancreatitis?
20%
What is the characteristic of acute pancreatitis?
Upper abdominal pain and/or emesis
What is the percentage of patients with evidence of CFLD?
25%
What is the mortality rate in CFRDM?
6-fold
What is the risk of malignancy in CFLD patients with cirrhosis?
3.1
What is the percentage of CF patients with osteoporosis?
Very common
What is the percentage of male infertility in CF patients?
98%
What is the risk of colorectal cancer in CF patients?
5-10 times
What is the purpose of cascade testing?
To identify carriers of a genetic disorder
What does an elevated NaCl in sweat indicate?
Cystic fibrosis
What is the term used to describe an individual with one variant identified?
Heterozygote
What is the function of the CFTR protein in the sweat duct?
Regulation of chloride transport
What percentage of eligible relatives underwent genetic testing to find out if they are carriers of CF?
12%
What is the classification of the F508del variant?
Class II
What type of screening is Medicare funded for?
Reproductive carrier screening
What is the term used to describe the genetic testing looking for LP / P variants?
All of the above
What is the approximate frequency of carriers of cystic fibrosis in people of northern European ancestry?
1 in 25
What is the correlation between the class of CFTR variant and phenotype?
Limited correlation between classes and phenotype
What is the purpose of high-throughput screening assays in CF research?
To develop new therapies for CF
What is the characteristic of Class III CFTR variants?
Defective channel regulation or gating
What is the inheritance pattern of cystic fibrosis?
Autosomal recessive
What is the effect of Class IV CFTR variants on channel function?
Defective ion conductance
What is the benefit of understanding the molecular defect of CFTR variants?
It allows for targeted therapies
What is the characteristic of Class VI CFTR variants?
Accelerated turnover from the cell surface
What is the primary reason for identifying genetic modifiers of CF?
To identify targets for novel therapies and understand disease variability
What is the significance of studying monozygotic twins in understanding the genetic control of CF?
To control for environmental factors and estimate genetic control
What is the expected characteristic of genetic modifiers identified in individuals with CF?
They are minimally penetrant in healthy individuals but have a significant impact in CF
What is the purpose of association studies in identifying genetic modifiers of CF?
To identify genetic modifiers that are associated with a specific phenotype
What is the potential benefit of identifying genetic modifiers of CF?
It may reveal an opportunity to re-purpose known medications for CF
What is the significance of genetic modifiers identified in individuals with CF in the general population?
They may contribute to the development or progression of common diseases
What is the approximate incidence of Cystic Fibrosis in people of European descent in the United States?
1 in 3000
What is the expected median life expectancy of individuals with Cystic Fibrosis born between 2017 and 2021?
53 years
What is the pattern of inheritance of Cystic Fibrosis?
Autosomal recessive
What is the term used to describe the degree to which a genetic variant causes disease in individuals who carry it?
Penetrance
What is the purpose of newborn screening for Cystic Fibrosis?
To identify babies at risk of developing the disease
What is the term used to describe the way in which a genetic condition manifests in individuals?
Expressivity
What is the risk of a child being affected by Cystic Fibrosis if both parents are carriers?
1 in 4
What is the purpose of genetic testing for Cystic Fibrosis?
To identify carriers of the disease
What is the worldwide prevalence of Cystic Fibrosis?
Over 100,000 people
What is the term used to describe the proportion of individuals who carry a genetic variant that actually develop the associated disease?
Penetrance
What is the name of the test that measures the concentration of chloride excreted in sweat?
Sweat test
What is the purpose of sequencing the entirety of the CFTR gene?
To detect all LP / P variants in the CFTR gene
What is the significance of the R117H variant?
Its penetrance depends on the polyT tract variant on the same allele
What is the next step after an infant's IRT level is elevated in newborn screening?
The infant undergoes genetic testing using a panel of known common LP / P gene variants
What is the significance of the phase of the variants in genetic testing?
It establishes on which allele a variant identified on testing lies
What is the purpose of a panel of known LP / P CFTR variants?
To detect the most common LP / P variants only
What is associated with poorer health outcomes in cystic fibrosis?
Lower socio-economic status
What is the primary function of the respiratory system?
Gas exchange takes place in the alveoli
What is a factor that may affect adherence to medical and dietary regimens in cystic fibrosis?
Female sex
What is the developmental stage of lung development from 26-36 weeks gestation?
Sacular/alveolar
What is the distal part of the respiratory system where gas exchange takes place?
Acinus
What is the term used to describe the region of the respiratory system that comprises respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli?
Acinus
What is the goal of CFTR modulators in cystic fibrosis treatment?
To restore CFTR function to normal or improve its function
What is the name of the first therapy to target the underlying defect in cystic fibrosis?
Ivacaftor (Kalydeco)
What is the result of using Potentiator Compounds in cystic fibrosis treatment?
Improved Cl- channel gating of CFTR
What is the name of the system used to test Potentiators in preclinical models?
High-throughput screening (HTS)
What is the primary purpose of using viral vectors in gene therapy?
To bypass the host immune response
What is the term used to describe the multidisciplinary team that cares for patients with cystic fibrosis?
CF Team
What is the goal of managing complications in cystic fibrosis?
To manage complications such as CFRDM and liver disease
What is the mechanism by which CRISPR gene editing tool corrects mutations?
By snipping out the mutated sequence and using a template to fix the DNA
What was the outcome of the Phase 2 trial of 140 patients with cystic fibrosis?
A 3.7% difference in FEV1 at 1 year in favor of the treatment group
What is the purpose of airway clearance in cystic fibrosis treatment?
To remove mucus from the airways
What is the name of the mutation that Ivacaftor targets?
G551D
What is the purpose of using non-viral vectors in gene therapy?
To avoid the host immune response
What is the function of the cell's DNA repair machinery in CRISPR gene editing?
To use a template to fix the broken DNA
What is the cost per patient per year of Ivacaftor treatment?
$294,000
What is the name of the system used to grow cells in the laboratory for research purposes?
Organ-on-a-chip system
What is the main function of the CFTR protein in the apical epithelial cells?
Regulation of anion transport and mucociliary clearance
What is the significance of the conserved structure of the four canonical domains of the CFTR protein?
They are linked into a single polypeptide chain
What is the role of the Walker A and B motifs in the NBD structures?
To bind and hydrolyse ATP
What is the significance of the coupling helices in the CFTR protein?
They facilitate the interaction between the MSDs and NBDs
What is the effect of cAMP-dependent phosphorylation on the CFTR protein?
It causes the channel to be maximally activated
What is the significance of the two-step activation process in the CFTR protein?
It allows for the regulation of ion transport
What is the role of the R domain in the CFTR protein?
It is phosphorylated by cAMP-dependent protein kinase
What is the significance of the asymmetry between NBD 1 and NBD 2 consensus motifs?
It leads to the formation of a head-to-tail dimer
What is the term used to describe the brief periods of channel closure that occur between bursts of channel opening?
Flickery closed events
What is the significance of the CFTR protein being part of the ABC superfamily of membrane transporters?
It is involved in ATP binding and hydrolysis
What is the primary function of cilia in the airway?
To beat constantly to move mucus from distal airway to the back of the throat
What is the term used to describe the study of lung function?
Pulmonology
What is the name of the test used to measure lung function?
Spirometry
What is the term used to describe the obstruction of airways in cystic fibrosis?
Bronchiectasis
What is the primary function of CFTR in the airway?
To regulate chloride secretion
What is the term used to describe the dehydration of the airway surface liquid in cystic fibrosis?
Airway surface dehydration
What is the primary cause of chronic infection in cystic fibrosis?
Pseudomonas aeruginosa
What is the term used to describe the process by which neutrophils trap and kill pathogens?
Netosis
What is the primary function of the pancreas in cystic fibrosis?
To produce digestive enzymes
What is the term used to describe the sweat test used to diagnose cystic fibrosis?
Pilocarpine iontophoresis test
What is the approximate number of alveoli present at birth compared to adulthood?
100 x 10^6 vs 300 x 10^6
During which stage of lung development do the acinar regions form?
Canalicular stage
What is the primary function of the phagocytes in the lung defense mechanism?
Trapping and killing pathogens
At which stage of lung development do the airways develop to the level of the terminal bronchioles?
Pseudoglandular stage
What is the approximate surface area of the lungs at birth compared to adulthood?
4m2 vs 10m2
During which stage of lung development do the saccules form into alveolar ducts and alveoli?
Sacular/Alveoli stage
What is the significance of establishing the phase of variants in genetic testing for CF?
To determine on which allele a variant lies
What is the primary difference between CFTR gene sequencing and a panel of known LP/P CFTR variants?
Sequencing targets the entirety of the CFTR gene
What is the interpretation of a sweat test result with a chloride concentration ≥ 60 mmol/L?
CF is confirmed
What is the purpose of measuring immunoreactive trypsinogen (IRT) in newborn screening?
To identify infants with elevated IRT levels
What is the significance of the R117H variant in the CFTR gene?
It is a pathogenic variant that affects penetrance
What is the purpose of a panel of known LP/P CFTR variants in genetic testing for CF?
To detect the most common LP/P variants in the CFTR gene
What is the approximate birth prevalence of cystic fibrosis among African Americans?
1 in 15,000-20,000
What is the median life expectancy of individuals with cystic fibrosis according to the data from 2017 to 2021?
53 years
What is the term used to describe the phenomenon where not all individuals who carry a disease-causing variant will develop the condition?
Penetrance
What is the primary purpose of cascade testing for cystic fibrosis?
To identify carriers who are relatives of diagnosed individuals
What is the term used to describe the way in which a genetic condition manifests in individuals, including the associated features and clinical problems?
Expressivity
What is the approximate number of people worldwide who have been diagnosed with cystic fibrosis?
100,000
What is the probability that a healthy sibling of an affected individual will be a carrier of cystic fibrosis?
2 in 3
What is the inheritance pattern of cystic fibrosis?
Autosomal recessive
What is the purpose of pre-conception carrier screening for cystic fibrosis?
To provide information about reproductive risk
What is the term used to describe the proportion of individuals who carry a genetic variant that actually develop the associated disease?
Penetrance
What is the primary effect of Class III CFTR variants on channel function?
Decrease in ATP binding and hydrolysis
What is the approximate frequency of carriers of cystic fibrosis in people of northern European ancestry?
1 in 25
What is the correlation between the class of CFTR variant and phenotype?
Limited correlation with exocrine pancreatic function
What is the primary effect of Class II CFTR variants on protein function?
Defective processing and premature degradation
What is the approximate percentage of CFTR variants accounted for by the F508del variant in people of northern European ancestry?
70-75%
What is the primary goal of understanding the molecular defect of CFTR variants?
To target therapies to the specific defect
What is the pattern of inheritance of cystic fibrosis?
Autosomal recessive
What is the primary mechanism of action of Ivacaftor in treating cystic fibrosis?
Improving the gating of CFTR protein at the cell surface
What is the effect of Class IV CFTR variants on channel function?
Reduced ion conductance
What is the purpose of class-specific therapies for CFTR variants?
To improve the processing and trafficking of the protein
What is the approximate percentage of cystic fibrosis patients who have the Gly551Asp mutation?
4%
What is the primary benefit of using CFTR modulators in the treatment of cystic fibrosis?
Restoring the normal function of the CFTR protein
What is the significance of the F508del variant in cystic fibrosis?
It is a common variant that accounts for most cases of cystic fibrosis
What is the name of the system used to test potentiators in preclinical models?
Organ-on-a-chip system
What is the primary goal of the CF team in managing cystic fibrosis patients?
Maintaining lung function and preventing complications
What is the term used to describe the wrinkling of palms observed in some cystic fibrosis patients?
Aquagenic wrinkling of palms
What is the primary advantage of using CFTR modulators over symptomatic treatments?
Targeting the underlying defect of the disease
What is the term used to describe the function of the CFTR protein in the cell?
Facilitating the transport of chloride ions
What is the primary benefit of using Ivacaftor in cystic fibrosis patients?
Prolonging the time to exacerbation
What is the name of the first therapy approved by the FDA to target the underlying defect of cystic fibrosis?
Kalydeco
Learn about the positional cloning technique used to identify genes of interest. This method uses chromosomal location to guide gene identification, such as the CFTR gene, which codes for a protein involved in cystic fibrosis.
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