9 - Single Genes Disorders Flashcards
What is a single gene disorder?
Also called “simply inherited trait”
Effect of one gene is responsible for the disorder. Inherited according to mendelian genetics.
What is forward genetics?
What is reverse genetics?
Forward: from phenotype to gene (start with disease and use linkage studies and positional cloning to find gene).
Reverse: from gene to phenotype (mutate gene and determine effect on phenotype. Most commonly done in exp organism in research setting)
What is positional cloning?
Finding genes of unknown function my mapping them relative to a gene or marker that you can clone and then walking down the chromosome to the desired gene.
What are informative markers?
Markers used to distinguish two parental alleles that are used to identify marker alleles that are co-inherited with a disease (and thus be causing the mutant gene)
What is the purpose of linkage analysis?
To identify a region of the genome that contains the mutation responsible for the gene.
When looking at a pedigree, what would lead you to believe that a marker is NOT closely linked to a disease?
If individuals who have the marker are healthy and do not have the disease.
What does the success of a linkage study depend on?
- Pedigree: more families means more meiosis can be observed to help identify chromosomal regions transmitted from affected parents to affected children
- Accurate phenotype: gene in question should have a large measurable effect. Diagnosis needs to be accurate.
Linkage between a genetic marker and the occurrence of the disorder is a function of ______?
The distance between the loci.
The closer together the marker and the gene involved, the better the linkage and usefulness of that marker in a diagnostic sense.
What are the steps in a linkage analysis?
- Collect DNA from large pedigree
- Genotype all individuals using ~300 markers
- Statistical analysis to determine which region of genome is linked to disease
- Analyze RNA expression of candidate genes (between healthy and control)
- Analyze DNA sequence differences paying attention to highly conserved regions or those that alter protein function.
What is the prevalence of CF? What type of disorder is it?
Aut recessive disorder. Most frequent lethal genetic disease of childhood. 1/3,900 live births.
Affects airways, pancreas, liver, sweat glands.
What is classic CF?
Chronic sinusitis with earlier and more severe deterioration of lung function.
Pancreatic insufficiency.
Greater incidence of malnutrition and severe liver disease.
What is non-classic CF?
Chronic sinusitis with later onset and milder lung disease.
Pancreas sufficient; less likely to have CF-related diabetes.
Later diagnosis, milder disease, more responsive to treatment.
What is the defect related to CF?
Defect in chloride ion transport, leading to thick viscous mucous secretions.
Causes respiratory problems with clearing mucous from airways, but also abnormalities in pancreas, liver, and sweat glands.
Where is the disease-causing mutation that causes CF located? How did they determine which gene in that region caused the disease?
A small region on 7q22.
In those with the disease, the interval contained 4 genes of which only one gene (CFTR) was expressed in all tissues affected by the disease but not in other tissues.
Describe the CTFR gene’s function. What is the result of a mutation in this gene?
Codes for membrane chloride channel that’s responsible for salt balance.
Mutations lead to impaired function or loss of channel protein from membrane.
