Phenotypic Variability Flashcards
Do the same diseases always lead to the same presentation and prognosis in different people?
No
Genetic diseases are rare and are classified by their symptoms, what is a consequence of this?
Diseases that don’t have the same cause are labelled with the same name.
To avid this, they can be split into sub types (eg osteogenesis imperfects is types I to VIII)
What are some factors that can effect the phenotype of a disease?
Environment
Sex
Other genes
Different mutations in the same gene
Environment?
Environment - eg MEN1 and hereditary haemachromatosis
Sex?
Sex - eg men with BRCA-1 and 2 mutations have an increased risk of prostate and breast cancer, but women with the mutation have a much higher risk of breast cancer. Also hereditary haemaxjromatosis, men present with symptoms more coz women lose some of the excess iron during the menstrual cycle. Also long QT syndrome
Other genes?
Other genes - either improve it or make it worse. ie at least 17 genes that contribute to eye colour
Different mutations in the same gene?
Different mutations in the same gene - some (sickle cell) are caused by only one gene, others more. Both duchenne and Becker muscular dystrophy are caused by a mutation in the same gene (dystrophin). Becker is more mild as it is not a frame shift but duchenne is
What are trinucleotide repeat disorders?
Causes diseases resulting from a region of three nucleotides in the genome increasing in number during DNA replication
Fewer than 27 repeats is okay and function of the protein remains, more makes the DNA unstable
The more repeats, the more severe the phenotype
The number of repeats increases with each round of replication, this leads to greater severity of symptoms
What is Huntington’s disease and how does it work?
Caused by an expansion of CAG repeats in the Huntington gene.
CAG is the cosine for glutamine so the chain of glutamines is known as the polyglutamine tract or poly Q tract.
Fewer than 27 repeats is normal and stable. 27-35 is an intermediate phenotype with minor effects, the region is unstable and can extend. 36-39 results in the characteristic phenotype but not all carriers will be effected by the diesease. 40 or more leads to Huntington’s in all carriers
