genetics Flashcards
what is Tuberous sclerosis
- one of the most common genodermatoses (genetic diseases that are expressed as skin conditions)
- autosomal dominant but new mutations are common
what are signs of Tuberous sclerosis
- infantile seizures
- periungual fibromata (around nails)
- longitudinal ridging
- earliest cutaneous sign is ash leaf macule (depigmented macule)
- facial angiofibromas
- hamartomas (overgrowth of normal tissues)
- bone cysts
- shagreen patches
- enamel pitting
what chromosomes are effected in tuberous sclerosis
- chromosomes 9q34 and 16p13.3
- gene mutation TSC1 and TSC2
- code for tuberin (chromosome 9) and hamartin (chromosome 16)
features of autosomal dominant
- disease seen in all generations
- 50% risk of affected child if parent is affected
- variable expressivity
- variable penetrance
what is a genetic variation that has no effect
polymorphism
what are types of mutations (wild type = normal)
missense
deletion (in frame)
premature stop
deletion (frameshift)
what does a genetic STRADA deficiency cause
intractable seizures through the same pathway
Tuberous sclerosis shows genetic heterogeneity what does this mean
A term used to describe different genetic mechanisms that produce the same or similar phenotypes.
what does penetrance mean
Penetrance measures the proportion of individuals in a population who carry a specific gene and express the related trait
what is the genetic features of epidermolysis bullosa
- dominant, recessive, new mutation or acquired
- variable severity - blistering at birth doesn’t determine prognosis
what are the 3 main types of epidermolysis bullosa
simplex - blistering occurs in the epidermis, the upper layer of the skin. It is characterized by a lack of adhesion in this layer —directly above the basement membrane — due to mutations that prevent the keratin proteins from forming strong networks in the epidermis.
junctional - Blistering in JEB occurs within the basement membrane of the skin. JEB is inherited in an autosomal recessive manner. This means the condition develops only when the defective gene is inherited from both biological parents, who are EB carriers and possibly do not know this, as they would not have symptoms themselves.
dystrophic - blistering occurs as a result of very fragile connections between skin layers, which can make them susceptible to blisters and tearing with the slightest movement. DEB can be milder or severe, depending on the extent of the deficiency in type VII collagen, a protein that connects the different layers of the skin and is affected by DEB-causative mutations.
what happens when one allele has a polymorphism
half of polypeptide has a sequence variation but there is a normal amount of protein complex
what happens when there is haploinsufficiency (one of the parental gene copies is deleted or mutated and the other parental copy of the gene is incapable of producing sufficient protein for a normal protein function.)
half protein is made and half as much functioning protein
what occurs due to a dominant negative disease mechanism.
mutant protein stops normal protein working. Mutant allele produces abnormal polypeptide. Abnormal polypeptide interferes with normal function
what does haploinsufficiency mean
only one copy of working - reduced protein production
