How Do Mutations Affect Health And Tooth Development- Exam IV Flashcards
The 3 nucleotide sequence: codon that specifies different amino acids:
Genetic code
Properties/ principle of the genetic code that many amino acids are encoded by multiple 3 nucleotide codons, as such- changes in the nucleic acid sequence may or may not alter the resulting amino acid:
Degenerative/ redundant genetic code
Mutation that results in increased function or new function in a protein:
Gain of function
Mutation that results in a decrease or absence of function:
Loss of function
Reduced gene dosage resulting in insufficient protein being made and diminished functioning of the cell:
Haploinsufficiency
Mutation resulting in an altered protein that reduces or inhibits the function of another normal protein in the cell:
Dominant negative mutation
Because genetic disorders represent a continuom of diseases, even if a disease is largely caused by the environment there may be _____ effective the outcome
Genetic factors
3 examples of environmentally caused disease:
- Influenza
- Measles
- Infectious disease
3 examples of disease that have equally environmental and genetic influences:
- Diabetes
- CV diseases
- Osteoporosis
2 examples of diseases fully caused by genetic factors:
- Cystic fibrosis
- Hemophilia A
Represent the largest number of mutations that have been identified that relate to disease:
Missense and nonsense
Mutations that result in either lower amounts, no function, or enzyme deficiencies:
Loss of function mutations
Haploinsufficiency is a subcategory of:
Loss of function mutations
Because you have two copies of each autosomal gene if one copy is expressed and the other is not due to a disease causing mutation, this is called:
Haploinsufficiency
Haploinsufficiency results in the amount of products to be producing being _____ compared to when no mutation is present:
About 50 % decrease
Some haploinsufficiency diseases may result in in _____ while in other cases it may result in_____.
No disease & disease
Example of a disease caused by a haploinsufficiency mutation:
Marfans syndrome (deals with fibrillin)
A mutation whose gene product adversely affects the normal wild type gene product within the same cell, usually by dimerizing with it:
Dominant negative mutation
A dominant negative mutation is a subcategory of:
Loss of function mutations
In the cases of polymeric molecules such as collagen, the dominant negative mutations are often _____ than the mutations causing the production of no gene products (Cancer)
More deleterious
Osteogenesis imperfecta is an example of a:
Dominant negative mutation
Charcot-Marie- tooth sensory neuropathy & cherubism are examples of:
Gain of function mutations
Over 300 genes identified that have mutations associated with: (3)
- Tooth patterning
- Morphogenesis defects
- Differentiation defects
As a collective group ____ genetic diseases are the most common
Craniofacial
Of all known genetic disease, craniofacial disease account for about:
30%
What is the hallmark of autosomal recessive diseases
Consanguineous mating
- Unaffected male
- Unaffected female
- Mating (single bar)
- Consanguineous mating (double bar)
- Identical twins
- Deceased female
- Lost pregnancy
- Affected male
- Affected female
- Fraternal twins
- Autosomal heterozygous carrier
- X-linked carrier
What does an arrow indicate on a family pedigree?
Proband (first case identified)
What cannot be ruled out even in the absence of consanguineous matings?
Autosomal recessive diseases
If the number of affected & unaffected individuals at each generational level is about 50/50, this suggests:
Dominant type of trait
To rule out if the trait is autosomal or sex linked, you should look at:
Female to male & male to female transmission
What are valuable tools in trying to categorize genetic disease:
Pedigrees
If you see male to male transmission of a trait in affected individuals, you know the trait is not moving on the:
X-chromosome
The developmental signaling pathways that drive _____ are also critical in the development of _____.
Tooth development : many other organs
Tooth development defects should perhaps be thought of as a potential _____ for other _____ that manifest later in life
Risk factor; diseases
There are numerous malocclusion syndromes that can be ______ or ______.
Inherited or non-inherited
Pierre-robin, treater collins, and Marfan syndrome are all examples of:
Malocclusion syndromes
Crouson, apert, pfeiffer, and clefting syndromes are all examples of:
Craniofacial malformaitons
Sclerosteosis and van Bushcem’s
High bone mass and OPPG
Paget’s disease
Are all examples of:
Bone mass traits
Dentinogenisis imperfecta and amelogenesisis imperfecta are both examples of:
Tooth development disorders
A very large category of genetic disease is _______ which encompasses a lot of different mutations:
Abnormal nails
Abnormal/missing teeth
Absent or very thin hair
Foul smelling nasal discharge
Absent tears
Decreased pigment
Etc.
Ectodermal dysplasia
More than the correct number of teeth:
Supernumerary teeth
With supernumerary teeth _____ is very common
Tooth impaction
With supernumerary teeth, multiple impacted teeth its:
Very rare
Both ___ and ____ give rise can give rise to supernumerary teeth:
Syndromic & and nonsyndromic disease
Another associated disease that coincident or contributing to the supernumerary phenotype:
Syndromic disease
If you had measles as a child which gave rise to supernumerary teeth:
Syndromic
When you don’t have a different disease associated with the supernumerary teeth, just strictly teeth issues:
Non-syndromic
Cleidocranial dysplasia, Gardner’s syndrome, Trichorchino phalanges syndrome, clef lip and palate are all examples of:
Syndromic associated disease
Cleidocranial dysplasia is a caused by a mutation in:
RUNX2 gene
A master regulator of osteoblastogenesis and bone formation:
RUNX2 gene
Disease characterized by the delayed closure of the sutures, aplastic or hypoplastic clavicle formation, short stature, and dental abnormalities:
Cleidocranial dysplasia
Refers to a condition of fewer teeth:
Tooth agenisis
Most common human developmental craniofacial anomaly:
Tooth agenesis
Missing 1 to 5 teeth excluding the 3rd molars:
Hypodontia
Missing 6 or more teeth excluding the 3rd molars
Oligodontia
Missing all teeth, very severe, very rare, mostly syndromic:
Anodontia
Worldwide, the prevalence rate:
Hypodontia:
3rd molars:
Primary teeth:
6.4% (ranging 4.4 to 13.4)
22.6 % (5.3-56%)
0.1-2.4%
There are over 60 conditions that we know of listed in OMIM of tooth agenesis that are considered:
Syndromic associated
The most common forms of tooth agenesis is:
Non syndromic
Associated phenotypes of tooth agenesis: (5)
- Conical crown shape
- Molar Taurodontism
- Enamel hypoplasia
- Transposition
- Canine misposition
Increased pulp chamber:
Taurodontism
The etiology of tooth agenesis is really due to ____ be _____ actions between _____ and ____.
Synergistic & antagonistic
Odontogenic epithelium & mesenchyme
Tooth development is directed by variable expression of:
Specific genes & transcription factors
Over 300 genes that are known to be expressed throughout:
Odontogenesis
Two of the most commonly mutated genes in tooth development:
MSX1 and PAX9
AXIN2 mutation impairs ____ in humans results in tooth agenesis and colorectal cancer.
WNT/B-catenin singaling
Stabilizes the amorphous Ca-P phase, control of apatite crystal morphology and organization, & control of enamel thickness:
Amelogenin
Amelogenins have the ability to self-assemble into nano sphere and thereby guide:
HAP crystal formation/growth
Cell adhesion proteins, controls cell differentiation, maintains rod integrity
Ameloblastin
Cooperates with amelogenin to control mineral nuclear ion and elongated growth
Enamelin
Digests enamel proteins during maturation stage facilitated their removal and hardening the final layer of enamel
Kallikrin 4
Cleaves amelogenin, ameloblastin & enamel at the secretory stage to produce stable intermediates with defined functions
MMP-20
When you have mutation in ename, this will give to:
Amelogenesis imperfecta
When you have mutations in the proteins that give rise to dentin, this will give rise to diseases collectively called:
Dentinogenisis imperfecta
A disorder of tooth development; causes teeth to be unusually small, discolored, pitted or groove, and prone to rapid wear or breakage:
Amelogenesis impoerfecta
Amelogenesis imperfecta is a condition that can affect:
Primary & permanent dentition
Type 1 collagen, SIBLING family proteins, Dentin sialophosphoproteins, Dentin matrix protein 1, bone sialoprotein, Osteopontin, MEPE are all:
Dentin ECM molecules
Dentin ECM molecule which is the major component found in dentin:
Type 1 collagen
Small integrin-binding ligand N-linked glycoproteins:
SIBLING family of proteins
Dentin ECM molecule that immediately is cleaved after secretion into DSP, DGP, and DPP
Dentin sialophosphoproteins (DSPP)
Dentin ECM molecule that plays a role in biomineralization:
Bone sialoprotein
Dentin ECM molecule produced by odontoblasts and early-stage osteocytes:
Dentin matrix protein 1 (DMP1)
Dentin ECM molecule that functions in HA binding and contain an RGD motif; mineralization inhibitor
Osteopontin
Dentin ECM molecule that functions in matrix extracellular pohopglycoprotein, contain an RGD motif and in bone appears to be an inhibitor of mineralization.
MEPE
Occurs in people who have osteogenesis imperfecta. The primary teeth tend to be more severely affected than the permanent teeth.
Type 1 dentinogenesis imperfecta
Usually occurs in people without other inherited disorders. The primarily dentition are usually more effected
Type 2 dentinogenesis imperfecta
Usually occurs in people without other inherited disorders. Both dentitions are equally effected; dentin is extremely thin and the pulp chamber is extremely enlarge. These teeth are often referred to as shell teeth:
Type 3 dentinogenesis imperfecta
Type 1 collagen genes ___ &____ are associated with osteogenesis imperfecta
COL1A1 & COL1A2
Dentinogenesis imperfecta type 1 occurs as part of:
Osteogenesis imperfecta
A deficiency of _____ has been suggested as a causative factor in dentinogenesis imperfecta
DSPP
Mutations in DSPP have been found in both:
Type 2 and 3 dentinogenesis imperfecta
Milder dentin defects than in dentinogenesis imperfecta 2 and 3
Dentin dysplasia
Gene mutation can broadly bel classified into two categories:
Gain-of-function & loss-of-function
