Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Applied Biochemistry > How Do Mutations Affect Health and Tooth Development > Flashcards

How Do Mutations Affect Health and Tooth Development Flashcards

1
Q

continuum of diseases

A

environmental to genetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

The new HGMD professional release becomes available with a total of 170,118 — —

A

mutation entries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Loss-of-function mutation

A

Absence results in dysfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what do loss of function mutations result in?

A

less or no function of certain proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

loss of function mutations constitute many — — cases in enzyme deficiency

A

autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

two subtypes of loss of function

A

halpoinsuffciency

dominant negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

haploinsufficiency

A

reduced gene dosage is not sufficient to permit the cell to function properly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

example of haploinsufficiency

A

Marfan syndrome with fibrillar mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

dominant negative

A

A mutation whose gene product adversely affects (like an antagonist) the normal,
wild-type gene product within the same cell, usually by dimerizing (combining)
with it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

In cases of polymeric molecules, such as collagen, dominant negative
mutations are often more

A

deleterious than mutations causing the production of

no gene product (cancer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

example of dominant negative

A

osteogenesis imperfecta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

with dominant negative, the mutant protein is happy, but

A

annoying and disturbing other good protein function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Gain-of-function mutation

A

Increased function results in dysfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

with gain of function mutations, mutations in certain genes gain a

A

new and abnormal function of the protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

example of gain of function mutation (2)

A

Charcot-Marie-Tooth sensory neuropathy, Cherubism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Over 300 genes identified that have

mutations associated with (3)

A

tooth patterning,

morphogenesis defects and cell differentiation defects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

As a collective group craniofacial genetic

diseases are the

A

most common, 1/3 of diseases involve the craniofacial region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Double Bar indicates

A

consanguineous mating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

— — diseases often present in

consanguineous marriages

A

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

—- is a deeply rooted social trend among one-fifth of the world population
mostly residing in the Middle East, West Asia and North Africa, as well as among
emigrants from these communities now residing in North America, Europe and Australia

A

Consanguinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

The developmental signaling pathways that drive

tooth development are also critical in the

A

development of many other organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Tooth developmental defects should perhaps be

thought of as a

A

potential risk factor for other

diseases that manifest later in life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

genetic diseases and the dentition (6)

A 
malocclusion syndromes 
craniofacial malformations
bone mass traits 
tooth genesis 
tooth movement 
tooth development disorders
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

malocclusion syndromes (3)

A

– Pierre-Robin
– Treacher Collins
– Marfan syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Craniofacial malformations (4)

A

– Crouson
– Apert
– Pfeiffer
– Clefting syndromes (lip and palate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Bone Mass Traits (3)

A

– Sclerosteosis and van Buschem’s
– High Bone Mass and OPPG
– Paget’s Disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Tooth Development Disorders (2)

A

– Dentinogenesis Imperfecta

– Amelogenesis Imperfecta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

symptoms of ectodermal dysplasia

A
  • Abnormal nails
  • Abnormal and missing teeth
  • Absent or very thin hair
  • Absent tears (occasional)
  • Decreased skin color (pigment)
  • Foul-smelling nasal discharge
  • Heat intolerance
  • Inability to sweat
  • Large forehead
  • Light coloring
  • Lower-than-normal number of teeth
  • Low nasal bridge
  • Poor temperature regulation
  • Thin hair
  • Thin skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q
  • – — is fairly common, but

- – — — is rare

A

Tooth impaction

multiple impacted teeth

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

supernumerary teeth (2)

A

Syndromic and non-syndromic diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Syndromic associated diseases (4)

A

– Cleidocranial dysplasia
– Gardner’s syndrome
– Trichorhino phalangic syndrome
– Cleft Lip and palate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Mutations in — gene identified as causal

A

RUNX2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

RUNX2 is a master regulator of

A

osteoblastogenesis and bone formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Characterized by (3)

A

delayed closure of the sutures, aplastic or hypoplastic

clavicle formation, short stature and dental abnormalities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Most common human developmental

craniofacial anomaly

A

tooth angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Hypodontia

A

Missing one to five teeth (excluding 3rd

molars)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Oligodontia

A

Missing six or more teeth (excluding 3rd

molars)

38
Q

Anodontia (2)

A

• Missing all teeth
• Most severe and rare form - mostly
syndromic

39
Q

Hypodontia (excluding 3rd molars) prevalence rate of tooth angenesis (2)

A
  • Worldwide – 6.4%

* Ranging from 4.4% (Caribbean) to 13.4% (Africa)

40
Q

Third molars prevalence rate of tooth angenesis

A

Worldwide – 22.6% (5.3 – 56.0%)

41
Q

Primary (deciduous) prevalence rate of tooth angenesis

A

Rare - 0.1 – 2.4%

42
Q

Presentation

A

• Syndromic association1
• Over 60 different conditions listed in OMIM
• Isolated, non-syndromic trait
• Most common presentation
• Mandibular 2nd premolar (3%), maxillary lateral incisor
(1.7%), maxillary 2nd premolar (1.5%), and mandibular
central incisor (0.3%)
• Associated phenotypes:
• Conical crown shape, molar taurodontism, enamel
hypoplasia, transposition, canine misposition, etc.

43
Q

two of the most commonly mutated genes in tooth angiogenesis

A

• MSX1 and PAX9

44
Q

on site subjects (4)

A

Received genetic variant lists of subjects following whole exome sequencing

Identified common variant(s) among variant lists of subjects with tooth agenesis

Excluded common variant(s) present in variant list of subject without tooth
agenesis

Candidate variant(s)

45
Q

Segregation of mutation in affected members of

—

A

kindred

46
Q

Variant Analysis: (3)

A

DOMINO, CADD, and pLI

47
Q

Literature based search to assess (2) of identified mutation

A

potential function

and/or consequences

48
Q

candidate variant identification results (4)

A

Whole Exome Sequencing of four on-site subjects

26 heterozygous variants segregated correctly with the tooth agenesis phenotype

Likelihood of autosomal dominant inheritance
evaluated by DOMINO

7 candidate variants identified

49
Q

how many candidate variant analysis genes identified

A

7

50
Q

RNF43 family

A

RING finger E3 ubiquitin ligase family

51
Q

RNF43 mechanism of action

A

Tumor suppressor that exerts a negative feedback mechanism in the Wnt/β-catenin signaling pathway

52
Q

Ubiquitinates Frizzled family of Wnt receptors for —

A

degradation

53
Q

Consequently downregulated — signaling

A

Wnt

54
Q

R-spondin family and receptors (Lgr4-6) involved in development of — teeth

A

murine

55
Q

Lgr/R-spondin complex has been shown to inactivate Rnf43 in intestinal epithelial crypt stem cells leading to enhancement of

A

Wnt signaling

56
Q

DKK1 is also a

A

Wnt signaling inhibitor

57
Q

Known to be associated with tooth agenesis when —

A

overexpressed

58
Q

AXIN2 mutation

A

impairs Wnt/b-catenin signaling in human results in tooth agenesis and colorectal cancer.

59
Q

major proteins of enamel (5)

A 
amelogenin 
ameloblastin
enamelin
kalikrin 4
mmp-20
60
Q

Amelogenin

A

Stabilizes the amorphous Ca-P phase, control of apatite crystal
morphology and organization, control of enamel thickness.
Amelogenins have the ability to self-assemble into nanosperes and
thereby guide HAP crystal formation/growth.

61
Q

Ameloblastin

A

Cell adhesion protein, controls cell differentiation, maintains rod
integrity

62
Q

Enamelin

A

Cooperates with amelogenin to control mineral nucleation and
elongated growth

63
Q

Kallikrin 4

A

Digests enamel proteins during maturation stage facilitating their
removal and hardening the final layer of enamel

64
Q

Mmp-20

A

Cleaves amelogenin, ameloblastin and enamelin at the secretory stage
to produce stable intermediates with defined functions.

65
Q

Amelogenesis imperfecta

A

disorder of tooth development. This condition causes teeth
to be unusually small, discolored, pitted or grooved, and prone to rapid wear and
breakage. Other dental abnormalities are also possible. These defects, which vary among
affected individuals, can affect both primary (baby) teeth and permanent teeth

66
Q

Amelogenin:
im protein in
x-linked to

A

forming enamel

amelogenesis imperfecta

67
Q

Enamelin:

A

~186kDa protein and ~5% of the enamel matrix.

68
Q

major dentin extracellular matrix molecules (7)

A 
type 1 collagen 
SIBLING family proteins 
DSPP
DMP1
bone sialoprotein 
osteopontin
MEPE
69
Q

major component found in dentin

A

type 1 collagen (90%)

70
Q

SIBLING family proteins

A

small integral binding ligand N linked glycoproteins

71
Q

Dentin Sialophosphoproteins

DSPP

A

Immediately cleaved after secretion into DSP,

DGP and DPP

72
Q

Dentin Matrix Protein 1 (DMP1)

A

Produced by odontoblasts and early-stage

osteocytes

73
Q

Bone Sialoprotein

A

Role in biomineralization

74
Q

Osteopontin

A

HA binding and contains an RGD motif,

mineralization inhibitor

75
Q

MEPE

A

Matrix Extracellular Phosphogylcoprotein,
contains an RDG motif and in bone appears to be
an inhibitor of mineralization

76
Q

Dentinogenesis imperfecta:

A

Dentinogenesis imperfecta is a disorder of tooth development. This condition causes the teeth to be discolored (most
often a blue-gray or yellow-brown color) and translucent. Teeth are also weaker than normal, making them prone to
rapid wear, breakage, and loss.
These problems can affect both primary (baby) teeth and permanent teeth. Researchers have described three types
of dentinogenesis imperfecta with often subtle differences in dental abnormalities.

77
Q

Dentinogenesis imperfecta: type 1

A

occurs in people who have osteogenesis imperfecta, a genetic condition in which bones are brittle and easily
broken. The primary teeth tend to be more severely affected than the permanent teeth.

78
Q

Dentinogenesis imperfecta: type 2 and 3

A

usually occur in people without other inherited disorders. In Type II both dentitions are equally
affected. In Type III the dentin is extremely thin and the pulp chamber is extremely enlarged. The teeth in Type III are
often referred to as “shell teeth”.

79
Q

Type I collagen genes (COL1A1 or COL1A2) associated with

A

osteogenesis imperfecta (OI) (DGI-I)

80
Q

Dentinogenesis imperfecta type I occurs as part of osteogenesis imperfecta, which is
caused by mutations in

A

one of several other genes (most often the COL1A1 or COL1A2
genes).

81
Q

A deficiency of dentin sialophosphoprotein (DSPP) had been suggested as a causative
factor in

A

dentinogenesis imperfecta (Takagi & Sasaki 1998)

82
Q

Dentin dysplasis (DD)

A

Milder dentin defects than DI-II&III

83
Q

Mutation (Y6D) in a signal peptide of DSPP (Dentin Sialophosphoprotein),
resulting in the reduction of the amount of

A

secreted DSPP protein into dentin matrix

84
Q

Gene mutations can be broadly classified into two categories,

A

gain-of-function mutations and loss-of-function mutations

85
Q

Affected children resulting from consanguinity in a family is an indicator of a

A

recessive trait disease

86
Q

Genetic diseases of the — — and dentition are collectively the most common of the genetic disorders

A

craniofacial skeleton

87
Q

— diseases of the dentition occur in combination with other diseases, while — diseases do not

A

Syndromic

non-syndromic

88
Q

Tooth number genetic disorders result from a wide variety of

A

genetic mutations

89
Q

Importantly mutations in many of the genes affecting tooth number/formation can be an early predictor of

A

potential future diseases such as cancer

90
Q

Most of the amelogenesis imperfecta is caused by mutations in (6)

A

amelogenin, ameloblastin, enamelin, amelotin, enamelysin (MMP-20), and kalliklein4

91
Q

Dentinogenesis imperfecta is caused by mutations in

A

type I collagen associated with osteogenesis imperfecta and in DSPP

Applied Biochemistry (52 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions