Genetic Diseases Flashcards
1
Q
define gene
A
a segment of DNA that codes for synthesis of a polypeptide; determines a component of a trait
2
Q
define allele
A
term describing a pair of like genes
3
Q
define autosomes
A
the 22 pairs of chromosomes (all except the sex chromosomes)
4
Q
define dominant
A
among alleles, typically one 1 determines the attribute. that gene is dominant
5
Q
define recessive
A
the allele of the pair that doesn’t have influence on the attribute
6
Q
define codominant
A
when both alleles have equal influence on an attribute and the attribute represent a blend
7
Q
define hemizygous
A
possessing only the gene (without the allele) as occurs with the X chromosome because the Y chromosome has no corresponding allele
8
Q
define penetrance
A
the outward expression of the gene makeup
9
Q
define expressivity
A
the degree to which a dominant gene expresses itself in a phenotype
10
Q
define forme fruste
A
a minimum expression of a dominant gene in the phenotype
11
Q
define proband
A
the original person that presents a genetic disease to your attention (ex. your patient)
12
Q
define kindred
A
the probands whole family
13
Q
define inherited
A
derived from your parent’s genes
14
Q
define familial
A
runs in families - often but not necessarily inherited
15
Q
define germline mutation
A
occurs in all body cells and germ cells and is thus passed on to children
16
Q
define somatic mutation
A
occurs in an isolated group of cells and is not heritable
17
Q
define hereditary disorders
A
transmitted through gametes from parents
18
Q
define syndrome
A
group of symptoms which consistently occur together, or a condition characterized by a set of associated symptoms
19
Q
trinucleotide repeats are made up of what and have which nucleotides
A
3 base pair sequences and is GC rich
20
Q
define cytogenetics
A
the study of inheritance in relation to the structure and function of chromosomes
21
Q
what is the short arm of the chromosome
A
p arm
22
Q
what is the long arm of the chromosome
A
q arm
23
Q
how is this read: 7 q 3 1.2
A
chromosome 7
q arm
region 3
band 1
sub-band 2
24
Q
what is the breakdown of chromosome location in order
A
chromosome number, arm, region, band and sub-band
25
define reciprocal translocation
fragments are exchanged between 2 chromosomes
26
define balanced translocation
all genetic material is maintained
27
define Roberstsonian translocation
between acrocentric chromosomes (centromere close to end = short p arm) resulting in subsequent loss of p arm
28
define isochromosome
centromere divides horizontally rather than vertically
29
define ring chromosome
the ends fuse together
30
define monosomy
loss of a whole chromosome
31
define trisomy
gain of a whole chromosome
32
what does this mean: 46, XX, t(2;5)(q31;p14)
46 = chromosome total count
XX = female
t = translocation between chromosomes 2 and 5
q31 on chromosome 2 switched with p14 on chromosome 5
33
are epigenetic modification heritable
yes
34
define epigenetics
changes in the regulation of gene expression that are not dependent on gene sequence
35
what are epigenetic changes often caused by
chemical modifications of the DNA or chromosomal proteins
36
what are four examples of epigenetic changes
- DNA methylation (mCpG islands = lots of C's and G's) typically cause silencing
- histone modifications: acetylation, methylation, phosphorylation, or other mods can silence or enhance gene expression
- non-coding RNAs; miRNAs and lncRNAs have regulatory functions to alter gene expression
- genomic imprinting; DNA or histone methylation silences one chromosome's allele while the non-imprinted allele on the other chromosome is expressed
---> imprinted chromosomes are at greater risk to express mutational events
37
feature of autosomal dominant defects
50% reduction in normal gene function causes clinical manifestations if the gene regulates a metabolic pathway or codes for structural proteins
38
feature of autosomal recessive defects
enzyme defects can be compensated for 50% of normal gene function such that enzyme defects often show autosomal recessive inheritance
39
define pleiotropy
single gene mutation having many phenotypic effects
40
define genetic heterogeneity
a mutation at several different loci causes that same trait
41
define modifier genes
affect the severity or extent of the phenotypes caused by a mutation
42
Marfan Sx is what kind of disease
autosomal dominant
43
Marfan is a mutation of what
fibrillin (ECM component of elastic fibers)
44
Marfan is an example of what
pleiotropy --> elastic fibers are present in many tissues throughout the body so the disease has wide ranging effects
45
Marfan clinical defects: (5)
- elongated hiatus: slender, long legs, arms and fingers
- hyperextensible joints
- oral: high arched palate
- ocular: dislocation of lens
- cardiavasc.: elastic fiber fragmentation of the tunica media --> aortic dilation and dissection
46
Ehlers-Danlos has defect in what
structure or function of collagen
47
t/f ehler-danlos is dominant
F. can be dominant or recessive
48
Ehlers-Danlos clinical features: (3)
- very stretchable and fragile skin
- hypermobile joints
- internal complications: colon rupture, ocular fragility, and diaphragmatic hernia
49
two forms of muscular dystrophy
Duchenne MD = severe
Becker MD = milder
50
MD is what kind of disease
X-linked recessive = expected to only affect males
51
MD has a mutation in what
dystrophin - whose protein protects m cells during contraction, links internal cytoskeleton to the ECM
52
MD clinical presentation
- progressive damage, inability to repair leads to m cell death and replacement by scar tissue and fat
- m weakness in childhood leading to death in early adulthood
53
familial hypercholesterolemia (FH) is what kind of disease
autosomal dominant
54
FH has a mutation in what
loss of function mutation of the LDL receptor
55
FH mutation leads to what:
- elevated LDL in the plasma
- lack of LDL uptake into liver cells induces HMG-CoA to activate cholesterol synthesis
56
clinical features of FH
- high blood LDL and cholesterol cause premature atherosclerosis and coronary artery disease
- cholesterol deposits in skin (xanthomas)
57
cystic fibrosis is what kind of disease
autosomal recessive
58
cystic fibrosis has a mutation in what, which causes what
CFTR gene cases protein misfolding and degradation in the ER
59
cystic fibrosis mutation also causes a defect in what, which leads to what
Cl- ion transport, which causes very thick, mucous secretions from exocrine glands
60
clinical features of cystic fibrosis
- chromic pulmonary infections (pseudomonas aeruginosa)
- pancreatic exocrine insufficiency due to progressive fibrosis leads to protein, fat malabsorption, and potentially fat-soluble vitamin deficiency, diarrhea
- fatty liver --> cirrhosis
- salty sweat gland secretion
61
neurofibromatosis is what kind of disease
autosomal dominant
62
neurofibromatosis is a ______________ disease of the skin
Von Recklinghausen
63
T/F neurofibromatosis has highly variable expressivity
T
64
neurofibromatosis has a mutation in what
NF1 (neurofibromin) gene leads to increase cell growth
65
neurofibromatosis clinical presentation
- neurofibromas: benign skin tumors
- cafe-au-lait spots: light brown skin macules
66
phenylketonuria (PKU) is a lack of what
phenylalanine hydroxylase enzyme, which leads to elevated levels of phenylalanine (can't convert it to tyrosine)
67
PKU clinical features
- common in Scandinavian
- impaired brain development
- decreased hair/skin pigmentation (tyrosine = precursor of melanin)
68
PKU tx
life-long diet restriction
69
PKU dental implications
- potential higher cariogenic diet and erosive supplements
- headaches, ADD and trouble focusing
70
what are lysosomes critical in
- breakdown of complex molecules (& autophagy)
- immunity = fuse with phagosomes
- membrane repair = fusion with plasma membrane
71
lack of lysosomal enzyme leads to what
- accumulation of paritally degraded metabolites (primary storage)
- defective degradation of organelles (secondary storage)
----> old mitochondria ---> triggers free rad production and apoptosis
72
cell dysfunction is made worse by what
macrophage activation and cytokine release
73
general features of lysosomal storage diseases
- autosomal recessive
- ashkenzai jews
- typically fatal in childhood
- frequent CNS involvement
74
examples of lysosomal storage diseases
- glycogenoses
- Tay-Sachs disease
- Niemann-Pick disease
- Gaucher disease
- mucopolysaccharidoses
75
clinical features of glycogen storage disease
- liver enlargement
- m weakness
76
examples of mucopolysaccharidoses
hunter syndrome
hurler syndrome
77
mucopolysaccharidoses causes what
caridac problems, mental retardation
78
define penetrance
proportion of individuals with a mutation that exhibit clinical symptoms
79
define expressivity
how severe or mild the symptoms are
80
penetrance and expressivity are features of which mutations
triple repeat mutations
81
define anticipation of triple repeat mutations
timing of disease is sooner and more severe from gen to gen
82
two examples of triple repeat mutations
huntington disease
fragile x syndrome
83
huntington is what kind of disease
autosomal dominant
84
huntington causes what to happen
misfolded proteins in the brain = uncontrolled movement (chorea), decreased cognition
85
fragile x syndrome is what kind of disease
x-linked
86
fragile x syndrome causes what to happen
moderate to severe retardation, post-pubertal macroorchidism (large testicles)
87
define genetic imprinting
epigenetic alteration --> silences a gene on one chromosome so only one is expressed
- if functional allele is deleted, disease occurs
88
define uniparental disomy
2 chromosomes from one parent and none from the other
89
what are examples of genomic imprinting and uiparental disomy
prader-willi syndrome
angelman syndrome
90
complex multigenic inheritance have to do what for phenotype to be expressed
total number of effector alleles needs to exceed a threshold
91
two examples of congenital defects of multigenic disorder
- cleft palate
- congenital heart defects
92
examples of multigenic diseaese
- type 1 and 2 diabetes
- hypetension
- gout
- cancer
- glaucoma
- epilepsy
- schizophrenia
93
is loss or gain of chromosomal material worse
loss is worse
94
down syndrome is trisomy of which chromosome
21
95
klinefelter sx is what
male with at least two X chromosomes and one or more Y chromosomes
96
clinical features of klinefelter sx
- decreased male traits
- infertility
- male breast development (gynecomastia)
97
Turner sx is what
female with loss of one X chromosome
98
clinical feature of Turner sx
- slowed growth
- infertility
- decreased female secondary sex characteristics
- cardiovasc. problems --> childhood death
99
dental findings of Turner sx
increased caries rate, hypoplasia of crowns and roots
100
