Genetics Flashcards
1
Q
What is the term codominance?
A
It meas that both alleles contribute to the phenotype of the heterozygote
2
Q
What are the examples of codominance?
A
Blood groups: A, B, AB
HLA groups
Alpha 1 anti trypsin
M allele: normal
Z allele: severely reduced
S: moderately reduced
Combo: MM: normal, ZZ: severely reduced, other combos make varying degrees
3
Q
What is term variable expressivity?
A
Same genotype: varying phenotypes
4
Q
What is the example of variable expressivity?
A
NF1
2 patients with neurofibromatosis type 1 may have varying disease severity
5
Q
What is term incomplete penetrance?
A
Not all individuals with the mutant genotype: show the mutant phenotype
6
Q
How to calculate incomplete penetrance?
A
% penetrance x probability of inheriting genotype= risk of expressing phenotype
7
Q
What does 100% penetrance means?
A
That all the individuals express the phenotype with the mutant gene
8
Q
What is the example of incomplete penetrance?
A
BRCA1 gene mutations do not always result in breast or ovarian cancer
9
Q
What is the term pleiotropy?
A
One gene= multiple phenotypic effects
10
Q
What is the example of pleiotropy?
A
Untreated PKU: light skin, intellectual disability, musty body odor
11
Q
What is the term anticipation?
A
Increased severity or earlier onset of disease in suceeding generations
12
Q
What is the example of anticipation?
A
huntington disease (trinucleotide repeat expansion)
13
Q
What is loss of heterozygosity?
A
If a patient inherits or develops a mutated tumor supressor gene, the complementary allele must be mutated in order for cancer to develop
14
Q
What is not true of oncogenes?
A
Loss of heterozygosity
15
Q
What is the example of loss of heterozygosity?
A
Retinoblastoma
Hereditary form: Germ line mutation, passed down to offspring (one hit), somatic mutation in second copy
(Second hit)——-> multiple tumors, tumors at younger age
Two hit theory
Sporadic form: requires two somatic hits. And possibility of acquiring mutation in both alleles is rare———> single tumors, tumors at later stage
HNPCC, Li- Fraumeni syndrome
16
Q
What is the term dominant negative mutation?
A
A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning
17
Q
What is the example of dominant negative mutation?
A
Mutation in transcription factor, nonfuntioning mutant can still bind to dna and prevent the wild type transcription factor from binding
18
Q
What is the term linkage disequilibrium?
A
Tendency for certain alleles at 2 linked loci to occur together more or less often than expected by chance
19
Q
Is linkage disequilibrium measured in families or populations?
A
Population, varies in different populations
20
Q
What is mosaicism?
A
It is the presence of genetically distint cell lines in the same individual
21
Q
Somatic mutation is the mutation that arises from ____________ and propagates through___________
A
Mitotic errors after fertilisation
Multiple tissues or organs
22
Q
Gonadal mosaicism is the mutation that only occurs in ________
A
Eggs or sperm cells
23
Q
If the parent does not have the disease, we can suspect?
A
Gonadal mosaicism
24
Q
What is the example of mosaicism?
A
Mc cune albright syndrome
25
McCune albright mutation is a mutation affecting_______
G protein signalling
26
McCune Albright syndrome patients have unilateral ________ and
Cafe au lait spots with ragged edges
Polyostotic fibrous dysplasia (bone is replaced by collagen and fibroblasts
27
What kind of endocrinopathy do patients with McCune Albright patients present with?
Precocious puberty
28
McCune Albright syndrome is lethal if mutation ________
Occurs before fertilisation, affects every cell. But survivable in patients with mosaicism
29
Locus heterogeneity is mutation at ________ and can produce a ________ phenotype
Different loci, similar
30
Allelic heterogeneity is mutation at ________ and can produce a ________ phenotype
In the same loci, same
31
Example of locus heterogeneity is?
Albinism
32
Example of allelic heterogeneity is?
Cystic fibrosis and b thalessemia
33
Heteroplasmy is presence of both mutated and normal _______, resulting in ________
Mtdsna
Variable expression in mitochrondrially inherited disease
34
Mtsdna is passed from?
Mother to all children
35
Uniparental disomy means offspring recieves ______ of chromosomes from _______ parent
2 copies of chromosomes
1 single parent
36
Heterodisomy results from
Meiotic error 1
37
Isodisomy results from?
Meiotic error 2
38
Uniparental is________
Euploid meaning correct number of chromosomes
39
Most occurences of uniparent disomy results in ________
Normal phenotype
40
Consider uniparental disomy in an individual manifesting a ________ disorder and only ________ is a _______
Recessive
1
Carrier
41
Examples of isoparental disomy are?
Prader willi, and angel man syndromes
42
Hardy weinberg is only applicable to a population if
No mutation occuring in the same locus
Large population
No intermixing
Natural selection is not occuring
No net migration
Natural Net intermixes with Large Mutation
43
Imprinting is _______ copy is _________ and only the copy __________
One
Silenced by methylation
Expressed
44
Imprinting has what origin?
Parent of origin effects
45
In prader willi syndrome _________ are silenced (imprinted). Disease occurs when the _______ allele is ________
Maternally derived genes
| Paternal allele is deleted
46
Prader willi is associated with the mutation or deletion of ______ of _____origin?
15 chromosome
| Paternal
47
How many number of cases are due to maternal uniparental disosmy (maternal non disjunction) in __________
25%
Prader willi
48
Prader willi is associated with _______
```
Hyperphagia
Obesity
Intellectual disability
Hypogonadism
Hypotonia
```
49
In AngelMan syndrome, the _________ is silenced and the _______ is deleted
Paternally derived UBE3A gene is silenced
| Maternal allele is deleted or mutated
50
AngelMan syndrome is associated with mutation or deletion of _______ on the ________copy of chromosome_______
Ube3A
Maternal
15
51
How many number of cases are due to paternal uniparental disosmy (parental non disjunction) in __________
5%
AngelMan syndrome
52
What are the symptoms of AngelMan syndrome?
Inappropriate laughter (happy puppet) and seizures
Ataxia, and severe intellectual disability
53
What are the five modes of inheritance?
Autosomal dom, Autosomal rec
X linked dom, X linked rec
Mitochondrial
54
Autosomal dominant is due to __________ genes
Defects in structural
55
Is there skipping in dominant disorders?
No
56
Are females affected in dominant disorders or males?
Both
57
Is there male to male transmission in autosomal disorders?
Yes
58
Which disorders are often pleiotropic and variably expressive between individuals?
Autosomal dominant
59
What is crucial to aut dom disorders?
Family history
60
One affected heterozygous parent, has on average how many affected children in autosomal dominant disorders?
1/2
a a
A Aa Aa
a aa. aa
61
Autosomal recessive disorders are due to ________
Enzyme def
62
Is there skipping in autosomal recessive disorders?
Yes
63
With 2 carrier parents, how many children will be affected, carriers, and non affected
1/4
1/2
1/4
64
Which is more severe, aut dom or aut recessive?
Aut rec
65
Patients with _________ often present with symptoms in childhood
Aut rec
66
In X linked recessive, sons of heterozygous mothers have _______ of being affected?
50 %
X Y
Xn Xn X XnY
X X X X Y
67
Is there male to male transmission in x linked disorders?
No
68
X linked recessive is more common in males or females?
Males
69
Females in X linked recessive must be _________ to be affected?
Homozygous
70
In X linked dominant, it is transmitted through ________ parent?
Both parents
71
In x linked dominant, daughters and sons of heterozygous mothers have ______ of being affected?
50 %
X Y
Xn Xn X XnY
X X X X Y
72
In which disorder do all fathers transmit the genes to all his daughters
X linked dominant
73
What is the example of x linked dominant disorder?
Hypophosphatemic defect
74
In vitamic D resistant, ________ in phosphate wasting, at _________ tubule
Increased
Proximal
75
Vitamin d resistant disorder results in which type of presentation?
Rickets like
76
Other examples of x linked dominant disorders are?
Fragile x and alport syndrome
77
In mitochondrial inheritance, only _______ transmits the disease?
Mother
78
Can all affected offspring show signs of disease in mitochondrial inherited disorder?
Yes
79
Why is there variable expression in a population or even within a family in mitochondrial inheritance?
Heteroplasmy
80
In mitochondrial myopathies, rare disorders, patients often present with __________
Myopathy
Lactic acidosis
Cns disease
81
What is MELAS syndrome?
Mitochondrial encephalopathy
Lactic acidosis
Stroke like episodes secondary to failure in oxidative phosphorylation
82
In MELAS syndrome, what does biopsy often shows?
Ragged red fibres, due to decreased mitochondria
83
What is example of mitochondrial inherited disease
Leber hereditary optic neuropathy
84
In Leber hereditary optic neuropathy __________ in optic nerve nuerons, there is permanent ___________ in teens/young adults
Cell death
| Subacute bilateral vision loss
85
In Leber hereditary optic neuropathy, how many males are affected?
90%
86
Fragile X syndrome is what type of disorder?
X linked dominant
87
In fragile X linked, there is __________ of ___________, which leads to __________ and ________ expression
Trinucleotide repeat, FMR1, hypermethylation, decreased
88
Trinucleotide expansions occur due to __________
Slipped strand mispairing
89
It is the most common cause of ___________ and second most common cause of _________ after down syndrome
Inherited intellectual disability, genetically associated mental deficiency after Down Syndrome
90
What are the findings of Fragile X syndrome?
Post pubertal macroorchidism (enlarged testes), long face with large jaw and everted ears, autism, mitral valve prolapse
91
Trinucleotide repeat expansions (CGG)n occurs in?
Oogensis
92
What are the examples of trinucleotide repeat expansions?
Try hunting for my fragile cage free eggs
Trinucleotide huntington disease, myotonic dystrophy, fragile x syndrome, and Friedreich ataxia
93
Trinucleotide repeat expansion diseases show genetic anticipation which means?
Severity increases, with the increased age of onset, and decreased sucessive generations
94
Hungtington disease
Trinucleotide repeat (________)
Mode of inheritance (______)
Mnemonic ......
CAG
AD
C: caudate
A: decreased Ach
G: Gaba
95
Myotonic dystrophy
Trinucleotide repeat (________)
Mode of inheritance (______)
Mnemonic ......
(CTG)n
AD
C: cataracts
T: toupee (early balding in men)
G: gonadal atrophy
96
Fragile X syndrome
Trinucleotide repeat (________)
Mode of inheritance (______)
Mnemonic ......
(CGG)n
XD
Chin protruding, Giant Gonads
97
Friedreich Ataxia
Trinucleotide repeat (________)
Mode of inheritance (______)
Mnemonic ......
(GAA)n
AR
Ataxic GAAit
98
Which trisomy is the most common liveborn chromosomal abnormality?
Down syndrome
99
Which disorder is the most common genetic intellectual disability?
Down syndrome
100
What are the findings for down syndrome, facial features?
depressed nasal bridge, low set ears, short neck, brachy cephaly
101
What are the findings for down syndrome, eye features?
Prominent epicanthal folds, palpebrel fissures, brush field spots
102
What are the findings for down syndrome, extremities features?
Sandle toe, single palmer crease
103
What are the five As of Down syndrome
```
Atresia
Advanced maternal age
Atrioventricular septal defect
Alzheimer disease (early onset) (codes for amyloid precursor protein, chromosome 21)
AML/ALL
hirschsprung disease
```
104
95% of the cases are due to ______________
Meiotic non disjunction
105
Which cause of down syndrome increases with advanced maternal age
Meiotic non disjunction
106
What is the incidence of Down syndrome in women less near 20 years of age
1:1500
107
What is the incidence of Down syndrome in women less near 45 years of age
1:25
108
4% of the cases are due to ______________
Unbalanced Robertsonian translocation, between 14 and 21 chromosomes
High occurence within families
No relation w maternal age
109
1% of the cases are due to ______________
Post fertilization mitotic error
Can lead to milder forms of DS
No association with advanced maternal age
110
What are the invasive methods of diagonising Down syndrome
Amniocentesis
| Chorionic villus sampling
111
What are the non invasive methods of diagnosing Down syndrome
Nuchal translucency, depressed nasal bones growth
112
Which trisomy is Edwards?
Trisomy 18
Election 18
113
What is the incidence of Edwards syndrome
1:8000
114
What is the second most common cause of autosomal trisomy resulting in live birth
Edwards syndrome
115
What are the findings of Edwards Syndrome
prince edward sissor hands
Low set ears
Clenched fists
```
Prominent occiput
Rocker bottom feet
Intellectual disability
Non disjunction
Clenched fists
Low set ears
```
116
What happens to the jaw in patients with edwards syndrome
Micrognathia
117
At what age do edwards syndrome patients die
Death occurs by 1, congenital heart disease
118
Which trisomy is Patau syndrome
Trisomy 13
Puberty 13
119
What are the common findings of Patau syndrome?
```
Cleft palate
Prosencephaly
Polydactyl
Polycystic kidney disease
Cutis A Plasia
```
120
What age do patients of Patau syndrome die?
Death occurs by age 1
121
What is the incidence of Patau Syndrome
1:15000
122
In the 1st trimester for 21, 18, 13
Beta hcg, and PAPP-A
All decreased except b hcg for down syndrome which increases
123
In the 2nd trimester for 21, 18, 13
AFP, b hcg, estriol, inhibin A
Normal for 13, decreased for 18, increased for b hcg and inhibin A for 21
124
In the 2nd trimester for 21, 18, 13
AFP:
Decreased, decreased, normal
125
Robertsonian translocation is a translocation that commonly involves the chromosome pairs:
13, 14, 15, 21, and 22
126
Robertsonian translocation occurs when the _________ fuse at the centromere and the ___________
Long arms of 2 acrocentric chromosomes (chromosomes with centromeres near the end)
And the 2 short arms are lost
127
Balanced translocation normally do not cause any ___________
Abnormal phenotype
128
Unbalanced translocations can result in __________
Miscarriage, still birth, and chromosomal imbalance e.g down syndrome, patau syndrome
129
Cri du chat syndrome is the ____________
Deletion on the short arm of chromosome 5
130
What are the findings in patients with cri du chat syndrome?
Microcephaly, moderate to severe intellectual disability, high pitched screaming, epicanthal folds, and cardiac abnormalities (VSD)
131
What is the genetic cause in Williams syndrome?
Microdeletion on chromosome 7 long arm
132
The deleted region in Williams syndrome includes the _______
Elastin gene
133
What are the findings in Williams syndrome
Elfin facies
Intellectual disability
Well developed verbal skills
Extreme friendliness with strangers
```
Hypercalcemia (sensitivity to vitamin D increases)
Cardiovascular problems (supravalvular aortic stenosis, renal artery stenosis)
```
134
What is the genetic cause in digeorge syndrome?
22q11
Microdeletion at chromosome 22 long arm region one band one
135
What are the findings of 22q11 syndrome
CATCH 22
cleft palate, Abnormal facies, Thmyic aplasia (t cell def), cardiac defects, hypocalcemia (parathyroid aplasia) due to aberrent development of 3th and 4th pharyngeal pouches
136
What are the findings of digeorge syndrome?
Thmyic, parathyroid and cardiac defects
137
What is the findings of Velocardiofacial syndrome?
Palate, facial and cardiac defects
