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Flashcards in Autosomal dominant Deck (37)
1

rare when a _______ dominant mutation causing disease

homozygous dominant
AA

2

example of complete penetrance

achondroplasia

3

achondroplasia is autosomal _____

dominant

4

de novo mutation

mutations that occur in the egg or sperm or immediately after fertilzation

5

de novo mutations would explain

autosomal dominant disorder seen in children without affected parents

6

clinical achondroplasia

1. short
2. rhizomelic limb shortening
3. short fingers
4. genu varum
5. trident hands
6. large/frontal bossing
7. midfacial retrusion
8. small foramen magnum/ craniocervical instability

7

achondroplasia is lethal in

homozygous dominant state

8

achondroplasia gene

FGFR3

fibroblast growth factor receptor 3

9

achondroplasia gene funct

regulates bone growth by limiting the formation of bone from cartilage

10

achondroplasia chrom

4p16.3

nucleotide 1138

11

achondroplasia mutation function

increases the activity of protein interfering with skeletal development

12

____ has highest new mutation rate known in man

Nucleotide 1138 of FGFR3 gene

13

Pure dominant

Homozygotes and Heterozygotes are both equally affected

14

incompletely dominant

homozygotes are affected most severely

15

reduced penetrance

1. retinoblastoma
2. BRCA mutation
3. huntongton's disease

16

variable expressivity examples

Neurofibromatosis type 1
osteoogenesis imperfect type 1

17

Neurofibromatosis type 1
new mutation rate

50%

18

Neurofibromatosis type 1
clinical

cafe au lair spots
neurofibromas
plexiform neurofibroma
freckling in axilla
optic glioma
lisch nodule
osseous lesions

19

Neurofibromatosis type 1
mutation

NF1
neurofibromin tumor suppressor gene
loss of function

20

Neurofibromatosis type 1
chromosome

17q11.2

21

locus heterogeneity

mutation in more than one locus causing same clinical condition

22

locus heterogeniety example

autosomal dominant polycystic kidney disease

23

Autosomal dominant polycystic kidney disease
new mutation rate

5%

24

Autosomal dominant polycystic kidney disease
clinical

1. bilateral renal cysts
2. cysts in other organs
3. vascular abnormalities
4. end stage renal disease

25

Autosomal dominant polycystic kidney disease
mutation

PKD1 chromosome 16p13.3

PKD2 chromosome 4q22.1

polycystin 1 and 2

produces truncated protein

26

familial hypercholesterolemia

new mutation rate

very low

27

familial hypercholesterolemia
clinical manifestations

high cholesterol
high LDL levels
xanthomas
premature coronary artery disease and death

28

familial hypercholesterolemia

mutations

1. LDLK
2. APOB
3. PCSK9

29

trinucleotide repeat disorders

1. expansion of segment of DNA consisting of 3 or more nucleotides
2. CAG
3. slipped mispairings
4. anticipation
5. parental transmission bias
6. AD, AR nd X-linked transmission

30

slipped mispairing

1. mispairings of bases in regions of repetitive DNA replications coupled with inadequate DNA repair systems
2. as the repeat grows longer, the probability of subsequent mispairings increases

31

anticipation

severity and onset of diseases increases in next generation

32

parental transmission bias

trinucleotide expansion more prone to occur in gametogenesis of male or female

33

Huntington's disease:

1. autosomal dominant
2. trinucleotide repeat disorder (CAG)
3. anticipation
4. paternal transmission

34

Huntington's disease
clinical

progressive neuronal degeneration causing motor cognitive and psychiatric distrubences

onset 35-44
death 15 years after onset

35

Huntington's disease
gene

HTT

36

Huntington's disease protein

huntingtin

37

Huntington's disease chromosome

4p16.3