Brainscape's Knowledge GenomeTM

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


See full index

KCSU17 Genetics > Autosomal Dominant Disorders > Flashcards

Autosomal Dominant Disorders Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

pleiotropy

A

when one gene effects multiple phenotypic traits and symptoms

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

age of onset of HD

A

typically 30-50 years old

progresses over 15 years and culminates in death

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

genetic abnormality of huntington’s disease (HD)

A

short arm of chromosome 4

mutation is a CAG expanded reapeat in the coding portion of hte gene

autosomal dominant

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

number of CAG repeats and Huntington’s Disease

A

Normal= 1-26

27-35 = unaffected

36+ = disease present, incomplete penetrance with 36-41

*** the larger number of repeats = earlier age of onset

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

protein affected in HD

A

huntingtin

involved in transport of vesicles in cellular secretory pathways

req. for normal produciton of BDNF

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

HD causes neuro degeneration of which areas in brain?

A

Basal ganglia (movement)

cortex (thoughts, memory)

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

Basal Ganglia

A

located on inner brain

control and coordination, muscle movement

HD specifically targets neurons of striatum (caudate nuclei and pallidum)

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

Cortex

A

outer surface of the brain

involved in perception, memory, and thought

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

Huntington’s disease pathophysiology

A

mutution in chromosome 4 causes increas in CAG repeats near huntingtin’s AA terminal

build up of CAG repeats causes production of abnormal huntingtin protein –> causes cell death

gain of function disease – over expression of abnormal huntingtin protein

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

HD imaging

A

loss of neurons on MRI

PET scan shows decreased glucose uptake in brain

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

clincial manifestations of HD

A

disease leads to brain weight loss (25% +)

  • a progressive loss of motor control
    • non-repetitive jerks; abnormal body movements that worsen over time
  • psychiatric problems
    • psychosis and schizophrenia
    • cognitive abnormalities dementia
  • behavioral disturbances
    • aggression, outbursts

HD patients eventually won’t be able to walk. Aspiration pneumonia (difficulty swallowing) is what causes death most often. The clinical course of HD is protracted (drawn out: 15-18 years before death)

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

HD:

Loss of motor control results in excessive uncontrollable movements of the head, face, trunk and limbs, controlled by?

A

basal ganglia

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

HD

Alterations in thought, perception, and memory are controlled by?

A

Cortex

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

HD expression

A

95% of cases are inherited (5% spontaneous)

affected homozygots display same course as heterozygotes

larger number of CAG repeats = earlier onset of disease

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

Juvenile Huntington Disease

A

HD onset before 20 years of age

paternally transmitted

esp. large number of repeats (>60 CAG repeats)

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

maternal v. paternal expression of HD

A

when the father transmits the disease there is a tendency for greater CAG repeat expansion

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

HD penetrance

A

incomplete pentrance occurs between 36-41 repeats

full penetrance occurs at >41

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

HD treatment

A

no curative treatment

drugs are available to treat symptoms

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

most common form of muscular dystrophy in adults

A

Myotonic Dystrophy

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

Genetic abnormality in Myotonic Dystrophy

A

autosomal dominant

nucleotide repeat expansion of CTG in DMPK on chromosome 19

number of repeats determins the degree of severity

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

CTG repeats in MD

A
  • 5 to 30 CTG repeats = unaffected individuals
  • 50 to 100 CTG repeats = mildly affected
  • 100 to 2000 CTG repeats = severely affected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

myotonic dystrophy (summary)

A
  • most common form of muscular dystrophy seen in adults
  • characterized by progressive muscle deterioration.
  • Caused by an abnormal nucleotide repeat expansion (CTG) in a non-coding region of DMPK gene on chromosome 19
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

protein affected in MD

A

DMPK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

pathophys of MD

A

The mutation is an expanded CTG trinucleotide repeat

The number of these repeats is strongly correlated with severity of the disease (like HD with CAG).

affect multiple systems: skeletal m, cardiac arrhythmias, and cataracts.

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

clincial manifestation of MD

A

Onset is usually prominent in the 2nd or 3rd generation; lifespan is typically six decades

Muscle weakness and wasting in the arms and legs and myotonia (muscle spasms/stiffening) tends to be the 1st symptoms noticed.

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

expression of MD

A

number of repeates increases with suceeding generations (anticipation)

number of repeats correlated with severtiy of disease

can be seen in infancy

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

congential MD

A

inherited from the mother

presents in infancy

characterized by an inverted “V” shaped upper lip and c_ompromised respiratory function_ (what generally kills them)

28
Q

MD penetrance

A

incomplete penetrance at 50-100 CTG repeats

full penetrance at 100-2000 CTG repeats

29
Q

MD treatment

A

anti-seizure medicin to treat myotonia

requires lots of PT/OT to treat muscle weakness and wasting

30
Q

HD general

A
  • autosomal dominant
  • a neurodegenerative disease that affects certain areas of the brain
  • Onset is dependent on age
    • typically 30-50 years old
    • progresses over 15 years
      • very rapidly, and culminates in death
  • Specifically affects cells of the basal ganglia
  • polyglutamine disease
  • involves expanded CAG repeats in gene product
    • affecting huntingtin protein
    • chromosome 4.
31
Q

Marfan Syndrome (general)

A

heritable disorder of connective tissue that affects fibrillin protein; it results in excessively “stretchy” connective tissue that allows for bone overgrowth to occur

32
Q

genetic abnormality in Marfan syndrome

A

autosomal dominant

mutation located on chromosome 15 gene that encodes fibrillin

33
Q

protein affected in Marfan Syndrome

A

fibrillin

connective tissue protien, major cmoponent of microfibrils

(suspensory ligaments of lens, aorta, and periosteum)

34
Q

pathophys of marfan syndrome

A

mutated fibrillin gene = excessively stretchy connective tissue

body systems affected: skeleton, heart and vessels, eyes, nervous system, skin, lungs

35
Q

skeletal clinical manifestations of Marfan

A

taller than average

chest wall deformiteis

steinberg thumb sign

36
Q

clinical manifestations of marfans

cardiovascular

A

widening of ascending aorta

can lead to CHF (must montitor)

37
Q

clinical manifestations of marfans

nervous

A

out poaching of dura in spinal cord = dura ectasia

38
Q

clincial manifestations of marfan’s

eyes

A

dislocation of one or both lenses of the eye

39
Q

clincial manifestations of marfan’s

skin

A

stretch marks

40
Q

clincial manifestations of marfan’s

lungs

A

connective tissue abnormalities

makes lungs less elastic –> causes lung collapse

41
Q

expression and penetrance pattern of marfan’s

A

40% of cases are spontaneous (60% inherited)

if parent has marfan, 50% risk they will pass gene to off spring

variable expression – same genotype can have large variety of phenotypes

42
Q

Marfan’s treatment interventions

A

require annual evaluations to detect changes in spine/sternum

must monitor for changes in defects, adverse effects

reg. eye exam, no smoking, avoid exercise, pregnancy risk

43
Q

Neurofibromitosis Type I

general

A

most common autosomal dominant

disturbs cell growth in nervous system

causes tumors to form on nervous tissue

Type 1 is 90% of cases, 50% of cases result from new mutation

44
Q

Neurofibromitosis Type I

genetic abnormality

A

type I is mapped to a gene on chromosome 17q

lg. gene = mutation target (accoutns for high mutation rate)

type 2 is chromosome 22

45
Q

Neurofibromitosis Type I

protein affected

A

encodes mRNA transcript and gene product: neurofromin

protein that acts as a tumor suppressor

46
Q

pathophysiology

Neurofibromitosis Type I

A

affected individuals develop tumors

cutantous neurofibromas are classic symptom

47
Q

Neurofibromitosis Type I

clincical manifestaitons

A

cutaneous neurofibromas (nodules/tumors on skin)

learning disabilities

lisch nodules (tumors on iris)

Cafe-au-lait (hyper pigmented skin)

NF1 is suspected if only 2+ present

tinnitus is present instead of iris nodules in NF2

48
Q

Neurofibromitosis Type I

expression and penetrance pattern

A

highly variable expression

49
Q

retinoblastoma (general)

A

most common childhood eye tumor

occurs during embryonic development when retinal cells are actively dividing/proliferating

Almost always presents by 5 years of age (40% familial/60% spontaneous mutations).

50
Q

genetic abnormality Retinoblastoma

A

chromosome 13

autosomal dominant, sporadic and non hereitary

51
Q

retinoblastoma protein affected

A

RB1 gene

52
Q

Retinoblastoma

types and expression

A

Non-hereditary (60% are spontaneous) and sporadic (not transmitted)

affected individuals will transmit gene to half of offspring (familiar ones are multi focal and bilateral)

53
Q

retinoblastoma

penetrance

A

reduced penetrance

not everyone with genotype gets phenotype because it requires a second hit in the same region of the DNA

54
Q

retinoblastoma treatment interventions

A

treated with radiation, cryotherapy or laster photocoagulation

detected with the white light shown on the eye

55
Q

Retinoblastoma reading assignment

A

There is reduced penetrance in inherited retinoblastoma because the normal RB1 allele requires a second hit in order for the tumor to develop.

The second hit has a low probability of occurring in any given cell.

Because the second hits are random events, a small fraction of persons who inherit the disease allele never experiences a second hit in any retinal cell and thus do not develop retinoblastoma.

The requirement for the second hit thus explains the reduced penetrance seen in the disorder.

56
Q

Factor V Leiden

A

autosomal dominant condition that results in factor V protein variant that can not be degrated by aPC

blood clotting factor

can easily lead to thromboembolism

57
Q

aPC

A

protein responsible for breaking down blood clot formed by factor V

58
Q

Achondroplasia

A

aka dwarfism

disorder of bone growth

most common type of short-limbed dwarfism

unable to convert cartilage to bone, particularly in the long bones of the arms and legs

59
Q

Achondroplasia

Genetic abnormality

A

mutation on the FGFR3 gene

60
Q

Achondroplasia

protein affeted

A

protein made by FBFR3

receptor that regulates bone growth by limiting formation of bone from cartilage (ossification)

61
Q

Achondroplasia

pathophys

A

FGFR 3 gene mutated

becomes overly active, interfearing with ossification and leads to disturbances with bone growth= short stature

bc this disease is in the long bones, it results in average size trunk

normal intelligence is seen with this disease

62
Q

Achondroplasia

clinical manifestations

A

short arms and legs byt average size trunk

breathing disorder (apnea)

normal intelligence

63
Q

Achondroplasia

expression and penetrance

A

trait appear in every generation

transmitted from either parent

64
Q

similaries between HD and MD

A

autosomal dominant with anticipation and early onset form

longer the repeat, earlier the disease occurs

65
Q

differences bt MD and HD

A

MD early form is from the mother, presents at birth

HD early form is paternal, presents in teens

HD mutation is on chromosome 4 with CAG repeats,MD mutation is chromosome 19 with CTG

HD fully penetrant at >41 repeats and affects huntingtin. MD is fully mutant 50-2000 repeats and affects and DMPK

66
Q
A

KCSU17 Genetics (14 decks)

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