Mendelian Inheritance Flashcards
1
Q
How does autosomal dominant manifest
A
it can manifest in the heterozygous state
2
Q
AD characteristics on pedigree - 4
A
- successive generation
- male and females can be affected
- both males and females can transmit
- male to male (father to son) transmission observed
3
Q
what is penetrance
A
the percentage of people expressing the disorder to any degree
4
Q
what is anticipation
A
worsening of the condition with each successive generation
5
Q
Penetrance in AD- 2
A
- may sometimes be incomplete
- shows penetrance in age dependant fashion (some may exhibit it later in life)
6
Q
2 subtypes of variable expressivity
A
- interfamilial - betwen different families
- intrafamilial - in the same family
7
Q
what is pleitropy
A
- manifestation of the AD disease in different body systems
- one gene affects multiple traits
8
Q
8 features of AD
A
- penetrance
- variable expressivity
- pleitropy
- anticipation
- allelic heterogenity
- new mutation rate
- somatic mosacisim
- gonadal mosacisim
9
Q
Allelic heterogenity
A
different mutations in the same locus (location) cause the same disorder
10
Q
classify neurofibromatosis type 1
A
AD disease
11
Q
A
12
Q
characteristics of NF1 - 4
A
- axillary and inguinal frecklings
- iris Lisch nodules
- neurofibromas
- cafe au lait macules
13
Q
what gene muatation causes NF1
A
NF1 gene on chromosome 17q11.2
14
Q
NF1-gene - 4
A
- tumor supressor gene
- large gene (many mutations) - allelic heterogenity
- encodes for neurofibromin
- loss of function mutation
15
Q
Principles of inheritance of NF1 - VANCAP
A
Variable expressivity
Autosomal dominant
New mutations - 50%
Complete tolerance
Allelic heterogenity
Pleitropy
16
Q
how does autosomal recessive maniest - 2
A
- homozygous state (2 mutant alleles)
- BOTH parents are carriers and they are clinically unaffected
17
Q
AR characteristics on pedigree - 4
A
- can skip generation
- affect both males and females
- males and females can transmit
- parents may be RELATED
18
Q
what increases the risk of an AR condtition
A
if the condition is common or wif there is consanguinity
19
Q
common AR conditions - 5
A
- cystic fibrosis
- pinal muscular atrophy
- oculocutaneous albinism
- inborn errors of metabolism - galactosemia
- fanconi anemia
20
Q
4 concepts of AR inheritence
A
- locus heterogenity = mutations at different loci
NB!! ALSO IN AD, just wasnt mentioned - allelic heterogenity = mutations at the same loci
- compound heterozygote = two mutations in the same locus (only two, while allelic is MANY) - one on each allele
- double heterozygote = two mutate alleles at differnt loci
21
Q
what mutations are we talking about in allelic heterogenity
A
- nonsense, missense, deletion etc… they all result in changes to the end product
22
Q
what is allelic heterogeneity related to
A
compound heterozytosity
23
Q
example of double heterozygosity
A
sensorineural hearing impairment
24
Q
OCA1 - 3
A
- more common in caucasians
- mutations in the TYR gene , on chromosome 11q14
- tyrosinase is responsible for the formation of melanin from tyrosine
25
OCA2
- OCA2 gene mutation in chromosomes 15q12
- encodes transmembrane p protein found on the melanosomal membrane
- 2.7kb deleltion mutation found in homozygous state
26
are X linked inheritence equally distributed
NO they are not
27
X inactivation
when one X chromosome in the female is inactivated to prevent women having double the amount of X gene related disorders than males
28
when does X inactivation occur
in the EARLY embryological stage
29
manifesting heterozygotes
emales who show symptoms of an X-linked recessive disorder (e.g., Duchenne muscular dystrophy) because the normal X chromosome is inactivated in more than 50% of cells, leading to more expression of the harmful allele. This is called skewed X-inactivation.
29
X inactivation centre
at X13.3... It involves the XIST gene and sends methylation inactivation signals up and down the X chromosome where it is located.
29
characteristics of XLD inheritence - 7
- in every generation
- affects both males and females
- females affected at varying degrees
- males are henizygous - more severe
- beware of history of miscarrages
- both males and females can transmit
- males can transmit to their daughters, BUT NOT SONS
29
examples of XLD - CCIRGX
Craniofrontonasal syndrome
Chondroplasia
Incontinentia
Rett syndrome
Goltz syndrome
X linked hypophosphotemic rickets
30
who is more prone to x linked recessive disorders
MALES
31
XLR transmission
- heterozygous females to affected males
- affected males to obligate carrier daughters
32
XLR characteristics
- skips generation
- affectes males only
- no male to male transmission
33
what are the exceptions for females to be affected - 4
- homozygosity
- skewed X inactivation
- X autosome translocation
- numerical x chromosome abnormality
34
DMD - 2
- severe and most common form of muscular atrophy
- progressive symmetrical muscle weakness (same on both sides)
35
Clinical characteristics of DMD - 7
- early onset (2-4 y/o)
- delayed walking, sitting, standing
- difficulty climbing steps
- abnormal gait (tip toe)
- clumsy
- muscle pain (esp calves)
36
complications of DMD
wheelchair dependancy and cardiomyopathy
37
DMD gene complication
- Xp21 gene
- encodes for dystropin protein
- mutations cause total/almost total loss of dystropin protein\- 2/3 inherited and 1/3 new mutation
38
BMD - 6
- milder clinical phenotype
- milder involvement of the skeletal muscles
- mean death age = mid 40s
- late onset - 8 years
- DMD gene mutation (Xp21)
- dilated cardiomyopathy is the cause of death and morbidity
39
DMD reccurence risk
2/3 of mothers of males with DMD with no family history are carriers
(de novo)
40
males affected with DMD fertility
do not reproduce
41
if mother does not have detectable DMD
15-20% recurrence risk
- otherwise its usually 50% for affected male and then 50% for carrier daughters
