Clinical genetics Flashcards
the aetiology of disease rests on 3 conditions
100% environmental
Single gene
polygenic
deine multifactorial disorder
multiple genes (genetic predisposition) and environmental factor
define single gene disorder
a mutation in a single gene = Mendelian inheritance
define chromosomal disorder
an imbalance or rearrangement in chromosome structure eg aneuploidy, deletion, translocation
define mitochondrial
a mutation in mitochondrial DNA
define somatic mutation
mutation(s) within a gene(s) in a defined population of cells that results in disease
what are the 4 gene modes of inheritance
autosomal dominant
autosomal recessive
X-linked
Mitochondrial
how many chromosomes do we have
46 chromosomes.
do autosomal dominant conditions run from generation to generation.
Yes.
Are males and females equally affected in autosomal dominant conditions
Yes.
what % does offspring of an affected person have of inheriting the condition
50%
what types of molecules do mutations of a autosomal dominate fashion affect.
structural proteins, receptors and transcriptional factors.
examples of conditions which are inherited in a autosomal dominant manner
myotonic dystrophy
marfans syndrome
Huntingtons disease
define penetrance
Frequency of people with the genotype who express certain charcterisitics.
define full penetrance
mutation results in have the disease.
define incomplete penetrance
mutation is present but they may not have the disease.
define expressivity
variation in expression ( the extent to which a heritable trait is manifested by an individual)
define anticipation
symptoms more apparent at an earlier age as it is passed from one generation to the next.
define de novo mutations
new mutation that has occurred during gametogenesis or in early embryonic development.
Do autosomal recessive conditions pass from generation to generation
No- parents typically affected .
what types of relationship increase risk of recessive disorders.
consanguineous
do autosomal recessive conditions affect males and females equally
Yes.
what % chance will the offspring of an affected person will get the condition
25%
what % chance is there that a affected person will have a offspring who is a carrier
2/3
66%
examples of autosomal recessive conditions
cystic fibrosis
metabolic disorders
sickle cells disease
Haemachromatosis.
which gender is affected in X-linked conditions
males.
(females can be mildly affected0
Can you have ale to male transmission of a X-linked condition
No.
examples of X-linked conditions
duchenne’s muscle dystrophy
fragile X syndrome
Red/green colur blindness
Haemophillia
if the mother is a carrier of a X-linked condition then what are the chances that the male is affected.
25%
If the mother is a carrier of a X-linked condition then what are the chances that the female is carrier
25%
If the father is affected by a X-linked condition then how will this affect all daughter and son offspring
all daughters are carriers.
all sons are unaffected.
what are the 2 main factors which cause females to have such variable X-linked phenotypes
X inactivation
XL dominant vs XL recessive inheritance inheritance
X inactivation is aka
Lyonisation
what happens in X-inactivation
The process of random inactivation of one of the X chromosomes in cells with more than one X chromosome.
Compensates for the presence of the double X gene dose.
what is the shut down X in lyonisation called
Barr body.
when does X inactivation take place
early embryogenesis.
define skewed X-inactiavtion
random preference for “normal” X chromosome to be inactivated
define tissue variability (int terms of X inactivation)
random preference for the X chromosome with the mutation to be active in crucial tissue group
define X linked dominance
a dominant gene is only carried on the X chromosome (less common than recessive condition)
define X linked recessive
a recessive gene is only found on the X chromosome ( more common that dominant condition)
example of XL dominant
Rett syndrome
Fragile X syndrome
examples of XL recessive
Red-green colour blindness
Haemophilia
Duchene Muscular dystrophy
is mitochondrial inheritance from the mother father or both.
All our mitochondria are inherited from our mother
how many genes have mitochondrial DNA
27
How will the children of a affected mother be affected
all have mutation
How will the children of a affected man be affected
not affected.
