GIM2 - Clinical Genetics Basics Flashcards
what are the 3 factors which makes up the aetiology of disease
environmental, single gene, polygenic
what is somatic mutation
when the disease is caused by the gene mutation during the life of the person but not born with the mutated gene
what are the 4 different modes of single gene modes of inheritance?
autosomal dominant, autosomal recessive, X-linked, Mitochondrial
what are some examples for autosomal dominant inheritance
marfan syndrome, huntington disease, myotonic dystrophy
what kind of defects do AD normally affect?
structural proteins, receptors, transcription factors (extra-cellular)
what is penetrance
frequency with which a specific genotype is expressed by those individuals that possess it, usually given as a percentage.
- may vary with age
- can be incomplete penetrance - not all who has the genes will have the condition
what is expressivity?
variation in expression - the extent to which a heritable trait is manifested by the individuals
what is anticipation
symptoms of a genetic disorder become apparent at an earlier stage in comparison to the previous generation as the gene is passed on
what is de novo/new dominant
new mutation that has occurred during gametogenesis or in early embryonic development
what is the risk of the offspring contracting the an autosomal recessive condition by parents who are both carrier
25%
what is compound heterozygous ?
Compound heterozygous is when the parents have different gene mutation of the same disease (cystic fibrosis one in the beginning and 1 in the end of the gene mutated) then the compound effect of the 2 different gene will contribute to the generation of the disease as they produce a non-functioning protein
what are some examples for autosomal recessive inheritance
CF, haemachromatosis, sickle cell disease
what is X-linked inheritance
only the X chromosome is affected ie male is for sure affected
female can also be affected but with varied degree of affectance
how is X-linked transmitted?
from mother to son
what are some examples for XL inheritance
duchenne muscular dystrophy, fragile X syndrome, red/green colour blindness, haemophilia
what is the risk of offspring having the condition if the condition is X-linked
25% affected boy, 25% carrier girl
what is the risk of offspring having the condition if the condition is X-linked and the father is affected
all daughters are carriers, all sons unaffected
what are the 2 factors which causes XL female carrier to have severe symptoms of the condtion
X inactivation & XL condition being dominant
what is another name for X-inactivation?
lyonisation
what is x-inactivation?
Occurs in early embryogenesis
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 skewed X inactivation
random favouring of one chromosome over the other - leading to significantly more cells with one particular X chromosome
what is tissue variability
– random preference for the X chromosome with the mutation to be active in crucial tissue group – eg muscle in Duchenne Muscular dystrophy
what are some examples for XL dominant
Rett syndrome (lethal in males, phenotype only in female)
FragileX syndrome - females:- asymptomatic to fully symptomatic ( due to X-inactivation pattern)
what are some examples for XL recessive
Red-green colour blindness
Haemophilia
Duchene Muscular dystrophy
Carrier girls usually unaffected BUT can have significant symptoms because of X-inactivation (switches off normal X)
what are some examples for mitochondrial inheritance
maternally inherited diabetes and deafness
where does all our mitchondrial genes come from
maternal
