basics of clinical genetics Flashcards
what does the triangle of disease aetiology represent?
for any condition, the balance between environmental and genetic factors can be represented by a point somewhere on the triangle
are strokes genetic or environmental?
they have environmental factors but also polygenic factors or a single gene making them multifactorial
which diseases are on each end of the genetic/environmental spectrum?
genetic - duchenne muscular dystrophy
in the middle there is spina bifida and pyloric stenosis and completely environmental - scurvy
what are the characteristics of genetic and environmental diseases?
genetic are rare - they have simple genetics and are unifactorial. They have a high recurrence rate. However, environmental have complex genetics, are multifactorial, have a low recurrent rate and are common.
what is the definition of multifactorial?
the interaction of multiple genes and environmental factors causing a condition
what mode of inheritance is common for single gene disorders?
these are mutations in single genes and therefore Mendelian inheritance is common - AD, AR, XL or mitochondrial
what is a chromosomal condition?
the rearrangement or imbalance in chromosome structure
what are somatic mutations?
mutation in a gene in a defined population of cells that results in a disease
what do gametes contain?
23 chromosomes - 1 copy of each
what is autosomal dominant inheritance?
when a trait or disease runs from one generation to the next. Affected individuals are heterozygous for the mutation. The chance that offspring are affected or unaffected is both 50%. These mutations tends to alter the structure of proteins.
define penetrance?
the frequency with which a specific genotype is expressed in those individuals affected by it - presented as a percentage. It can alter with age or there can be incomplete penetrance whereby not every member of the family that inherits the mutation develops the disease.
what is the term for variation in expression? and describe it?
expressivity - extent to which a heritable trait is manifested by an individual. This may be 100% but there are different expressions.
what is anticipation?
the symptoms of a genetic disorder appear earlier as it is passed down through generations and usually an increase in severity of symptoms too
what is a de novo mutation?
it is a new dominant mutation that has occurred during gametogenesis or early in embryonic development - not inherited but can be passed on
what is autosomal recessive inheritance?
it is when disease is seen in one generation and does not tend to pass to the next as the parents are generally unaffected. The affected individuals are homozygous or compound heterozygous for the mutation. The risk to offspring is 25% to have the disorder and to be a carrier is 2/3.
what is the cause of milder phenotypes?
it is when some people have different mutations on different point of their genes and therefore it makes a compound heterozygous mutation
what are haemochromatosis, sickle cell, CF and many other metabolic disorders examples of?
autosomal recessive inheritance
who is affected in X linked disorders and what are they?
males (some females - less severe), it cannot have male to male transmission however all daughters will have the mutation. It can be gene and chromosome related.
what is the risk of offspring being affected by a XL disease?
with a carrier mother: 25% for both affected boys and carrier girls and 25% not affected for boys and girls. With a carrier father: no chance for boys and all daughters are carriers (most asymptomatic or have mild symptoms)
what are examples of XL diseases?
duchenne muscular dystrophy, Fragile X syndrome, red and green colour blindness, haemophilia
what affects the expression of the phenotype of XL diseases in females?
X inactivation and XL dominant or XL recessive
what is lyonisation?
X inactivation. The process of random inactivation of one of the X chromosomes in cells that have more than one X chromosome. All daughter cells have the same X chromosome switched off. It occurs early in embryogenesis and remains inactive throughout the whole lifetime of cell and all of it’s descendants. Most but not all of the genes will be switched off on the inactivated X. The inactivated one is the Barr Body.
what is skewed X inactivation?
the random preference for normal X chromosome to be inactivated - therefore resulting in a significant phenotype - the preference usually has preference for the mutated in a certain tissue group. It may not be same throughout the whole body.
what is XL dominant expression?
it is rare where most carrier women are fine but could have a full disorder. Examples are Rett and Fragile X syndromes.
