GiM week 1 Flashcards
What is pseudohypoaldosteronism an example of?
rare genetic disease that causes hypotension
what is liddle’s syndrome an example of?
rare genetic disorder that causes hypertension
what 3 types of tests could you do for genetic disorders?
blood tests (enzyme assays or haematology)
x-rays (checking for skeletal dysplasia)
genetic tests
what is an example of an inherited skeletal dysplasia?
achondroplasia
what 5 different types of genetic tests can you do?
genomic architecture:
- cytogenetics
- array based techniques
gene faults
- sequencing
- OLA assays
- MLPA tests
what is pharmacogenomics?
analysing entire genomes, across groups of individuals, to identify the genetic factors influencing responses to a drug
what is pharmacogenetics?
studying an individual’s genetic make up in order to predict responses to a drug and guide prescription
what is gleevec?
a treatment for Chronic Myeloid Leukaemia (CML)
it targets the novel fusion protein, the product of the translocation seen in CML
(works on a somatic mutation, not germ line!)
what is CADASIL?
Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
- most common form of hereditary stroke disorder
what are the 5 types of genetic disorders?
- multifactorial/complex
- single gene
- chromosomal
- mitochondrial
- somatic (cancer)
what do dominant genetic conditions tend to affect?
structural proteins
what do recessive genetic conditions tend to affect?
metabolic proteins
what type of inheritance do almost all chromosomal disorders show?
dominant
what are 3 examples of dominantly inherited disorders?
- myotonic dystrophy
- hunting tons disease
- marfan syndrome
what does penetrance mean?
the frequency with which a specific genotype is expressed by those individuals that possess it (usually given as a percentage)
(eg huntingtons has 100% penetrance, BRCA1 mutation has 80% penetrance)
what does expressivity mean?
variation in expression of a genetic disease
- the extent to which a heritable trait is manifested by an individual
(eg in marfan syndrome, an individual could have aortic dilatation OR lens dislocation OR BOTH)
what does anticipation mean?
the symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next
in most cases there is an increase in the severity of symptoms too
(to do with triplet expansion)
if both parents have a particular autosomal recessive condition, what is the risk that an unaffected child will be a carrier?
2 in 3
1 will be affected, 2 will be carriers and 1 will be normal
name some common autosomal recessive conditions
- cystic fibrosis
- haemachromatosis (excess absorption of iron)
- sickle cell disease
many of the metabolic disorders
can you have father to son transmission in X-linked conditions?
no
what two main factors influence the expression of the phenotype in ‘carrier’ women of X-linked conditions?
- X inactivation
- whether it is a X-linked dominant or X-linked recessive condition
what is X-inactivation and what is it also known as?
aka lyonisation
the normal 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)
occurs in early embryogenesis, once inactivated an X-chromosome remains inactive throughout the lifetime of the cell and all its descendants
it is random as to which X is silenced
- most, but not all, genes switched off on the inactivated X
how does X-inactivation in X-linked recessive conditions in females affect the phenotype?
approximately 50% of cells express the normal gene
- however if there is SKEWED INACTIVATION then either more, or less, of the ‘normal’ gene could be switched on
if more normal switched on = milder phenotype
if more mutated switched on = more severe phenotype
also there may be TISSUE VARIABILITY
- random preference for the mutation to be active in any given tissue group, if turned on more in a crucial tissue group (e.g. muscles for muscular dystrophy) when stronger phenotype
name two X-linked dominant conditions
- Rett syndrome = learning disabilities (lethal in males, phenotype only in females)
- fragile X-syndrome = learning disabilities and autism (asymptomatic to fully symptomatic, depending on X-inactivation)
