Inheritable Diseases Flashcards
how to investigate a congenital dysfunction?
detailed history of family, pregnancy, examination
find out possible cause.
is it de novo, or syndromic, is it familial or sporadic?
when to use karyotyping vs chromosome microarray
usually do CMA first then if abnormality found, do karyotyping. CMA is faster, but doesn’t tell you about balanced translocations. karyotyping takes 14 days
what is the challenge with whole exome sequencing?
finding out which variants are significant in causing phenotype
what are the rules of inheritance in X linked diseases?
affected males cannot pass it to their sons
carrier moms have 1/4 chance of passing it onto their children
all affected males will pass it onto their daughters
how can women be affected by X linked diseases?
thru random X inactivation
what are the steps in invesigating familial diseases
make the right clinical diagnosis draw the pedigree choose the right genetic test do molecular genetic diagnosis if necessary do cascade genetic test
how many % of x linked diseases happen de novo and how many are inherited?
1/3 are de novo
2/3 are from carrier mothers
(if from father, will know)
if a male child is affected, what are the chances that his grandmother was a carrier?
2/3 chance his mother was carrier
2/3 chance her mother was carrier, therefore 4/9 chance grandma was carrier
if a mother carries an X linked recessive gene has a daughter, what are the chances that the daughter will also be a carrier?
1/2, because the father will pass on healthy copy
what does imprinting mean?
means that depending on maternal or paternal derived copy, the gene can be silenced or unsilenced, thus masking the true status of the gene. even if it was faulty
what do oncogenes generally do?
promote cellular proliferation
when are oncogenes usually switched on and off?
usually on during embryogenesis and off by adulthood.
what happens if the RET oncogene is switched off in fetal stage?
Hirschsprungs disease
what is the APC gene associated with?
FAP
what is the RB1 gene associated with
retinoblastoma
what gene is associated with breast and/or ovarian cancer?
brca1 and brca2
what gene is li fraumeni syndrome associated with?
TP53
what are the two common pathways of colorectal carcinogenesis?
mutator pathway or suppresor pathways
what disease is associated with mutator pathway route of CRC and what disease is associated with the suppresor pathway of CRC?
mutator: Lynch syndrome
suppresor: FAP
describe classical FAP
thousands of adenomas in the colon
how does lynch syndrome compare with FAP?
LSd onset is usually younger, fewer adenomas, malignancy can appear anywhere in the body, commonly colon and endometrium
FAP has more polyps usually in colonc
describe MSI in LSd and how it causes disease
micro satellite instabilities
due to mutations in gene responsible for replication/correcting errors in copying repetitive genes.
this leads to frameshift errors in translation and production of novel peptides, triggering immune response
how to differentiate sporadic CRC from lynch Sd?
amsterdam 3 2 1 criteria
presence of BRAF mutation
and IHC proteins
what is the amsterdam 321 criteria?
3 colorectal tumours in the family
2 generations across
1 diagnosed <50 y/o