Genetic Variation & disease Flashcards
(42 cards)
what is a karyotype?
when you look at chromosomes down a microscope and then you can line them all up and look at problems
what is polymorphism?
genetic variation that is prevelant in population but not in itself, disease causing
what is focused testing example and what does it allow us to do?
PCR (polymerase chain reaction)
= allows us to select one small piece of the human genome from a patient (100 to 10,000 bases) and amplify it i.e. make lots of copies of one short stretch of the genome
what is one of the requirements for PCR to be useful?
you need to know where to look like what part of genome, within a few hundred base pairs
what is affect of mutation on promoter sequence of gene?
then no transcription so no protein produced
what happens when splice consensus altered?
mRNA decay (if intron left in) and abnormal or absent protein
what are chromosomes recognised by?
-size
-position of centromere
-banding pattern
what does a metacentric chromosome look like?
has centromere close to middle
-shorter p arm and longer q arm
-telomere at either end
what does an acrocentric chromosome look like?
-has centromere at one end with only satellite DNA (like tRNA’s etc) on short “p” arm
when are chromosomes visualised?
at metaphase in mitosis
when is a chromosome said to be balanced?
-when there’s a normal amount of each chromosome (all chromosomal material present)
when is a chromosome complement said to be unbalanced?
if there’s missing or extra chromosomal material
what is affect of base change mutation?
-can have no effect if still codes for same amino acid
-it can code for stop protein producing shorter protein
-it can change amino acid sequence making non-functioning or different protein
how do you describe a mutation?
standard nomenclature
what are the 2 types of deletion?
-in frame (when 3 deleted so only misses out 1 amino acid, less drastic change)
-out of frame (when only 1 or 2 deletions so whole frame reading thrown off)
how do we define normal genome?
by using most common sequence at that point (for example, for caucasian males)
what is p.?
change in peptide sequence (amino acid)
what is c.?
change in mature mRNA sequence (bases after splicing)
what does nomenclature c.4A>T and p.Lys2Ter mean?
it means that at 4th base position adenosine was swapped for thymine which at 2nd amino acid position meant Lys amino acid was terminated
what does p.ile122Thrfs nomenclature mean?
the peptide (amino acid) sequence at position 122 ile was swapped to Thr causing frameshift (from nucleotide deletion)
what does these key nomeclatures mean?
a) c.267G>A
b) c.267delG
c) c. 267InsA
d) c. 267 + 2T>A
a) at position 267, G swapped for A = substitution
b) at position 267, deletion of G
c) at position 267, insertion of an A
d) at position 267, substitution of an intron for A (means no amino acid sequence as introns = non coding)
explain mutation affecting splicing
just after an exon, changing the consensus signal 2 base pairs into the intron - it’s expected to lead to abnormal RNA that would undergo nonsense mediated decay
how do you differentiate between polymorphism or disease causing mutation?
does it match expected inheritance?
is it in right gene?
has it been reported before? (some variants are listed)
what does it do to protein?
does it explain a phenotype?
what are the 5 classes of variant classification?
class 1 = defo polymorphism
class 2 = probably polymorphism
class 3 = unclassifiable
class 4 = probably pathogenic
class 5 = definetely pathogenic
