Lec 12 - Mutations Flashcards
Define mutation
a heritable change in a gene or a chromosome
and also
the process that produces a change
source of genome variaiton
may cause disease or drive evolution
may or may not cause a change in the phenotype
explain mutation and mutagenisis
a change in the nucleotide sequence is a mutation
mutagenisis is the process of mutation generation
give an example of a spontaneous mutation
cytosine deamination into uracil
NH2 to a double bond O
this produces DNA copies with multiple different genetic codes
what are some causes of mutagenisis
DNA replication stress ionising radiation Mutageic chemicals and anti cancer drugs Ionisning radiation free radicals transposable elements
what is a transposable element ?
a specific DNA sequence >1 gene
the move about within a DNA as a descrete unit to random sites
there are many copies of them
may activate or inactivate genes
larger genes have a greater chance to be inactivated by transpons
Explain Single Nucleotide Polymorphisms (SNP) types
occurs when an single neucleotide is changed
this is on the micro scale
an anonymous SNP has no known affect
a non-coding SNP is outside a gene
a coding SNP is inside a gene
Name three micro mutations
a deletion
a insertion
a substitution
micro mutations occur on the individual base pair level
what are macro mutations
mutations on a chromosonal level
you get deletions, duplications, inversions(paracentric and pericentric) , Insteritions, substitutions and translocations (reciprocal or robertsonian), ring chromosones
what are the two types of substitution ?
Transition - Purine to Purine of Pyr - Pyr
A->G , T->C
Transversion - Purine to pyrimidine or vice versa
A or G to C or T
what can SNP’s do
change the gene product (protein)
change the amount of gene product
change polypeptide length
can have no effect
what is the sickle cell mutation
mutation in codon seven of HBB (heamagobin coder)
it is a missense mutation - base substitution
one amino acid is changes - the 6th amino acid
the changes GLU to VAL
known as HBs - as there are many different mutations to the HBB gene that give different phenotypes
what are silent/neutral mutations/ synonymous
have no effect
what is a missense mutation / non synonymous
a change in the gene product gives a change to an amino acid
what is a frame shift mutation
change in polypeptide length
shifts the reading frame
often wont make sense any more - ie protein not produced
caused by single base deletions or additionsyo
what is a nonsense mutaiton
a single base substitution or frame shift can introduce a STOP codon into the gene
will cause a stop in translation in a odd place
what are mutations that affect how much protein is being made ?
mutations that affect regulatory sequences
- alter promoter activity
- alter translation initation at AUG
- prevent mRNA splicing
- reduce mRNA stability (polyA tail length)
this changes the amount of gene product
you can also get deletion, insertion or 3 BP or multiples of 3 BP….
this does not give a frame shift
but can be a severe change
explain a robertsonian translocaiton
a break in the P and Q arms. split at the centromere
parts of different chromosomes join together
you get centric fusion
one new chromosone formed, other is just the junk chromosone - useless
so individuals have 45 chromosomes in balanced carriers
a trivalent will form in meiosis - risk of aneuploidy
parent with a robertsonian translocation on the 21 and 14 chromosomes will have a child with downs syndrome
what is polyploidy ?
a numerical chromosome abnormality
a gain of an entire haploid set of chromosones
ofterncaused by polyspermy
3n = 69
what is an aneuploidy ?
loss or gain of a whole chromosone
this is only viable in certain chromosones, others non viable
caused by a non disjunction in meiosis
47,xx,+21 is downs syndrome, there are others such as the not very noticible 47, xxy kleinfelter syndrome
what is mosaicism ?
presence of two or more cell lines in a individual, tissue wide or body specific - caused by a NDJ in second post miotic division or later
How do we test for chromosonal abnormalities ?
we can do a cytogenic testing analysis - karyotypoing - accuratley diagnoses clinical problems
allows us to better manage unknown conditions
assess future reproductive risks
prenatal diagnosis
FISH - florescence in situ hybridisation
microarray hybridisation
DNA sequencing
why do we use cytogenic testing ?
accuratley diagnoses clinical problems
allows us to better manage conditions as we find out cause
assess future reproductive risks
prenatal diagnosis
what is a reciprocal abnormality ?
illustrate the 4 separations using the arrow technique
2 chromosomes swap part of there genetic info
due to sequence similarity identification , the two swapped chromosomes can now find each other and form a qaudrivalent
when pulled apart this gives many possible different results such as
3:1 non dis junction
alternate segregation - one centromere from each chromosone pair - reuslts in normal or balanced chromosones
adjacent 1 - non homologous centromeres gives unbalanced (not healthy) chromosones
adjacent 2 - non homologous centromeres gives unbalanced (not healthy) chromosones
