Lec 12 - Mutations

Question 1

Define mutation

Answer 1

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

Question 2

explain mutation and mutagenisis

Answer 2

a change in the nucleotide sequence is a mutation

mutagenisis is the process of mutation generation

Question 3

give an example of a spontaneous mutation

Answer 3

cytosine deamination into uracil
NH2 to a double bond O

this produces DNA copies with multiple different genetic codes

Question 4

what are some causes of mutagenisis

Answer 4

DNA replication stress
ionising radiation
Mutageic chemicals and anti cancer drugs
Ionisning radiation
free radicals
transposable elements

Question 5

what is a transposable element ?

Answer 5

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

Question 6

Explain Single Nucleotide Polymorphisms (SNP) types

Answer 6

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

Question 7

Name three micro mutations

Answer 7

a deletion
a insertion
a substitution

micro mutations occur on the individual base pair level

Question 8

what are macro mutations

Answer 8

mutations on a chromosonal level

you get deletions, duplications, inversions(paracentric and pericentric) , Insteritions, substitutions and translocations (reciprocal or robertsonian), ring chromosones

Question 9

what are the two types of substitution ?

Answer 9

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

Question 10

what can SNP’s do

Answer 10

change the gene product (protein)
change the amount of gene product
change polypeptide length
can have no effect

Question 11

what is the sickle cell mutation

Answer 11

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

Question 12

what are silent/neutral mutations/ synonymous

Answer 12

have no effect

Question 13

what is a missense mutation / non synonymous

Answer 13

a change in the gene product gives a change to an amino acid

Question 14

what is a frame shift mutation

Answer 14

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

Question 15

what is a nonsense mutaiton

Answer 15

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

Question 16

what are mutations that affect how much protein is being made ?

Answer 16

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

Question 17

you can also get deletion, insertion or 3 BP or multiples of 3 BP….

Answer 17

this does not give a frame shift

but can be a severe change

Question 18

explain a robertsonian translocaiton

Answer 18

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

Question 19

what is polyploidy ?

Answer 19

a numerical chromosome abnormality
a gain of an entire haploid set of chromosones
ofterncaused by polyspermy
3n = 69

Question 20

what is an aneuploidy ?

Answer 20

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

Question 21

what is mosaicism ?

Answer 21

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

Question 22

How do we test for chromosonal abnormalities ?

Answer 22

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

Question 23

why do we use cytogenic testing ?

Answer 23

accuratley diagnoses clinical problems
allows us to better manage conditions as we find out cause
assess future reproductive risks
prenatal diagnosis

Question 24

what is a reciprocal abnormality ?

illustrate the 4 separations using the arrow technique

Answer 24

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