Mutations and Genetic Analysis

Question 1

What are the different types of chromosomal abnormalities?

Answer 1

numerical
structural
mutational

Question 2

What does trisomy mean?

Answer 2

instead of two pairs of chromosomes , three pairs of chromosomes in your cells

Question 3

What system of abnormalities are responsible for 50% of trimester miscarriages?

Answer 3

trisomys

Question 4

Describe Patau syndrome?

Answer 4

47, xx + 13

Question 5

Describe Edwards syndrome?

Answer 5

47 xy + 18

Question 6

Describe downs syndrome?

Answer 6

47 xx + 21

Question 7

Describe klinefelter syndrome?

Answer 7

47 , XXY

Question 8

What happens in normal meiosis?

Answer 8

cell duplicates the genomic material
then gets split into two daughter cells
then in meiosis 2, split what they have into 4 haploid cells

Question 9

Describe non-disjunction?

Answer 9

the cell does not divide into daughter cells and then the one cell with duplicated material divides and have 2 complete cells and 2 empty.

and another way of non disjunction

successful meiosis 1 and duplicated material is successfully divided into daughter cells however in meiosis 2 one of daughter cells gets two of of chromatids instead of single.

Question 10

What alleles are major contributor for trisomys?

Answer 10

maternal

Question 11

What allele is the contributing factor for monosomy?

Answer 11

paternal as there should be a Y

Question 12

What causes 95% of down syndrome?

Answer 12

Trisomy 21: non-dysjunction (95%), usually maternal origin
Unbalanced Robertsonian translocation (4%)
Mosaicism (1%)

Question 13

What is trisomy 21?

Answer 13

Trisomy 21 (Down syndrome)
Incidence: 1 in 650 to 1 in 700
Increases with advancing maternal age
Characteristic facial dysmorphologies
IQ less than 50
Average life expectancy (50-60 years)
Alzheimer’s disease in later life
Chromosomal findings
Trisomy 21: non-dysjunction (95%), usually maternal origin
Unbalanced Robertsonian translocation (4%)
Mosaicism (1%)

Question 14

What is trisomy 13?

Answer 14

Incidence: 1 in 5000
Multiple dysmorphic features and mental retardation
About 5% die within first month, very few survive beyond first year
Non-dysjunction (90%), maternal origin
Unbalanced Robertsonian translocation (10%)

Question 15

What is trisomy 18?

Answer 15

Incidence: 1 in 3000
Severe developmental problems; most patients die within first year, many within first month
Non-disjunction (90%), maternal origin

Question 16

What is Turner syndrome?

Answer 16

Incidence: 1 in 5000 to 1 in 10000 (liveborn)
Incidence at conception much greater, about 97% result in spontaneous loss
Females of short stature and infertile
Neck webbing and widely spaced nipples
Intelligence and lifespan is normal

Question 17

What is Klinefelter syndrome?

Answer 17

Incidence: 1 in 1000
Tall stature, long limbs
Male but infertile, small testes, about 50% gynaecomastia
Mild learning difficulties

Question 18

Give examples of structural abnormalities?

Answer 18

Balanced or unbalanced rearrangements

Translocations
Reciprocal: involving breaks in two chromosomes with formation of two new derivative chromosomes
Robertsonian: fusion of two acrocentric chromosomes

Deletions

Insertions

Inversions

Question 19

What happens with unbalanced conditions in reciprocal translocations?

Answer 19

normal

balanced

one chromosome that has been unaffected and one that has been translocated. When this gets duplicated again, get an unaffected chromosome and one affected one.
Causing partial trisomy and partial monosomy.

One affected and one fine, when fertilised you have a partial monogamy and a partial trisomy.

Question 20

Describe robertsonian translocation?

Answer 20

starts because of having two acrocentric chromosomes (p arm inactive)
q arms get joined together as one chromosome

Question 21

What are the acrocentric chromosomes?

Answer 21

13 14 15 21 22

Question 22

What are the different outcomes of a robertsonian translocation carrier?

Answer 22

refer to minutes 29;50

Question 23

Describe chromosomal deletions?

Answer 23

breaks in chromosomes and part gets deleted out `

Question 24

Describe inversions?

Answer 24

genetic material that is put into chromosome in one way but then through some mechanism-gets flipped around and genes now in diff position. Repressed, activated and changes outcome of gene transcription.

Question 25

Describe genetic mutations?

Answer 25

level of DNA

disruptions of gene

SNP polymorphism- one nucleotide in a dna code gets changed

Question 26

Describe coding mutations?

Answer 26

in coding regions

Question 27

What are the different types of coding mutations?

Answer 27

silent -no effect
missense e.g. CGA to GGA and diff amino acid expressed
nonsense- stop codon where AA should be
shift-deletion/ insertion

Question 28

How to name mutation of an adenine in position 1298 getting changed to guanine?

Answer 28

1298A>G

Question 29

What does 1294del40 mean?

Answer 29

deletion of 40 base pairs

Question 30

What does M252X mean?

Answer 30

instead of methionine on position 252, there’s a premature stop codon

Question 31

What does Cys64Arg mean?

Answer 31

changed into argenine

Question 32

What are the ways of detecting mutations?

Answer 32

polymerase chain reaction (PCR) - making more of DNA

gel electrophoresis

restriction fragment length polymorphism (RFLP)

amplification refractory mutation system (ARMS)

DNA sequencing

Question 33

What do we need for PCR?

Answer 33

sequence information
oligonucleotide primers
DNA
Nucleotides
DNA Polymerase

Question 34

How does PCR work?

Answer 34

split the DNA apart- denaturation at 93-95 degrees)
primer can anneal (50-70 degrees)
extending (70-75 degrees)
repeat 20-30 times

Question 35

Describe gel electrophoresis?

Answer 35

separates DNA from PCR
fragments by size
apply an electric field
DNA is negatively
charged
separate through agarose gel matrix
visualise DNA fragments
SMALLER FRAGMENTS ON BOTTOM

Question 36

Advantages of PCR?

Answer 36

speed
ease of use
sensitive
robust

Question 37

Describe how restriction digest assay works?

Answer 37

have control samples that show what it should look like compared to test samples with mutations

Question 38

What do restriction endonucleases do?

Answer 38

Degrade DNA of invading viruses
recognize specific DNA sequences
usually 4-8bp
always cuts DNA at same site