types of mutations- genetics 2

Question 1

what are the different types of genetic mutations

Answer 1

Single-gene (monogenic) -Mitochondrial disorder -Chromosomal imbalance -Polygenic -Multifactorial (part genetic, part environmental

Question 2

Describe the different components of DNA and which parts are spliced together

Answer 2

• basic architecture: - ACTG bases pared together - one strange going in the 5’->3’ direction - the other strand doing in the 3’->5’ direction genetic makeup; - promotor sequence - followed by start codon - followed by introns and exons - then terminated by a stop codon exons are spliced together the spliced together exons are transcribed and then translated

Question 3

what happens in a missense mutation?

Answer 3

replacement of one amino acid with another

Question 4

what happens in a nonsense mutation?

Answer 4

premature stop codon

Question 5

what happens in a frameshift mutation?

Answer 5

caused by a deletion or insertion in a DNA sequence that shifts the way the sequence is read

Question 6

what happens in a dynamic mutation?

Answer 6

e.g. trinucleotide repeat expansions

Question 7

what are 2 examples of autosomal recessive disorders?

Answer 7

Cystic fibrosis PKU

Question 8

what is the most common cystic fibrosis mutation?

Answer 8

• CFTR on chromosome 7 - regulates passage of Cl- across membranes. - Mucus becomes thickened= symptoms - Delta F 508- class 2 mutation - phenylalanine is swapped for glycine

Question 9

which mutation causes PKU?

Answer 9

Caused by mutations in phenylalanine hydroxylase (PAH) exon 7 chromosome 12

Question 10

How many different classes of mutation are there for cystic fibrosis- which is the most severe?

Answer 10

6 1 is most severe 6 is least severe

Question 11

what is genetic imprinting?

Answer 11

mammalian epigenetic process that distinguishes maternal and paternal alleles to ensure parent-specific (monoallelic) expression of imprinted genes

Question 12

Which parent allele is responsible for the expression of insulin like growth factor?

Answer 12

fathers

Question 13

What is the parent conflict hypothesis?

Answer 13

Conflict of interest - mother wants baby to be small easy to birth - dad wants baby to be big and strong to show of to friends

Question 14

What is the mechanism for genomic imprinting?

Answer 14

Closed down genes are modified using methylation this is controlled by the imprinting center which is located nearby imprinted areas on the same chromosome

Question 15

Which chromosome is involved in Angelman and prader willi syndrome?

Answer 15

15

Question 16

what happens in prayer willi syndrome?

Answer 16

• there is a mutation on chromosome 15 for the gene that is usually paternally expressed - although maternal chromosome 15 will carry an intact gene it will not be expressed due to genome imprinting - so only the mutated/ deleted gene on the fathers chromosome will be expressed

Question 17

what is the phenotype for prader willi synrome?

Answer 17

mental retardation
Hypotonia
gross obesity (diabetes)
male hypogenitalism

Question 18

what happens in angelmans syndrome?

Answer 18

Deletion in 15q11-13 region
This is the main cause
Although the paternal chr 15 contains intact copies of the 15q11-13 region, they are not expressed due to genomic imprinting

Question 19

what is the phenotype of angelmans syndrome?

Answer 19

Mental retardation
Lack of speech
Growth retardation
Hyperactivity
Inappropriate laughter

Question 20

what is an example of a denovo mutation?

Answer 20

• Achondroplasia
• (fibroblast growth factor receptor 3 (FGFR3) mutation
• which causes an abnormality of cartilage formation)

7/8 of all cases caused by new mutations.

Question 21

what is an example of a genetic disease that has reduced penetrance?

Answer 21

this type of inheritance pattern can be observed in retinoblastoma

10% of retinoblastoma population are obligate carriers. Disorder therefore has 90% penetrance

Question 22

define obligate carrier

Answer 22

An obligate carrier is an individual who may be clinically unaffected but who must carry a gene mutation based on analysis of the family history;

Question 23

what is penetrance?

Answer 23

Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait

Question 24

what does this pedigree show?

Answer 24

• an obligate carrier

Question 25

give an example of a genetic disease with varable expression?

Answer 25

• neurofibramatosis

Question 26

what is the inheritence pattern for huntingtons?

Answer 26

autosomal dominant

Question 27

• what are the trinucleotide repeats in huntingtons and what do they code for?

Answer 27

• CAG
• Glutamine

Question 28

what are the number of repeats in huntintons that are stable vs unstable?

Answer 28

stable repeat number is 6 - 35- asymptomatic
unstable repeat number is 36 - >100- symptomatic

Question 29

which chromosome is affected in huntingtons?

Answer 29

4

Question 30

decribe the phenomenon of anicipation which occurs in huntingtons

Answer 30

gene expands through generations

• futhergenerations will become symptomatic earlier = anticipation

Question 31

what is the phenotype in huntingtons disease?

Answer 31

Progressive neurodegenerative disease
Strikes in mid (50s) or later life
Dementia
Severe depression
Chorea (involuntary, dance-like movement)

Question 32

What are examples of x linked disorders?

Answer 32

Hemophilia
- Fragile x- most widespread cause of single gene autism

Question 33

What genetic repeat causes fragile x?

Answer 33

CGC

Question 34

what does this pedigree show?

Answer 34

• germline mutation
• probably x linked

Question 35

what is an x linked disorder which can arrise due to germline mutations?

Answer 35

DUCHENNE MUSCULAR DYSTROPHY:

15% CASES RESULT FROM GERMLINE MOSAICS

Question 36

what is an example of a mitochondrial disease?

Answer 36

Leber hereditary optic neuropathy (retinal regeneration)