SINGLE GENE DISORDERS

Question 1

what is an elctropherogram?

Answer 1

e

Question 2

what are point mutations that cause disease?

Answer 2

Substitutions (missense)
Nonsense mutations
Insertion mutations
Deletion mutations

Question 3

what mutation is sickle cell anaemia caused by?

Answer 3

β-globin gene

Question 4

what is the β-globin gene lead to in sickle cell anaemia?

Answer 4

leads to a glutamic acid (E) being replaced by a valine (V) instead at position 6 in the protein
E6V

Question 5

give an example of substitution (missense) mutation?

Answer 5

sickle cell anaemia

Question 6

give an example of nonsense mutation?

Answer 6

Duchenne muscular dystrophy

Question 7

what mutation is Duchenne muscular dystrophy caused by?

Answer 7

by nonsense mutations in dystrophin gene

Question 8

what is the mutations in dystrophin gene cause in Duchenne muscular dystrophy?

Answer 8

Lysine (K) > unknown/unspecified (X) i.e. stop codon

K1524X

Question 9

give an example of Insertion mutations?

Answer 9

Familial Hypercholesterolemia (FH)

Question 10

what does Familial Hypercholesterolemia (FH) result in?

Answer 10

elevated levels of blood lipid

Question 11

what mutation causes Familial Hypercholesterolemia (FH)?

Answer 11

mutation in exon 17 of the LDLR gene

c.2416_2417InsG

Question 12

what does the c. stand for in the mutation codes?

Answer 12

cDNA

Question 13

give an example of deletion mutation?

Answer 13

cystic fibrosis

Question 14

what mutation causes cystic fibrosis?

Answer 14

deletion mutation that deletes the phenylalanine (F) residue at position 508 in the protein.
ΔUUU codon CFTR gene on chr. 7.
ΔF508

Question 15

what does deletion mutation cause in the intron?

Answer 15

induces aberrant splicing of the DMD gene causing Duchene Muscular Dystrophy

Question 16

what effect does Autosomal Dominant Inheritance have on characteristics?

Answer 16

Characteristic is manifested in the heterozygote of both sexes

Question 17

is Autosomal Dominant Inheritance linked to a sex chromosome?

Answer 17

no

Question 18

what is the chance of passing Autosomal Dominant Inheritance to offspring?

Answer 18

1 in 2

Question 19

are homozygotes for Autosomal Dominant Inheritance rare?

Answer 19

are very rare and often have a more severe phenotype or show characteristic much earlier

Question 20

what effect does homozygous for BMPR2 have?

Answer 20

embryonically lethal

Question 21

what is Autosomal Dominant Inheritance?

Answer 21

both sexes affected and equally

likely to pass on the affected characteristic, e.g. PAH

Question 22

what effect does Autosomal Recessive Inheritance have on characteristics?

Answer 22

Characteristic is not manifested in the heterozygote of both sexes

Question 23

is Autosomal Recessive Inheritance linked to a sex chromosome?

Answer 23

no

Question 24

is Autosomal Recessive Inheritance double defect?

Answer 24

yes

Question 25

who does Autosomal Recessive Inheritance effect?

Answer 25

Affected individuals are born to unaffected parents

Question 26

what is the chance of an affected parent passing on Autosomal Recessive Inheritance?

Answer 26

¼ as each parent has one WT allele and one mutant (affected) allele

Question 27

what is Compound heterozygote?

Answer 27

refers to an affected individual with 2 different mutant alleles

Question 28

what is true homozygotes?

Answer 28

Where an affected individual is from a consanguinous relationship then the 2 different mutant alleles will be the same

Question 29

what are most classical genetic diseases?

Answer 29

autosomal recessive

Question 30

what is Autosomal Recessive Inheritance?

Answer 30

both sexes affected. | The parents of the affected children in IV are both carriers

Question 31

what do mutations responsible for recessive traits usually lead to?

Answer 31

Lack of gene expression Lack of protein production Production of a protein with reduced or absent function

Question 32

what effect does X-linked Dominant Inheritance have on characteristics?

Answer 32

Characteristic is manifested in the heterozygote of both sexes

Question 33

who is affected by X-linked Dominant Inheritance?

Answer 33

One parent is affected | There are significantly more affected females than males

Question 34

what do females affected by X-linked Dominant Inheritance show?

Answer 34

typically show milder characteristics (and more variable expression) than males

Question 35

what is the chance of a child being affected is this mother is affected by X-linked Dominant Inheritance?

Answer 35

1 in 2 chance

Question 36

what is the effect of a male child having a father affected by X-linked Dominant Inheritance?

Answer 36

child will be unaffected (male child receives the Y chromosome from their father) but every daughter will be affected but show milder characteristics.

Question 37

what effect does X-linked Recessive Inheritance have on characteristics?

Answer 37

Characteristic is not manifested in the heterozygote of both sexes

Question 38

who are mostly affect by X-linked Recessive Inheritance?

Answer 38

males Affected males are born to unaffected parents No male- to male inheritance

Question 39

what are the chances of sons and daughters being affected in X-linked Recessive Inheritance?

Answer 39

Sons -1 in 2 risk of being affected daughters -not affected they have a 1 in 2 risk of being a carrier.

Question 40

what is manifesting heterozygotes?

Answer 40

Females through non-random mosaicism (X-chromosome inactivation) can show affects

Question 41

can one gene cause different diseases?

Answer 41

yes more diseases attributed to mutations in single genes than genes mutated

Question 42

what is Genetic Heterogeneity?

Answer 42

Different mutation in the same gene can lead to different diseases

Question 43

what is Achondroplasia caused by?

Answer 43

by constitutively active –’Gain of function’ mutation

Question 44

what mutation causes Achondroplasia?

Answer 44

Mutation in the fibroblast growth factor type 3 receptor leads to constitutive activity un-regulated by the receptor (FGFR3) function

Question 45

what does FGFR3 do?

Answer 45

promotes differentiation of cartilage into bone

Question 46

what does Gain-of-function mutation activate?

Answer 46

activates the receptor causing premature conversion of the growth plate into bone

Question 47

can multiple genes cause one disease?

Answer 47

yes

Question 48

give an example of when multiple genes cause one disease?

Answer 48

Xeroderma pigmentosum (XP)

Question 49

how does Xeroderma pigmentosum (XP) occur?

Answer 49

Mutations in 8 different genes that all function in DNA-damage repair lead to XP (8 variants) / DNA replication

Question 50

what other factors influence the phenotype of single gene disorders?

Answer 50

penetrance expressivity phenocopy environmental effects

Question 51

what is penetrance?

Answer 51

The frequency with which a person manifests the gene that they possess

Question 52

do all dominant mutations display penetrance?

Answer 52

Not all display 100% penetrance

Question 53

what is penetrance determined by?

Answer 53

genetic and environmental factors

Question 54

what is expressivity?

Answer 54

Variation in the severity of the symptoms caused by a mutation

Question 55

give an example of expressivity?

Answer 55

in sickle cell anaemia (which is always caused by the same mutation) symptoms range from very severe to extremely mild

Question 56

what is phenocopy?

Answer 56

An environmental modification that mimics a genetic disease

Question 57

give an example of phenocopy?

Answer 57

confusing genetic deafness with deafness caused by Rubella during pregnancy

Question 58

give examples of environmental effects that influence the phenotype of single gene disorders?

Answer 58

phenylketonuria, a disease that once diagnosed is treatable via provision of a low phenylalanine diet hypoxia many induce pulmonary arterial hypertension (PAH)

Question 59

what types of tests are carried out?

Answer 59

``` Newborn screening Diagnostic testing Carrier testing (test for parents if carry one copy of mutation, that in 2 copies causes a disorder) Prenatal testing Preimplantation genetic diagnosis Predictive and presymptomatic testing ```