Random Facts

Question 1

Fragile X frequency

Answer 1

1/1000 males

1/500 females

Question 2

Fragile X premutation length

Answer 2

56-200 repeats

Question 3

How many mutations in beta thalassemia?

Answer 3

250 mutations in beta globin gene

Question 4

What genes are involved in XP?

Answer 4

ERCC2, ERCC3, POLH, XPA, XPC

Question 5

What genes are involved in cockayne syndrome?

Answer 5

ERCC6, ERCC8

Question 6

What genes are involved in trichothiodystrophy?

Answer 6

ERCC2, ERCC3, GRF2H5

Question 7

Cockayne syndrome frequency

Answer 7

1 in 2 million

Question 8

Trichothiodystrophy frequency

Answer 8

1 in 1 million

Question 9

What are the two alleles for Adh? Point mutation / deletion?

Answer 9

Adh-f
Adh-S

One change in AA (Threonine –> Lysine)

Question 10

What is the gene for cystic fibrosis?
What type of mutation? How many identified?
How big is the gene?

Answer 10

CFTR (cystic fibrosis transmembrane conductance regulator) - pumps Cl- out of cells

Delta508 (85% cases) - single AA removed by 3bp deletion NOT FRAMESHIFT MUTATION

Over 1800 mutations identified

250kb

Question 11

How many people are heterozygotes for Cystic fibrosis ?

Answer 11

1/20 to 1/44

Question 12

How does CF have heterozygote advantage?

Answer 12

Not as many deaths related to diarrheic cholera

Question 13

What is the gene involved with HIV-1?
What is mutation?
What are genotypes?

Answer 13

CCR5 (encodes CCR5 protein - receptor for HIV-1)

Delta 32 = 32 base pair deletion
1/1 = reistant to most HIV-1
1/Delta32 = susceptible, but slow transition to AIDS
Delta32/Delta32 = resistance to most ST HIV-1

Question 14

Consequences of consanguinity?

Answer 14

More chance of revealing deleterious recessive alleles

Everyone has about 4 genes that would be lethal if they were homozygous recessive

Question 15

What is coefficient of inbreeding?

Interpret

Answer 15

F = quantifies the probability that an individual has two alleles that are identical because they are descended from a single gene copy from the same ancestor

F = 1 (all individuals in the population are homozygous - both alleles all come from a common ancestor)

F = 0 (no individual has the same copy of an allele - none derived from a common ancestor)

Question 16

How similar are humans….

Answer 16

99. 7% to neanderthals

98. 8% to chimpanzees

Question 17

Stuttering is related to what chromosome? How many genes? What is one called?

Answer 17

Chromsome 12
87 genes within the sequence
Likely candidate gene is called GNPTAB

Question 18

How far does LD extend between neighbouring common sites

Answer 18

3 to 8kb (theoretically)

Question 19

Prader Willi can be caused by: _________

Answer 19

Paternal deletion
Uniparental disomy (2x maternal)
Mutation + translocation (rare)

Question 20

Angelman syndrome can be caused by: __________

Answer 20

Maternal deletion
Uniparental disomy (2x paternal)
Maternal point mutation in UBE3A

Question 21

What are key gene effects for Prader Willi?

Answer 21

Absence of guide RNAs
snoRNAs
SNORD116

Question 22

What are symptoms for PRader Willi?

Answer 22

ABLOS

excessive Amniotic fluid
Breech birth (low foetal movement)
Lethargy
Overeating --> obesity
Squinty / Strabismus

Question 23

What are symptoms for Angelman?

Answer 23

AE PMI

Ataxia
Epilepsy
Peculiar gait
Microcephaly
Intellectual disability

Question 24

What are gene effects for Angelman?

Answer 24

UBE3A (encodes enzyme that targets protein for destruction)

Also - incident loss of OCA2 –> hypopigmetnation of skin, hair, eyes

Question 25

What chromosome is Prader Willi and Angelman linked to?

Answer 25

Chr 15 q11-13

Question 26

What chromosome is Beckwith Weideman and Silver Russell Syndrome linke to?

Answer 26

Chr 11 q15.5

Question 27

BWS and SRS occur due to:

Answer 27

Differential methylation

Question 28

What are the genes involved in BWS and SRS? Which does what?

Answer 28

``` H19 = noncoding RNA = growth repressor IGF2 = insulin growth factor 2 = stimulates growth ``` ``` BWS = IGF2 increased, H19 decreased SRS = IGF2 decreased, H19 increased ```

Question 29

What are causes of BWS?

Answer 29

Mutation causing hypermethylation of DMR | Uniparental disomy of paternal chromosome

Question 30

What are causes of SRS?

Answer 30

Hypomethylation of DMR | Uniparental disomy of maternal chromosome

Question 31

What are the symptoms of BWS?

Answer 31

OMMGV ``` Obesity Macrosomia (big body) - height 2.5 SD above mean at puberty Macroglossia - large tongue Genital overgrowth Visceromegaly - enlarged viscera ```

Question 32

What are the symptoms of SRS?

Answer 32

DD LHJ ``` Dwarf syndrome Delayed development Low birth weight Head normal (relative to body) Small jaw ```

Question 33

Frequency of Prader Willi.

Answer 33

1/15,000

Question 34

Frequency of Angelman.

Answer 34

1/20,000

Question 35

What is the allele for Agouti? Dominant/recessive? Phenotype?

Answer 35

Avy - inserted by transposon in response to BPA DOMINANT lethal Yellow coat, obese, prone to cancer, diabetes

Question 36

What occurs in Dutch Winter Famine?

Answer 36

Hypomethylation of IGF2 (unregulated) | Hypermethylation of leptin (satiety hormone) (downregulated)

Question 37

Frequency of ASD

Answer 37

3.4/1,000

Question 38

Frequency of WBS

Answer 38

1/20,000

Question 39

ASD chromsome?

Answer 39

Chr 7 q 11

Question 40

WBS chromsome?

Answer 40

Chr 7 q 11

Question 41

Where is the HER-2 gene?

Answer 41

Chromsome 17

Question 42

Warfarin is associated with which genes?

Answer 42

Mutation in CYP2C9 --> reduce elimination of warfarin and Mutation in VKORC --> less activation of vitamin K clotting factors (increases sensitivity to warfarin) Require lower dose of warfarin

Question 43

Fragile X gene region

Answer 43

Xp27 | Causes methylation of nearby gene: FMR1