GENETICS - Mutations and Defects

Question 1

Red-Green defects are in which disease?

Answer 1

acquired optic nerve disease (except glaucoma and autosomal dominant optic atrophy)

Question 2

What are the main examples of trinucleotide repeat disorders? (7)

Answer 2

1. Fragile X syndrome
2. Friedrich’s ataxia
3. Machado-Joseph ataxia
4. Spinocerebellar ataxia
5. Spinobulbar muscular atrophy
6. Myotonic dystrophy
7. Huntington chorea

Question 3

Blue-yellow defects are in which disease

Answer 3

Acquired retina disease (except cone dystrophy and Stargardt’s)

Question 4

What are the X-linked dominant conditions? (3)

Answer 4

1. Aicardi syndrome
2. Incontinentia pigmentii
3. Alport’s syndrome

Question 5

Which chromosome defect is associated with retinoblastoma?

Answer 5

Rb gene located on long arm chromosome 13

Question 6

What diseases are examples of mitrochondrial inheritance? (6)

Answer 6

1. Lebers hereditary optic atrophy
2. Mitochondrial encephalopathy, lactic acidosis and stroke (MELAS)
3. Myoclonus epilepsy associated with ragged-red fibres (MERRF)
4. Kearns-Sayre syndrome (KSS)
5. Pearson syndrome
6. Diabetes/Deafness

Question 7

Which mutations causes MEN 2a and MEN2b?

Answer 7

RET proto-oncogene on chromosome 10

Question 8

What is a mutation? What external factors can cause a mutation?

Answer 8

any permanent change in DNA

1) Ionising radiation
2) Chemicals
3) UV light

Question 9

What are the three types of point mutations?

Answer 9

1 - missense mutation - different amino acids are transcribed altering the sense of the code (haemoglobinopathies

2 - nonsense mutation - mutation leads to premature stop codon - NF type 1

3 - splice mutation - mutation alters a critical splice junction

Question 10

What examples are there for triplet expansion diseases? (4)

Answer 10

1. myotonic dystrophy
2. Fragile-X
3. Huntington’s
4. Spinocerebellar ataxia

Question 11

What examples are there of microdeletion syndromes? (4)

Answer 11

1. Prader Willi
2. Williams syndrome
3. Di George
4. Rubinstein Taybi

Question 12

Consanguinity is more likely to have which type of inheritance?

Answer 12

Recessive

Question 13

What is a Robertsonian translocation?

Answer 13

a chromosome rearrangement where the two long arms of two acrocentric chromosomes (non central centromeres) fuse to form a single chromosome - leading to loss of the short arms

Question 14

How many chromosomes do robertsonian individuals have? what is their risk of trisomy in offspring?

Answer 14

1. 45 chromosomes (normal phenotype)
2. increased risk

Question 15

What is lyonisation? What does it give rise to in terms of expression?

Answer 15

Lyonisation is a physiological process where one of the two X chromosomes in cells of a female is inactivated during embryonic development (male/female X chromosome is randomly affected).

gives rise to patchy expression of X-linked mutations in female carriers

Question 16

What chromosome carries the blue pigment gene?

Answer 16

Chromosome 7

Question 17

How does aneuploidy (abnormal numbers) occur?

Answer 17

usually in Non-disjunction during meosis I

Question 18

How do structural changes in chromosomes occur and what is the difference between balanced and unbalanced recombination?

Answer 18

structural changes occur due to breakage then abnormal recombination

Balanced recombination results in chromosomes with normal amount of genetic information

Unbalanced recombination occurs when there is loss or gain of gentic material

Question 19

What are the difference types and subtypes of balanced rearrangements? What can it do to future generations

Answer 19

Can affect future generations by increasing likelihood of producing unbalanced genes

1. Inversions - occur when chromosome segment inverts after breaking and rejoining - can be pericentric or paracentric.
   Pericentric: Include centromere
   Paracentric: Both breaks are in same arm
2. Translocations - exchange of segments between non-homologous chromosomes

Question 20

What is the mutation and gene implicated in Leber’s hereditary optic neuropathy?

Answer 20

Gene: MT-ND1 gene involved in synthesis of NADH dehydrogenase

Mutation: 50% is G to A nucleotide change at position 11778 in ND-4 gene

Question 21

What is a coloboma? What is the gene associated with this? Which condition is it associated with?

Answer 21

Coloboma: Failure of closure of inferonasal optic fissure

Gene: CHD7 gene found in 65% patients with CHARGE syndrome (Coloboma, heart disease, atresia choanae, retardation of growth)

Question 22

What are the main examples of mitochondrial eye disease (4)

Answer 22

1. MELAS
2. Leber hereditary optic neuropathy
3. Chronic progressive external ophthalmoloplegia
4. Neuropathy, ataxia, retinitis pigmentosa

Question 23

Why do mitochondrial diseases worsen with age?

Answer 23

REPLICATIVE SEGREGATION
Mitochondrial DNA deletions occur over time, which results in perferential replication of smaller deleted molecules –> increased number of deleted copies over time

Question 24

HEXA gene mutation is associated with what condition?

Answer 24

Tay-Sach’s syndrome

Question 25

What chromosome is implicated in NF-1
What chromosome is implicated in NF-2
What chromosome is implicated in tuberous sclerosis
What chromosome is implicatd in pseudoxanthoma elasticum?

Answer 25

NF-1 : chromosome 17
NF-2: chromosome 22
tuberous sclerosis: chromosome 9, 16
pseudoxanthoma elasticum: chromosome 16