X linked and Mitochondrial

Question 1

Sex-linked vs sex-limited inheritance

Answer 1

Sex-linked traits
-Only on sex chromosomes
-Dominant or recessive

Sex-limited
-Phenotype observed in 1 sex
-X-linked or autosomal

Question 2

How do males and females express X-linked traits

Answer 2

M= Always express the trait (single X)

F= Can show dominant or recessive phenotype

Question 3

X-linked dominant features

Answer 3

Affected father passes onto all daughters but no sons

50% chance that affected female (hetero) passes on

2:1 female: male

Severity (largest –> smallest) : homozygous female –> hemizygous male –> heterozygous females

Question 4

X-linked recessive features

Answer 4

Knight’s move

Parents and children usually healthy

Affects mostly males as females have 2 X

½ chance subsequent brother impacted

½ chance sisters if affected boy impacted

Question 5

What gene is involved in colour blindess?

Answer 5

Gene
-OPN1LW (yellow/orange)
-OPN1MW (yellow/green)

Question 6

Is colour blindness X-linked recessive or dominant?

Answer 6

recessive

Question 7

Is Hypophosphatemic rickets X-linked recessive or dominant?

Answer 7

dominant

Question 7

gene affected in hypophosphatemic rickets

Answer 7

PHEX gene

Question 8

incidence of rickets

Answer 8

1/ 20 000 newborns

Question 9

colour blindness incidence

Answer 9

1/2 males
1/200 females

Question 10

What is the normal gene and gene products of Duchenne Muscular Dystrophy?

Answer 10

DMD gene

produces dystrophin (under sarcolemma, critical structural protein)

Question 11

Is Duchene Muscular Dystrophy recessive or dominant?

Answer 11

recessive

Question 11

Who does DM dystrophy mainly affect and why?

Answer 11

Affects mainly males
(females protected by second X but still vulnerable to cardiac muscle weakness)

Question 12

Clinical features of Dm Dystrophy

Answer 12

Gower’s maneuverer to raise

Pseudohypertrophy of calf muscles

Question 13

Progression of DM Dystrophy

Answer 13

normal 1-3yrs
-wheelcahirs 10-12
-death 20

Question 14

What is the most common cause of death for patients with DM dystrophy?

Answer 14

cardiac muscle/ respiratory failure

Question 15

potential therapies for DM dystrophy

Answer 15

Exon skipping

Reading through STOP codon

Question 16

What are the two type of haemophilia and what genes impact them?

Answer 16

A= F8 gene (clotting factor VIII deficiency)

B= F9 gene (clotting factor IX deficiency)

Question 17

Old and new treatments of Haemophlia

Answer 17

Old
-blood trans
-infuse anti-haemophilic factor

New
-recombinant clotting factors

Question 18

Why is haemophilia A more serious?

Answer 18

A is more serious
-clotting factor VII affects both intrinsic and extrinsic pathways

Question 19

Affected gene and mutation of Kennedy’s disease

Answer 19

Gene
AR
Mutation
CAG repeats greater than 35 in AR protein

Question 20

Clinical features of Kennedy’s disease

Answer 20

Toxic motor neurons
-spinal and bulbar muscle atrophy

Progressive muscular atrophy of motor neurons in spinal cord

Question 21

What group of those with Kennedy’s Diseases is usually asymptomatic?

Answer 21

Heterozygous females

protected by X

Question 22

What does mitochondrial encode for and how is it stored?

Answer 22

Store
-As a single circular chromosome

Encode
-Ribosomes and OXPHCS proteins

Question 23

heteroplasmy

Answer 23

cell or organism in which ALL copies of mitochondiral DNA are NOT the same

Question 24

homoplasmy

Answer 24

mitochondrial genome are EXACTLY the same

Question 25

How does heteroplasmy relate to disease penetrance?

Answer 25

proportion of mutant disease copies determines penetrance and expressivity

Question 26

What is the gene affected in Leigh Disease and what does it cause?

Answer 26

Gene MTATP6 (encodes ATP synthase 6) Deficiencies in ATP production and oxidative phosphorylation

Question 27

what are the X-linked recessive diseases?

Answer 27

Kennedy's Disease Haemophilia DM Dystrophy Colour blindness

Question 28

Compare mutations on X chromsomes for males vs females.

Answer 28

Expression -male always Severity -male more as females may mask carrier -only females compensation -females have x-inactivation inheritance -X from mother, passes to daughter (male)

Question 29

Describe the inheritance of X-linked mutations for females vs males

Answer 29

females -one X from each parent males -X from mother -passes onto daughter

Question 30

Compare mitochondrial and autosomal inheritance.

Answer 30

Location M= mitochondira A= Autosomes Inheritance pattern M= maternal A= both Penetrance and expression M= maternal lineage, varies in severity A= more varible as more genes present

Question 31

Examples of mitochondrial inheritance

Answer 31

Leber's Hereditary Optic Neuropathy, MELAS syndrome

Question 32

What types of disorders can mitochondrial inheritance lead to?

Answer 32

affect energy production