X linked and Mitochondrial Flashcards
Week 7
Sex-linked vs sex-limited inheritance
Sex-linked traits
-Only on sex chromosomes
-Dominant or recessive
Sex-limited
-Phenotype observed in 1 sex
-X-linked or autosomal
How do males and females express X-linked traits
M= Always express the trait (single X)
F= Can show dominant or recessive phenotype
X-linked dominant features
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
X-linked recessive features
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
What gene is involved in colour blindess?
Gene
-OPN1LW (yellow/orange)
-OPN1MW (yellow/green)
Is colour blindness X-linked recessive or dominant?
recessive
Is Hypophosphatemic rickets X-linked recessive or dominant?
dominant
gene affected in hypophosphatemic rickets
PHEX gene
incidence of rickets
1/ 20 000 newborns
colour blindness incidence
1/2 males
1/200 females
What is the normal gene and gene products of Duchenne Muscular Dystrophy?
DMD gene
produces dystrophin (under sarcolemma, critical structural protein)
Is Duchene Muscular Dystrophy recessive or dominant?
recessive
Who does DM dystrophy mainly affect and why?
Affects mainly males
(females protected by second X but still vulnerable to cardiac muscle weakness)
Clinical features of Dm Dystrophy
Gower’s maneuverer to raise
Pseudohypertrophy of calf muscles
Progression of DM Dystrophy
normal 1-3yrs
-wheelcahirs 10-12
-death 20
What is the most common cause of death for patients with DM dystrophy?
cardiac muscle/ respiratory failure
potential therapies for DM dystrophy
Exon skipping
Reading through STOP codon
What are the two type of haemophilia and what genes impact them?
A= F8 gene (clotting factor VIII deficiency)
B= F9 gene (clotting factor IX deficiency)
Old and new treatments of Haemophlia
Old
-blood trans
-infuse anti-haemophilic factor
New
-recombinant clotting factors
Why is haemophilia A more serious?
A is more serious
-clotting factor VII affects both intrinsic and extrinsic pathways
Affected gene and mutation of Kennedy’s disease
Gene
AR
Mutation
CAG repeats greater than 35 in AR protein
Clinical features of Kennedy’s disease
Toxic motor neurons
-spinal and bulbar muscle atrophy
Progressive muscular atrophy of motor neurons in spinal cord
What group of those with Kennedy’s Diseases is usually asymptomatic?
Heterozygous females
protected by X
What does mitochondrial encode for and how is it stored?
Store
-As a single circular chromosome
Encode
-Ribosomes and OXPHCS proteins
heteroplasmy
cell or organism in which ALL copies of mitochondiral DNA are NOT the same
homoplasmy
mitochondrial genome are EXACTLY the same
How does heteroplasmy relate to disease penetrance?
proportion of mutant disease copies determines penetrance and expressivity
What is the gene affected in Leigh Disease and what does it cause?
Gene
MTATP6
(encodes ATP synthase 6)
Deficiencies in ATP production and oxidative phosphorylation
what are the X-linked recessive diseases?
Kennedy’s Disease
Haemophilia
DM Dystrophy
Colour blindness
Compare mutations on X chromsomes for males vs females.
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)
Describe the inheritance of X-linked mutations for females vs males
females
-one X from each parent
males
-X from mother
-passes onto daughter
Compare mitochondrial and autosomal inheritance.
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
Examples of mitochondrial inheritance
Leber’s Hereditary Optic Neuropathy, MELAS syndrome
What types of disorders can mitochondrial inheritance lead to?
affect energy production
