Pedigree Flashcards
What is pedigree?
Visual representation of a family
- Used to study single gene disorders
If both parents are carriers of a AR gene what are the chances of the child being being homozygous recessive (affected by disease)?
25%
If the mother comes from a population with a 1/50 chance of being a carrier of disease and the father a 1/100 what are the chances that both parents are carriers?
(1/50) * (1/100) = 1/5,000
If the mother comes from a population with a 1/50 chance of being a carrier of a Recessive disease and the father a 1/100 what are the chances that there child will be affected by the AR disease?
(1/50) * (1/100) = 1/5,000
(1/5000) * (1/4) = 1/20,000
Why are X-linked dominant genes never passed through the male line?
Male only passes y chromosome
In an aut dominant disease if there is one affected parent what percentage of offpsring will have the disease?
50%
What is Incomplete dominance?
Aut dom disease where the heteroztgote phenotype is different (less severe) than the homozygote (more severe)
- E.g familial hypercholesterolemia and achondroplasia
What is an example of a disease with incomplete dominance, where in homozygote individuals it is fatal?
Achondroplasia
- In heterozygotes it causes dwarfism
Why in X-linked disorders are males always affected (whether it is dominant or recessive)?
They only have one X chromosome
How can a X-linked recessive disorder be identified?
All males with gene will be affected
- No females affected (usually)
- No male to male transmission
How can a X-linked dominant disorder be identified?
All males with gene will be affected and will have it transmitted through the mother’s side
- Females will be affected
- Affected father MUST give diseased X chromosome to daughter
- NO male to male transmission, affected father will NOT pass disease to son
What percentage of sons of heterozygous mothers with an AR allele will be affected by disease?
50%
What are the 2 ways a female may develop an X-linked recessive gene?
- If homozygous for gene (father affected and mother a carrier)
- Skewed lionization
What is lyonization?
Inactivated of X chromosome in females
What is the lyonized X chromosome known as?
Barr body
How is the X chromosome lyonized or inactivated?
Condensed into heterochromatin w. methylated DNA
When does lyonization occur?
Early in development
- Embryo <100 cells
What does lyonization result in?
Mosaicism
- Different inactive X chromosomes in different cells as it is a random process
How can you differentiate an X-linked dominant disorder from an Aut Dom pattern?
No male-male transmission in X-linked disease
- Father always passes Y chromosome
Whaty is the second most common cause of intellectual disability?
Fragile X syndrome
What are the features of fragile X syndrome?
- Long, narrow face, large eears and jaw
- Features of autism
- More severe in males
What organs are most affected by mitochondrial gene mutations?
- CNS
- Skeletal muscle
Both heavily rely on aerobic metabolism
A mixture of abnormal and normal genes in mitochondria is known as what?
Heteroplasmy
What does the mutant gene expression levels depend on?
- Amount of normal vs abnormal genes
- Number of mutant mitochondria in each cell/tissue
What is the difference beetween a homoplasmic and heteroplasmic mother?
Homoplasmic mothers
- All children have mutation
Heteroplasmic
- Variable
Why may not all children display disease if their mother has a mitochondrial disease?
Mother may be heteroplasmic
What are the 3 classic signs of mitochondrial myopathies?
- Weakness
- Confusion
- Lactic acidosis
Wwhat is the classic sign of mitochondrial myopathy on biopsy?
Red ragged fibres
- compensatory proliferation of mitochondria which accumulate and appear bright red on blue background
Multifactorial inheritance is what?
Genes, lifestyle and environemnt contributing toward disease
What is polygenic inheritence?
inheritance of a trait governed by more than one genes
