Lecture 2 GiM Flashcards
What is complex/multifactorial genetic disorders?
The interaction of multiple genes (genetic predisposition) in combination with environmental factors
What is the example of complex/multifactorial genetic disorders?
Type II diabetes and Ischemic heart disease
What is the example of single gene inheritance disease?
Cystic fibrosis
Identify 5 different types of genetic disorders?
Multifactorial/Complex, Single gene, Chromosomal, Mitochondria and Somatic mutations
Identify 4 different types of single genes mode of inheritance
Autosomal Dominance
Autosomal Recessive
X-linked
Mitochondrial
Identify the characteristic of Autosomal Dominance inheritance pattern
Males and females equally affected
Offspring of affected person has a 50% chance of inheriting the condition
What are the example of diseases caused by Autosomal Dominance inheritance pattern?
Myotonic dystrophy
Marfan syndrome
Huntington disease
What is penetrance
The frequency with which a specific genotype is expressed by those individuals that possess it, usually given as a percentage.
What is incomplete penetrance?
Not all relatives who inherit the mutation develop the disorder – eg BRCA1 mutations 80% life time chance of developing breast cancer
What is Expressivity?
The extent to which a heritable trait is manifested by individual
What are the symptoms of Marfan Syndrome?
Aortic dilatation, lens dislocation, stretch marks
BRCA1 and BRCA2 mutation increased the susceptibility of what type of diseases?
Ovarian and breast cancer
What is anticipation?
The symptoms of a genetic disorder become apparent at an earlier age as it is passed from one generation to the next.
In most cases, it also increase the severity of the diseases too.
What is de novo/new dominant mutation?
A new mutation that has occurred during gametogenesis or in early embryonic development.
What are the patterns of Autosomal Recessive inheritance?
Disease seen in one generation (typically not seen in every generation of an affected family)
Parents usually unaffected
Offspring of affected individual has low risk of disease – unless in consanguineous relationship
Relatives may be asymptomatic carriers of the disease
Affects males and females equally
Gene mutations, not chromosomes
What are the example of diseases that follow Autosomal Recessive inheritance pattern?
Cystic fibrosis
Many of the metabolic disorders
Haemachromatosis
Sickle cell disease
What are the patterns of X-linked inheritance?
Males affected
Females may be unaffected, mildly through to fully affected
Males usually more severely affected than females
Can NOT have male to male transmission
Gene mutations and chromosome deletions/ duplications
What are the example of X-linked inherited diseases?
Duchenne Muscular dystrophy,
Fragile X syndrome
Red / green colour-blindness
Haemophilia
For X-linked inheritance pattern, why females have such a variable phenotype?
Due to 2 factors:
- X inactivation
- X-linked dominance vs X-linked recessive inheritance
Can you predict female phenotype accurately in prenatal testing?
No
What is X-inactivation?
The process of random inactivation of one of the X chromosomes in cells with more than one X chromosome.
Compensates for the presence of the double X gene dose.
What is characteristic of X-inactivation?
Is normal and occurs when there is 2 or more X chromosomes in a cell
Occurs in early embryogenesis
Random – which X is silenced
Once inactivated an X-chromosome remains inactive throughout the lifetime of the cell and all its descendants
Most, but not all genes switched off on the inactivated X
What is the percentage of cells which express the normal gene?
Approximately 50%
What is the preference for X-inactivation?
random preference for “normal” X chromosome to be inactivated (skewed X-inactivation)
What is the example of X-linked inheritance?
Rett syndrome (lethal in males, phenotype only in females) Fragile X syndrome – females:- asymptomatic to fully symptomatic ( due to X-inactivation pattern)
What is the example of X-linked recessive?
Red-green colour blindness
Haemophilia
Duchene Muscular dystrophy
Carrier girls usually unaffected BUT can have significant symptoms because of X-inactivation (switches off normal X)
Girls fully affected if inherit mutation from mum and dad
What is the example of disease that follow mitochondrial inheritance pattern?
Maternally inherited diabetes and deafness
Where does human inherit their mitochondria from?
Their mother (the sperm does not any mitochondria)
What are the characteristic of mitochondrial inheritance pattern?
Rare, males and females affected equally
Only 27 genes within mitochondrial DNA
Each cell has many mitochondria
Every mitochondrium has many copies of each gene
Mitochondria are inherited from the mother’s egg
An affected mother will give all her children the mutation
Highly variable expressivity and therefore severity of phenotype between relatives
All the children of an affected man will be unaffected
