Genetics Flashcards
From which parent is the mitochondrial DNA inherited?
Mother
What is an allele?
A variation of the same gene
What is meant by Dominant Autosomal?
Characteristic is dominant if it manifests in a heterozygote
This characteristic is then expressed in the phenotype
Certain genes being activated (dominant gene), triggers a change in the phenotype
What is a dominant autosomal disorder?
Single gene disease or trait passed down to offspring with multiple generations affected
Each affected child normally has one affected parent
Each child of an affected person has a 1 in 2 chance of being affected
What is meant by a vertical pedigree pattern?
Males and females are equally affected and equally likely to pass on the condition
How could you make a genetic mutation dominant?
Mutations resulting from a DNA expansion of a CAG repeat on chromosome
What are the three consequences a dominant autosomal disorder can incur?
- *Gain of function** - Gene now makes a protein with a new function, e.g - longer lifespan or new location to increase effect
- *Dominant negative effect** - Mutated form interferes with the activity of proteins it binds to, e.g - dimers reduce activity
- *Insufficient** - Mutant in one gene results in 1/2 amount of a protein that is not enough for normal function
What is meant by an Autosomal Recessive Disorder?
2 copies of recessive allele must be present in order for trait/disease to develop
Tend to be ‘loss of function’ mutations
What do carriers of autosomal recessive disorders have?
Lost a single copy of a gene but the normal one is sufficient enough to maintain normal function
What is the lowest probability that a sibling of an affected child will be affected?
25% (1 in 4)
What does a horizontal pedigree pattern show?
Affected individuals are often seen in more than one child in a family and not in all generations
What effect does consanguinity have on the occurrence of autosomal recessive disorders?
Increases probability of occurrence
Which sex do X-linked disorders (recessive) mainly affect and why?
Males - only one X chromosome so it is effectively dominant
If a father is affected by X-linked dominant disorder, what will be the effects on the sons and daughters?
No sons will be affected
All daughters will be affected
Why might X-linked dominant disorders affect males and females differently?
Females can be less affected because the normal X gene may be active in some cells rather than the mutant gene
The process is called X inactivation and is random
What is usually an effect of X-linked dominant disorders?
Increase of current function
What is meant by a Y-linked disorder?
Only affects males
All sons of an affected father are affected
If a father is affected by a mitochondrial disease, what is the effect on the children?
None are affected
Mitochondrial DNA will not be passed down by the father, however, if the mother was affected, all the children would be affected
What causes mitochondrial disease variability and what does the severity of symptoms depend on?
Random segregation of genes during binary fission so some mutant forms may be removed from a mitochondrion
Depends on the number of affected mitochondria as in the future more mutant mitochondria may accumulate to become a larger proportion of the mitochondria in the organism
How you would show a carrier of an autosomal and one of an x-linked trait on a pedigree diagram?
Autosomal - square/circle half-shaded
X-linked - circle with a black dot in the center
How you would show someone who is deceased on a pedigree diagram?
With a diagonal line across the square/circle (top part of line on right side and bottom on left)
How you would show the first person who sought medical attention on a pedigree diagram and what are they called?
They’re called proband. Shown as an arrow pointing to the bottom left corner of their symbol (circle/square)
How are monozygotic twins drawn on a pedigree diagram?
Their lines have the same origin (like the top vertex of a triangle) and there is a horizontal line connecting them.
How are dizygotic twins drawn on a pedigree diagram?
Their lines have the same origin (like the top vertex of a triangle) with no horizontal line connecting them.
What are the conditions for a pedigree diagram to show an Autosomal Dominant trait?
Vertical Transmission
Not all offspring affected usually
Males and Females can be affected
At least one affected parent - can be mother or father
What are the conditions for a pedigree diagram to show an X-linked recessive trait?
Not all generations are affected
Not all offspring are affected
Only females affected if father is affected
What are the conditions for a pedigree diagram to show a Mitochondrial-inherited trait?
Vertical transmission All generations affected All offspring affected Males and females affected Inherited from mother
What are the conditions for a pedigree diagram to show an Autosomal Recessive trait?
Usually no history of family disease / Distant relative affected
Horizontal Transmission
Males and females affected
Describe the steps involved when calculating the risk that a person is a carrier of an inherited disease?
Work with the closest relatives on either side of the proband’s family
Multiply risks of each person carrying the disease to find the probability that the proband is a carrier
Is Type VIIII more or less severe than Type I Osteogenesis Imperfect?
More severe
In Multiple Endocrine Neoplasia type 1 (MEN1), why do not all people with a mutation in the MEN1 tumor suppressor gene develop the same type of adenoma at the same time?
A second event has to occur to promote tumor formation, which is based on environmental differences
Why do only 10% of people with hereditary hemochromatosis have clinically relevant iron accumulation?
Dietary load of iron can vary considerably
Lower levels of intake are associated with improved disease prognosis
What causes the difference in disease progression between Duchenne and Becker muscular dystrophy?
In DMD there is a frameshift deletion in the dystrophin gene and so no active dystrophin is produced
In Becker Muscular dystrophy the mutation does not result in a frame shift and so active dystrophin is produced whilst in shorter form, retains activity
What is a trinucleotide repeat expansion?
Mutation in which a region of 3 repeated nucleotides in the genome increases in number during DNA replication
As the number of repeats increases, it reaches a threshold above which they are no longer stable during DNA replication and the number of repeats increases each subsequent round of DNA replication
This alters protein function
Greater number of repeats results in a more severe phenotype. Therefore, usually, future generations have more severe phenotypes.
What is meant by karyotype?
An individual’s collection of chromosomes
How do you prepare a karyotype?
- Collect ~5ml ** heparinized venous blood** (can use amniotic cells or chronic villus sample - CVS)
- Isolate white cells
- Culture in presence of phytohemagglutinin (stimulates T-lymphocyte growth and differentiation)
- After 48 hours add colchicine (causes mitotic arrest - do at metaphase or prophase)
- Place in hypotonic saline
- Place on the slide
- Fix and stain (Gisema stain or fluorescent stain)
- Cut out the individual chromosomes and arrange them in a karyotype.
