W1 - Inheritance Patterns Flashcards
How are males represented on a pedigree drawings?
Squares
How are females represented in pedigree drawings?
Circles
How are partners represented in pedigree drawings?
Has a line between them
How are siblings represented in pedigree drawings?
Has a line above them
How are children represented in pedigree drawings?
Line down
How are affected people represented in pedigree drawings?
Affected = shaded
Carriers = dot
How are unions of consanguineous (of the same blood) couples represented in pedigree drawings?
Double lines connecting the two
How are still born babies of unknown sex represented in pedigree drawings?
Diamond with SB next to it
How are spontaneous abortions represented in pedigree drawings?
Triangle
How are therapeutic abortions represented in pedigree drawings?
Triangle with a diagonal line
How are identical twins represented in pedigree drawings?
Has a line connecting the line coming from the parents to form a triangle at the top.
How are non-identical twins represented in pedigree drawings?
Triangular stem without line joining them.
How is pregnancy represented in pedigree drawings?
Diamond with a ‘p’ inside.
How are no offsprings represented in pedigree drawings?
Upside down T underlined.
How are unaffected people with unknown sex represented in pedigree drawings?
Diamond
What are autosomal dominant conditions?
- Manifest in HETEROZYGOUS form
- Multiple generations affected
- Both sexes affected
- Male to female & female to male transmission
- Often an affected parent
- 50% risk to offspring
What are the features of dominant inheritance to be aware of?
- Incomplete/reduced penetrance: some people have the mutation but do not have the disease
- Variable expressivity: variation in severity/symptoms of disorder between individuals with the same mutation
- De novo mutation rate: not all affected individuals have an affected parent; often depends on severity of disorder; varies greatly between conditions
- Mosaicism: mutation only present in a proportion of cells
- Anticipation: worsening of disease severity in successive generations, e.g. expansion disorders
What is incomplete or reduced penetrance?
- Penetrance - Percentage of individuals who carry the mutation AND develop symptoms of the disorder
- many dominant disorders show age-dependant penetrance
Eg. if every one who has the disease has a parent with that same disorder it has high penetrance. But if not everyone that has that disorder has a parent with the same condition, it less penetrance.
What is variable expressivity?
- Variation in severity/symptoms of disorder between individuals with same mut^n
What is autosomal recessive inheritance?
- Manifest in HOMOZYGOUS/ COMPOUND HETEROZYGOUS form
- Carriers (heterozygote) not affected
- Both sexes affected
- Male to female and female to male transmission
- Usually one generation affected
- May be consanguinity- e.g. cousin marriages
What are compound heterozygote or homozygote?
Compound heterozygous
* 2 mutns in same gene
* Mutns are different
Homozygote
* 2 mutns in same gene
* Identical mutns
Cystic fibrosis
* ∆F508
* ∆F508
May suggest consanguinity.
What are features of autosomal recessive inheritance?
- Trait often found in clusters of siblings but not in parents & offspring.
- Recurrence risk = 1/4 for each sibling of affected person.
- Carrier probability =2/3 for unaffected siblings of affected person.
- All offspring of affected person are obligate carriers.
What is X-linked inheritance?
Females have two X chromosomes
* Two copies of X-linked genes
* Can be homozygous or heterozgous
Males have one X and a Y
* Only a single copy of X-linked genes
* Hemizygous
What are recessive and dominant X-linked inheritances?
Recessive
- Females are carriers + unaffected
* No male to male transmission
Dominant
* Females are affected
* Males more severely affected/lethal
What are features of X-linked recessive inheritances?
- X-linked genes never passed from father to son.
- All daughters of affected males are obligate carriers.
- Children of carrier females have a 50% chance of inheriting mutant allele.
- Skewed X-inactivation: generally random but ~10% of females have uneven or skewed X-inactivation.
- Manifesting carriers: some females have some symptoms in X-linked recessive conditions e.g. cardiomyopathy in DMD.
What are characteristics of Y-linked inheritances?
- Always and only passed from
fathers to sons
What are mutations and variants of these ?
- Mutation: a change in the genetic material
- A pathogenic mutation (pathogenic variant) results in an alteration of the function of the gene product and can cause a disease phenotype
- What types of mutations are there?
- What happens when the amino acid sequence of a protein isn’t what it should be?
What are the different types of mutations and where can they be found?
Types:
* Substitutions (point mutations)
* Deletions
* Insertions
Found in:
* Coding DNA
* Non-coding DNA (such as promoters and introns)
What are synonymous substitutions?
These are silent mutations - basically there is a base change but it does not change the amino acid. This is usually the 3rd base that is alright to change. Changing the first or second base in a codon means the amino acid changes typically.
What are non synonymous missense?
This is where a base change leads to a change in the amino acid sequence. It is difficult to predict their effect.
What is the impact of amino acid substitution?
- Physicochemical similarity between the two amino acids
- Functional role of the specific domain of the protein affected - is it going to effect it’s ability to function?
- Phylogenetic conservation of original aminoacid amongst diverse species
What is non-synonymous nonsense?
If you have a premature stop codon, it is quite likely to cause a biological effect. It depends on where it is. They are not all damaging.
What is insertion of a base?
- In-frame (multiple of three) or
frameshift (not multiple of three)
What is deletion of a base?
- In-frame (multiple of three) or
frameshift (not multiple of three)
What are De novo mutations?
Mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease.
