Patterns of Inheritance Flashcards
What are the main symbols used in Pedigree drawings?
- Males are squares.
- Females are circles.
- Partners have a line between them.
- Siblings have a line above them.
- Line down for children.
- Affected people are shaded.
- Carriers have dots in.
What are some other symbols used in Pedigree diagrams?
- Diagonal line through shape = Diseased person
- No offspring = double bar underneath shape.
- Pregnant: line from mother (circle) to diamond (with a ‘P’ in the diamond) if the gender is not yet known.
- Person whose sex is unknown: diamond
- Monozygotic (identical) twins —> same gender –> same shapes.
- Dizygotic (non-identical) twins –> different gender –> different shapes.
- Double line joins union of consanguineous (same blood) couple.
- ‘SB’ next to a diamond denotes a stillborn baby (born dead) of unknown sex.
- Spontaneous abortion are triangles.
- Therapeutic abortion is a triangle with a line through it.
Describe the characteristics of the Autosomal Dominant inheritance pattern.
- Most individuals have an affected parent (not everybody due to cases of new mutations or incomplete penetrance)
- Males and females are equally likely to inherit the allele and be affected.
- The risk for each child of an affected parent is 50%
- If an unaffected individual’s siblings/children are not affected, and they do not carry the mutation, then they cannot pass it on to their own offspring.
What is penetrance and how is it calculated?
Penetrance is the percentage of individuals who carry the mutation AND develop symptoms of the disorder - many dominant disorders show age-dependent penetrance.
Penetrance = number of people with disease / number of people with the genotype for the disease.
x100%
What are obligate carriers and how does this relate to reduced penetrance?
Obligate carriers are individuals who’ve got the disease causing genotype (heterozygous for mutation) but haven’t got the disease themselves, but they can still pass on the disease to their offspring.
This is reduced penetrance as the number of people with the disease is less than the number of people with the genotype (for the disease) thus giving a reduced overall percentage (reduced penetrance).
List and describe some features of autosomal dominant inheritance patterns. (5)
- VARIABLE EXPRESSIVITY: variation in severity/nature of symptoms of a disorder between individuals with same mutation.
- NEW MUTATION RATE: de novo mutation rate varies considerably between AD (different) conditions.
- SOMATIC MOSAICISM: new mutations arising at an early stage in embryogenesis - present in only some tissues/cells.
- GERM-LINE MOSAICISM (gonadal mosaicism): new mutation arises during oogenesis or spermatogenesis - mutation must be present in a variable proportion of gametes; can be transmitted to offspring (depends on chance).
- ANTICIPATION: the worsening of disease severity in successive generations - characteristically occurs in triplet repeat disorders (expansion disorders). - often seen in young age.
Describe the characteristics of autosomal recessive inheritance.
- Manifest in homozygous/compound heterozygous form.
- Carriers (heterozygous) not affected.
- Both sexes affected.
- Male to female and female to male transmission.
- Usually, one generation affected.
- May be consanguinity (eg. cousin marriages).
What is the difference between compound heterozygote and homozygote?
Compound Heterozygote: - 2 mutations are in the same gene - the mutations are different - In Cystic Fibrosis: o ΔF508 o ΔF508
Compound Homozygote: - 2 mutations are in the same gene - they are identical mutations - May suggest consanguinity - In Cystic Fibrosis: o ΔF508 o G542X
List some features of autosomal recessive inheritance.
- The traits are often found in clusters of siblings, but not in parents and offspring.
- The recurrence risk is 1/4 for each sibling of an unaffected person.
- The carrier probability is 2/3 for unaffected siblings of the affected person.
- All offspring of the affected person are obligate carriers.
Describe how the difference in sex chromosomes affects X-linked inheritance.
Women have 2 X chromosomes.
- Thus, they have 2 copies of X-linked genes, giving slight protection.
- They can be homozygous or heterozygous for these disorders.
Men have one X and one Y chromosome.
- Thus, they only have a single copy of X-linked genes.
- They are said to be hemizygous.
How is X-linked inheritance recessive or dominant?
X-linked inheritance can be:
RECESSIVE:
- Women are carriers + unaffected.
- No male to male transmission.
DOMINANT:
- Women are affected.
- Males more severely affected/lethal.
Describe the characteristics of X-linked recessive inheritance.
X-linked genes are never passed from father to son.
- all daughters of affected males are obligate carriers.
- children of carrier females have a 50% chance of inheriting the mutant allele.
Skewed X-Inactivation: normally, the majority of genes on one of a woman’s X-chromosomes are inactivated (it’s generally random, but ~10% of women have uneven or skewed X-inactivation)
Manifesting Carriers: some women have some symptoms in X-linked recessive conditions (eg. cardiomyopathy in DMD)
What is Y-linked (a.k.a. holandric inheritance) inheritance?
Inheritance of genes on the Y chromosome. Always and only from father to sons.
So a mutation on the Y allele can only be passed to sons and not to daughter.
Define a pathogenic mutation.
A mutation is a change in genetic material.
A pathogenic mutation (pathogenic variant) results in an altercation of the function of the gene product and can cause a disease phenotype.
List the types of mutations and where they are found.
Types of mutations:
- substitutions (point mutations)
- deletions
- insertions
Found in:
- coding DNA
- non-coding DNA (such as promoters and introns)
