Patterns of inheritance Flashcards
Define autosomal dominant
One copy of a mutated gene from one parent can cause genetic inheritance of a child, and a child who has a parent with the mutated gene has a 50% chance of inheritance
Define autosomal recessive
Two copies of a mutated gene from one parent can cause genetic inheritance of a child, or both parent carry one copy of the mutated gene (homozygous recessive or homozygous dominant but they’re a carrier)
- Affected individuals offspring have 25% chance of being affected
- Unaffected siblings of an affected individual have 2/3 chance of being a carrier
Define X-linked genetic disease
Genetic conditions associated with mutations in genes on the X chromosome
Offspring of carrier female have 50% chance of inheriting pathogenic variant
- Females with variant will be carriers unless skewed X-inactivation
- Males with variant will be affect, not carriers
X-linked genes are never passed from father to son (only pass on Y chromosome)
All daughters of an affected father are obligate carriers (as they pass on only X chromosome which has variant)
Affected males may have de novo effect
Describe X-linked dominant inheritance
- Genetic condition caused by variant in a gene on X chromsome where only ONE copy of the gene is needed to inherit the condition
- For this reason, both males and females can be affected by X-linked dominant conditions.
Describe X-linked recessive inheritance
Main features of X-linked recessive inheritance include:
- Affected males cannot pass condition to sons
- Males affected almost exclusively
- Variant can be passed from unaffected female carriers to sons
Define multifactorial genetic disease
More than 1 factor causes a trait or health problem. Factors can be both genetic and environmental
Define mitochondrial genetic disease
Genetic diseases that result in impaired function of the mitochondria
- Mitochondria have their own small, circular molecules of DNA - 37 genes.
- Variants are maternally inherited
Describe the factors that influence inheritance patterns
- De novo - Variant arise spontaneously in early embryogenesis
- Variable expressivity - Individuals develop different phenotype severity with the same variant
- Penetrance - Not all individuals who inherit the variant will develop the condition
- Anticipation - Disease severity increases and generally age of onset decreases in each generation. Usually seen in trinucleotide repeat expansion conditions such as Huntington disease
- Skewed X inactivation - ‘Turning off’ of one X chromosome, occurs more oftehn than the other copy of the chromosome, present in approx 10% of women
- Mosaicism:
- Germline - Variant present in gametes only
- Somatic - Variant arises in a cell line so some cells in body carry variant whilsts others do not
What does polygenic mean?
Combination of different gene variants contributing to disease
Differs from multifactorial as it only looks at genetic component, not other modifying/influencing factors (environmental)
What is the Hardy-Weinberg principle?
Allele and genotype frequencies in a population remain constant in successive generations. There are no other evolutionary influences
P squared + 2pq + q squared = 1
P + q = 1
Why is it useful to know carrier risk?
- To determine if carrier testing is indicated
- To calculate risk of an affected child
Population risk = 1/50 - This is the probability of the general population carrying the disease by chance, and the chance it passes on is 1/2 for both known carrier and unknown carrier
