CPPS403 - PatternsofInheritance - 5 Flashcards
(23 cards)
What are the different Mendelian inheritance patterns?
Autosomal Dominant, Autosomal Recessive, X-Linked Recessive, X-Linked Dominant, Pseudoautosomal and Y-Linked Inheritance, Digenic Inheritance, Mitochondrial Inheritance.
Each pattern has specific characteristics related to how traits are transmitted through generations.
How can pedigrees be used in genetics?
Pedigrees are used to infer modes of inheritance by visually representing family relationships and the occurrence of traits across generations.
They help identify patterns of inheritance, such as autosomal or X-linked traits.
What is autosomal dominant inheritance?
Both sexes are affected and equally likely to transmit the disorder; affected individuals are typically heterozygotes and usually have at least one affected parent.
Examples include conditions like Huntington’s disease.
What is autosomal recessive inheritance?
Both sexes are affected and equally likely to transmit the disorder; affected individuals carry two mutant alleles and are typically born to unaffected parents who are carriers.
Examples include cystic fibrosis and sickle cell anemia.
Define compound heterozygotes.
An affected individual with two different mutant alleles.
This can occur in autosomal recessive conditions.
What is the significance of consanguinity in genetics?
Consanguinity often results in affected individuals with two identical mutant alleles, increasing the likelihood of autosomal recessive disorders.
This is due to the increased probability of both parents carrying the same recessive allele.
What characterizes X-linked recessive inheritance?
Affected individuals are mostly male and born to unaffected parents; no male-to-male transmission occurs.
Examples include hemophilia and Duchenne muscular dystrophy.
What is X-linked dominant inheritance?
Affected individuals can be of either sex, but there are more affected females; usually, at least one parent is affected.
Examples include Rett syndrome.
Describe pseudoautosomal and Y-linked inheritance.
In male meiosis, recombination between the X and Y is limited to the pseudoautosomal region; alleles can be transposed between the X and Y chromosomes.
This region contains very few genes.
What is digenic inheritance?
Pathogenic variants in two genes must be inherited together to cause disease.
It is rare and challenging to identify.
What is mitochondrial inheritance?
Mitochondrial disorders are transmitted by females only, and mutations in mtDNA can cause highly variable phenotypes within families.
The human mitochondrial genome has 13 protein-encoding genes and 24 RNA genes.
Define heteroplasmy.
The presence of more than one type of organellar genome within a cell or individual.
This can lead to variable expression of mitochondrial disorders.
What is germline mosaicism?
Mutation occurs during germ cell development and can be inherited by the next generation.
This may lead to affected offspring from unaffected parents.
What is somatic mosaicism?
Mutation occurs early during embryonic development, leading to mild phenotypes or variable tissues affected.
It can result in phenotypic variability in individuals.
Can phenotypes always be predicted from a specific genotype?
No! Genotype-phenotype correlations are influenced by several factors including locus/phenotypic heterogeneity and penetrance.
Modifier genes, epigenetics, and environment also play a role.
What is locus heterogeneity?
The same clinical phenotype can be produced by mutations at two or more loci.
Different affected genes often work together in a common pathway.
Give an example of locus heterogeneity.
Autosomal recessive deafness can be caused by mutations in different genes such as DEAF1 and DEAF2.
Parents affected with this condition can have unaffected offspring.
What is allelic/phenotypic heterogeneity?
Different mutations in a single gene can result in different phenotypes, ranging from mild to severe forms of the same condition.
An example is Lamin A (LMNA) mutations.
Define penetrance.
The probability that a person with a mutant allele will express the disease phenotype; can be variable.
Non-penetrance means a person inherits the allele but is unaffected.
What is age-related penetrance?
Initially low penetrance that increases with age, often due to accumulation of harmful gene products.
An example is Huntington disease, which manifests later in life.
What are modifier genes?
Genes that influence disease penetrance and can lead to variability in phenotypes among individuals with the same causal mutation.
For example, different mutations in hypertrophic cardiomyopathy (HCM) can lead to varying degrees of heart muscle thickening.
How can modifier genes be identified?
Through genome-wide approaches or candidate gene approaches.
Examples include studying variations in the ACE1 gene in HCM.
What is the etiology of achondroplasia?
Achondroplasia is caused by mutations in FGFR3 and is the most common cause of human dwarfism.
It is an autosomal dominant disorder characterized by a Gly380Arg substitution.
