Mendelian Genetics and Non-Mendelian Flashcards
Autosomal Dominant: definition transmission gender biases expression hot spots
- only one copy of an allele is required to express the phenotype
- vertical transmission
- ratio of females: males affected is 50:50
- disorder may arise as a de novo mutation
- variable expression
clinical manifestations of autosomal dominant disorders:
expressivity
penetrance
- variably expressive, even within the same family
- penetrance is the heterozygous population that shows phenotypes of the disorder (can be complete or reduced)
- de novo: often found at hot spotsin the genome. the rate of mutations increases with paternal age due to increased number of cel divs to produce sperm
autosomal recessive inheritance: definition parents family history gender biases ethnicity expressivity penetrance
- two copies of a mutated gene are needed to express a given phenotype
- parents of affected are typically heterozygotes
- family history may be negative
- equal among male and femal
- evaluate for consanguinity in the family
- may be an ethnic disposition
- less clinical variability
- penetrance is usually complete
X-linked recessive: definition gender biases transmission restriction generations carrier female characteristics obligate carriers
- mutated allele is only found on the X chromosome and hemizygous males and homozygous females are affected
- much higher incidence in males than females
- male to male transmission does not occur
- multiple generations are often affected
- carrier females may show mild or variable expression of the trait
- obligate carries are women who through family history have to have the gene, these are daughters of affected men
lyonization (X inactivation):
definition
cell bias
cell division
- only one X chromosome is active in each somatic cell of a female mammal
- inactivation occurs ranmdomly in embryonic life
- either the paternal or maternal X can be inactivated
- once this has occured in a cell, any cell derived from that cell will have the same X inactivated (random but fixed)
X linked recessive disorders in females
-slewed X inactivation can cause carriers to be symptomatic
symptoms tend to be less severe than in fully effected males
X linked dominant: definition gender bias gender "seriousness" gender transmission restriction prevalence
- only one copy of the X linked mutation is required to confer the phenotype
- females are much more likely to be affected
- often lethal in males (usually prenatal)
- male to male transmission is not observed
- much less common than x linked recessive
mtDNA: definition encodes structure transcription inheritance
- mitchondrial DNA, encodes some of the proteins necessary for oxidative phosphorylation (most are on genomic)
- circular, hundreds of copies per cell as there are hundreds of mitochondria
- transcription takes place in the mitochondria and is independent of the nucleus
- passed on maternallty
heteroplasmy and homoplasmy
- heteroplasmy: mixture of normal and abnormal mitochondrial DNA
- homoplasmy: all mtDNA is the same (whether normal or abnormal)
separation of mtDNA during cell division
-this is completely random and due to the location of each indiviual mitochondria during the division process
change in mutant mtDNA over time
-this could be due to chance variation (genetic drift) or because of selective advantages (replicative) of the wild type mtDNA (smaller mtDNA might multiply faster)
threshold effect
- certain number of abnormal mtDNA molecules may be tolerated without symptoms
- however, there is a threeshold for this number and when this is reached, symptoms appear
age effect and mitochondria description hypothesis on cause, 2 effect theory on aging
- it is postulated that mitochondrial function decreases with age
- this could be due to free radicals from ox phos, increased mutation rate due to lack of DNA repair enzymes
- this could result to a worsening of a genetic mitochondrial diseae with age
- loss of mitochondrial function may contribute to the aging process in general
organ systems most effected by genetic mitochondrial disorders
- organ that require a large amount of energy to function
- central nervous system, skeletal muscle, eye muscle, heart
- less commonly GI, pancreas, BM, autonomic NS
diagnosis of mitochondrial disorders
not straight forward, often a muscle biopsy for anzyme or mtDNA analysis is needed but ften not definitive
-this process is complicated by heteroplasmy
