Autosomal Disorders Flashcards
Autosomes
Chromosomes 1-22, not sex chromosomes, source of most genetic information, majority of DNA and genes, show Mendelian inheritance patterns
Mendel’s principle of segregation
Two copies of each gene, one per offspring, equal probability for each copy
Mendel’s principle of independent assortment
Each gene inherited independently of other genes, genes affecting same function not inherited as a group
Multiplication rule of probability
Probability of multiple events occurring together, multiply the risks of each event to get overall risk
Addition rule of probability
Probability of either one or another of multiple events occurring, add risks of each to get overall risk, all add up to 1
Genotype
Genetic makeup
Phenotype
Observable results, some genes have no outward effect on an organism, expression can depend on environmental factors such as diet
Autosomal dominant disorders
About 1 in 200 people have autosomal dominant disorder, rare for affected people to mate, usually single affected parent, 50% recurrence risk, requires only one of the affected gene for disease
Autosomal dominant inheritance
Affected individuals in each generation, one parent should be affected, both sexes equally affected, father-son transmission is possible, 1/2 of children will be affected
Retinoblastoma
Dominant disorder, tumor forms in retina
Other dominant disorders
Postaxial polydactylyl, achondroplasia
Autosomal recessive disorders
Often the result of mating two carriers, result in 1/4 normal, 1/2 carriers, 1/4 affected, recurrence risk is 25% for each child
Autosomal recessive inheritance
May not be found in previous generations, male and females equally affected, 1/4 of offspring will be affected, consanguinity may be a factor (increased risk of same recessive allele in both parents)
Albinism
Autosomal recessive disorder, inability to produce melanin from tyrosine
Cystic fibrosis
Autosomal recessive disorder, disrupts chloride transport, affects pancreatic secretions due to clogging of ducts, enzymes do not reach intestine, lungs affected by thickened secretions, cannot clear material, excess chloride in sweat
Dominant vs. recessive
Homozygotes for dominant disorder are more severely affected, some disorders due to both dominant and recessive genes, categories are for traits not genes
New mutation
New mutations occur, suspected when inheritance pattern shows no other affected individuals, parentage of child is confirmed and neither parent has evidence of carrying the mutation
Germline mosaicism
Mutation occurs in one of many cells, may be in a few germ cells, cause autosomal dominant or X-linked disorders to appear in unlikely pedigrees
Delayed age of onset
Some disorders are not evident until adulthood, children are already produced, too late to make decisions
Reduced penetrance
Phenotype mild to non-existent in some individuals due to modifying genes, may affect children much more severely
Age-dependent penetrance
Combination delayed age of onset and penetrance, disorder is not obvious until adulthood and may be mild, may affect children more severely
Variable expression
Severity of disorder depends on expression, modifying genes can limit expression, appear unaffected, no guarantee that their children will have the same expression
Neurofibromatosis
Autosomal dominant with variable expression, some get only a few skin lesions, others get large tumors, “cafe au lait” spots
Pleiotropy
Multiple effects from one mutation, single gene affects multiple tissues
DNA transcription factors
Used by several specific tissues, example of pleiotropy
Extracellular matrix proteins
Expressed at different levels in different tissues, example of pleiotropy
Allelic heterogeneity
Multiple mutant forms, different effects, same gene- hemoglobin disorders, sickle cell, beta-thalassemia
Locus heterogeneity
Multiple genes affect one pathway, similar disorders but different genetics- 4 of 5 urea cycle disorders
Anticipation
Some dominant disorders are more severe in later generations, some age-delayed disorders occur earlier in succeeding generations
Repeat expansion
Short sequence of direct repeats in genes, some repeated codons, repeats get longer during meiosis, some threshold number causes disease, greater number can cause earlier and more severe disorder
