Genetics Flashcards
3 categories of genetic DOs
mutation in a single gene with large effects (Mendelian DOs)
chromosomal DOs
Complex multigenic DOs
Mendelian DOs
rare, high penetrance
Sickle cell anemia: strong selective forces (malaria) maintain mutation in population
Chromosomal DOs
structural or numerical alterations in autosomes and sex chromosomes
uncommon
high penetrance
Complex multigenic DOs
more common
Low penetrance
environment and gene interactions (aka polymorphisms)
no single gene necessary or sufficient to produce disease
Examples of complex multigenic DOs
atherosclerosis, diabetes, hypertension, autoimmune diseases, ht and wt
Mutation
permanent change in the DNA
Germ cell mutations give rise to
inherited disease
Somatic cells give rise to
cancer and some congenital malformations
Point mutations within coding sequence
Missense: alter meaning of sequence of encoded protein (sickle cell–>Glu to Val)
Nonsense: stop codon
Mutations in non-coding sequences
promotor or enhancer sequences
defective splicing of intervening sequences
no translation
transcription factors
3 most common transcription factors
MYC, JUN, p53
Deletions and insertions
if multiple of 3, reading frame is intact–>abnormal protein
Frameshift mutation
deletion or insertion not in a multiple of 3–>altering of reading frame
Trinucleotide repeat
amplification of a sequence of 3 nucleotides
almost all contain guanine and cytosine
Anticipation
a genetic disorder is passed on to the next generation, the symptoms become apparent at an earlier age with each generation
increase in severity of symptoms
Huntington’s disease, myotonic dystrophy
Mendelian disorders
every individual is a carrier of 5-8 deleterious genes, most are recessive and no serious phenotypic effects
Codominance
both alleles contribute to phenotype
Pleiotropism
single mutant gene–>many end effects
Genetic heterogeneity
mutations at several loci may produce the same trait
Autosomal dominant (AD) DOs
manifest in the heterozygous state (only one gene affected) so 1 parent is usually affected
New mutations in AD DOs
seem to occur in germ cells of relatively older fathers
if disease decreases reproductive fitness, then most cases would have to be from new mutations
Incomplete penetrance
positive mutation but normal phenotype
Variable expressivity
all positive traits, but expressed differently
Example of variable expressivity
Neurofibromatosis type 1: can have or not have cafe-au-lait spots, skeletal deformities, and/or neurofibromas