Mutation and Polymorphism Flashcards
DNA is what percent identical b/w individuals
99.9% identical
only a small fraction that is different is responsible for human genetic variability
some differences= little/no effect
some differences- disease or death
B/w the extremes- narmal variation b/w people
Categories of mutation
What is a mutation
Genome mutations create?
Chromosome mutations do what?
Gene mutations do?
Mutation is any change in nucleotide sequence or DNA arrangement
Genome Mutation- create aneuploidy
Chromosome Mutations-alter structure of individual chromosomes
Gene muation- alter genes
Range from single nucleotide ot millions of bps
Germ Line Mutation
VS
Somatic Mutation
Occurs during gamete formation- perpetuated to offspring
Creates somatic mosaicism- not tx to offspring
Origin of Mutations
Genome Mutations?
Chromosome mutations?
Gene Mutations?
2 mechanisms?
Genome mutaions - mis segregation causing monosomy or trisomy
Chromo- rarely perpetuated, as normally incompatible with survival
bp subs, insertions or deletions
DNA replication error or problem during DNA repair
Origin of mutations
DNA Replication errors
Majority rapidly repaired by repair enzymes
recognize incorrect strand and replace nucleotide
w.o proofreading level of mutation would be intolerable
Origin of mutation
Repair of DNA damage
10k-100k nucleotides damaged per day
some bu not all damage is repaired
repair machinery may misread comp strand and create mutations
Nucleotide Substitutions
Missense
Missense mutations- point mutations alters triplet, replaces one aa with another
alters sense of coding strand
ex hemoglobinopathies
can cause dz when outside coding region
Nucleotide Substitutions
Chain Termination Mutations
cause normal codon to become termination codon
translation ceases- partially translated polypeptides
Creates unstable mRNA, and unstable trunctated proteins
also can destory termination codons
Deletions and Insertions
Small number of nucleotides to large segments
small detected by nucleotide sequencing
large detected by southern pr PCR
rare deletions large enough to be seen on karyotype
Small deletions and insetions
not a multiple of 3?
Multiple of 3?
frameshift mutation
add or delete aa
Deletions and Insertions
LARGE DELETION AND INSERTIONS
generally uncommon
DMD, alpha thalassemia
Insertion much rarer than deletion
Deletion and Insertion
Effects of Recombo
Deletion or duplication by recomb
normally d/t unequal crossing over
deletion of alpha globin gene in some alpha thalasemmias
DYNAMIC MUTATIONS
involve what
Amplification of trinucleotide repeat sequence
Huntingtons, fragile x
repreat can be coding or in transcribed by untranslated region
repeat may expand during gametogenesis = fynamic mutation
Estimates of germ line mutation rates
number of new mutation per locus per generation
measure indcidence of new, sporadic causes of autosomal dom or x linked disease
Sex differences in mutation rates d/t?
d/t differences in rate and timing of sperm vs oocyte formation
RFs differ b/w sexes
females: non disjunct with age
Males: rep erors with age
