chapter 15 Flashcards
Mutation
a change in the nucleotide sequence that can be passed on from one cell or organism to another
Somatic Mutations
occur in the body cells; passed to daughter cells in mitosis but not to offspring
Germ line mutations
occur in cells that give rise to gametes; passed to offspring at fertilization
loss of function mutations
gene is not expressed at all, or protein does not function; nearly always recessive
gain of function mutation
produces a protein with altered function; usually dominant
common in cancer
new proteins stimulate cell division
conditional mutation
phenotype is altered only under certain (restrictive) conditions (example: protein may be unstable at high temperatures)
the mutation is not detectable under permissive conditions
Ex: point restriction phenotype in Siamese cats
reversion mutation
the gene is mutated a second time and DNA reverts to the original sequence or to a different sequence that results in the non-mutant phenotype
many mutations occur in nonfunctional regions of DNA and don’t affect phenotype
Point mutation
insertion or deletion of a single base pair, or substitution of one base pair for another
2 types of subs
- transition - the purine is replaced by the other purine
- transversion - the purine is replaced by a pyrimidine or vice versa
silent mutation
substitution that results in a codon a codon that codes for the same amino acid
missense mutation
substitution resulting in a codon for a different amino acid
often have no effect on protein function
nonsense mutaion
substitution results in a stop codon somewhere in the mRNA
Results in a shortened protein, usually not functional
Loss of stop mutation
base pair substitution that changes a stop codon to a sense codon; extra amino acids are added to the polypeptide
Frame shift mutation
insertion or deletion of a base pair
Alters the mRNA reading frame (consecutive triplets) during translation; produces nonfunctional proteins
mutations outside coding regions can have no effect or significant effects
- promoter mutations may alter the rate of transcription of the gene
- mutations at RNA splicing sites may lead to abnormal mRNA
chromosomal rearrangements
result in extensive changes in DNA
Break and rejoin
Can be caused by damage to chromosomes by mutagens or by errors in chromosome replication
deletion
chromosome breaks in two places and rejoins, leaving out part of the DNA
duplication
homologous chromosomes break at different positions and reconnect to the wrong partners. Can also be caused by inappropriate followed by crossing over
inversion
chromosome breaks and rejoins with one segment flipped
translocation
segment of DNA breaks off and attaches to another chromosome; can cause duplications and deletions
Downs Syndrome is caused by translocation of chromosome 21
retroviruses
inset their DNA into the host genome, viral DNA can remain there
Transposons
aka transposable elements, insert themselves into genes and cause mutations
spontaneous mutations
happen with no outside influence by many mechanisms
mistakes during replication
more likely if the template base has undergone spontaneous chem arrangement
bases can exist in diff forms
one form is rare (tautomers)
if base forms rare tautomer, can pair w wrong base resulting in mismatch pair
if mismatch repaired incorrectly or replicated before repair, causes point mutation
chem reactions can alter bases
ex: loss amino group (deamination)
meiotic errors
nondisjunction & random breaking and rejoining of chromosomes
induced mutation
agent from outside cell causing change in DNA
Mechanisms of induced mutation
chem mutagens can alter bases
some chemicals add other groups to bases
Radiation damages DNA
about 80% DNA damage can be repaired
some bases pairs more vulnerable than others
cytosine often methylated at 5’ position. If 5 meth loses amino acid, becomes thymine
mutations have benefits
provide genetic diversity for nat selection
mutations in somatic cells may benefit an organism immediately
mutations in germ lines may cause advantageous change in offspring’s phenotype
Gene duplication through transposons not always bad, is a source of genetic variation
one gene may continue in its og role and other my get a gain of function mutation
in genes whose products are needed for normal cell processes, mutations are often deleterious esp in germ line cells
somatic cell mutations can also be harmful
mutations can be expressed phenotypically as proteins
things implicated in genetic diseases
abnormalities in: enzymes, receptor, transport, and structural proteins
Loss of enzyme function: phenylketonuria
results from abnormal enzyme, phenylalanine hydroxylase which normally catalyzes the conversion of dietary phenylalanine to tyrosine
loss of enzyme function causes accumulation of phenylalanine phenylpyruvic
sickle-cell disease
one amino acid in the beta-globin polypeptide is abnormal
The abnormal protein results in sickle-shaped cells that block capillaries and impair the ability to carry oxygen
large deletions
deletions in the X chromosome that include the gene for the muscle protein dystrophin result in Duchenne muscular dystrophy
sometimes only part of gene is missing leading to partly functional protein
Chromosomal abnormalities
Gain / loss of complete chromosomes (aka aneuploidy) or segments
Fragile X syndrome is the Restriction in tip of X chromosome resulting in intellectual disability
Expanding triplet repeats
gene responsible for fragile X syndrome has repeated triplet, CGG, in promoter region
Usually repeat 6 to 54 times in normal people, 200 to 2,000 times in people with fragile X
Somatic cells and cancer
Mutations in them can lead to cancer, more than two are usually needed
Three tumor suppressor genes and one oncogene must be mutated in sequence
Many phenotypes are multifactorial
Caused by interactions of many genes and proteins with one or more factors in environment
Molecular genetic methods for detecting mutations
Restriction enzymes are when bacteriophages inject DNA into host bacteria cell causing cell to produce more virus particles
Bacteria defenses include restriction enzymes cutting DNA into smaller non-infectious fragments
More on restriction enzymes
Each type of restriction enzyme Cuts DNA at specific sequence: restriction site or recognition sequence
Bacterial restriction enzymes can be isolated and used to identify DNA sequences of other organisms
Restriction sites
If DNA from any organism is incubated into with restriction enzyme, DNA will be cut wherever restriction site occurs
DNA fragments must be separated to identify where cuts made
Reaction sites are not at regular intervals, so fragments are different sizes and can be separated by gel electrophoresis
Gel electrophoresis gives 3 types of info
Number of fragments, how many times recognition sequence occurs in Sample
sizes of fragments
relative abundance of fragments
DNA fingerprinting
Uses restriction digestion and gel electrophoresis to identify individuals based on differences in DNA sequences
Types of polymorphisms used #1: Single nucleotide polymorphisms
inherited variations in a single base (point mutation)
If SNP occurs in restriction enzyme recognition site, and enzymes don’t recognize one variant, individuals can be distinguished
Types of polymorphisms used #2: Short tandem repeats
Short repetitive sequences, usually a non-coding regions that are inherited
Polymerase chain reactions are used to amplify fragments containing short tandem repeats. fragment lengths are different and can be separated by gel electrophoresis
FBI uses 13 of these repeats loci and combined DNA index system, probability that people have the same of these 13 is small
Genetic markers
Reference points for Gene isolation. Linkage analysis allows genes to be identified
STRs & SNPs are types
Genetic screening
Test to determine if person has genetic disease, predisposed, or is a carrier
Ex: Prenatal screening, screening of newborns, screening of asymptomatic people who have relatives with genetic diseases
Screening may involve analysis for abnormal protein function
DNA testing
Direct analysis of DNA for mutations, the most accurate way to detect abnormal alleles
Any cell and body can be analyzed and PCR amplification means only few cells are needed
Testing can be done on cells from embryos or various fetal stages
DNA hybridization
Used to detect mutations
PCR amplifies regions where sequence might occur
A short synthetic DNA strand called oligonucleotide probe labeled and hybridized with denatured PCR products
