mutation
a change in a DNA sequence that is rare in a population and typically affects the phenotype also known as gene variant
refers to the process of altering a DNA sequence
loss-of-function
mutation when the gene's product is reduced or absent
gain-of-action
mutations that are dominant cause this mutation
polymorphism
involves the presence of two or more variants of a particular DNA sequence
single nucleotide polymorphism
disorder being studied in the human genome to have correlations with disease, drug response, and other phenotypes
mutation
refers to genotype wherein there is a change at the DNA or chromosomal level
essential to life while it produces individuals with variant phenotypes who have more ability to survive specific environmental challenges, including illness.
mutant
refers to the phenotype
germline mutation
occur in different stages of cells, starting from germ cells to sex cells
change that occurs during DNA replication that precedes meiosis
resulting gamete and all the cells that descend from it after fertilization have the mutation in every cell in the body
transmitted to the next generation of individuals, since it is a heritable change in the DNA of a germ cell
somatic mutation
occur in a single body cell due to the exposure to external environmental factors and cannot be inherited
also known as acquired mutations
happens during DNA replication before mitotic cell division and is passed to the next generation, not individuals
sickle cell disease
results from a single DNA base change in the b-globin gene, which replaces glutamic acid (6th position) with valine
altered surface of hemoglobin allows molecules to link in low oxygen conditions which creates sickle shape of RBC
causes anemia, joint pain, and organ damage when RBC becomes lodged in small blood vessels
sickle cell anemia
single DNA base change that substitutes one amino acid in the protein (Valine replaces Glutamic acid).
this changes the surface of the molecules, and they aggregate into long curved rods that deform the RBC forming a sickled cell
collagen
major component of connective tissues - bone, cartilage, skin, ligament, tendon, and tooth dentin
triple helix of two a1 and one a2 polypeptides
structure of collagen
alport syndrome
interferes with tissue boundaries causing deafness and inflamed kidneys
aortic aneurysm
missense mutation where Arginine replace Glycine in 𝞪1 gene causing aorta to burst
chondrodysplasia
deletion, insertion or missense mutation where glycine is replaced by bulky amino acids causing deformed joints and stunted growth
dystrophic epidermolysis bullosa
collagen fibril that attach epidermis to dermis breakdown causing skin blisters on any touch
ehler's danlos syndrome
missense mutation where glycine is replaced by bulky amino acids causing stretchy, easy scarred skin and lax joints
osteoarthritis
missense mutation where Arginine replace Cysteine in 𝞪1 gene causing joint pains
osteogenesis imperfecta
inactivation of 𝜶 allele reduces collagen triple helix b 50% causing deafness, easily broken bones and blue eye sclerae
stickler syndrome
nonsense mutation in procollagen causing joint pains, degeneration of vitreous gel and retina
spontaneous mutation
result from errors in DNA replication where DNA bases have slight chemical instability
formula for the mutation rate of autosomal genes
crossing over
exchange of genetic material between non-sister chromatids of homologous chromosomes during meiosis
induced mutation
caused by mutagens, which many are also carcinogens that may cause cancer
site-directed mutagenesis
changing a gene in a desired way
ames test
discovered by Bruce Ames to identify mutagens in the 1970s
bacteria are exposed to test substances, then its growth on media without histidine is recorded
prototrophic
refer to reverse mutation
(1) workplace, (2) industrial accidents, (3) Chernobyl, (4) medical treatments, (5) weapons, (6) natural sources, (7) cosmic rays, (8) sunlight, (9) earth's crust
places where mutagen exposure may happen
point mutations / splice-site mutation
change of a single nucleotide
transition
purine replaces purine or pyrimidine replaces pyrimidine
ex. A to G or G to A / C to T or T to C
transversion
purine replaces pyrimidine or pyrimidine replaces purine
ex. A or G to T or C / T or C to A or G
missense mutation
replaces one amino acid with another
nonsense mutation
changes a codon for an amino acid into a stop codon
splice site mutations
alters a site where an intron is normally removed from mRNA
deletion
removal of genetic materialin
insertion
addition of genetic material
tandem duplication
insertion of identical sequences side by side
pseudogenes
DNA sequence similar to a gene but which is not translated
may have evolved from original gene by duplication and acquired mutation
myonic dystrophy
triplet repeat disease
worsens with each generation while the gene expands on Chromosome 19 that has an area of several repeats of the DNA triplet CTG
copy number variants
sequences that vary in number from person to person that range in size from a few bases to millions
account for about 25% of our genome
globlin mutation
mutation that can cause anemia with or without sickling of RBC, or cause cyanosis
considered as clinically silent, having no effect at all
alter hemoglobin's oxygen binding capacity
silent mutation
mutations that do not alter the encoded amino acid
missense mutation
alters the encoded amino acid to another amino acid
conditional mutation
produces a phenotype under particular conditions or environments
photoreactivation repair
enzymes called photolyases use light energy to break the extra bonds in a pyrimidine dimer
enables UV-damaged fungi to recover from exposure to sunlight. Humans do not have this type of repair
excision repair
type of repair wherein pyrimidine dimers and surrounding bases are removed and replaced
p53
transcription factor that binds to defined consensus sites within DNA
repress genes involved in cell growth stimulation while activating alternate genes involved in cell cycle control
has a significant role in growth arrest before either DNA replication in the G1 phase or before mitosis in the G2 phase
MDM2
a p53-inducible phosphoprotein that binds to the N-terminus of p53 and negatively regulates its activity
(1) Phe19, (2) Trp23, (3) Leu26
amino acids essential for the transactivation of p53