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

of new cases / 2X

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