C12 Genetics

mutation

change in DNA sequence that typically affects phenotype

polymorphism

'many forms': change in gene less rare than a mutation and more prevalent in a population

gene variant

includes both mutations and polymorphisms

loss of func vs gain of func mutations

loss = recessive

gain = dominant

mutant

the different phenotype

germline mutation

occurs during DNA replication prior to meiosis; transmitted to next gen

somatic mutation

happens during DNA replication prior to mitosis; only affects cells descending from changed cell.

person w this has somatic mosaicism; it doesn't affect all cells in their body (as in Proteus syndrome)

sickle cell disease

result from single DNA base change in B-globin gene. sickled RBCs destroyed in liver and spleen.

causes anemia.

thalassemia

too few beta-goblin chains; excess alpha-globin prevents hemoglobin formation. Liberated iron slowly damages heart, liver, endo glands.

Can be minor (hetero) or major (homo)

collagen

major component of connective tissue (bones, cartilage, tendon, skin). >35 genes encode >20 types

procollagen

longer precursor to collagen

Ehlers-Danlos Syndrome

mutation preventing procollagen chains from being cut. collagen molecules can't assemble, so skin becomes stretchy

allelic diseases

different disease manifestations caused by mutations in the same gene.

may arise from a mutation that affects a protein used in different tissues.

mutagen

mutation-causing agent

tautomers

alternating forms of DNA bases

gonadal mosaicism

when parent has mutation in some sperm/oocytes because spontaneous mutation occured in the developing testis/ovary

mutation rate (autosomal genes)

# of new cases/2X

X = number of individuals examined

hot spots

places in DNA where mutations are more likely to occur. include short repetitive sequences and palindromes (latter oft assoc with insertions/deletions)

induced mutations

are caused by mutagens. many are carcinogens. examples:

alkylating agents remove a base;

acridine dyes add/remove a base;

X rays break chromosomes;

UV radiation creates thymine dimers

Ames test

in vitro test of mutagenicity of substance. Bacteria exposed to test substance, growth on media ws/o histidine is recorded; bacteria only grow if mutations have occurred

missense mutation

replaces one amino acid with another

nonsense mutation

changes a normal codon into a stop codon

expanding mutation

duplication runs over and over again; repetitive sequence gets longer and longer again (F1, F2, ...)

(example: Huntington disease)

anticipation

expansion of the triplet repeat with an increase in phenotype severity with subsequent generations

transition

point mutation where purine replaces purine (GA) or pyrimidine replaces pyrimidine (CT)

transversion

point mutation where purine replaces pyrimidine and vice versa

nonsense-mediated decay

cell response to shortened proteins that result from nonsense mutations

splice site mutation

alters site where intron is normally removed from mRNA. if exon is skipped, it's called exon skipping huhhh

tandem duplication

insertion of identical sequences side by side

pseudogene

DNA sequence similar to a gene, but not translated. Crossing over between it and a functional gene can disrupt gene expression

transposons

'jumping genes' can disrupt the site they jump from/into, or alter reading frame if not multiple of 3 bases

CNVs

copy number variants; sequences that vary in number of copies from person to person. repeats called Short Tandem Repeats (STRs); more common in people with behavioral disorders

silent mutations

don't alter encoded amino acid; could be cuz of synonymous codons

conditional mutation

produces phenotype under particular conditions/environments (glucose 6-phosphate dehydrogenase deficiency, where enzyme responds to oxidants)

3 types of DNA repair

photoreactivation, excision, mismatch

photoreactivation repair

photolyases (enzymes) absorb energy from visible light and use it to detect and bind to pyrimidine dimers to break those extra bonds. Works in fungi to recover from sunlight exposure

excision repair

pyrimidine dimers & surrounding bases removed and replaced.

nucleotide excision repair: replaces up to 30 bases.

base excision repair: replaces 1-5 bases; specific to oxidative damage

mismatch repair

enzymes check newly replicated DNA for loops. incorrect base is excised and replaced

protein p53

monitors repair of DNA. if damage too severe, it promotes apoptosis

DNA repair disorders

- trichothiodystrophy

- inherited colon cancer

- xeroderma pigmentosum

- ataxia telangiectasia

trichothiodystrophy

at worst causes dwarfism, intellectual disability, brittle hair, scaly skin. only about 100 cases known worldwide; symptoms reflect accumulating oxidative damage. Result from faulty nucleotide/base excision repair or both

inherited colon cancer

defect in mismatch repair that normally keeps person's microsatellites all the same length. In group of 7 disorders known as Lynch syndrome

xeroderma pimgmentosum

autosomal recessive disorder where nucleotide excision repair's broken, or DNA polymerase is 'sloppy' so thymine dimers remain and block replication.

must avoid sunlight!

ataxia telangiectasia

autosomal recessive disorder resulting from defect in cell cycle checkpoint kinase. Have 50x risk of developing cancer over general population.