genetic mutations and repair ch.18

human gene Nkx2.5 similar to Dm tinman mutant—abnormal hearts

transcription factor for heart

Lou Gehrig Disease ALS- autosomal dominant trait. expension of sequence repeat in dna. chromosome 9. C9orf72. ALS have 770-1600 GGGGCC repaeats

gene mutations: somatic mutations and germ line mutations

types of gene mutations (based on molecular nature)

base substitutions: transition from purine-purine (A-G) and pyrimidine to pyrimidine (T to C, C to T) purines going to fit in the same wy

tranversion-pyrimdiine; purine to pyrimidine

insertions and deletions

frameshift mutations

in-frame insertions and deletions-add tripplet in rna extra amino acid. depends on struture of protien/function

expanding nucleotide repeats-may cause diseases—inc in the number of a copies of a set of nucleotides

expanding nucleotide repeats-fragile x syndrome

phenotypic affects of mutation-

phenotypic affects of mutation:

synonymous sub(silent sub though they are not always silent): produced amino acid sequence is not modified/changed.

nonsynonymous sub: nucleotid emutation alters amino acid sequnce in a protein; bio change, natural selection.

dN/dS ratio-indicates evolution of gene dN/dS < 1 the protein encoding gene is constrained indicating positive selection and important bio role.

phenotytpic effects of mutation

neutral mutation-changes the protein aa sequence but does not alter funcion

loss of function-causes complete or partial absence of normal function

gain of function-new trait

dna replication errors-mutations or be correcrte dby proofreading capability of DNA polymerase enzyme

1 error/10 bill nt

spoontaneous chem changes in dna: cyotsine (deamination)-Uracil

methylcytosine (deamination)-thymine

UV radiation-pyrimidine dimers from ultarviolet light thymine dimer, results in disorted dna

mutations caused by: transposons,

fix: dna repair mechanisms (encode genes that encode this job). mismatch, direct, base excision,nucleotide excision,homologous recomb, nonhomologous end joining

mismatch: bacteria distinguish old and new dna strands by methylatoin status. eukaryotes-unknown

direct repair change: nucleotides back to og structures.

base excision repair-modified based and then replaices one or more nucleotides. bacteria use DNA poly 1 to repair DNA. eukaryotes use DNA polymerase b to repair DNA error prone, AP has proofereding capability and removes mismatvhes bevore ligation reaction

repair mech: detect, excise, polymerization dna dependent dna poly, ligation