WEEK 4.pdf

GENOMIC VARIATION & SINGLE NUCLEOTIDE POLYMORPHISMS(SNPs) MUTATION CLASSIFICATIONS ◦ Gene mutations ⁃ most common of genetic disorders ⁃ Types: point mutations and single nucleotide substitutions ◦ Chromosome mutations ⁃ Rearrangement of chromosomal material ◦ Genome mutations ⁃ Los...

GENOMIC VARIATION & SINGLE NUCLEOTIDE POLYMORPHISMS(SNPs) MUTATION CLASSIFICATIONS ◦ Gene mutations ⁃ most common of genetic disorders ⁃ Types: point mutations and single nucleotide substitutions ◦ Chromosome mutations ⁃ Rearrangement of chromosomal material ◦ Genome mutations ⁃ Loss or gain of whole chromosomes NATURE OF NUCLEOTIDE SUBSTITUTION ◦ Substitution location affects impact ◦ Diff. Selective Contraints: ⁃ Structural genes: if mutated affects physical structure of organism ⁃ Synonymous variant: no change in amino acid sequence ⁃ Example: UCU, UCC, UCA,UCG all codons for serine even w/ alter ⁃ Non-synonymous variant: change in amino acid (AA) sequence ⁃ Example: AUC - Isoleucine to AUG - methionine altered the AA ⁃ Noncoding regions: when and how often a gene will be transcribed CODING POINT MUTATIONS ◦ Nucleotide change at one point in genome ◦ Transition: purine to purine, pyrimidine to pyrimidine (changing like to like) ⁃ 2x more frequent in coding regions ⁃ Single ring structure substitution - more likely ◦ Transversion: Purine to pyrimidine or vice versa (changing into opposite) ◦ Ratio of transition to transversion can tell if you’re looking at coding region CONSEQUNCES OF POINT MUTATIONS ◦ Missense: AA sequence changes (look at chart below for groups/properties) ⁃ Conservative: replacing AA with another AA that has the same qualities ⁃ Non-conservative: replacing AA with another AA that has diff. qualities ⁃ Example: AUC - Isoleucine changed to AUG - Methionine (diff. qualities) ◦ Nonsense: makes STOP codons ◦ Silent: AA sequence stays the same (like synonymous nucleotide variant) CODON USAGE BIAS ◦ Codons that appear frequently ◦ Synonymous condons occur at different frequencies INSERTIONS AND DELETIONS ◦ Large section of chromosomes can be duplicated or deleted ◦ Larger changes than copy number variations (CNVs) ⁃ Observable under microscope (karyotype) ◦ Cytogenetics: study of chromosomes under different colors “chromosome paint” FRAME SHIFT INDEL ◦ Removal or addition of nucleotide(s) that change codon reading frameshift ⁃ Results in large change in protein structure and/or function INSERTIONS AND DELETIONS ◦ Accounts for >15% of human genetic polymorphism ⁃ Microindels: indels that are