1-15-25 Flashcards
lecture 2 yyPGx Basics
what is an allele?
the DNA sequence at a locus of one of the two homologous chromosome
what is a genotype?
the combination of alleles at the same locus of the homologous chromosomes in a genome/cell
what is a homozygote?
pair of identical alleles at the locus
what is heterozygote?
two different alleles at the same locus
what is hemizygous/hemiygote?
one allele present while another allele is missing
genotype is still heterozygous
what is mendel’s law?
each of the parents passes a randomly selected allele to the offspring via the law of segregation
what is single nucleotide polymorphism (SNP)?
when a single nucleotide is changed to another
most common variation and accounts for 90% of all differences
most PGx polymorphisms
what are the types of SNPs?
non-synonymous SNP
synonymous SNP
noncoding region SNPs
what is non-synonymous SNP?
changing amino acid in the protein
either missense or nonsense
what is missense SNP?
amino acid substitution
could lead to either gain or loss of function for the protein depending on what amino acid it changes to
what is a nonsense SNP?
amino acid changes to a stop codon leading to loss of function
what is synonymous SNP?
does not change amino acids and usually does not change gene/protein function
also referred to as silent SNP
what is non-coding region SNP?
itronic SNP, SNP in the gene flanking regions and intergenic regions, or SNPs in the UTR region
what is a copy number variation (CNV)?
when a DNA region has 0-n copies in a population
structural variation
makes each chromosome longer or shorter
what is indel polymorphism?
insertion/deletion
causes frameshift of the open reading frame leading to truncate protein for degradation
what is a truncate protein?
loss-of-function
Nonsense mutation results in a similar consequence
what are the changes associated with CNV?
7 copies of CYP in genome in transcription
70K drug molecules metabolize
GAIN-OF-FUNCTION
what are the changes associated with repetitive DNA variation?
makes 50 copies of mRNA in transcription
5K drug molecules metabolized
LOSS-OF-FUNCTION
what are the changes associated with missense?
results in either GoF or LoF
hyperactivation of protein that metabolizes 15K drug molecules
what is the changes associated with nonsense?
LoF
truncated non-functional protein
non-function protein all degraded thus 0 metabolized drug molecules
what is the rs number?
reference SNP
what encompasses a gene name?
the super family (CYP), family (2), subfamily (C), and isoform (19)
what does 1A mean in the CYP2C19* protein?
no change
normal function
what does 2D mean in the CYP2C19* protein?
splicing defect
LoF
what does 3A mean in the CYP2C19* protein?
nonsense (stop codon)
LoF
what does 17 mean in the CYP2C19* protein?
missense (point mutation)
GoF
