quiz 1 Flashcards
Pharmacogenomics is the study of the impact of — on medication response.
genetic polymorphisms
While the discovery of genetic contributions to medication response dates back to the —, interest in clinical pharmacogenomics began in earnest with the sequencing of the human genome in —–
- 1950s
- 2003
The International HapMap Project followed the Human Genome Project and aimed to identify common patterns of heritability, called —-, in the human genome.
haplotypes
AUTOSOME (AUTOSOMAL)—any chromosome other than the
sex chromosomes or the mitochondrial DNA.
genome is the total genetic material contained within the chromosomes of an organism. In humans —— make up the genome, and almost all cells contain an entire copy of the genome
46 chromosomes (23 pairs of chromosomes)
Survey of several genetic variants in different individuals to study if there is an association with traits such as disease susceptibility or how individuals respond to certain drugs.
GENOME-WIDE ASSOCIATION STUDY (GWAS)
Any genetic variation in the DNA sequence is called
Polymorphism/variant- the terms can be used interchangeably.
Humans have two different genomes:
-a nuclear genome (— base pairs)
-a mitochondrial genome (— base pairs)
- ~3.2 billion
- ~16,500
Human genome contains about – to – genes
19,000 to 20,000
– % of the genetic makeup of human beings is the same
– % variation that makes each individual unique
99.9%
0.1%
—- Statement on the Pharmacists Role in Clinical Pharmacogenomics
ASHP Statement
DNA for genotyping can theoretically be obtained from any nucleated cell in the body
Most common sources:
- ?
- ?
Other methods include:
- ?
- ?
-Buccal swabs
-Blood samples to isolate lymphocytes
Other methods include:
-Saliva samples
-Skin biopsies
hereditary genetic variations are called:
germline mutations
Acquired genetic variations are called:
somatic mutations
- they CANNOT be passed to the next generation
The influence of heredity on medication response was demonstrated as early as 1956 with the discovery that an inherited deficiency of glucose6phosphate dehydrogenase (G6PD) was responsible for hemolytic reactions to the —- drug.
antimalarial drug primaquine.
Pharmacogenomic variations have a——-inheritance pattern
germline/hereditary
Most pharmacogenes expressions are —-
co-dominant
Function of both alleles of the gene make up a person’s —–
phenotype
before Human Genome Project, which location was used to locate pharmacogene ?
Cytogenetic location:
-for example chromosome 4
short arm: 4p
long arm: 4q
The Human Genome Project, an international research effort completed in —, determined the ——- for each human chromosome.
- 2003
- sequence of nucleotides
-This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes.
so cytogenic location is LESS SPECIFIC
A gene’s molecular address pinpoints the:
- location of that gene in terms of nucleotides.
- the gene’s precise position on a chromosome.
- the size of the gene.
Mendel’s work suggested that ——
just two alleles existed for each gene
which testing platform is used for next-generation sequencing
Whole Genome Sequencing (WGS)
which testing platform is used for identifying Single Nucleotide Polymorphism (SNP) and other variation
Variant specific testing
what are the 4 pharmacogenomic resources
- US FDA medication labels.
- CPIC guidelines (clinical pharmacogenetics implementation consortium)
- pharmacogenomics knowledgebase.
- pharmacogene variation consortium
DNA and RNA are polymers composed of long strands of similar units (nucleotides) connected to each other via —- bonds
covalent phosphodiester bonds
Primes are used in the numbering of the ring positions in the — to differentiate them from the ring positions of the —–.
- sugars
- bases
Both sugars (ribose and deoxyribose) have an —- as a member of the five-member ring
oxygen
- the —carbon is outside the ring.
-The sugars differ only in the presence or absence (“deoxy”) of an oxygen in the – position.
-5′
-2′
-This minor distinction between RNA and DNA dramatically influences their function.
Two DNA strands are held together by bonds between —-.
nucleotide bases
(nucleotide nitrogenous bases)
One of the forces holding the two strands together are —- bonds formed between the nucleotide bases of the opposite strands called base pairs.
-hydrogen
-(A and T form two and C and G form three hydrogen bonds).
Genomic DNA (gDNA) is associated with many proteins, among them —- that help organize these macromolecules into chromosomes.
histones
The phosphate functional group (PO4) gives DNA and RNA the property of an —
acid (a substance that releases an H+ ion or proton in solution) at physiological pH, hence the name “nucleic acid.”
The linking bonds that are formed from phosphates are — that have the property of being stable
esters
(phosphodiester bonds).
what are differences between nucleosides and nucleotides ?
nucleoside does not have a phosphate, only sugar and base.
The basic unit of DNA is a
deoxyribonucleotide.
- The symbol 5′ refers to the carbon in the sugar to which a phosphate (PO4)
functional group is attached. - The symbol 3′ refers to the carbon in the sugar ring to which a hydroxyl (OH) functional group is attached.
- 5’ phosphate (PO4)
- 3’ hydroxyl (OH)
The asymmetry of the ends of a DNA strand implies that each strand has a
—- determined by which end bears the 5′-phosphate and which end bears
the 3′-hydroxyl group.
- polarity
- This 5′ → 3′ directionality of a nucleic acid strand is an extremely important property of the molecule.
DNA sequence is written with the 5′ end to the –, and the 3′ end to the —. This is also the direction of synthesis
- left
- right
A 5′OH of one deoxyribonucleotide unit binds to the 3′OH of another unit via a
phosphodiester bond
new strand of DNA is synthesized from ——-(directions), Nucleotides are added one at a time to the ——–end of the DNA chain, forming new phosphodiester bonds.
5′ to 3′
-3′ hydroxyl end
Deoxynucleoside 5′ triphosphates (dNTPs) are the building blocks. The terminal two phosphates are lost in the reaction, making the reaction essentially ——–
irreversible
The number of —– is used as a measure of length of a double-stranded DNA.
base pairs (bp)
In practice, the unit of length used for DNA is the
—–, corresponding to 1000 base pairs, or the ———–corresponding to 1,000,000 base pairs
-kilobase pair (kb or kbp)
-megabase pair (Mb or Mbp)
DNA polymerase can catalyze the formation of a phosphodiester bond between the first —- group of a NEW dNTP and the ——- group of the LAST nucleotide in the newly synthesized strand.
- 5′-phosphate
- 3′-hydroxyl
- it canNOT work in the opposite.
DNA polymerases catalyze the synthesis of new DNA strands by adding a complementary nucleotide to the ——- group on the – end of the growing DNA strand, and they also correct errors that occur during DNA synthesis.
hydroxyl group on the 3′ end
– Mitochondria have a small amount of their own DNA: mitochondrial DNA (mtDNA)
Small: ~16,500 DNA base pairs
37 genes:
-13 genes provide instructions for making ENZYMES involved in ——–
-24 genes provide instructions for making ———.
- oxidative phosphorylation.
- tRNA, rRNA
—– are the basic unit of heredity and play a role in determining most characteristics of an organism.
genes
—– are the basic unit of heredity and play a role in determining most characteristics of an organism.
genes
—– are the basic unit of heredity and play a role in determining most characteristics of an organism.
genes
—– are the basic unit of heredity and play a role in determining most characteristics of an organism.
genes
Most multicellular organisms possess—- of each chromosome.
two copies
The number of human protein-coding genes is estimated to range between — and —–
20,000 and 25,000.
During DNA — and —, the strands of the helix must separate transiently and reversibly.
replication and transcription
DNA replication is termed ——- as each newly synthesized double stranded DNA is made of one old and one new strand of DNA.
semi-conservative
- Several proteins and enzymes participate in DNA replication, including ——— enzymes that are equipped with proofreading and repair systems.
- what enzyme is responsible for transcription of genes ?
- DNA polymerases (REPLICATION)
- RNA Polymerase (TRANSCRIPTION)
Nucleotide sequence located upstream of a gene: what is it called?
Promoter region: Where RNA polymerase binds at the 5’ UPSTREAM to start the transcription of a gene
Transcription and translation are known as ————-
gene expression
genes also have regulatory sequences located before or upstream (5′) of the coding sequence called ———, and after or downstream (3′) of the coding sequence called ——-. These untranslated regions are transcribed into mRNA but are not translated into amino acids
- 5′ untranslated region (5′ UTR)
- 3′ untranslated region (3′ UTR)
ribosomes are made of —%protein and —%RNA.
-30 - 40% protein
-60 - 70% rRNA
The way the codons are read depends on the first nucleotide that is read in the sequence, and each of the three possible ways of reading a nucleotide sequence is a ——
reading frame
——— gene codes for the —— enzyme which is responsible for the metabolism ~10% of drugs currently in clinical use
CYP2C19
examples of drugs metabolized by CYP2C19
clopidogrel and voriconazole
