E9 and E10. Genetics and pharmacy Flashcards
importance of genetics in pharmacy?
personalised medicine
most diseases are caused by what?
genetic and environmental component. Very rarely only genetic unless inbreeding.
phenotype
variant of characteristic in an individual
allele
one of the different variants of a gene
polymorphisms (variants)?
differences in the DNA between alleles
Genotype?
combination of alleles in the DNA sequences of individual
chromosome for female
XX
chromosome for men
XY
Why do X linked mutations have a sex bias?
Because men have only one X chromosome, recessive alleles on the X chromosome affect them more often:
X linked mutations or variants have a sex bias e.g colour blindness (one note)
genetic variation can be…
dominant, recessive, X-linked or mitochondrial (one note)
-most are recessive and rare
-mitochondrial mutations are inherited from mother only
Describe mitochondrial mutation
-Most mitochondrial proteins are encoded in the nucleus
-Mitochondria have a small genome on a circular chromosome of their own
-Multiple mitochondrial genomes are inherited from the mother in the egg, descended from 10-20 original copies
-Mitochondria are frequently involved in drug metabolism, and the mitochondrial genome has a greater importance for pharmacology than its small size indicates
-Mitochondrial inheritance of variants often has gradual effects, because the ratio between variants changes by accident
-ONE NOTE FOR DIAGRAM
what does meiotic recombination do?
reshuffle gene variant. Each chromosome is inherited from a parent but they are not identical to the parental chromosomes (one note)
Describe gene mapping
-an inherited trait is attributed to a certain gene
-Genetic mapping is based on linkage, the fact that polymorphisms are more likely to be inherited together if they are close together on the same chromosome. During meiotic recombination, the closer they are together, the more likely they are not recombined (ONE NOTE)
How are genes mapped?
thousands of polymorphisms have to be examined in this way to find the gene responsible for a genetic condition. Today, typically using modern microarray techniques (SNP-Chips). This type of study is called genome wide association studies
how are common and complex diseases mapped to genes?
-most modern families are too small and too genetically diverse to discover the genetic risk factors for common diseases
-most common diseases have multiple cases (genetic and environment)
-alternative is to study a whole population to see if a SNP occurs more frequently in people with a disease
what is next generation sequencing?
advanced technology used to speed up the process enormously and bring down the cost of whole genome sequencing, potentially making mapping a matter of weeks
what is a bottleneck
event that drastically reduces a population
what are currently 2 bottlenecks in the genomic revolution?
-obtaining enough DNA samples (with good clinical data and patient permission)
-analysing the huge amount of data
Describe the human genome
Diploid, 46 chromosomes, 44 autosomal chromosomes, 2 sex chromosomes (XX, XY)
Genetic causes of diseases are caused by?
protein coding and non- coding regions (introns and extrons)
Detailed analysis shows that most of our DNA is transcribed into…
RNA, although some of these transcripts are very unstable (mRNAs with short open reading frames, long non-coding RNAs, IncRNAs, microRNA genes)
what do regions that don’t code for proteins or functional RNA do?
can regulate transcription (eg promoters) and affect RNA production from neighbouring genes
what is a pharmacogenetic variant?
polymorphism that is linked to the efficacy or toxicity of a drug
pharmacogenetic variants can be…
dominant, recessive, X-linked or mitochondrial
what is Aminoglycosides?
Aminoglycosides (e.g. streptomycin) are antibiotics that act on the bacterial ribosomal RNA (more in Bacterial and Fungal Infections)
what is the problem with Aminoglycosides
-A polymorphism in the mitochondrial ribosomal RNA is linked to deafness after treatment with aminoglycoside antibiotics
-Some mutations in 12S ribosomal RNA gene (MTRNR1) make the mitochondral ribosome sensitive to aminoglycosides
-The structure of the mitochondrial ribosome is closer to the bacterial ribosome than to the human ribosome
-People with sudden deafness in their maternal line should consider being tested before taking aminoglycosides and/or use alternative antibiotics
are somatic mutations inherited?
no, only mutations in reproductive cells
what is a common feature of cancer?
overactivation of receptor kinases. We want to make drugs to inhibit this
what is responsible for a variety of cancers?
-Many cancer genetic studies indicate that somatic mutations in kinases are responsible for a variety of cancers
-Kinase inhibitors are among the most promising new classes of cancer drugs
what is a philadelphia chromosome abnormaility and why is this a problem?
-The Philadelphia chromosome abnormality results from a translocation in somatic cells
-Generation of a fusion gene in a blood stem cell generates a tyrosine kinase that causes leukemia
-This dominant mutation is usually not present in the germ line (=somatic mutation)
-The disease is now treated with the tyrosine kinase inhibitor imatinib (Glivec, Novartis)
why do private genetic tests need to be regulated?
-Web-based genetic testing companies are providing tests for specific genes at steadily decreasing costs (e.g. ancestry tests, paternity tests, genetic disease tests)
-It is unethical to submit someone else’s DNA without consent, so controlled sampling may become the norm
-Many people still want to know about their genetic risks for disease. Properly trained pharmacists could help
