E9 and E10. Genetics and pharmacy

Question 1

importance of genetics in pharmacy?

Answer 1

personalised medicine

Question 2

most diseases are caused by what?

Answer 2

genetic and environmental component. Very rarely only genetic unless inbreeding.

Question 3

phenotype

Answer 3

variant of characteristic in an individual

Question 4

allele

Answer 4

one of the different variants of a gene

Question 5

polymorphisms (variants)?

Answer 5

differences in the DNA between alleles

Question 6

Genotype?

Answer 6

combination of alleles in the DNA sequences of individual

Question 7

chromosome for female

Answer 7

XX

Question 8

chromosome for men

Answer 8

XY

Question 9

Why do X linked mutations have a sex bias?

Answer 9

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)

Question 10

genetic variation can be…

Answer 10

dominant, recessive, X-linked or mitochondrial (one note)
-most are recessive and rare
-mitochondrial mutations are inherited from mother only

Question 11

Describe mitochondrial mutation

Answer 11

-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

Question 12

what does meiotic recombination do?

Answer 12

reshuffle gene variant. Each chromosome is inherited from a parent but they are not identical to the parental chromosomes (one note)

Question 13

Describe gene mapping

Answer 13

-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)

Question 14

How are genes mapped?

Answer 14

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

Question 15

how are common and complex diseases mapped to genes?

Answer 15

-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

Question 16

what is next generation sequencing?

Answer 16

speeding up the process enormously and bring down the cost of whole genome sequencing, potentially making mapping a matter of weeks

Question 17

what is a bottleneck

Answer 17

event that drastically reduces a population

Question 18

what are currently 2 bottlenecks in the genomic revolution?

Answer 18

-obtaining enough DNA samples (with good clinical data and patient permission)
-analysing the huge amount of data

Question 19

Describe the human genome

Answer 19

Diploid, 46 chromosomes, 44 autosomal chromosomes, 2 sex chromosomes (XX, XY)

Question 20

Genetic causes of diseases are caused by?

Answer 20

protein coding and non- coding regions (introns and extrons)

Question 21

Detailed analysis shows that most of our DNA is transcribed into…

Answer 21

RNA, although some of these transcripts are very unstable (mRNAs with short open reading frames, long non-coding RNAs, IncRNAs, microRNA genes)

Question 22

what do regions that don’t code for proteins or functional RNA do?

Answer 22

can regulate transcription (eg promoters) and affect RNA production from neighbouring genes

Question 23

what is a pharmacogenetic variant?

Answer 23

polymorphism that is linked to the efficacy or toxicity of a drug

Question 24

pharmacogenetic variants can be…

Answer 24

dominant, recessive, X-linked or mitochondrial

Question 25

what is Aminoglycosides?

Answer 25

Aminoglycosides (e.g. streptomycin) are antibiotics that act on the bacterial ribosomal RNA (more in Bacterial and Fungal Infections)

Question 26

what is the problem with Aminoglycosides

Answer 26

-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

Question 27

are somatic mutations inherited?

Answer 27

no, only mutations in reproductive cells

Question 28

what is a common feature of cancer?

Answer 28

overactivation of receptor kinases. We want to make drugs to inhibit this

Question 29

what is responsible for a variety of cancers?

Answer 29

-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

Question 30

what is a philadelphia chromosome abnormaility and why is this a problem?

Answer 30

-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)

Question 31

why do private genetic tests need to be regulated?

Answer 31

-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