genetic variations and its role in health/ pharmacologysrivani mandaloju
Here is the reference for the above topic. I have collected the maximum information that i got from the internet. If any one need the complete information comment here.
Extrapolation of in vitro data to preclinical and.pptxARSHIKHANAM4
Extrapolation of in vitro data to preclinical.
the topic is included in m.pharmacy 1st sem syllabus. which is essential for the study and that include the details about how you deal with the preclinical data that will help to decide the NOEAL and LOEAL, the humane dose of the drug can be calculated and further formation is also done.
genetic variations and its role in health/ pharmacologysrivani mandaloju
Here is the reference for the above topic. I have collected the maximum information that i got from the internet. If any one need the complete information comment here.
Extrapolation of in vitro data to preclinical and.pptxARSHIKHANAM4
Extrapolation of in vitro data to preclinical.
the topic is included in m.pharmacy 1st sem syllabus. which is essential for the study and that include the details about how you deal with the preclinical data that will help to decide the NOEAL and LOEAL, the humane dose of the drug can be calculated and further formation is also done.
Preclinical Screening of Antiasthmatic DrugsShubham Kolge
Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This presentation intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods.
Alternative methods to animals testing are the development and implementation of test method that avoid use of live animals or use of less animals in method.
The council directive on protection of animals used for experiments and scientific purpose in article 23
“The commission and member states should encourage
research into development and validation of alternative methods which could provide the same level of information as that obtained in experiment using animals but which involves less animal”.
Alternative methods able to do:
Reduce Refine Replace
collectively called as “The 3Rs Principle”.
Needs for alternative methods
Because in laboratory animals may be:
Poisoned.
Deprived of food water and sleep.
Applied with skin and eye irritants.
Subjected to psychological stress.
Deliberately infected with the infected disease.
In vivo is the Latin word which means with in the living body.
When effects of various biological entities are tested on whole, living organism or cells, usually animals including humans and plants.
Animal testing and clinical trials are major elements of in-vivo research.
In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject in drug discovery.
example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug.
Harry Smith found that sterile filtrates of serum from animals infected with Bacillus anthracis were lethal for other animals, whereas extracts of culture fluid from the same organism grown in vitro were not.
In microbiology Once cells are disrupted and individual parts are tested or analyzed, this is known as in vitro.
In vitro studies within the glass, i.e., in a laboratory environment using test tubes, petri dishes, etc. Examples of investigations in vivo include: the pathogenesis of disease.
In vitro toxicology:-
The bridge exists between new drug discovery and drug development.-
Provide information on mechanism of action of a drug
Provides an early indication of the potential for some kinds of toxic effects, allowing a decision to terminate or to proceed further.
In vitro methods are widely used for:-
Screening and ranking chemicals
Get a platform for animal studies for physiological actions
Studying cell, tissue, or target specific effects
Improve subsequent study design
Advantages and Disadvantages:-
Faster than in vivo studies
Less expensive to run
Less predictive of toxicity in intact organisms
In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.
The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests.
Results obtained from in vitro experiments cannot often be directly applied to predict biological responses of organisms to chemical exposure in vivo.
Therefore, it is extremely important to build a consistent and reliable in vitro to in vivo extrapolation method.
Two solutions are now commonly accepted:
Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems).
Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model.
The two approaches can be applied simultaneously allowing in vitro systems to provide adequate data for the development of mathematical models. To comply with push for the development of alternative testing methods.
In this slide contains definition, types, causes, inducers and inhibitors, complex drug interactions.
Presented by: SUMASHREE AGGIM (Department of pharmacology).
RIPER, anantapur
Introduction to Screening Models of Anti-Atherosclerosis
Atherosclerosis, Screening models, In vitro models, In vivo models
Presented by
SHAIK FIRDOUS BANU
Department of Pharmacology
Assignment on Preclinical Screening of ImmunomodulatorsDeepak Kumar
Assignment on Preclinical screening of new substances for the pharmacological activity using in vivo, in vitro, and other possible animal alternative models
genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic
Preclinical Screening of Antiasthmatic DrugsShubham Kolge
Bronchial asthma is characterized by both bronchoconstriction and airway inflammation which leads to bronchial hyperresponsiveness to various stimuli. Different mediators are implicated in asthma. As the precise etiology is not known and multiple biochemical processes are triggered by different causative factors, it is difficult to have a single drug which can effectively and simultaneously act upon different mediators. This led to an intense search for potent and safe antiasthmatic drugs. This presentation intends to compile different screening methods for the evaluation of new candidate drugs with potential for the treatment of asthma. These include in vitro, in vivo, receptor binding and enzymatic methods.
Alternative methods to animals testing are the development and implementation of test method that avoid use of live animals or use of less animals in method.
The council directive on protection of animals used for experiments and scientific purpose in article 23
“The commission and member states should encourage
research into development and validation of alternative methods which could provide the same level of information as that obtained in experiment using animals but which involves less animal”.
Alternative methods able to do:
Reduce Refine Replace
collectively called as “The 3Rs Principle”.
Needs for alternative methods
Because in laboratory animals may be:
Poisoned.
Deprived of food water and sleep.
Applied with skin and eye irritants.
Subjected to psychological stress.
Deliberately infected with the infected disease.
In vivo is the Latin word which means with in the living body.
When effects of various biological entities are tested on whole, living organism or cells, usually animals including humans and plants.
Animal testing and clinical trials are major elements of in-vivo research.
In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject in drug discovery.
example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug.
Harry Smith found that sterile filtrates of serum from animals infected with Bacillus anthracis were lethal for other animals, whereas extracts of culture fluid from the same organism grown in vitro were not.
In microbiology Once cells are disrupted and individual parts are tested or analyzed, this is known as in vitro.
In vitro studies within the glass, i.e., in a laboratory environment using test tubes, petri dishes, etc. Examples of investigations in vivo include: the pathogenesis of disease.
In vitro toxicology:-
The bridge exists between new drug discovery and drug development.-
Provide information on mechanism of action of a drug
Provides an early indication of the potential for some kinds of toxic effects, allowing a decision to terminate or to proceed further.
In vitro methods are widely used for:-
Screening and ranking chemicals
Get a platform for animal studies for physiological actions
Studying cell, tissue, or target specific effects
Improve subsequent study design
Advantages and Disadvantages:-
Faster than in vivo studies
Less expensive to run
Less predictive of toxicity in intact organisms
In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.
The problem of transposing in vitro results is particularly acute in areas such as toxicology where animal experiments are being phased out and are increasingly being replaced by alternative tests.
Results obtained from in vitro experiments cannot often be directly applied to predict biological responses of organisms to chemical exposure in vivo.
Therefore, it is extremely important to build a consistent and reliable in vitro to in vivo extrapolation method.
Two solutions are now commonly accepted:
Increasing the complexity of in vitro systems where multiple cells can interact with each other in order recapitulate cell-cell interactions present in tissues (as in "human on chip" systems).
Using mathematical modeling to numerically simulate the behavior of a complex system, whereby in vitro data provides the parameter values for developing a model.
The two approaches can be applied simultaneously allowing in vitro systems to provide adequate data for the development of mathematical models. To comply with push for the development of alternative testing methods.
In this slide contains definition, types, causes, inducers and inhibitors, complex drug interactions.
Presented by: SUMASHREE AGGIM (Department of pharmacology).
RIPER, anantapur
Introduction to Screening Models of Anti-Atherosclerosis
Atherosclerosis, Screening models, In vitro models, In vivo models
Presented by
SHAIK FIRDOUS BANU
Department of Pharmacology
Assignment on Preclinical Screening of ImmunomodulatorsDeepak Kumar
Assignment on Preclinical screening of new substances for the pharmacological activity using in vivo, in vitro, and other possible animal alternative models
genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic
This is PPT on Evolution. This is just and introductory PPT. Soon There will be a PPT with much more on Evolution. Hope That you all like it. please like and share. each like Counts.
Protozoal infections and antiprotozoal drugs(therapy).Gagandeep Jaiswal
presentation comprising knowledge about various protozoal infections and therapy options available for the treatment of those infections. various different drugs used in the therapy with their proposed mechanism of action. Hope it will be useful for understanding the pharmacology of antiprotozoals.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Genetic variation and its role in health and pharmacology
1. GENETIC VARIATION AND ITS ROLE
IN HEALTH AND PHARMACOLOGY
PRESENTED BY:-GAGANDEEP JAISWAL
(M. PHARM. PHARMACOLOGY) 1
Department of Pharmaceutical Sciences And Technology,MRSPTU
3. Key Terms:-
• Genetic variation:- In a very simple language, genetic variation is a measure of the
variation that exists in the genetic makeup of individuals within population.
variation in alleles of genes that occurs both within and among populations
• Genetic Diversity: the level of biodiversity, refers to the total number of genetic
characteristics in the genetic makeup of a species
• Crossing Over: the exchange of genetic material between homologous
chromosomes that results in recombinant chromosomes
• Phenotypic Variation: variation (due to underlying heritable genetic variation); a
fundamental prerequisite for evolution by natural selection
• Genetic Variation: variation in alleles of genes that occurs both within and among
populations
• Alleles:-each of two or more alternative forms of a gene that arise by mutation and
are found at the same place on a chromosome.
• Natural Selection:- the process whereby organisms better adapted to their
environment tend to survive and produce more offspring. The theory of its action
was first fully expounded by Charles Darwin, and it is now regarded as be the main
process that brings about evolution.
3
4. WHAT IS GENETIC VARIATION?
Genetic variation generally refers to the differences in genes between individual
members of a population, or the frequency in which the various gene types are
expressed. Genetic variation is incredibly important for the survival and adaptation
of a species, as it helps in terms of natural selection and evolution.
Individuals of a species have similar characteristics but they are rarely identical, the
difference between them is called variation.
In genetic variation, the genes of organisms within a population change.
Gene alleles determine distinct traits that can be passed on from parents to
offspring. Gene variation is important to the process of natural selection. The
genetic variations that arise in a population happen by chance, but the process of
natural selection does not.
4
6. Sources of Genetic Variation
• Gene duplication, mutation, or other processes can
produce new genes and alleles and increase genetic
variation. New genetic variation can be created within
generations in a population, so a population with rapid
reproduction rates will probably have high genetic
variation. However, existing genes can be arranged in new
ways from chromosomal crossing over and recombination
in sexual reproduction. Overall, the main sources of genetic
variation are the formation of new alleles, the altering of
gene number or position, rapid reproduction, and sexual
reproduction.
6
7. Causes of Genetic Variation
• Genetic variation occurs mainly through DNA mutation,
gene flow , crossing over and sexual reproduction. Due to
the fact that environments are unstable, populations that
are genetically variable will be able to adapt to changing
situations better than those that do not contain genetic
variation. Gene flow and sexual reproduction reshuffle
alleles within a population, giving offspring combinations
which differ from their parents and from others.
Nonrandom Mating and Environmental Variance are some
other factors which leads to the genetic variation.
7
8. Causes In Detail
A. DNA Mutation:-Mutations are changes to an organism’s DNA and
are an important driver of diversity in populations. Species evolve
because of the accumulation of mutations that occur over time.
The appearance of new mutations is the most common way to
introduce novel genotypic and phenotypic variance. Some
mutations are unfavorable or harmful and are quickly eliminated
from the population by natural selection. Others are beneficial
and will spread through the population. Whether or not a
mutation is beneficial or harmful is determined by whether it
helps an organism survive to sexual maturity and reproduce.
Some mutations have no effect on an organism and can linger,
unaffected by natural selection, in the genome while others can
have a dramatic effect on a gene and the resulting phenotype.
8
9. Mutation in a garden rose: A mutation has caused this garden moss rose to produce
flowers of different colors. This mutation has introduce a new allele into the
population that increases genetic variation and may be passed on the next generation.9
10. B. Gene Flow:-An important evolutionary force is gene flow: the flow of
alleles in and out of a population due to the migration of individuals or
gametes. While some populations are fairly stable, others experience
more movement and fluctuation.
Many plants, for example, send their pollen by wind, insects, or birds to
pollinate other populations of the same species some distance away. Even
a population that may initially appear to be stable, such as a pride of lions,
can receive new genetic variation as developing males leave their mothers
to form new prides with genetically-unrelated females.
This variable flow of individuals in and out of the group not only changes
the gene structure of the population, but can also introduce new genetic
variation to populations in different geological locations and habitats.
Maintained gene flow between two populations can also lead to a
combination of the two gene pools, reducing the genetic variation
between the two groups. Gene flow strongly acts against speciation, by
recombining the gene pools of the groups, and thus, repairing the
developing differences in genetic variation that would have led to full
speciation and creation of daughter species.
For example, if a species of grass grows on both sides of a highway, pollen
is likely to be transported from one side to the other and vice versa. If this
pollen is able to fertilize the plant where it ends up and produce viable
offspring, then the alleles in the pollen have effectively linked the
population on one side of the highway with the other. 10
11. Gene flow: Gene flow can occur when an individual travels from one
geographic location to another. 11
12. C. Crossing over and sexual reproduction:-
Chromosomal crossover (or crossing over) is the
exchange of genetic material between 2 homologous
chromosomes non-sister chromatids that results in
recombinant chromosomes during sexual
reproduction. Crossing over accounts for genetic
variation, because due to the swapping
of genetic material during crossing over, the
chromatids held together by the centromere are no
longer identical. Sexual reproduction promotes
genetic variation by producing different gene
combinations. Meiosis is the process by which sex
cells or gametes are created. Genetic variation occurs
as alleles in gametes are separated and randomly
united upon fertilization.
12
14. Nonrandom Mating and Environmental Variance
Population structure can be altered by nonrandom mating (the preference
of certain individuals for mates) as well as the environment.
Nonrandom mating can occur when individuals prefer mates with
particular superior physical characteristics or by the preference of
individuals to mate with individuals similar to themselves.
14
Assortative mating in the American
Robin: The American Robin may practice
assortative mating on plumage color, a
melanin based trait, and mate with other
robins who have the most similar shade
of color. However, there may also be
some sexual selection for more vibrant
plumage which indicates health and
reproductive performance.
15. Environmental Variance
• Genes are not the only players involved in determining
population variation. Phenotypes are also influenced by other
factors, such as the environment.
15
Temperature-dependent sex
determination: The sex of the
American alligator (Alligator
mississippiensis) is determined
by the temperature at which
the eggs are incubated. Eggs
incubated at 30 degrees C
produce females, and eggs
incubated at 33 degrees C
produce males.
16. Genetic variation in the shells of Donax variabilis: An enormous
amount of phenotypic variation exists in the shells of Donax varabilis16
17. Human genetic variation
• Human genetic variation is the genetic differences in and among populations.
• There may be multiple variants of any given gene in the human population
(alleles), a situation called polymorphism.
• No two humans are genetically identical. Even monozygotic twins (who develop
from one zygote) have infrequent genetic differences due to mutations occurring
during development.
• The study of human genetic variation has evolutionary significance and medical
applications. It can help scientists understand ancient human population
migrations as well as how human groups are biologically related to one another.
• For medicine, study of human genetic variation may be important because some
disease-causing alleles occur more often in people from specific geographic
regions. New findings show that each human has on average 60 new mutations
compared to their parents.
17
18. Role of genetic variation in health and pharmacology
• Differences in allele frequencies contribute to group differences in the incidence of
some monogenic diseases, and they may contribute to differences in the incidence
of some common diseases. For the monogenic diseases, the frequency of
causative alleles usually correlates best with ancestry, whether familial (for
example, Ellis-van Creveld syndromeamong the Pennsylvania Amish), ethnic (Tay-
Sachs disease among Ashkenazi Jewish populations), or geographical
(hemoglobinopathies among people with ancestors who lived in malarial regions).
To the extent that ancestry corresponds with racial or ethnic groups or subgroups,
the incidence of monogenic diseases can differ between groups categorized by race
or ethnicity, and health-care professionals typically take these patterns into
account in making diagnoses.
• Some other variations on the other hand are beneficial to human, as they prevent
certain diseases and increase the chance to adapt to the environment. For
example, mutation in CCR5 gene that protects against AIDS. CCR5 gene is absent on
the surface of cell due to mutation. Without CCR5 gene on the surface, there is
nothing for HIV viruses to grab on and bind into. Therefore the mutation on CCR5
gene decreases the chance of an individual’s risk with AIDS. The mutation in CCR5
is also quite popular in certain areas, with more than 14% of the population carry
the mutation in Europe and about 6-10% in Asia and North Afriac.
18
20. • Apart from mutations, many genes that may have aided humans in ancient
times plague humans today. For example, it is suspected that genes that
allow humans to more efficiently process food are those that make people
susceptible to obesity and diabetes today.
• As far as pharmacological role of genetic variation is concerned, Variability
in drug efficacy and adverse effects are observed in clinical practice
• Drug-related genes show high extent of genetic variability across millions of
individuals
• Cancer drug target genes have many germ line functional-variants:-
Especially in cancer therapy, genetic variation in drug targets has been
recognized to play a crucial role for treatment success. While some cancer
drugs do not act in the tumor tissue, the cancer drug’s primary site of
action usually is in the tumor, whose genome contains tumor specific
somatic variants as well as a subset of patient-specific germ line variants30.
Information on somatic variants from tumor samples is thus increasingly
used to enable research on drug design and to implement stratified or
personalized cancer therapy.
• For instance, the DRPs of taxanes (docetaxel, paclitaxel, and cabazitaxel) are
30 percentage points higher in the cohorts of South Asian and European
ancestry compared to the cohort of African ancestry (DRPSAS/NFE = 85% vs
DRPAFR = 45%) due to functional variants in the four taxane
targets, TUBB1, MAP2, MAP4, and MAPT.
20
22. • Dopamine D2 (encoded by the DRD2 gene) receptors are primarily
expressed in the terminal regions of dopaminergic neurons. Studies in
DRD2-null mice suggest that the D2 receptor functions as an auto receptor
on dopamine neurons. The most well-established polymorphism in the
DRD2 gene is Taq1A, a C>T substitution located 10kb (kilobases)3’ of the
DRD2 gene. This Taq1A polymorphism is associated with an increased risk
for multiple types of substance abuse , including heroin use , cocaine
dependency , psychostimulant polysubstance abuse , and smoking.
• In addition to the dopaminergic system, nicotinic acetylcholine receptors
have been implicated in nicotine reward and dependency. Two non
synonymous SNPs on exon5 (rs1044396/1629G>T
andrs1044397/1659G>A)of the gene encoding for the α4 subunit of the
nicotinic acetylcholine receptor (CHRNA4) were associated with a lower risk
of nicotine dependency in Chinese men (96), which was recently replicated
in a European population. A G>A variant, rs2236196, in the 3 untranslated
region of CHRNA4, was associated with greater subjective effects of
nicotine and higher risk of nicotine dependency.
22
23. IS GENETIC DIVERSITY GOOD OR BAD?
Genetic diversity is, in general, a good thing for a population, for a simple reason:
adaptation via natural selection depends on the existence of variation (there cannot
be selection in the absence of alternatives). Other things being equal, a population
possessing a greater amount of genetic diversity has a greater probability of
already possessing adaptive alleles that might be necessary to meet new
environmental challenges (e.g., pathogens).
Even the boundaries between the useful/neutral/deleterious categories are blurred.
Deleterious anaemia-causing mutations are known to have benefits of malaria-
resistance.
Neutral variants may be “useful” ones in waiting: for example, lactase persistent
mutants may have existed in the human species for hundreds of thousands of years,
appearing and re-appearing by mutation, but it is when they encountered cow’s
milk and the need to drink it that they shifted from “neutral” to “useful”.
And, even useful alleles can cease to be so, e.g., the eradication of swamps and
malaria in Greece has removed the benefit of malaria-resistence, and left only the
harm of anaemia.
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a Availability of documented pharmacogenetic associations for 1236 FDA-approved drugs in public repositories such as the PharmGKB database [22] (left) is less abundant than functional variants observed in the population for the drug target genes (right). b, c Examples of known and novel genetic variants (green) in the target genes of warfarin and taxanes that could affect drug efficacy due to effects on the binding site (ligand highlighted in orange)