Genetic variation is the driving force of evolution and is important in medicine. Single nucleotide polymorphisms are the most common genetic variation and can influence disease risk and drug responses between individuals and populations. Understanding genetic variation through studies of populations and single genes can provide insights into human evolutionary history, disease susceptibility, and treatment effectiveness.
In biology, a mutation is the permanent alteration of the nucleotide sequence of the genome of an organism, virus, or extra chromosomal DNA or other genetic elements.
Mutations result from errors during DNA replication (especially during meiosis) or other types of damage to DNA (such as may be caused by exposure to radiation or carcinogens), which then may undergo error-prone repair or cause an error during other forms of repair,
In biology, a mutation is the permanent alteration of the nucleotide sequence of the genome of an organism, virus, or extra chromosomal DNA or other genetic elements.
Mutations result from errors during DNA replication (especially during meiosis) or other types of damage to DNA (such as may be caused by exposure to radiation or carcinogens), which then may undergo error-prone repair or cause an error during other forms of repair,
potassium, chloride, bicarbonate, blood urea nitrogen (BUN), magnesium, creatinine, glucose, and sometimes calcium. Tests that focus on cholesterol levels can determine LDL and HDL cholesterol levels, as well as triglyceride levels.[6]
Cytogenetic an Experimental Monitoring Test for Plant ExtractsIOSRJPBS
More than two centuries have been passed since the chromosomes have been firstly observed in plant cells by Nageli in 1842. During this long period, chromosomes have been discovered in human cells and well recognized as a source of genes locations. The effects of chemicals and environmental pollution in human health and caners became an interested field of studying diver mutagens and their role in affecting the genetic materials. Cytogenetic tests were the main tools to evaluate the effects of those mutagens on human genome and chromosomes. Many techniques have been used for these purposes including in vitro and in vivo analyzing tests using human and animal cells. The intent of this article is to review the role of cytogenetic techniques in detecting the effects of mutagens on chromosomal aberrations and the role of plant extracts in monitoring these effects
Genetic Resistance to Infectious Diseases in the Era of Personalized Medicine...CrimsonpublishersCJMI
Genetic Resistance to Infectious Diseases in the Era of Personalized Medicine by Andrei Alimov in Cohesive Journal of Microbiology & Infectious Disease
Genetic factors in pathogen colonisation is emerging as a new field of research as " infectogenomics". The susceptible host to periodontal disease directs towards genetic factors playing a role in periodontal disease pathogenesis. Earlier identification of gene polymorphisms associated with periodontal disease preogression may help in early diagnosis, treatment of such susceptible host.
Genomics in Society: Genomics, Preventive Medicine, and SocietyLarry Smarr
11.10.06
Guest Lecture to UCSD Medical and Pharmaceutical Students
Foundations of Human Biology--Lecture #41
Title: Genomics in Society: Genomics, Preventive Medicine, and Society
UC San Diego
PharmaCon2007 Congress, Dubrovnik, Croatia "New Technologies and Trends in Pharmacy, Pharmaceutical Industry and Education" http://www.pharmacon2007.com
Abstract is available at http://www.pharmaconnectme.com
Cancer gwas and genetic risk predictionDavid Enoma
Genome wide association studes and its application in cancer as well as genetic risk prediction scoring for cancers. Especially in populations of African ancestry.
Studies of African Genetics including pharmacogenetics, disparities and GWAS approaches to solving the cancer disparity between people of African Ancestry and other populations.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
2. OUTLINE
INTRODUCTION
EVOLUTION AND ITS APPLICATIONS
GENETIC VARIATION
SOURCES OF GENETIC VARIATION
SIGNIFICANCE OF GENETIC VARIATION IN MEDICINE
SINGLE NUCLEOTIDE POLYMORPHISMS
PHARMACOGENOMICS
APPLICATIONS OF GENETIC VARIATION
GENETIC TESTING AND SCREENING
2
3. INTRODUCTION
In the mid-19th century, Charles Darwin formulated the
scientific theory of evolution by natural selection,
published in his book On the Origin of Species (1859).
The central concept of natural selection is the
evolutionary fitness of an organism.
Fitness is measured by an organism's ability to survive
and reproduce.
3
4. INTRODUCTION CONTD.
An evolutionary perspective challenges the prevalent
but fundamentally incorrect metaphor of the body as a
machine designed by an engineer.
Understanding the body as a product of natural
selection, not design, offers new research questions and
a framework for making medical education more
coherent. (Nesse & Stearns, 2008)
4
5. INTRODUCTION CONTD.
Genetic variation is the driving force of evolution.
(Arber, 2005).
Evolutionary processes are generally thought of as
processes by which these changes occur.
Four processes are widely recognized: natural
selection (in the broad sense, to include sexual
selection), genetic drift, mutation, and migration
(Scott‐Phillips et al., 2014)
5
6. INTRODUCTION CONTD.
A complete genetic stability would not allow biological
evolution to occur, while a very high genetic instability
would not allow a concerned species to persist(Arber,
2005).
Instead of phenomena as specific as acid–base
balance, evolution can help doctors make sense of
why a disease exists at all, what environments increase
the risk, and how treatments work (Nesse & Stearns,
2008).
6
7. EVOLUTIONARY RELATIONSHIP
OF PRIMATES
7
Figure 1: The hominoids are descendants of a
common ancestor.
Comparative studies
across ethnically
diverse human
populations and across
human and nonhuman
primate species is
important for
reconstructing human
evolutionary history
(Tishkoff & Verrelli,
2003)
9. APPLICATIONS OF EVOLUTION
TO MEDICINE
Phylogenetics is the study of evolutionary relationships
among biological entities - often species, individuals or
genes (which may be referred to as taxa).
Phylogenetic analysis also was used to falsify the
hypothesis that HIV was introduced into Africa via polio
vaccine.
Rambaut et al. (2001) performed an evolutionary
analysis of HIV-1 subtypes from Congo.
9
10. APPLICATIONS OF EVOLUTION
TO MEDICINE CONTD.
The analysis indicate that the common ancestor to
HIV-1 group M, which gave rise to the pandemic
strains, was present in a human host long before the
first OPV field trials were conducted in the Congo
during the late 1950s.
Tracing pathogen phylogenies can be very useful.
Influenza phylogenies suggest which strains are likely
to spread in future epidemics (Smith, 2006).
10
11. APPLICATIONS OF EVOLUTION
TO MEDICINE CONTD.
The complete genome sequence of the severely
pathogenic Shigella flexneri reveals that it is
phylogenetically indistinguishable from the Escherichia
coli that lives normally in the human gut (Wei et al.
2003).
Applications of evolutionary biology to infectious
disease are also very direct.
Antibiotic resistance is an arms race; we invent new
defenses, the enemy quickly finds ways around them,
and we try to find new defenses.
11
13. SOURCES OF GENETIC
VARIATION
Random mutations are the ultimate source of genetic
variation.
Polyploidy is an example of chromosomal mutation.
Crossing over (genetic recombination) and random
segregation during meiosis can result in the production
of new alleles
Variation and recombination can be facilitated by
transposable genetic elements, endogenous retroviruses,
transposons, etc.
13
15. IMPORTANCE OF GENETIC
VARIATION IN MEDICINE
Specific gene-disease relationships (variations both
within and between groups in disease susceptibility or
resistance according to genotype).
Gene-environment interactions—phenotypic variation
and pharmacogenetic implications.
Complex genetic traits associated with specific aberrant
behavioral characteristics, such as aggressivity and
alcoholism;
15
16. IMPORTANCE OF GENETIC
VARIATION IN MEDICINE CONTD.
Genetic factors linked to multivariate non-disease-related
characteristics, such as height, intelligence, and aging.
Genotype associations—predisposition to particular
cancers, autoimmune disease, and other disorders.
HLA and other immune-response-related genotypes in
diverse populations and their implications for
transplantation, vaccine development, and related
therapies.
16
17. GENETIC VARIATION IN
INDIVIDUALS AND POPULATION
By characterizing genetic variation among individuals
and populations, we may gain a better understanding
of differential susceptibility to diseases.
We may also gain better understanding of differential
responses to pharmacological agents and the complex
interaction of genetic and environmental factors in
producing phenotypes (Collins et al., 2003).
17
18. GENETIC VARIATION AND
RACISM
Populations outside Africa derive from one or more
migration events out of Africa within the last 100,000
years.
The greatest genetic variation occurs within Africans,
with variation outside Africa representing either a
subset of African diversity or newly arisen variants
(Risch et al., 2002).
Racial and ethnic groups should not be assumed to be
equivalent, either in terms of disease risk or drug
response.
18
19. GENETIC VARIABILITY IN RACE
AND DISEASE RISK ASSOCIATION
Furthermore, a 'race-neutral' approach to biomedical
research is neither equitable nor advantageous, and
would not lead to a reduction of disparities in disease risk
or treatment efficacy.
Whether each race responds equally to a particular drug
is an empirical question that can only be addressed by
group study.
Avoid naïve inferences about between racial/ethnic
groups
19
20. RACE AND GENETICS IN
MEDICINE
Sickle-cell disease is much more common in African and
Mediterranean populations than in northern European
populations, whereas the reverse is true for cystic fibrosis
and hemochromatosis. (Jorde & Wooding, 2004)
Ge et al. (2009) report that a genetic polymorphism near
the IL28B gene, encoding interferon-λ-3 (IFN-λ-3), is
associated with difference in response to treatment for
Hepatitis virus between African-Americans and patients of
European ancestry.
20
21. SINGLE NUCLEOTIDE
POLYMORPHISM
Each of us is at some genetic risk, and therefore can
benefit, at least theoretically, from the progress
scientists are making in understanding and learning
how to respond to these risks.
Single nucleotide polymorphism (SNP) is the most
common sequence variation
in coding and noncoding genomes in diverse taxa
across life from viruses and bacteria to humans (Nevo
and Beiles, 2011).
21
22. SINGLE NUCLEOTIDE
POLYMORPHISM CONTD.
From the efforts of an international Single Nucleotide
Polymorphism (SNP) consortium, over six million SNPs
have currently been identified, ∼1every 1–2 kilobases (kb)
(http://www.ncbi.nlm.nih.gov/SNP/snp summary.cgi)
For studies of demographic history, analysis of genetic
variation in noncoding regions (i.e., selectively neutral) will
be most informative.
22
23. MOLECULAR EVOLUTION OF FOXP2
GENE IN SPEECH
A work has shown that that human FOXP2 contains
changes in amino-acid coding and a pattern of
nucleotide polymorphism, which strongly suggest that
this gene has been the target of selection during recent
human evolution. (Enard et al., 2002).
FOXP2 is the first gene relevant to the human ability to
develop language.
23
24. SINGLE GENE DISORDERS OF
OBESITY
Some of the single-gene disorders associated with
severe obesity are also characterized by drastic changes
in eating behavior.
Obese patients with mutations in leptin (LEP),
melanocortin 4 receptor (MC4R), and neurotrophic
tyrosine kinase receptor type 2 (NTRK2) genes have
been also diagnosed with severe hyperphagia (Rankinen
& Bouchard, 2006)
24
25. RELEVANT SINGLE NUCLEOTIDE
POLYMORPHISMS
For example, we already know that single base
differences in the APOE gene are associated with
Artherosclerosis and Alzheimer's disease.
Also that a simple deletion within the chemokine-
receptor gene CCR5 leads to resistance to HIV and AIDS.
(Chakravarti, 2001).
Evaluating the contributions of individual genes to
diseases that have a complex, multigene basis.
And gene variants leading to tissue and organ
incompatibility
25
27. WIDE ARRAY OF APPLICATION OF
GENETIC MAPPING IN HEALTH
27
28. GENETIC TESTING AND
SCREENING
Genetic testing is not a new health care strategy.
Newborn screening for diseases like PKU has been
going on for 30 years in many states. Institutes of
Health (US), 2007)
The identification of the BRCA1and BRCA2 genes and
variants of these genes are associated with an
increased risk of breast and ovarian cancer have paved
the way for the development of guidelines and
protocols.
28
29. CONCLUSION
Advances in molecular biology, genetics, evolutionary
biology, omics technologies have endowed us with
powerful tools to answer important questions- Who we
are, Where we come from and Why we respond the way
we do.
These questions have impacted the study of our
evolutionary history which has stimulated progress in
medicine.
29
30. REFERENCES
Collins, F. S., Green, E. D., Guttmacher, A. E., & Guyer, M. S. (2003). A vision for
the future of genomics research. Nature, 422: 835. doi: 10.1038/nature01626
Chakravarti, A. (2001). . . .to a future of genetic medicine. Nature, 409: 822.
doi: 10.1038/35057281
National Research Council (US) Committee on Human Genome
Diversity.(1998). Evaluating Human Genetic Diversity: National Academies
Press. ISBN NO. 9780309184748Arber, W. (2005).
The theory of molecular evolution and its medical implications. In R. Paton &
L. A. McNamara (Eds.), Studies in Multidisciplinarity (Vol. 3, pp. 31-45):
Elsevier. ISBN NO. 1571-0831
Evolutionary processes are generally thought of as processes by which these
changes occur. Four such processes are widely recognized: natural selection
(in the broad sense, to include sexual selection), genetic drift, mutation, and
migration
30
31. REFERENCES
Smith, D. J. 2006. Predictability and preparedness in influenza
control. Science312:392–394.
Risch, N., Burchard, E., Ziv, E., & Tang, H. (2002). Categorization of humans in
biomedical research: genes, race and disease. Genome Biology, 3(7):
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National Institutes of Health (US); Biological Sciences Curriculum Study. NIH
Curriculum Supplement Series [Internet]. Bethesda (MD): National Institutes of
Health (US); 2007. Understanding Human Genetic Variation. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK20363/
Eviatar Nevo and Avigdor Beiles (2011) Genetic variation in nature. Scholarpedia,
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Rankinen, T., & Bouchard, C. (2006). Genetics of Food Intake and Eating Behavior
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