Mutations are heritable changes in DNA that occur spontaneously due to errors in DNA replication or are induced by environmental mutagens like chemicals or radiation. Spontaneous mutations arise from replication errors or chemical changes to bases, while induced mutations are caused by agents that damage DNA like base analogs, alkylating agents, or radiation. Genetic mosaics occur when two or more cell populations with different genotypes arise from a single fertilized egg due to mitotic errors, causing somatic or gonadal mosaicism.
A complementation test (sometimes called a "cis-trans" test) can be used to test whether the mutations in two strains are in different genes. By taking an example of Benzer's work, complementation has been explained.
What is Genome,Genome mapping,types of Genome mapping,linkage or genetic mapping,Physical mapping,Somatic cell hybridization
Radiation hybridization ,Fish( =fluorescence in - situ hybridization),Types of probes for FISH,applications,Molecular markers,Rflp(= Restriction fragment length polymorphism),RFLPs may have the following Applications;Advantages of rflp,disAdvantages of rflp, Rapd(=Random amplification of polymorphic DNA),Process of rapd, Difference between rflp &rapd
Prokaryotic and eukaryotic gene structurestusharamodugu
Organization of genome in Prokaryotes:
The term prokaryote means “primitive nucleus”. Cell in prokaryotes have no nucleus. The prokaryotic chromosome is dispersed within the cell and is not enclosed by a separate membrane. Much of the information about the structure of DNA comes from studies of prokaryotes, because they are less complex than eukaryotes. Prokaryotes are monoploids they have only one set of genes (one copy of the genome). In most viruses and prokaryotes, the single set of genes is stored in a single chromosome (single molecule either RNA or DNA).
Organization of genome in Prokaryotes:
The term prokaryote means “primitive nucleus”. Cell in prokaryotes have no nucleus. The prokaryotic chromosome is dispersed within the cell and is not enclosed by a separate membrane. Much of the information about the structure of DNA comes from studies of prokaryotes, because they are less complex than eukaryotes. Prokaryotes are monoploids they have only one set of genes (one copy of the genome). In most viruses and prokaryotes, the single set of genes is stored in a single chromosome (single molecule either RNA or DNA). Organization of genome in Prokaryotes:
The term prokaryote means “primitive nucleus”. Cell in prokaryotes have no nucleus. The prokaryotic chromosome is dispersed within the cell and is not enclosed by a separate membrane. Much of the information about the structure of DNA comes from studies of prokaryotes, because they are less complex than eukaryotes. Prokaryotes are monoploids they have only one set of genes (one copy of the genome). In most viruses and prokaryotes, the single set of genes is stored in a single chromosome (single molecule either RNA or DNA).
One of the first plausible models to account for the preceding observations was
formulated by Robin Holliday.
The key features of the Holliday model are the formation of heteroduplex DNA; the
creation of a cross bridge; its migration along the two heteroduplex strands,
termed branch migration; the occurrence of mismatch repair; and the
subsequent resolution, or splicing, of the intermediate structure to yield different
typesof recombinant molecules.
A complementation test (sometimes called a "cis-trans" test) can be used to test whether the mutations in two strains are in different genes. By taking an example of Benzer's work, complementation has been explained.
What is Genome,Genome mapping,types of Genome mapping,linkage or genetic mapping,Physical mapping,Somatic cell hybridization
Radiation hybridization ,Fish( =fluorescence in - situ hybridization),Types of probes for FISH,applications,Molecular markers,Rflp(= Restriction fragment length polymorphism),RFLPs may have the following Applications;Advantages of rflp,disAdvantages of rflp, Rapd(=Random amplification of polymorphic DNA),Process of rapd, Difference between rflp &rapd
Prokaryotic and eukaryotic gene structurestusharamodugu
Organization of genome in Prokaryotes:
The term prokaryote means “primitive nucleus”. Cell in prokaryotes have no nucleus. The prokaryotic chromosome is dispersed within the cell and is not enclosed by a separate membrane. Much of the information about the structure of DNA comes from studies of prokaryotes, because they are less complex than eukaryotes. Prokaryotes are monoploids they have only one set of genes (one copy of the genome). In most viruses and prokaryotes, the single set of genes is stored in a single chromosome (single molecule either RNA or DNA).
Organization of genome in Prokaryotes:
The term prokaryote means “primitive nucleus”. Cell in prokaryotes have no nucleus. The prokaryotic chromosome is dispersed within the cell and is not enclosed by a separate membrane. Much of the information about the structure of DNA comes from studies of prokaryotes, because they are less complex than eukaryotes. Prokaryotes are monoploids they have only one set of genes (one copy of the genome). In most viruses and prokaryotes, the single set of genes is stored in a single chromosome (single molecule either RNA or DNA). Organization of genome in Prokaryotes:
The term prokaryote means “primitive nucleus”. Cell in prokaryotes have no nucleus. The prokaryotic chromosome is dispersed within the cell and is not enclosed by a separate membrane. Much of the information about the structure of DNA comes from studies of prokaryotes, because they are less complex than eukaryotes. Prokaryotes are monoploids they have only one set of genes (one copy of the genome). In most viruses and prokaryotes, the single set of genes is stored in a single chromosome (single molecule either RNA or DNA).
One of the first plausible models to account for the preceding observations was
formulated by Robin Holliday.
The key features of the Holliday model are the formation of heteroduplex DNA; the
creation of a cross bridge; its migration along the two heteroduplex strands,
termed branch migration; the occurrence of mismatch repair; and the
subsequent resolution, or splicing, of the intermediate structure to yield different
typesof recombinant molecules.
Science and technology of manipulating and improving microbial strains, in order to enhance their metabolic capacities for biotechnological applications, are referred to as strain improvement.
Mutation Repair and DNA Replication.pptxhamzalatif40
In this Presentation Chapter 7 & 8 from the book Advanced Molecular Biology are discussed. Focus has been given to the mutation, its types, mutation repair, Different Repairing mechanisms and DNA Replication is explained with details.
This presentation will help students to brush up their basic concepts and along with that it will help them to understand what are mutations and what are its causes.
DNA Repair and its cause of emergence. Mutation and its types. Various repair mechanisms in living organisms with its distinctive types along with two common examples: Progeria and Multiple Sclerosis(MS).
Cell Biology and genetics paper - Mutation a basic touch to b.sc students with examples. DNA, genome, gene level mutation and chromosome level with examples. Touched some of the mutation types.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
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.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
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.
2. MUTATIONS
• Mutations are heritable changes in the DNA.
• They are essential to the study of genetics and are useful in many
other biological fields.
• Somatic mutations: occur in non reproductive cells.
• Germ-line mutations: occur in cells that give rise to gametes.
3. Spontaneous mutations
Mutations that are a result of natural changes in DNA structure.
1. All types of point mutations can occur spontaneously,
during S, G1 and G2 phases of the cell cycle, or by the
movement of transposons.
2. The spontaneous mutation rate in eukaryotes is between
10-4-to-10-6 per gene per generation, and in bacteria and
phages 10-5-to-10-7/gene/generation.
a. Genetic constitution of the organism affects its mutation rate.
i. In Drosophila, males and females of the same strain have
similar mutation rates.
ii. Flies of different strains, however, may have different
mutation rates.
b. Many spontaneous errors are corrected by the cellular repair
systems, and so do not become fixed in DNA.
5. Tautomeric shifts
• Purine and pyrimidine bases exist in different chemical forms called
tautomers
• The positions of protons in the DNA bases change.
6. Wobble base pairing
• Normal, protonated, and other forms of the bases are able to
pair because of flexibility in the DNA helical structure
7. Strand slippage
• Strand slippage may occur when one nucleotide strand forms a small loop .
• If the looped-out nucleotides are on the newly synthesized strand, an
insertion results.
8. Unequal crossing over
• During normal crossing over, the homologous sequences of the two DNA
molecules align, and crossing over produces no net change in the number
of nucleotides in either molecule.
• Misaligned pairing may cause unequal crossing over
• which results in one DNA molecule with an insertion and the other with a
deletion
10. Deamination
• Deamination: the loss of an amino group (NH2) from a base.
• Deamination may occur spontaneously or be induced by mutagenic
chemicals.
12. Induced Mutations
• Mutations those that result from changes caused by environmental
chemicals or radiation are called as induced mutations.
• A number of environmental agents are capable of damaging DNA including
certain chemicals and radiation.
• Mutagen: Any environmental agent that significantly increases the rate of
mutation above the spontaneous rate.
• The first discovery of a chemical mutagen was made by Charlotte
Auerbach.
Charlotte Auerbach
14. Base analogs
• chemicals with structures similar to that of any of the four standard bases
of DNA.
• DNA polymerases cannot distinguish these analogs from the standard
bases;
• so, if base analogs are present during replication, they may be
incorporated into newly synthesized DNA molecules.
• Eg. 5-Bromouracil
16. Alkylating agents
• chemicals that donate alkyl groups. These agents include methyl (CH3)
and ethyl (CH3–CH2) groups, which are added to nucleotide bases by
some chemicals.
• Example, ethylmethanesulfonate (EMS) adds an ethyl group to guanine,
producing 6-ethylguanine, which pairs with thymine.
17. Deamination
• In addition to its spontaneous occurrence, deamination can be induced by
some chemicals.
• E.g.: nitrous acid deaminates cytosine, creating uracil, which in the next
round of replication pairs with adenine producing a CG:TA transition
mutation.
18. Hydroxylamine
• Hydroxylamine is a very specific base modifying mutagen that adds a
hydroxyl group to cytosine.
• It converts cytosine into hydroxylaminocytosine .
• This conversion increases the frequency of a rare tautomer.
• The tautomer pairs with adenine instead of guanine and leads to CG:TA
transitions.
• Because hydroxylamine acts only on cytosine, it will not generate TA:CG
transitions.
19. Oxidative reactions
• Reactive forms of oxygen damage DNA and induce mutations by bringing
about chemical changes to DNA.
• Reactive forms of oxygen includes:
• Superoxide radicals
• Hydrogen peroxide
• Hydroxyl radicals
• They are produced in the course of normal aerobic metabolism, as well as
by radiation, ozone, peroxides, and certain drugs.
20. Intercalating agents
• Intercalating agents produce mutations by sandwiching themselves
(intercalating) between adjacent bases in DNA .
• They distorts the three-dimensional structure of the helix and causing
single-nucleotide insertions and deletions in replication.
• These insertions and deletions frequently produce frameshift mutations.
• And so the mutagenic effects of intercalating agents are often severe.
• Because intercalating agents generate both additions and deletions, they
can reverse the effects of their own mutations.
• E.g. : proflavin, acridine orange, ethidium bromide, and dioxin
21. Radiation
• Ionizing radiation breaks covalent bonds including those in DNA and is the
leading cause of chromosome mutations.
• Ionizing radiation also frequently results in double-strand breaks in DNA
• Ionizing radiation has a cumulative effect and kills cells at high doses.
• UV (254-260 nm) causes purines and pyrimidines to form abnormal dimer
bonds and bulges in the DNA strands.
• Eg : UV,X-Rays etc.
23. Genetic mosaics
• Presence of two or more populations of cells with
different genotypes in one individual who has developed from
a single fertilized egg.
• The phenomenon was discovered by Curt Stern.
24. Somatic mosaicism
• Somatic cells of the body are of more than one genotype.
• Different genotypes arise from a single fertilized egg cell, due to
mitotic errors at first or later cleavages.
• In rare cases, Intersex conditions can be caused by mosaicism where some
cells in the body have XX and others XY chromosomes (46, XX/XY).
• Milder forms of Klinefelter syndrome, called 46/47 XY/XXY mosaic where
in some of the patient's cells contain XY chromosomes, and some contain
XXY chromosomes.
• Around 30% of Turner's syndrome cases demonstrate mosaicism, while
complete monosomy (45,X) occurs in about 50–60% of cases.
25. Gonadal mosaicism
• Gonadal mosaicism or germline mosaicism is a special form of mosaicism,
where some gametes, i.e. either sperm or oocytes, carry a mutation, but
the rest are normal.
• The cause is usually a mutation that occurred in an early stem cell that
gave rise to all or part of the gonadal tissue.
• This can cause only some children to be affected, even for a dominant
disease.
26. Factors inducing mosaicism
• Endogenous factors: Mobile elements, DNA polymerase slippage, and
unbalanced chromosomal segregation.
• Exogenous factors :Nicotine and UV radiation.
• Somatic mosaics have been created in Drosophila using x-ray treatment
and the use of irradiation to induce somatic mutation has been a useful
technique in the study of genetics.
27. Reference & further reading
• Benjamin A. Pierce Genetics A Conceptual Approach 3rd edition
W.H.Freeman and Company New York.
• Gerald Karp Cell and Molecular biology – Concepts and Experiments 6th
edition John Wiley & Sons Inc.
• Bruce Alberts Molecular biology of the Cell.
• Jeff Hardin Gregory Bertoni Lewis J. Kleinsmith BECKER’S World of the Cell
8th edition Benjamin Cummings.
• http:/en.wikipedia.org/wiki/Mosaic_(genetics)
• http://evolution.berkeley.edu/evolibrary/article/mutations_01