Chromosomes contain DNA and play an important role in heredity. They are composed of chromatin, which contains DNA wrapped around histone proteins. Chromosomes replicate and separate precisely during cell division. Mutations in genes can cause genetic disorders and occur through changes in DNA sequence or chromosome structure. Gene expression involves transcription of DNA into RNA and translation of RNA into protein. The structure and behavior of chromosomes during mitosis and meiosis explains patterns of inheritance for autosomal and sex-linked traits.
Ischemic condition affecting the eye.
The ischemia can occur secondary to systemically problem [or] particulary the eye.
Many retinal vascular disorders {like CRAO,CRVO,Diabetic retinopathy,Hypertensive Retinopathy} shows ischemic signs.
Ischemic condition affecting the eye.
The ischemia can occur secondary to systemically problem [or] particulary the eye.
Many retinal vascular disorders {like CRAO,CRVO,Diabetic retinopathy,Hypertensive Retinopathy} shows ischemic signs.
Diagnosis of Vertical Root Fracture Using Digital Radiography, Helical Comput...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
OCT-Angiography is a dye-less method, unlike traditional Fluorescein Angiography and ICG. OCT-Angiography is three dimensional, which allows to scroll through depths and layers, showing superficial and deeper capillaries.
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Presentation from OIS@ASRS 2016.
Participant:
David Huang, MD, PhD - Peterson Professor of Ophthalmology and Professor of Biomedical Engineering at OHSU
Powered by:
Healthegy
For more ophthalmology innovation
Visit us at www.ois.net
Nucleic acids are macromolecules that store genetic information and enable protein production. Nucleic acids include DNA and RNA. These molecules are composed of long strands of nucleotides. Nucleotides are composed of a nitrogenous base, a five-carbon sugar, and a phosphate group.
Please find the answers and explanations belowPart 1 (TrueFalse).pdfaparnatiwari291
Please find the answers and explanations below:
Part 1 (True/False)
1. Replication and transcription proceed in 5\' to 3\' direction: TRUE (Both DNA replication and
transcription of mRNA proceed in 5\' to 3\' direcition. This is because the firstly, the DNA
polymerase retains only 5\' to 3\' directionality and thus, replication begins only in this direction.
.Secondarily, there must be sequence similarity between the DNA and the RNA transcribed from
it thus the orientation of transcription is necessarily 5\' to 3\' in nature)
2. All cells have telomerase activity : FALSE (Telomerase or terminal transferase is an enzyme
which is required for maintenance of terminal positions of chromosomes by self-replication and
prevents shortening of chromosomes. It also prevents sticking of chromosomes together and thus
clumping of chromosomes. Telomerase acitivty is absent in majority of somatic cells in the
body.)
3. Only mRNA is transcribed: TRUE (Only the mRNA which carries the necessary information
for translation is transcribed from the DNA template. The tRNA is utilized to transfer the
transcribed information and rRNA is utilized to generate the polypeptide on the ribosomal
surface during translation)
4. Promoter regions are upstream from the gene: TRUE (A gene promoter is the region of DNA
located upstream the gene to be transcribed and carries the consensus sequence which could be
recognized by RNA polymerase for its binding and carrying on transcription)
5. A single tRNA can carry several different amino acids: FALSE (The tRNA is specific for only
one kind of amino acid which it could carry. It is a highly stringent and specific nature of this
biomolecule which determines the specificness for the amino acid which will be synthesized
from the codon)
Part 2
Please find the definitions below:
1. Semi-conservative replication: The mode of replication of double stranded DNA in which a
daughter DNA molecules carries a strand from parent DNA and the complementary strand is
synthesized de novo is called semi-conservative replication.
2. Okazaki fragments: Okazaki fragments are short stretches of DNA synthesized
discountinuously on the lagging strand on the open frame of the parent DNA. These stretches of
DNA are finally conjoined together to form a continous strand of newly synthesized DNA.
3. Consensus sequence: Consensus sequences are those genetically conserved sequences of DNA
which remain similar (upto 99%) within organisms of same or different species and are actively
engaged in crucial functions such as promoter region binding, transcription sites for transcription
factors, enzymatic genes etc. Any change or deterioration in these consesus sequence might be
highly deletrious for the cells.
4. Codon: A codon can be defined as a triplet set of nucleotides which come in a specific order
and encode for a specific type of amino acid upon translation. For example, the codon AAA
encodes for amino acid lysine. Exceptionally, codons UAA, UAG and UGA do not .
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
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June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
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This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
6. The structure of chromosomes
• Chromosomes: are coiled up strands of DNA
- Each metaphase chromosome is composed of two sister chromatids connected
by a centromere
- Centromeres are responsible for movement of chromosomes at cell division
- The ends of chromosomes are protected by telomeres, which are tandem
repeats of a hexameric DNA sequence, ending in a 3 ′ - single-stranded
overhanging sequence of 50–400 nucleotides, which loops back on itself to
form the T-loop. Telomeres prevent abnormal fusion between chromosomes,
protect the ends of chromosomes from degradation, ensure complete DNA
replication, and have a role in chromosome pairing during meiosis.
7. Definitions
- Locus: location of a specific gene on a chromosome
- Allele: One of the alternative versions of a gene at a given location (locus)
along a chromosome
An individual inherits two alleles for each gene, one from each parent.
If the two alleles are the same, the individual is homozygous for that gene.
If the alleles are different, the individual is heterozygous.
8. The structure of chromosomes
• Chromatin: complex of DNA + Histone ocatmers + acidic non-histone
proteins
• Nucleosomes : is the basic structural unit of chromatin. Composed of :
Segments of the DNA double helix wrap around histone octamers. These histone
cores are linked by spacer segments of DNA
• Solenoid: Long strings of nucleosomes are compacted into a helical structure,
each turn of the solenoid containing about six nucleosomes.
The solenoids themselves are arranged into loops attached to a central scaffold.
Octamer of histone protein, contains a high proportion of positively charged
amino-acid residues, can form ionic bonds with the negatively charged DNA
9. The structure of chromosomes
• Nucleotides: molecules, that when combined, form the structural units of DNA
and RNA. [RNA and DNA are polymers are created by long chains of nucleotides]
Composition of nucleotide:
Sugar molecule that is attached to a phosphate group and a nitrogen-containing base.
Linkage:
- 3'-5' phosphodiester bonds: link adjacent nucleotides in a polynucleotide chain
- Hydrogen bonds link pairs of bases
13. The structure of chromosomes
Less than 10% of the DNA in the genome encodes for genes.
There are 3 classes of DNA in the human genome:
1. Single copy DNA 75%: in which the nucleotide sequence is represented only
once per haploid genome
2. Dispersed repetitive DNA families 15%: repetitive sequences that are
dispersed throughout the genome, there are two major families in this group:
- Alu family
- L1 family
3. Satellite DNA: repeat sequences tend to be arranged in tandem, in a head to
tail fashion, and are often found in specific sites such as centromeres or
telomeres.
14. Genes are made up of DNA. Each chromosome contains many genes.
15. Chromosomes in human
Human cells contain 46 chromosomes (diploid)
22 pairs of autosomal chromosomes (numbered 1 to 22 in order of decreasing size) + one
pair of sex chromosome (XX or XY)
17. Stages of gene expression
1. Transcription: RNA polymerase initiates transcription from the "non-coding"
or "antisense" strand of the DNA.
Synthesis of the primary RNA transcript (which includes introns) proceeds in a
5'-3' direction beyond the position on the chromosome that corresponds to the 3'
end of the mature RNA.
A "CAP" structure is then added to the 5' end of the RNA and a polyA tail is
added after cleavage of the 3' end downstream of the coding information.
2. RNA processing and splicing: removal of the introns from the RNA transcript
takes place in the nucleus.
Then the mature mRNA is transported to the cytoplasm.
18. Stages of gene expression
3. Translation: tRNA molecules (each specific for an amino acid) transport
amino acids from the cytoplasm to the mRNA template located on ribosomes, so
adding to the polypeptide chain.
Each set of three bases in the mRNA constitutes a codon.
There are 64 (43) possible triplet combinations and as there are only 20 amino
acids, most amino acids are specified by more than one codon.
Translation is always initiated at a codon specifying methionine, so establishing a
reading frame for the mRNA.
The ribosome then moves along the mRNA three base pairs at a time until a stop
codon is reached.
The completed polypetide is then released.
19.
20. The cell cycle
Cell enters interphase when a mitotic cell division is complete
Interphase consists of: G1, S phase and G2
- G1 (Gap 1): Variable duration (depending on cell type).
- S phase: Stage of DNA synthesis during which each chromosome replicates to
form two daughter chromatids.
- G2 (Gap 2): cell undergoes further enlargement, is ended by mitosis.
In some cell lines G1 may be only a few hours
In other cells, such as neurones and red blood cells, do not divide once they are
fully differentiated and are permanently stopped in a gap phase known as G0.
21.
22. Mitosis
Process by which a cell divides into two daughter cells, each of which receives a
complete set of genetic information.
Stages:
1. Prophase: chromosomes condense, the nucleolus disappears and the mitotic
spindle begins to form.
2. Pro-metaphase: When the nuclear membrane breaks up, with subsequent
dispersal of the chromosomes within the cell. Kinetochores located at the
centromeres facilitate attachment of the chromosomes to the micro tubules of the
mitotic spindle.
23. Mitosis
3. Metaphase the chromosomes are maximally condensed and arranged in the
equatorial plane of the cell.
4. Anaphase: when the chromosomes separate at the centromere and the two
chromatids move to opposite poles of the cell.
5. Telophase: reformation of the nuclear membranes and decondensation of the
chromosomes, accompanied by cytokinesis (division of the cytoplasm).
24. Mieosis
Process by which a primary spermatocyte or oocyte divides to form two cells
(gametes), each with a haploid number of chromosomes.
25. Mieosis
Meiosis I: is a reductive division and has several similarities with mitosis.
1. Prophase I (is considerably more involved than that of mitosis).
A. Leptotene: chromosomes become visible
B. Zygotene: Pairing of homologous chromosomes along their entire length, a
process of synapsis that precisely aligns corresponding DNA sequences.
C. Pachytene: The homologous chromosomes now appear as bivalents + crossing
over occurs (exchange of homologous segments between non-sister chromatids)
D. Diplotene: The homologous chromosomes then begin to repel one another,
although they remain attached at points known as chiasmata.
These chiasmata are thought to mark the sites of cross over.
26. 2. Metaphase I
3. Anaphase I: The most error prone phase in meiosis.
During anaphase I the bivalents separate independently of each other, so the
paternal and maternal set of chromosomes are sorted into a random combination.
Meiosis II is NOT preceded by an S phase and is similar to mitotic cell division.
Further segregation of paternal and maternal alleles may occur during meiosis II,
depending on whether they have been involved in a cross over during meiosis I.
27. Mutations
Any permanent change in the DNA.
The change may be:
1. Genome mutations: The most common, with a frequency of 10-2 per cell
division. They are the result of chromosomal mis-segregation.
2. Chromosome mutations: are the result of chromosomal rearrangements, and
have a frequency of 6 x 10 −4 per cell division.
3. Gene mutations are the least common form of mutation in the human genome,
with a frequency of 10-10 per base pair per cell division.
Although the DNA polymerase introduces one incorrect nucleotide every 107 base pairs,
DNA repair enzymes recognize and repair 99.9% of all replication errors.
28. Mind Map: Gene Mutations
1. Nucleotide substitutions:
A. Missense mutations
B. Nonsense mutations
C. RNA splicing mutations
2. Deletions and insertions:
A. Frame-shift mutations
B. Codon insertions or deletions
C. Gene deletions and duplications
3. Misalignment and pairing
29. Gene mutations
1. Nucleotide substitutions: can take the form of:
A. Missense mutations: point mutations amino acid substitutions that alter the
"sense" of the coding strand of the gene, as in the haemoglobinopathies
B. Non-sense mutations: inclusion of a premature stop codon premature
termination of translation e.g. in the neurofibromatosis type 1 gene
C. RNA splicing mutations (=Splice site mutation): which alter the sites;
involved with the recognition of intron/exon (acceptor sites) or exon/intron
(donor sites) boundaries faulty RNA splicing.
30.
31. Gene Mutations
2. Deletions and insertions: can take the form of:
A. Frameshift mutations: in which the reading frame of translation will be altered
by a deletion or an insertion when the number of bases involved is NOT a
multiple of three
B. Codon insertions or deletions: The bases involved are a multiple of three
C. Gene deletions and duplications, mutations that tend to occur in identical or
near identical DNA sequences.
32. Gene Mutations
3. Misalignment and pairing out of register may occur in both meiosis and
mitosis.
Recombination between mispaired chromosomes or sister chromatids gene
deletion or duplication.
This unequal crossing over is responsible for the variation in the number and
structure of red and green visual pigment genes between normal individuals and
males with defective red or green colour vision.
DNA can also be damaged by extrinsic influences such as ultraviolet or ionising
radiation, and chemical processes such as deamination or depurination.
34. Chromosomal abnormalities
1. Abnormal chromosome number (aneuploidy) : The most common
3-4% of all clinically recognized pregnancies.
Mechanism:
A. Nondisjunction in meiosis I Gamete with 24 chromosomes containing
both the maternal and paternal members of the pair.
B. Nondisjunction in meiosis II when die? gamete will have both copies of
either the paternal or maternal chromosome.
35. Chromosomal abnormalities
2. Abnormal structure of chromosome:
d.t. a breakage in the chromosome followed by an abnormal recombination
Types:
A. Balanced: if the recombination produces a chromosome with a normal
amount of genetic information
B. Unbalanced: if the recombination produces a chromosome with additional or
missing information.
36. Chromosomal abnormalities
Balanced Unbalanced
Amount of genetic
information
normal Abnormal
Phenotype Normal Abnormal
Changes occur • Inversions
• Translocations
• Deletions
• Duplications
• Ring chromosomes
• Isochromosomes
40. Chromosomal abnormalities: Balanced
A. Balanced rearrangements:
NO abnormal phenotype, but can pose a threat to subsequent generations because
carriers are more likely to produce unbalanced gametes.
Examples:
1. Inversions: a chromosome sustains two breaks and the segment inverts before
rejoining the chromosome.
- Pericentric inversion: If the inverted segment includes the centromere
- Paracentric inversion: If both breaks occur in the same arm of a chromosome
41.
42. Chromosomal abnormalities: Balanced
2. Translocations: Exchange of chromosome segments between non-
homologous chromosomes.
- Reciprocal translocation: reciprocal exchange of the broken-off segments “the
total number of chromosomes is unchanged”
- Robertsonian translocation: rearrangement that involves two acrocentric
chromosomes that fuse near the centromere, with subsequent loss of the short
arms. Although the balanced karyotype has only 45 chromosomes (including the
translocation chromosome), the phenotype is invariably unaffected as the short
arms of all five pairs of acrocentric chromosomes have multiple copies of genes
for ribosomal RNA. Therefore deletion of two short arms is not deleterious to the
carrier.
43.
44. Chromosomal abnormalities: Unbalanced
Unbalanced rearrangements: Abnormal phenotype.
Types:
1. Deletions: may be terminal or interstitial
2. Duplications: Less harmful than deletions
3. Ring chromosomes: chromosome undergoes two breaks and the broken ends
unite
4. Isochromosomes: chromosomes that have one arm missing and the other
duplicated.
The clinical effect depends on the size of the deleted segment and the number
and function of the genes it coded for
45. Autosomal dominant (A.D) trait with 100% penetrance
Autosomal dominant traits account for more than 50% of all mendelian phenotypes.??
Affected children usually have one unaffected parent and one who is
heterozygous for the mutation (As the prevalence of the abnormal gene is low
compared with that of normal alleles)
Any child with such parents will have a 50% chance of inheriting the trait.
47. No skipped generations = each affected person having an affected parent
Except ?
- If fresh mutation in the gamete of a phenotypically normal parent, disorder is
not expressed (non-penetrant) or is expressed very mildly.
In AD disorders, Homozygotes are more severely affected than heterozygotes
in most autosomal dominant disorders, except is Huntington’s disease.
48. Autosomal recessive (A.R) trait
A.R. disorders are expressed only in homozygotes and account for
approximately 1/3 of the recognized mendelian phenotypes.
The most common scenario is the mating of two carriers.
49. Autosomal recessive (A.R) trait
- Sex: Both males and females are equally affected.
- Consanguinity:
Consanguinity between parents of an affected person is more likely if the gene
responsible for the condition is rare in the general population.
Consanguinity in previous generations is usually irrelevant
51. Autosomal recessive (A.R) trait
Parents Risk to offspring
Genotype Phenotype
Carrier x carrier = R/r x R/r ¼ R/R, ½ R/r, ¼
r/r
¾ Unaffected,
¼ affected
Carrier x affected: R/r x r/r ½ R/r, ½ r/r ½ Unaffected,
½ affected*
Affected x affected: r/r x r/r All r/r All affected
* The mating of a carrier and an affected homozygote leads to a quasi-dominant inheritance
pattern, with 50% of the siblings being affected. This pattern can be distinguished from a
true autosomal dominant pedigree as it rarely persists over more than two generations.
53. X inactivation = Lyonization
The principle of X inactivation was first put forward by Mary Lyon in 1961-2.
Lyon hypothesis (has three main points):
1. In somatic cells of female mammals: Only one X chromosome is active & the
second is inactive and appears in interphase cells as a Barr body.
(The exact mechanism of this inactivation is unknown)
2. Inactivation occurs from 3 days (16-64 cell stage) after fertilization and is
normally complete by the end of the first week
3. In any somatic cell, inactivation is purely random (the inactive X may be the
paternal or maternal X);
however, all the clonal descendants of that cell will have the same inactive X.
54. X inactivation
X inactivation explains “dosage compensation”: Quantity of a product
produced by a single allele in a male is equivalent to that produced by a pair of
alleles in a female.
55. X inactivation
NOT all of the condensed X chromosome is inactive; some segments, such as
the distal region of the short arm, remain active.
Females are mosaics with respect to their X-linked genes, that is, they have
two cell populations in which one or the other X chromosome is the active one.
In carrier females, the proportion of cells in which a particular allele is active is
variable considerable phenotypic variability in X-linked disorders (ranging
from a normal individual to a full manifestation of the defect), that is, a
manifesting heterozygote.
56. X-linked recessive trait
The gene responsible for X-linked recessive traits is transmitted from an affected
male through all his daughters.
[The gene is never transmitted directly from father to son]
- Any son of a carrier female will have a 50% chance of inheriting the trait.
57. X-linked recessive trait
X-linked recessive traits are much more common in males, females may be
affected in the following situations:
1. Homozygous females, for example the daughter of an affected father and a
carrier mother
2. Manifesting heterozygotes
The genes responsible for X-linked recessive disorders are exposed to selection that may
be complete or partial, depending on the fitness of the genotype, and therefore tend to be
lost.
In cases where the mutation is genetically lethal (e.g. Duchenne muscular dystrophy),
selection will mitigate against the persistence of the trait and new mutations rather than
inheritance from a carrier mother account for a significant proportion of casts.
58. X-linked dominant trait
Genetic disorder is located on the X chromosome, and only one copy of the allele
is sufficient to cause the disorder when inherited from a parent who has the
disorder.
X-linked dominant traits do NOT necessarily affect males more than females
(unlike X-linked recessive traits)
Pedigree:
- Affected male affects all the daughters but none of the sons
- Affected female Like in autosomal dominant traits.
Example: hypOphosphataemic rickets (Vitamin D resistant rickets)
61. Mitochondrial inheritance
Each cell contains multiple mitochondria, mitochondrion contains 2-10 DNA
molecules
Both normal & mutant mDNA can coexist = heteroplasmy
1. The proportion of normal to mutant mDNA: will fluctuate through the
process of replicative segregation.
2. The proportion of normal to mutant mDNA: required to produce a
disease phenotype = threshold effect,
and varies from organ to organ and person to person. This explains why,
although carrier females will pass on the defect to all their children, not all of
them will be manifestly affected.
62.
63.
64.
65. Mitochondrial inheritance
mDNA contains 37 genes, all of which are essential for normal mitochondrial
function
- 30 genes provide instructions for making enzymes involved in oxidative
phosphorylation
- 7 genes provide instructions for making molecules called transfer RNA (tRNA)
and ribosomal RNA (rRNA)
NO introns in mitochondrial DNA (mtDNA)
67. Mitochondrial inheritance
All our mitochondrial DNA is maternally inherited, because the mitochondria
of the sperm are lost after fusion with the egg.
Therefore in mitochondrial inheritance an affected mother passes the defect to all
her children, but only her daughters will transmit the trait to subsequent
generations.
68. Mitochondrial inheritance
Diseases related to mDNA changes:
• Leber hereditary optic neuropathy
• Neuropathy, ataxia, and retinitis pigmentosa (NARP)
• Progressive external ophthalmoplegia (Kearns-Sayre syndrome)
69. Mitochondrial inheritance
mtDNA has a mutation rate 10-17 times higher than that of the nuclear genome d.t. :
1. DNA polymerase misincorporation: beta & gamma DNA polymerases are
highly inaccurate, and a substitution rate of 1 in 3-8000 base pairs causes random
misincorporations
2. Oxidative stress: DNA damage d.t. superoxide radicals, hydrogen peroxide
and hydroxyl radicals.
Mitochondria use 90% of cellular oxygen and in addition mtDNA is not bound to
histones, and is therefore more susceptible to damage by these oxidised species
3. Alkylating agents: some of these agents have been shown to modify the
mtDNA five times more efficiently than nuclear DNA in vitro
70. Mitochondrial inheritance
mtDNA has a mutation rate 10-17 times higher than that of the nuclear genome d.t. :
4. The "DNA repair repertoire" of mtDNA is underdeveloped in comparison
with that of nuclear DNA.
A rudimentary excision repair mechanism is able to prevent mutations, but the
mitochondrial polymerase cannot proofread and remove certain modified bases
5. The mtDNA is devoid of introns, so a random mutation is more likely to
strike a coding DNA sequence.
73. Molecular cloning
Restriction endonucleases are enzymes that recognise specific sequences at
double-stranded DNA and cleave the DNA at or near these recognition sites.
DNA ligase catalyses the formation of phosphodiester bonds on each strand, so
creating a "recombinant" DNA molecule.
These sites tend to be palindromes, that is they read the same 5' to 3' on both strands.
Their discovery has been instrumental in the development of molecular cloning, as they
enabled DNA to be broken up into a characteristic and reproducible collection of
fragments.
These fragments will all have identical single stranded sticky ends; any two DNA
fragments produced by a particular restriction endonuclease digest can therefore be joined
together.
74. Molecular cloning
A vector: is a DNA molecule into which the gene or DNA fragment of interest is
cloned.
They can replicate autonomously in a host such as bacterial or yeast cells.
Commonly used vectors include:
- Plasmids
- Bacteriophages
- Cosmids.
75. Molecular cloning
(1) Plasmids: are circular, double-stranded DNA molecules that replicate extra-
chromosomally in bacteria or yeast. Cloning into plasmids is a standard
technique for the analysis of short DNA molecules.
(2) Bacteriophage lambda: is a bacterial virus that replicates during growth in
E-coli and produces large numbers of infectious double-stranded DNA viruses.
These eventually kill the host cell, which ruptures and releases the
bacteriophages. As about one-third of the bacteriophage genome is non-essential
it can be replaced by other DNA sequences, making it ideal for cloning pieces of
human DNA up to 20 kb
(3) Cosmids: are essentially plasmids that use infectious bacteriophage lambda
particles to process and introduce large DNA fragments (up to 50 kb) into
bacterial cells.
76. Molecular cloning
Complementary DNA (cDNA) is a synthetic single-strand DNA that is copied
directly from RNA by reverse transcriptase.
cDNA has several advantages over genomic DNA:
1. It contains NO introns nor non-coding sequences
2. mRNA isolated from specific tissues will be a good source of clones expressed
preferentially in that tissue.
cDNA library
Single-stranded cDNA can be converted to a double-stranded molecule, which can then be
ligated into a vector to create a cDNA library encompassing all the mRNA transcripts from
that cell type or tissue.
77. Molecular cloning
Probes: are cloned DNA or RNA molecules that can be used to detect
homolgous sequences in nucleic acids.
Nucleic acid hybridization is a technique used to find and analyse specific DNA
or RNA fragments;
Single-stranded nucleic acids are mixed with a specific probe in conditions that
promote the formation of double- stranded nucleic acid.
The probe only hybridises to its complementary strand sequence in the DNA or
RNA sample, which is now marked by a radioactive tag.
They are often labelled with a radioactive tracer
to facilitate detection and analysis.
79. Definitions
- Hybridization: Process of establishing sequence-specific interaction between
two or more complementary strands of nucleic acids into a single complex
تهجين=بعض مع يتحدوا مختلفين مصدرين من جزئين
- Denaturation: process by which double-stranded DNA unwinds and
separates into single strand
بعض عن يفصلوا اتنين
- Annealing: Complementary sequences of single-stranded DNA or RNA to
pair to form a double-stranded polynucleotide
اتنين يبقى واحد
80. Biochemical and molecular biological techniques
The process of extracting nucleic acids from cells
It relies on:
- Their different solubility when compared to other cellular constituents
or
- On their binding to synthetic resins.
81. Biochemical and molecular biological techniques
1. Restriction enzymes are endonucleases that cleave DNA on recognizing a
specific sequence.
[These sequences are between four and six base sequences long]*
Thus, a six basepair cutter will produce many fragments with an average length of 4 kb. Since
the genome is random, the fragment sizes will be variable about a mean.
2. Separation of these fragments by gel electrophoresis.
Fragments are loaded into wells in a tray of agarose gel, across which an electric
field is applied.
DNA is negatively charged will move towards the positive charge, with small
fragments migrating more quickly than large fragments.
Ultraviolet light is used to visualize DNA after staining with ethidium bromide.
83. The polymerase chain reaction (PCR)
It can amplify a single molecule of DNA million fold in 20 cycles enabling
the detection & analysis of specific gene sequences without cloning, and without
the need for Southern or Northern blotting.
Advantage of PCR over Southern or Northern blotting:
- Faster
- Less expensive
- More sensitive
- Less technically demanding
- It requires only a fraction of the genomic DNA or RNA for analysis
The PCR made a revolution in the analysis of DNA and RNA
The identification of a single sequence is possible
86. PCR procedure
PCR consists of a series of 20–40 repeated temperature changes “cycles”
1. Target DNA, two oligonucleotide primers and heat stable DNA polymerase are
placed in a tube.
2. Denaturation: The mixture is heated to just below 100°C DNA is
denatured to form single-strand nucleic acids
3. Annealing step: The reaction temperature is lowered to 50–65 °C
Allowing annealing of the primers to the single-stranded DNA template allow
for hybridization of the primer to the strand.
The polymerase binds to the primer-template hybrid and begins DNA formation.
87. PCR procedure
4. Elongation step: Taq polymerase (type of DNA polymerase) synthesizes a
new DNA strand complementary to the DNA template strand
5. Continue for 20-40 cycles
RNA samples can also be amplified
Complementary DNA (cDNA) is produced using a reverse transcriptase enzyme. PCR
primers are then added with DNA polymerase, and one of these oligonucleotides primes
the synthesis of the second cDNA strand. The double-stranded DNA can then be
amplified as above.
88. PCR
PCR is highly specific & highly sensitive*
The high sensitivity is one of its major drawbacks !!
becasuse of the major risk of false positive reaction caused by
contamination
90. Southern blotting
Used for detection of a specific DNA sequence in DNA sample
It is NOT able to detect single base mutations.
91. Technique of southern blotting
(1) Genomic DNA is digested by restriction enzyme
(2) The fragments of DNA generated are separated on the basis of size by agarose
gel electrophoresis
(3) The DNA is then denatured with a strong base to form complementary single-
strand nucleic acid strands. These single strands are transferred to a nitrocellulose
or nylon filter paper by blotting or capillarity
(4) A radiolabelled probe (single-stranded DNA) and the filter paper are
incubated together, allowing the probe to hybridise with matching fragments on
the filter
(5) Unbound probe is washed off and the filter is exposed to x-ray film, to reveal
the positions to which the probe hybridised.
92. Northern blotting
This is a technique used to study the expression of genes
Molecules of RNA (or isolated mRNA) are separated by electrophoresis
Single base mutations can be detected using allele-specific oligonucleotides (ASOs).
These probes are synthesized from individual nucleotides and correspond to a known segment of a
particular gene; they are usually around 10—20 base pairs in length. These short probes can be
manufactured to correspond with either the normal or an imperfect DNA sequence, hence their
ability to detect such small mutations.
However, if false negative results are to be avoided, the outcome of ASO analysis should be
interpreted with caution, as not all mutant genes at a given locus have exactly the same mutation.
Northern blotting is the RNA equivalent of Southern blotting.
But, RNA can NOT be cleaved by restriction enzymes; cellular DNA or purified
mRNA is therefore separated by agarose gel electrophoresis and transferred to a
nylon or nitrocellulose membrane
93. Western blotting
This is the protein equivalent of the above techniques.
Gel electrophoresis is used to separate the denatured proteins by mass. These are then transferred
to a nitrocellulose membrane and probed for using a specific fluorescently labelled antibody,
which binds only to the protein under investigation.
NO Eastern blotting
94. MCQs (to be added later in its place)
Karyotype
Systemic display chromosomes from a single somatic cell
• 23 pairs
NOT obtained from:
Sperms & germ cells (contain 23 chromosomes only)
RBCs (No nucleus)
95. MCQs (to be added later in its place)
• Isochromosome: abnormal chromosome created by deletion of one arm or
duplication of other arm* (Chua)
• Genocopy: different non-allelic genotypes that result in a similar
phenotype
• Autosome: chromosomes other than sex chromosomes (22 pairs in
humans)
• Synteny: presence of genes on the same chromosomes
• Heteroplasmy: presence of 2 or more different populations of
mitochondria within a cell.
97. Gene therapy
Gene therapy has already been attempted with some success
Examples :
- Leber’s congenital amaurosis.
- Inhalation of the CFTR gene in a disabled adenovirus proved temporarily
successful in cystic fibrosis patients.
- The adenosine deaminase gene has successfully been inserted into the bone-
marrow cells of children with subacute combined immunodeficiency (SCID)
98. Gene therapy ???
Pre-requisites are that the gene concerned and its control elements must be fully
characterized and cloned.
Accessible target cells must be identified that have a reasonable and productive
life span.
Finally the chosen vector must be efficient and safe
99. Gene therapy
Methods used for gene sequence introduction:
1. Viruses have been manipulated to use their inherent ability to insert genetic
material into their host cells.
2. Non-viral delivery methods include the introduction of naked DNA directly
into the cell and the use of liposome-mediated DNA transfer.
More recently
Stem cells utilize their pluripotency and multipotency to replace
defective organ cells.
These are already commonplace for some haematological conditions such
as leukaemia.
The hope is that soon structures in which the cells do not multiply, such as
the RPE, might be replaced using stem cells.
Editor's Notes
(Chromo= Colour; Soma=body)
(Chromo= Colour; Soma=body)
(Chromo= Colour; Soma=body)
(Chromo= Colour; Soma=body)
Allele = "reciprocal" or "each other"
(Chromo= Colour; Soma=body)
scaffold : سقالة
(Chromo= Colour; Soma=body)
?? هيه نفس المعلومة الصفحة الجاية ؟.؟؟
??????
The chromosomes are numbered 1 to 22 in order of decreasing size
$ DNA mRNA protein
Transcription – RNA processing - Translation
$ DNA mRNA protein
Transcription – RNA processing - Translation
G1 –: duration (cell wait only)
S: Synthesis
G2: duration between synthesis & start of Mitosis
$ People Meet And Talk
$ I Picked My Apple’s Today
?? Which is correct ?? A kinetochore is an organelle located at the centromere region which facilitates spindle formation by polymerization of tubulin dimers to form microtubules during mitosis
$ People Meet And Talk
$ لب زي باقي الدب
Any deviation from the normal karyotype is known as a chromosome abnormality
50 % ???
غالبا واحد م الابوين سليم تمام والتاني هجين
50 ???
اتاكد من المعلومتين
اكيد لو الكروموسوميين بايظين هايبقى البوظان اكتر
ماعدا الهنط
???? Ferris
An autosomal recessive phenotype is often isolated; if it appears in more than one member of a kindred, typically it is seen only in the sibship of the proband and not in the parents, offspring, or other relatives
Quasi = تشبه
جبنا اتنين اكس بوظنا واحد ف اسبوع
بوظنا
واحد = أي واحد
اسبوع
مثلا اكس الام اللي باظ .. هيفضل بايظ طول العمر
Equalize gene dosage between males & females
Selection: الانتخاب الطبيعي
?? Mesh fahem el n.b. kewayessss ???
اتاكد
Function ?? again
Function ?? again
Function ?? again
Function ?? again
$ phosphodiester bonds is th bond between nucleotides
صور بلازميد والبافي
$ pBC
Synthetic resins: viscous liquids that are capable of hardening permanently.
#chua: restriction fragment length polymorphism occur mainly in the coding region of the DNA*
Bp: Base-pair
Kb: kilo-bases
Kbp: kilo-base-pair
كلهم نفس المعني
PCR Need prior knowledge of DNA sequence being tested (true)
Analyze BOTH DNA – RNA
Need small fraction
DNA – RNA
Need small fraction
DNA + Primers + DNA polymerase
Synteny = تصاحب جيني
Genocopy is a trait that is a phenotypic copy of a genetic trait but is caused by a different genotype
“Stem cell therapy in retina still under trials …. NOW Everything done in market is fake” Dr Gehad El Nahry