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Genomic DNA, Genes, Chromatin ومن أحياها
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GENETICS
الفريق الطبي
االكاديمي
Genomic DNA, Genes, Chromatin
DONE BY :
Obadah Abubaker &
Shady Soghayr
GENETICS
Genomic DNA, Genes, Chromatin ومن أحياها
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Genomic DNA, Genes, Chromatin
Dr. Nabil Bashir
Genomic DNA, Genes, Chromatin
a). Genetic dogma
b). forces that affect DNA double helical stability
c). Complexity of chromosomal DNA
i). DNA denaturation
ii). Repetitive DNA and Alu sequences
iii). Genome size and complexity of genomic DNA
d). Gene structure
i). Introns and exons
ii). Properties of the human genome
iii). Mutations caused by Alu sequences
e). Chromosome structure - packaging of genomic DNA
i). Nucleosomes
ii). Histones
iii). Nucleofilament structure
Genomic DNA, Genes, Chromatin ومن أحياها
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Learning Objectives • Know what is meant by Genetic dogma • Understand the nature of the forces contributing to the
stability of the DNA double helix • Understand the process of DNA denaturation and the
relationship between melting temperature and the base composition of DNA
• know what repetitive sequences are and how they are arranged in the human genome
• Understand the mechanism by which Alu sequences have affected the LDL receptor gene
• recognize basic gene structure. • Know the basic characteristics of human nuclear and
mitochondrial DNA • Understand basic chromosome structure and how
DNA is packaged into chromosomes
Genetic dogma : THE FLOW OF GENETIC
INFORMATION
1. REPLICATION (DNA SYNTHESIS) 2. TRANSCRIPTION (RNA SYNTHESIS) 3. TRANSLATION (PROTEIN SYNTHESIS)
• DNA replication :transferring genetic information
from a DNA molecule to form a new DNA molecule (
will be identical to the precursor).
• Transcription : transfer genetic information from DNA
to RNA(RNA is synthesized from a single strand
DNA (template DNA )).
Genomic DNA, Genes, Chromatin ومن أحياها
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• Translation (protein synthesis) : transfer of genetic
information from RNA to protein
• Reverse transcription : transfer genetic information
from RNA to DNA (happens in many viruses)
DNA needs enzyme activity to replicate.
• Genetic diseases occur because of mutations in DNA.
Many of these mutations affect the repair of other
mutations that occur during DNA replication or at other
times, which in turn affect the flow of genetic information
from DNA to RNA (transcription and processing) and
from RNA to protein synthesis (translation). Many of these
mutations also affect the structures of the resulting
proteins, affecting their functions.
• Mutation :change in the sequence
• Mutation is the base to all genetic diseases
5-Methylcytosine (5mC).
A common base modification in DNA results from the
methylation of cytosine, giving rise to 5-methylcytosine (5mC).
5mC is highly mutagenic.
(5mC) residues are often clustered near the promoters of genes
in so-called "CpG islands.“
when this mutation is in the promoter region it is called
CG(island) hotspot
The problem that arises from these methylations is that
subsequent deamination of a 5mC results in the production of
thymine, which is not foreign to DNA. As such, 5'-mCG-3' sites
(or mCpG sites) are "hot-spots" for mutation, and when mutated
are a common cause of cancer.
Genomic DNA, Genes, Chromatin ومن أحياها
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structure of the nucleic acid :
1.Nitrogenous base ( purines and pyrimidines)
Purines have 2 rings while pyrimidines have 1 ring
Ex. Of purines : Adenine and Guanine
Ex. Of pyrimidines : Thymine ,Cytosine and Uresile
2.Sugar (pentose)
In the case of DNA :at carbon (2) there is no oxygen (just hydrogen)
There is a phosphodiester bond between the carbon (5) (hydroxyl group) and the phosphate ( can be α,β or Ɣ )
3.Phosphate
Can be divided to :
Poly deoxy nucleotide (eg.DNA)
Poly nucleutide (eg.RNA)
Pentose sugar is attached to the nitrogenous base by a N-glycosidic bond (covalent bond between a nitrogen of a nitrogenous base and the sugar).
Genomic DNA, Genes, Chromatin ومن أحياها
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On carbon number 5 of the sugar there is a phosphodiester bond
between the hydroxyl group of the sugar on carbon number 5 and a
phosphate (alpha phosphate or beta phosphate or gama phosphate)
There are three phosphate group attached in a phosphoester bond
with the oxygen of the deoxyribose in the deoxynucleutides.
The left structure in the figure is called deoxynucleotide triphosphate
, if one phosphate is removed then the name is
deoxynucleotidediphosphate , if only one phosphate is found then
the name is called deoxynucleotidemonophosphate , if the base is
adenine then the structure that has adenine, sugar and phosphate is
abbreviated as dAMP(d: deoxy , A: adenosine (not adenine) , M:
mono , P: phosphate) if 2 phosphates are there : dADP , if 3
phosphates : dATP.
The same thing for the dGMP (dGDP or dGTP ً حكٌناه فوق ٌعنً نفس الل
and pyrimidines(dCMP ,dCDP,dCTP and the same thing for the(ممكن
rest).
The only structure difference between ribonucleotide and
deoxyribonucleotide in carbon number 2 of the sugar there is a
Genomic DNA, Genes, Chromatin ومن أحياها
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hydroxyl group in ribonucleotide.
(oxynucleotide)((ribonucleotidefound in RNA)) and there is a
hydrogen group in deoxyribonucleotide((deoxyribonucleotide
found in DNA))
deoxyribonucleotide in DNA gives stability to the DNA
ribonucleotides found in RNA they cause instability
So, it is very important to have deoxy sugars in our DNA for the sake
of stability of our genes, if we have ribonucleotides our genes will be
unstable ,and they will always be destroyed .
**Not necessary to memorize the structure but you must remember
the features of each of the nitrogen bases at least differentiate
between purines and pyrimidines and if you are good ,also
differentiate between adenine and guanine as well as between
different pyrimidines (which one has amino group , which one has
oxyketo group , which one has methel group, remember these
general features.)
One strand of DNA
Genomic DNA, Genes, Chromatin ومن أحياها
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when these nucleotides (deoxyribonucleotides or polyribnucleotides) are
linked to each other they will form polydeoxyribonucleotides (means
DNA) or polyribnucleotides (means RNA)
From the 3 prime carbon of first sugar there is a phosphoester bond
with the alpha phosphate (the first phosphate) of the second
nucleotide
So, between 3 prime of the first sugar with the 5 prime of the second
deoxy sugar you have a phosphodiester bond and this is repeated
between 3 prime of the second with the 5 prime of the third and it
goes to the end .
The polynucleotide that is form has 2 ends : one end is called 5 prime
end and the other end is called 3 prime end .
Why we named it as 5 prime end ?
Because there is a phosphate which is 3 on the 5 prime of the first
nucleotide so this is the beginning of the DNA molecule.
Why we named it as 3 prime end ?
Genomic DNA, Genes, Chromatin ومن أحياها
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Because there is 3 hydroxyl group at the last nucleotide in the nucleic
acid .
So each nucleic acid has 2 ends ,the first on the beginning of any of
nucleic acid is called 5 prime end , and last nucleotide of any nucleic
acid is called 3 prime end.
What are the feature of 3 prime end and 5 prime end ?
5 prime ends have free phosphate groups while 3 prime end of any
nucleic acid has free hydroxyl group at the 3 prime end.
So nucleic acid (when we talk about one strand) it runs from 5 prime
to 3 prime ,you read it from 5 prime to 3 prime,
براٌم بحٌث 3براٌم الى 5ٌعنً لما ٌعطٌك ستراند مثل الصورة فً األعلى نقرأها من
هو الذي Cوفً حالة أعطٌت هذا الترتٌب علٌك أن تعلم أن C , G , A , Tٌكون الترتٌب
Tوهو اول نٌكلٌوتاٌد وال prime(has a free phosphate group) 5ٌحتوٌعلى ال
وهو اخر نٌكلٌوتاٌد . 3prime (has a free hydroxyl group) ٌحتوي على ال
تقرٌبا. 33:03مالحظة هذه الفكرة مشروحة فً الدقٌقة
Genomic DNA, Genes, Chromatin ومن أحياها
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Genes are composed of sequence of deoxynucleotides they are
arranged in specific positions if any position has been changed that
means we have mutation .
DNA is found in a double strand )there are two deoxy
polynucleotides attached to each other ( while RNA is found in a
single strand but sometime you will see that single stranded of RNA
forming some double stranded regions within the RNA molecule for
specific reasons we will talk about it later.
Double stranded which is composed of two strands which are
complementary to each other and they run antiparallel and they
run in a helical structure or twisted .
This structure (helical) was discover in 1953 by Watson and Crick and
they published a paper and saying that DNA is composed of double
stranded molecules and they are in a helical structure .
Antiparallel: one strand runs from 5 prime to 3 prime and the
second strand runs in opposite (from 3 prime to 5 prime)
Genomic DNA, Genes, Chromatin ومن أحياها
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Complementary:means that always thymine base pair with
adenine , cytosine base pair with guanine .
That means guanine can not base pair with adenine or thymine
because there are spaces that units this type of base pairs. (like
the prenciple of the ligand and the receptor) #specificity
The outside of the structure (the backbone )is rich in
phosphates and sugars and from the inside (inside the helical
structure) there are nitrogen bases.
The backbone is stabilized by covalent bonds (phosphodiester
bonds) while the inside base pairing is stabilized mainly by
hydrogen bonds and you will see 2 hydrogen bonds always
between adenine and thymine and 3 hydrogen bonds
between guanine and cytosine.
If any information was written badly (hard to study) or
was not clear
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