Chromosomes inside the nucleus

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Chromosomes inside the nucleus

• Chromosomes are usually seen as a network of
  chromatin inside the nucleus
• They separate out into individual chromosomes
  during cell division
• After division they again go back to their
  original network status

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Cell Divisions

• Mitosis
• Happens only in normal somatic (body) cells
• One diploid (2n 46 chromosomes) cell divides to
  give rise to 2 daughter cells each of which are
  identical to the mother cell
• Includes 4 stages Prophase, Metaphase, Anaphase,
  Telophase and Cytokinesis (division of
  cytoplasm)

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Prophase

• Condensation of chromosomes
• Disappearance of nuclear membrane

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Metaphase

• Alignment of chromosomes along equator of the
  cell
• Formation of spindle fibers

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Anaphase

• Chromosomes begin moving to the poles (pulled by
  the spindle fibers)

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Telophase

• Alignment into two daughter cells identical to
  parents
• Process called Cytokinesis (splitting of cell)

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Meiosis

• Happens only in sex chromosomes
• Gives rise to the gametes (sperm and ovum)
• In two stages
• Meiosis I (Reduction division where in a diploid
  cell (2n) becomes haploid (n))
• Meiosis II (Equational division, where in the
  haploid cells undergo mitosis to result in two
  haploid cells

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Chromosomal Aberrations

• Chromosomal errors either in
• Structure of chromosomes
• Deletion, Inversion, Duplication and
  Translocation
• of chromosomes
• Euploidy (Polyploidy)
• Alterations in whole chromosome sets (addition of
  a whole set of chromosomes to the genome)
• Aneuploidy (Polysomics)
• Alteration in the number of chromosomes may be
  chromosome number being less than or more than 46

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Nondisjunction of sex chromosomes

• Nondisjunction is the failure of chromosomes or
  chromatid pairs to separate in Meiosis I or II
• Abnormal chromosome movement during meiosis.
  Gametes too few or too many chromosomes
• Age of mother influences
• See Study guide

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Polyploids

• Individuals have 3 or more of each chromosome
• i.e., in place of being diploid (2n), they end up
  being triploid (3n), tetraploid (4n), hexaploid
  (6n) etc.
• Lethal in humans
• This is how we get most of our cereals

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Polysomics

• Alteration in the number of autosomes
• Downs syndrome (Trisomy 21 as there are 3 copies
  of chromosome 21 in Downs kids as opposed to
  normal 2 copies)
• Cri-du-chat
• Fragile X syndrome
• Alterations of the number of sex chromosomes
• XYY Jacobs syndrome
• XXY Klinefelters syndrome
• XXX Poly-X syndrome
• XO Turners syndrome, (no Y)

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Monosomics (deficiency of chromosome)

• XO Turner Syndrome
• Female resulting from non-disjunction during egg
  or sperm formation
• Sterile, failure to enlarged breasts hips,
  shortness, no menstruation
• YO not viable

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Trisomics (excess of chromosomes)

• XXY Klinefelters Syndrome
• sterile, small testes, enlarged breasts
• How many ever X in the genome, still if there
  is a Y, the zygote develops into a male
• XXXY, XXYY, XXXXY are more mentally challenged
  than the XXY

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Trisomics (excess of chromosomes)

• XXX Metafemale
• limited fertility but otherwise normal
• Some mental retardation possible
• XYY Jacobs syndrome
• male, may be taller than usual

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Alterations of Chromosome Structure

• Inversion
• A segment of the chromosome is turned 180 degrees
• Changes linkage group
• Extremely damaging that most embryos die
• ABCD becomes DCBA

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Alterations of Chromosome Structure

• Translocation
• A broken piece of a chromosome attaches to itself
  to another
• Can change gene expression
• It is seen in some forms of cancer, when a
  segment of chromosome 8 is translocated to 14
• Can lead to Downs Syndrome

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Alterations of Chromosome Structure

• Deletion
• A segment (portion) of the chromosome is missing
• Caused by viruses, chemicals or irradiation
• Loss of a portion of chromosome 5 causes
  Cri-du-chat
• Rounded moonlike face, cat like cry, mental
  physical retardation

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Alterations of Chromosome Structure

• Duplication
• A segment of the chromosome is repeated
• Fragile X syndrome, results in a form of mental
  retardation
• Myotonic dystrophy and Huntingtons Disease

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• Mechanism
• Most mutations usually involve recessive alleles
• Phenylketonuria
• Tay-Sachs Disease
• Dominant lethal allele
• Huntington Disease
• Always expressed, though at midlife
• Always lethal

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Genes and Behavior

• Mechanism
• Product from gene-specific proteins
• Proteins have specific functions leading to
  phenotypes
• Protein functions
• hormones, enzymes, structural, neurotransmitters

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DNA structure and Function

• DNA Replication
• Flow of Genetic information
• Transcription
• Translation

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So where are the blueprints?

• The key is in the memory of the cell
• DNA (deoxyribonucleic acid)
• RNA (ribonucleic acid)
• DNA / RNA is composed of nucleotides
• Nucleotides have three components
• 1. One of five heterocyclic nitrogen containing
  bases
• 2. Sugar D- ribose (RNA) / Deoxy- ribose (DNA)
• 3. Phosphoric acid

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Surprising Results

• 30,000 genes
• Every person shares 99.99 of their genetic code
  with all other people
• race although culturally important reflects
  just a few traits determined by a fraction of our
  genes

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Human Genome Entire Code FYI

• 3 billion letters (bases) in the genetic code
• Located in every cell. It contains the
  instructions for building that cell and making it
  do its job.

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What are chromosomes doing inside a cell?

• In the 1890s, chromosomes were observed to occur
  in pairs
• They double before cell division
• Chromosomes were suspected to be carriers of
  heredity

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1944 Genes are made of DNA

• DNA was discovered to be the genetic material
  inside a cell

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What is a Gene?

• The basic unit of heredity
• A sequence of DNA nucleotides on a chromosome
  that encodes for a polypeptide
• Determines an individuals inherited traits

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What is a gene?
DNA that contains the instructions to make gene
products (proteins)
Cytoplasm of cell
Nucleus
DNA ? RNA ? Protein
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Chromosomes in a dividing cell
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Modifying DNA

• Recombinant DNA technology
• cutting, splicing and copying DNA, Polymerase
  chain reaction (PCR)
• Genetic engineering
• Microorganisms factories for human proteins,
  vaccines, environmental applications
• New plants for agriculture
• New uses for domestic animals
• Human gene therapy

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Number of diploid chromosomes FYI
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X-ray diffraction
DNA
Rosalind Franklin
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1953 Structure of DNA discovered

• Watson and Crick proposed the model of DNA double
  helix using X-ray diffraction method
• Winners of 1962 Nobel prize in Physiology or
  Medicine category

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Watson and Crick
1953
1993
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1962 Nobel Prize
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DNA structure
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5
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• Just like a Spiral Staircase

• The two poles are composed of the Phosphate and
  sugar molecules
• While the rungs are the nucleotides (A,T,C,G)

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A

• 4 Genetic letters of the DNA
• DNA nucleotides also called Bases
• Adenine and Guanine are called Purines
• Cytosine and Thymine are called Pyrimidines

T
C
G
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Nucleic acid bases

• A Adenine
• T Thymine
• C Cytosine
• G Guanine

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DNA building blocks

• There are 3 nucleotides that make up a codon (out
  of the 4 nucleotides in DNA)
• Here ATG can be considered a codon
• Or TGC can be considered a codon

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FYI

• The 4 nucleotides combine 43 64 different
  combinations (because 3 bases make a codon and
  there are 4 bases available for combination)
• The 64 combinations code for 20 amino acids (that
  is the total of amino acids in our body)
• More than one set of codons code for the same
  amino acid (that is why 64 combos but just 20
  amino acids)

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The genetic code
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• Base Pairing Rule
• A always pairs with T
• A T (2 Hydrogen bonds)
• C always pairs with G
• C ?G (3 Hydrogen bonds)

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Complementary base pairing

• We know that one strand of DNA is complement of
  the other strand
• If one of the strand has the sequence of letters
  ATTGCGGTTACC
• Then, the other strand should have the
  complementary sequence which is TAACGCCAATGG
• Because A T and C ? G

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Deoxyribo nucleic acid
Deoxyribo Nucleic Acid
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DNA versus RNA
Ribo Nucleic Acid (RNA)

• Has bases A, U (Uracil), C and G
• Thymine (T) in DNA is replaced by Uracil (U) in
  RNA

Deoxyribo Nucleic Acid (DNA)
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DNA and RNA bases
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DNA Replication

• Semi-Conservative model
• Two strands separate
• One old strand forms template and makes a new
  strand
• So 2 new strands produced, each having one old
  and one new strand

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DNA replication
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DNA replicationUnwinding the helix
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The genetic code
DNA
RNA-like strand
5
3
5
3
Template strand
mRNA
5
3
Polypeptide
N
C
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The Genetic Code
The code consists of triplet codons
(three Nucleotides correspond to one amino acid)
ATT
DNA
AAT
mRNA
AUU
Polypeptide (protein chain)
Ile
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The genetic code
The codons are Non-overlapping, Degenerate and
Universal
ATTTCT
DNA
AGAAAT
mRNA
AUUUCU
Ile-Ser
Polypeptide
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Flow of genetic information
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DNA to mRNA

• DNA ATTGCGGTTACC
• mRNA UAACGCCAAUGG
• The only difference is that T in DNA changes to
  U in RNA

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Transcription

• The first stage of gene expression
• Information in DNA (Double strand) is taken out
  of the nucleus in the form of mRNA (Single
  strand)
• This transfer from DNA to mRNA is made possible
  by RNA Polymerase enzyme
• The sequence of the mRNA molecule will be
  complementary to DNA

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Why do we need mRNA if DNA holds all the genetic
information, the instructions for the proteins
the cell is supposed to produce?
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DNA is our only source of genetic information
has to be carefully protected from any kind of
damage
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Role of Messenger RNA (mRNA)

• Encoding genetic information from DNA and
  conveying it to ribosomes
• This transcription process is the most imperative
  step in Gene expression
• The information is then translated into Amino
  acid sequences in the ribosomes

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• The sequence of nucleotides of the mRNA molecule
  dictates the sequence of amino acids of the
  polypeptide

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Transcription
Messenger RNA
Nuclear membrane
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Translation

• The second stage of gene expression
• A ribosome assembles a polypeptide, using the
  mRNA to specify the amino acids

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Translation

• tRNA possesses anti-codons for the 3 letter codes
  on the mRNA
• charges itself with the proper amino acid
  specified by the three letter code
• If mRNA has AUG, tRNA will bring in UAC
• AUG of mRNA bonds with UAC of tRNA to produce
  one amino acid

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The role of Ribosomes

• To assemble the amino acids that are brought by
  the tRNA into peptides

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Protein synthesisTranslation
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Translation in action
mRNA
Nascent polypeptide
Ribosome
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Translation
Ribosome
tRNA
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Translation

• mRNA Protein
• 3 bases 1 codon 1 amino acid
• Peptide bonds (CN) connects the amino acids
  together

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Protein synthesis inhibitors