The DNA

Structure and Replication

Human Chromosomes
Human Chromosomes
 2n = 23 pairs = 46 chromosomes
 22 pairs of autosomes
 1 pair of sex chromosomes
 22AA + XX  female
 22AA + XY  male
 2 meter of DNA arranged into 46 chromosomes
(23 homologous pairs)
 1 chromosome consists of two chromatids
 3 billion base pairs
DNA Structure
 DNA is a polymer.
 The monomer units of DNA are nucleotides,
 The polymer is known as a "polynucleotide.“
 Each nucleotide consists of:
 a 5-carbon sugar (deoxyribose),
 a nitrogen containing base attached to the
sugar
 a phosphate group
Common Structure of Nucleotide

H
2-Deoxyribose
5 principal bases
PURINE PYRIMIDIEN

H
2-Deoxyribose
Phosphodiester Bonds

Nucleotide subunits are 
linked together by 
phosphodiester bonds 
Native DNA is a double
helix of complementary
antiparallel chains held
together by:

Hydrogen bonding between

complementary base pairs
(A-T or G-C)
 Double Helical Structure
 Forms a right-handed helix.
 The strands run antiparallel.
 There are about 10 base pairs per turn of the
helix.
 One turn of the helix is 34 Å.
 The base pairs are 3.4 Å apart.
 Sugar phosphates on outside, base pairs on
inside.
 Double Helical Structure
Structure of the Double Helix
 Three Major Forms
 B-DNA
 A-DNA
 Z-DNA
 B-DNA is biologically the most common
 Right-handed (20 Angstrom (A) diameter)
 Complementary base-pairing (Watson-
Crick)
 A-T
 G-C
B-form
DNA Replication
(a) Hypothesis 1: (b) Hypothesis 2: (c) Hypothesis 3:
Semi-conservative Conservative replication Dispersive replication
replication

Intermediate molecule
DNA Replication
1) Semiconservative model:
Daughter DNA molecules contain one parental
strand and one newly-replicated strand
DNA Replication
Requirements
 Enzyme: DNA Polymerase
 DNA Template
 3’ OH (primer of DNA or RNA)
 Deoxynucleoside triphosphates: dATP, dGTP,
dCTP, dTTP
 Synthesis is 5’ to 3’
Replication as a Process
 Double-stranded DNA
unwinds.
 The junction of the
unwound molecules is a
replication fork.
 A new strand is formed by
pairing complementary
bases with the old strand.
 Two molecules are made.
 Each has one new and one
old DNA strand.
 5’
 
   
   

 
 
3’-OH attack
incoming nucleotide 
 
 
3’
Problem:
Q: If DNA can only be synthesized in a 5’ to 3’
direction, and both strands are simultaneously
replicated, how can this occur? 5’
3’

? growing
3’ 5’
5’ 3’ fork

5’
A: Discontinuous DNA Replication 3’
The Solution
The Solution
DNA replication is semi­discontinuous
Continuous synthesis

Discontinuous synthesis
Features of DNA Replication
 DNA replication is semiconservative
 Each strand of template DNA is being copied.
 DNA replication is bidirectional
 Bidirectional replication involves two replication forks,
which move in opposite directions
 DNA replication is semidiscontinuous
 The leading strand copies continuously
 The lagging strand copies in segments (Okazaki
fragments) which must be joined
Cell Division
 Mitosis  two
identical daughter
cells
Cell Division
 Meiosis  four cell,
half # chromosomes
 Sperm and ovum are
the products of
meiosis.
Crossing Over
 Crossing over occurs during meiosis
between two non-sister chromatids
Example

e E
♀ x ♂
b B

e E e = esotropic eye
E = straight eye
♀
b = brown eye
b B B = blue eye
Example

e E

E b B
e
♀ Normal meiosis

b B
e E

B b

Cross over
Taking An Ophthalmic Family History
 Complete history
 Pregnancy and birth
 Past medical history
 Medication use
 Detail family history
Pattern of Inheritance
 Autosomal Dominant Disorders
 Autosomal Recessive Disorders
 X-linked Disorders
 Non-Mendelian Inheritance
 Mitochondrial Disorders
 Polygenic Disorders
 Chromosomal Abnormalities
Autosomal Dominant Disorders
 Manifested when only one copy of the gene is
abnormal.
 Passed directly from parents to children of both
sexes.
 The risk of having affected offspring is 50%.
 Doesn’t mean it is “safe” after having one or two
affected children.
 If neither parents is affected, the risk of each
future affected child is not greater than the
population risk.
 Coloboma and neurofibromatosis have variable
expressivity.
 Retinoblastoma
Autosomal Dominant Disorders

II

III

IV
Autosomal Recessive Disorders
 Two copies of an abnormal gene are required.
 Once parents have a child with a recessive
disorder, the risk of having another affected
child is 25%.
 Recessive disorder, on average, more severe
than dominant ones.
 Increases dramatically with
 Consanguinity
 Inbreeding
 Geographically isolated population
Autosomal Recessive Disorders

II

III

IV
X-linked Disorders
 Only males are affected.
 All carrier females have affected father.
 X-linked dominant disorders are very
rare.
 Females are severely affected.
 Females cannot survive, die in utero.
 Examples:
 Incontinentiapigmenti (IP)
 Aicardi’s Syndrome.
X-linked Disorders

II

III
X-linked Disorders

II
Non-Medelian Inheritance
Mitochondrial Disorder
 Mitochondria are organelles within human cell.
 Residing in the cytoplasm.
 Inherited from mother only.
 Disorders run in families through the maternal
lineage.
 Affected women or women carriers never have
affected fathers.
 Examples:
 Leber’s hereditary optic neuropathy
 Chronic progressive external ophthalmoplegia
Non-Medelian Inheritance
Polygenic Disorder
 Not perfect fit with any of the known modes of
inheritance.
 May be due to an environmental component.
 Example: refractive error.
 Also may be considered a multifactoral disorder.
Non-Medelian Inheritance

II

III

IV
Chromosome Abnormalities
 Trisomy (2n + 1)
 Klinefelter Syndrome
 24,XX + 23,Y  47,XXY
 1 in 1000 males
 Hypogonadism (small reproductive organ)
 Gynaecomastia (enlargement of male breast)
 Infertile
 Monosomy (2n – 1)
 Turner Syndrome
 Complete or partial monosomy (45,X)
 1 in 10 000 female
Chromosome Abnormalities
 Autosomal Trisomy
 Down Syndrome (trisomy 21)
 Edward Syndrome (trisomy 18)
 Patau Syndrome (trisomy 13)
 Structural abnormality
 Translocation
 Inversion
 Deletion
 Insertion
Thank You