Dna Structure

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

H 2-Deoxyribose

PYRIMIDIEN

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 (WatsonCrick)  A-T  G-C

B-form

DNA Replication (a) Hypothesis 1:

(b) Hypothesis 2:

(c) Hypothesis 3:

Semi-conservative replication

Conservative replication

Dispersive 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’

3’ 5’

5’ 3’

?

growing 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 



DNA replication is bidirectional 



Each strand of template DNA is being copied. 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

b

B

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

Example

♀

e

E

e

E

b

B 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 I

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 I

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:  Incontinentia

pigmenti (IP)  Aicardi’s Syndrome.

X-linked Disorders I

II

III

X-linked Disorders

I

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

I

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

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