Perez, Glenn Richmond R.

CYTOGENETICS
BSMLS IIIA

THE MOLECULAR BASIS OF INHERITANCE

A. History of DNA

Deoxyribonucleic acid (DNA) is the blueprint for life. It is present in
organisms ranging from the smallest bacterium to the largest whale. The
molecule determines not only what physical characteristics you will have, such as
hair and eye color, but also what diseases you may develop. It is a nucleic
acid containing the genetic information used in the development and functioning
of all known living organisms.


YEAR SCIENTIST CONTRIBUTION
1866 Gregor Mendel Published the results of his investigations of
the inheritance of "factors" in pea plants.
1869 Johann Friedrich Miescher Identifies a weakly acidic substance of
unknown function in the nuclei of human white
blood cells. (later will be known as DNA)
1912 Sir William Henry Bragg, and
his son, Sir William
Lawrence Bragg
Discover that they can deduce the atomic
structure of crystals from their X-ray diffraction
patterns. This scientific tool will be key in
helping Watson and Crick determine DNA's
structure.
1924 Microscope studies using stains for DNA and
protein show that both substances are
present in chromosomes.
1928 Franklin Griffith Discovered that genetic information can be
transferred from heat-killed bacteria cells to
live ones. This phenomenon, called
transformation, provides the first evidence
that the genetic material is a heat-stable
chemical.
1944 Oswald Avery with his
colleagues, Maclyn McCarty
and Colin MacLeod
Identify Griffith's transforming agent as DNA
1949 Erwin Chargaff Reported that DNA composition is species
specific; that is, that the amount of DNA and
its nitrogenous bases varies from one species
to another


1952 Alfred Hershey and Martha
Chase
Conducted series of experiment using
bacteriophage proving that the DNA was the
biomolecule that carried genetic information
Rosalind Franklin Known for her work on the X-ray diffraction
images of DNA which led to the discovery of
the DNA double helix.
1953 James Dewey Watson and
Francis Harry Compton Crick
Discover the molecular structure of DNA
1956 Arthur Konberg First scientist to identify deoxyribonucleic acid
(DNA) polymerase in the intestinal
bacterium E coli
1975 Frederick Sanger Developed chain termination method of DNA
sequencing which lead to the determination of
base sequences of nucleic acid
1977-1979 Scientists at Genentech, the worlds first
genetic engineering company, were the first to
genetically modify an microorganism to
produce human somatostatin, insulin and
growth hormone
1983 Kary Mullis Developed Polymerase Chain Reaction
(PCR) which is used to make copies of even
tiny amounts of DNA quickly
1990 Gene therapy was used on patients for the
first time
1993 The FDA approved the first genetically
engineered food -- FlavrSavr tomatoes which
was given genes resistant to rotting
1996 Dolly the Sheep, the first mammal to be
cloned from an adult somatic cell using
nuclear transfer
2003 Human Genome Project is declared complete












B. The Role of DNA in Heredity

Heredity is the sum of all biological processes by which particular characteristics
are transmitted from parents to their offspring. DNA (deoxyribonucleic acid)--in the form
of large molecules known as chromosomes--is the carrier of genetic instructions for the
development and functioning of living organisms. Each chromosome contains
many genes, or locatable regions along the chromosome that can be thought of as a
"unit" of inheritance. The physical appearance of an organisms can be thought of as the
product of genes interacting with each other and with the environment.
Scientists had criteria for DNA to be accepted as the genetic material, including that it:
Be present in the cell nucleus and in chromosomes
Doubles in the cell cycle
Is twice as abundant in diploid cells
Has same the pattern of transmission as its genetic information

The role that it play is that DNA controls the production of the proteins that determine all
of the traits passed on from parents to their offspring.
Heredity plays a key role in the development of traits and is transmitted through genes.
The traits we inherit help shape our behavior, are determined by pairs of genes, one
from each parent. Genes are the building blocks of heredity. Genes are found in
threadlike structures called chromosomes, which are made of DNA.
Genes are composed of DNA.
Most normal human cells have 46 pairs of chromosomes divided into 23 pairs.
In each pair, one chromosome is from the father and one is from the mother.
The twenty-third pair determines gender.
When a child is born without all 46 chromosomes, physical and behavioral
disorders may result.









C. DNA Replication and Repair

DNA replication is the process of a DNA molecule making a copy of itself. DNA
replication occurs before mitosis begins and before the first division of meiosis. It
ensures that each daughter cell has an exact copy of the genetic material from the
parent cell. DNA carries the information for making all of the cell's proteins. These pro-
teins implement all of the functions of a living organism and determine the organism's
characteristics. When the cell reproduces, it has to pass all of this information on to the
daughter cells.

Before a cell can reproduce, it must first replicate, or make a copy of, its DNA.
Where DNA replication occurs depends upon whether the cells is a prokaryote or a
eukaryote. DNA replication occurs in the cytoplasm of prokaryotes and in the nucleus of
eukaryotes. Regardless of where DNA replication occurs, the basic process is the
same.

The structure of DNA lends itself easily to DNA replication. Each side of the
double helix runs in opposite (anti-parallel) directions. The beauty of this structure is that
it can unzip down the middle and each side can serve as a pattern or template for the
other side (called semi-conservative replication). However, DNA does not unzip entirely.
It unzips in a small area called a replication fork, which then moves down the entire
length of the molecule.

An enzyme called DNA gyrase makes a nick in the double helix and each side
separates
An enzyme called helicase unwinds the double-stranded DNA
Several small proteins called single strand binding proteins (SSB) temporarily
bind to each side and keep them separated
An enzyme complex called DNA polymerase "walks" down the DNA strands and
adds new nucleotides to each strand. The nucleotides pair with the
complementary nucleotides on the existing stand (A with T, G with C).
A subunit of the DNA polymerase proofreads the new DNA
An enzyme called DNA ligase seals up the fragments into one long continuous
strand
The new copies automatically wind up again

Different types of cells replicated their DNA at different rates. Some cells
constantly divide, like those in your hair and fingernails and bone marrow cells. Other
cells go through several rounds of cell division and stop (including specialized cells, like
those in your brain, muscle and heart). Finally, some cells stop dividing, but can be
induced to divide to repair injury (such as skin cells and liver cells). In cells that do not
constantly divide, the cues for DNA replication/cell division come in the form of
chemicals. These chemicals can come from other parts of the body (hormones) or from
the environment.

DNA repair is a collection of processes by which a cell identifies and corrects
damage to the DNA molecules that encode its genome. In human cells, both
normal metabolic activities and environmental factors such as UV light and radiation can
cause DNA damage, resulting in as many as 1 million individual molecular lesions per
cell per day.
The rate of DNA repair is dependent on many factors, including the cell type, the
age of the cell, and the extracellular environment. A cell that has accumulated a large
amount of DNA damage, or one that no longer effectively repairs damage incurred to its
DNA, can enter one of three possible states:
an irreversible state of dormancy, known as senescence
cell suicide, also known as apoptosis or programmed cell death
unregulated cell division, which can lead to the formation of a tumor that
is cancerous
The DNA repair ability of a cell is vital to the integrity of its genome and thus to the
normal functionality of that organism. Many genes that were initially shown to
influence life span have turned out to be involved in DNA damage repair and protection