Beruflich Dokumente
Kultur Dokumente
CYTOGENETICS
UNIVERSITY OF SAN AGUSTIN
COLLEGE OF PHARMACY AND MEDICAL TECHNOLOGY
Cyto = Cell
Genes= Elements of heredity (carrying inherited traits) that are transmitted from
parents to offspring during reproduction .
Genetics= The study of biologically inherited traits./ The study of genes.
Genomics= The study of all the genes in an organism to understand their
molecular organization, function, interaction and evolutionary history.
Chapter 1.The Genetic Code of Genes & Genomes
History:
1860s- Existence of genes and the rules governing their transmission from
generation to generation were discovered by Gregor Mendel. His work with
garden peas represents the beginning of what would become the science of
Genetics.
1869- Friedrich Miescher discovered a new type of weak acid abundant in the
nuclei of WBCs that turned out to be the chemical substance of which genes are
made. These acid would later be known (until today) as Deoxyribonucleic acid.
1870s- The nuclei of the male and female reproductive cells were observed to fuse
in the process of fertilization. This later led to the discovery of thread-like objects
with characteristic splitting behavior inside the nucleus that become visible in the
light microscope when stained with dyes. These would later be known
as
Chromosomes.
1900s- Chromosomes are indeed carriers of genes.
1920s- DNA and other various types of proteins are present in chromosomes.
DNA- Deoxyribonuleic acid. Considered as the Molecule of Heredity.
- According to studies by James Watson and Francis Crick at Cambridge
University (1953), DNA consists of two long chains of subunits twisted
around one another to form a double-stranded helix.
- The subunits of each strand are called nucleotides, each of which
contains any one of four chemical constituents called bases (Adenine;
Thymine; Guanine and Cytosine).
- The base pairing between A and T and between G and C is said to be
complementary base pairing; the complement of A is T, and the
complement of G is C. The complementary pairing in the duplex molecule
means that each base along one strand of the DNA is matched with a base
in the opposite position on the other strand.
- Each DNA strand has a polarity or directionality, like a chain of circus
elephants linked trunk to tail. In this analogy, each elephant corresponds
to one nucleotide along the DNA strand. The trunk end of the strand is
called the 5 end of the strand, and the tail end is called the 3 end. In
double stranded DNA, the paired strands are oriented in opposite
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directions: The 5end of one strand is aligned with the 3 end of the other.
The oppositely oriented strands are said to be Antiparallel.
Replication- The copying process in which a single DNA molecule becomes two
identical molecules. In
this process, each parental DNA strand directs the synthesis of a new
partner strand.
For most genes, the genetic information contained in the nucleotide
sequence specifies a particular type of protein. Proteins control the chemical
and physical processes of cells known as metabolism. Many proteins are
enzymes , a term introduced in 1878 to refer to the biological catalysts that
accelerate biochemical reactions.
Archibald Garrod- A British physician who studied genetic diseases caused by
inherited defects in
metabolism. He concluded that an inherited defect in metabolism results
from an inherited defect in an enzyme.
- Example: PKU (Phenylketonuria) results from the absence of (or a defect
in) the enzyme Phenylalanine hydroxylase (PAH). When this step in the
pathway is blocked, phenylalanine accumulates. The excess phenylalanine
is broken down into harmful metabolites that cause defects in myelin
formation that damage a childs developing nervous system and lead to
severe mental retardation.
The Central Dogma of Molecular Genetics
The details of how genes code for proteins were not understood until the 1960s
when the Dogma was formulated. Since then, it has become the fundamental
principle of molecular genetics because it summarizes how the genetic information
in DNA becomes expressed in the amino acid sequence in a polypeptide chain.
DNA
transcription
RNA
translation
PROTEIN
The main concept in the central dogma is that DNA does not code for protein
directly but rather acts through an intermediary molecule of Ribonucleic acid. The
structure of RNA is similar to, but not identical with, that of DNA.
Features
1. Sugar
2. Strandedness
DNA
Deoxyribose
Double stranded
2
RNA
Ribose
Single stranded
3. Base
Thymine
Uracil
2.) His preliminary studies had indicated that peas normally reproduce by
self- fertilization, in which pollen produced in a flower is used to fertilize the eggs in
the same flower. Left alone, pea flowers always self- fertilize .
- He did a crossbreeding between two different varieties by opening the keel
petal (which encloses the reproductive structures), removing the immature anthers
(the pollen- producing structures) before they shed pollen, and dust the stigma(part
of the female structure) with mature pollen taken from a flower on a different plant.
- He established true- breeding varieties in which the plants produced only
progeny like themselves when allowed to self- fertilize. (Ex. One true- breeding
variety always yielded round seeds, whereas another true- breeding variety always
yielded wrinkled seeds.)
-For his experiments, Mendel chose seven pairs of varieties, each of which
was true- breeding for a different trait. The contrasting traits affected: seed shape
(round vs wrinkled), seed color (yellow vs green), flower color (purple vs white), pod
shape (smooth vs constricted), pod color (green vs yellow), flower and pod position
(axial vs terminal) and stem length (standard vs dwarf). When two varieties that
differ in one or more traits are crossed, the progeny constitute a hybrid between
the parental varieties. Crosses in which the parental varieties differ in one, two or
three traits of interest are called: Monohybrid, Dihybrid and Trihybrid
respectively.
Geneticists call the true- breeding parents the P1 generation and the hybrid
filial seeds or plants the F1 generation.
One pair of traits studied was round vs wrinkled seeds. When pollen from a
variety of plants with wrinkled seeds was used to cross- pollinate plants from a
variety with round seeds, all of the resulting hybrid seeds were round. When plants
from the variety with round seeds were used as the pollen parents and those from
the variety with wrinkled seeds as the female parents (reciprocal cross), all of the F1
seeds turned out to be round.
Generalizations:
1.) The Traits expressed in the hybrids were called the Dominant traits;
while the traits not expressed in the hybrids were called Recessive
traits.
2.) Two plants with the same outward appearance (for example with round
seeds) might nevertheless differ in their hereditary makeup.
3.) The normal gene encodes an enzyme, starch-branching enzyme I (SBEI),
required to synthesize a branched chain form of starch known as
Amylopectin. As pea seeds dry, they lose water and shrink. Round seeds
contain amylopectin and shrink uniformly.Wrinkled seeds lack amylopectin
and shrink irregularly. In other words, wrinkled peas have an inborn error
in starch metabolism. The molecular basis of the wrinkled mutation is that
the SBEI gene has become interrupted by the insertion of aDNA sequence
called a transposable element. These are DNA sequences that are
capable of moving (transposition) from one location to another within a
farther than the w fragment because the w fragment is larger owing to the insertion
of the transposable element. The separation of the fragments is indicated by the
dark rectangles called bands.
9. Morphological trait- one that is manifest, plainly shown, and readily
perceived by the senses. Frequently dominant or recessive.
10.Molecular trait- one that can be perceived only by means of special
methods(such as gel electrophoresis)that enable differences between
molecules to be visualized. Often (but not always) codominant.
11.Codominant genes- Alternative forms of a gene (W and w) which can
both be detected when they are present in a cell or organism using
special methods (e.g. gel electrophoresis showing single rapidly migrating
band of the true- breeding strain with round seeds; and the single slowly
migrating band of the true-breeding strain with wrinkled seeds; and the
progeny of the cross which has round seeds BUT exhibit BOTH bands ).
The Human ABO blood groups illustrate both Dominance and codominance.
Incomplete dominance- the phenotype of the heterozygous genotype is
intermediate between those of the homozygous genotypes. It is more frequent for
morphologic traits than for molecular traits. (Ex. The color pink of snapdragon
flower that is formed is intermediate between red and white from the parent
flowers.)
Codominance- the heterozygous genotype exhibits the traits associated with
both homozygous genotypes. It is more frequent for molecular traits than for
morphologic traits.
ABO blood groups- determined by polysaccharides (polymers of sugars) present on
the surface of red blood cells. Both the A and B polysaccharides are formed from a
precursor substance that is modifeied by the enzyme product of either the IA or the
IB allele. The gene products are transferase enzymes that attach either of two types
of sugar units to the precursor.
People of genotype IAIA- produce RBCs having only the A polysaccharide and
are said to have blood typeA.
People of genotype IBIB- produce RBCs having only the B polysaccharide and
are said to have blood type B.
Heterozygous IAIB people have RBCs with both A and B polysaccharides and
are said to have blood type AB. This genotype illustrates codominance because
heterozygous genotype has the characteristic of both homozygous genotypes- in
this case, the presence of both the A and the B carbohydrate on the RBCs. Although
the polypeptides encoded by the IA and the IB differ in only 4 out of 355 amino
acids, these differences are at strategic positions in the molecules and change their
substrate specificity. Both the IA and the IB are dominant to the recessive allele IO.
The IO allele has a single base deletion in codon 86 that shifts the translational
reading frame of the mRNA resulting in an incomplete, inactive enzyme. The
precursor substrate remains unchanged and neither the A nor the B type of
polysaccharide is produced.
People of genotype IOIO therefore lack both the A and the B polysaccharide
and thus said to have blood type O.
In IAIO heterozygotes, presence of the IA allele results in production of the A
polysaccharide, and correspondingly in IBIO heterozygotes, presence of the IB allele
results in production of the B polysaccharide. Thus persons with IAIO have blood
type A and persons with IBIO have blood type B.
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Mitosis
Meiosis
The Sex chromosomes an exception to the rule that all chromosomes of diploid
organisms are present in pairs of morphologically similar homologs. As early as
1891, microscopic analysis showed that one of the chromosomes in males of some
insects (grasshoppers) does not have a homolog. This unpaired chromosome was
called the X chromosome and it was present in all somatic cells of the males but in
only half the sperm cells. The biological significance of these observations became
clear when females of the same species were shown to have two X chromosomes.
In other species in which the females have two X chromosomes, the male has
one X chromosome along with a morphologically different chromosome, later known
to be the Y chromosome. The difference in the chromosomal constitution of males
and females is a chromosomal mechanism for determining sex at the time of
fertilization. Whereas every egg cell contains an X chromosome, half the sperm cells
contain an X chromosome and the rest contain a Y chromosome. Fertilization of an
X- bearing sperm results in an XX zygote which normally develops into a female;
and fertilization by a Y- bearing sperm results in an XY zygote, which normally
develops into a male. The result is a criss- cross pattern of inheritance of the X
chromosome in which a male receives his X chromosome from his mother and
transmits it only to his daughters.
3. A woman whose father was affected has normal sons and affected sons in the
ratio of 1:1. This is true because any daughter of an affected male must be
heterozygous for the recessive allele.
Small deletions are often viable when they are heterozygous with a
structurally normal homolog, because the normal homolog supplies gene
products that are necessary for survival.
- However, even small deletions are usually lethal when both members of a
pair of homologous chromosomes carry the deletion.
Example: ASD (Autism Spectrum Disorders)- characterized by communication
deficits, social impairment and repetitive behaviors occurring prior to the age of 3,
usually requiring extensive family support and medical intervention. Males: Females
ratio 5:1; Identical twin chance of acquiring the defect: 70 90% if the other twin is
affected.
Deletions can be formed in 2 major ways:
1. Chromosome breakage and reunion- Chromosome breaks result from doublestranded breaks in the DNA backbone. May occur spontaneously at a slow
rate or can be induced by xrays and chemicals.
2. Ectopic recombination- pairing and homologous recombination between
repeated DNA sequences (direct repeats) present at different sites along the
DNA results in deletion of the material between the repeats.
B. Duplication- Abnormal chromosomes having a region that is present twice.
- Tandem duplication- the duplicated segment is present in the same
orientation
immediately adjacent to the normal region in the
chromosome. This produces even more copies of the duplicated region by
means of a process called unequal crossing over.
Human color blindness a result of unequal crossing over
- Human color vision is mediated by 3 light- sensitive protein pigments
present in the cone cells of the retina. Each of the pigments is related to
Rhodopsin, the pigment found in he rod cells that mediates vision in dim
light. The light sensitivities of the cone pigments are toward blue, red and
green (primary colors).Perception of all other colors are brought about by
mixtures of these primaries. The gene for the blue- sensitive pigment is in
chromosome 7, whereas the genes for the red and green pigments are in
the X chromosome (arose from the duplication of a single ancestral
pigment gene, are still 96% identical in amino acid sequence and are
similar enough that they can pair and undergo unequal crossing over).
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