Download GENE”.

CS 159: GENETICS
LECTURERS:
1.Prof. Richard Akromah [BSc
Agric.(Kumasi), MSc (Birmingham),
PhD (Reading)]
2.Mr. Alexander Wireko Kena [BSc
Agric. (Kumasi), MSc (Ibadan)]
What is Genetics?
The term GENETICS comes from the word
“GENE”. Genes are the focus of the subject.
Genes are the biological elements or factors that
determine the inherent properties or characteristics
of organisms (HEREDITY), which are transmitted
from parents to offspring from generation to
generation.
Technically, a gene is a section of a threadlike
double helical molecule called deoxyribonucleic
acid (DNA).
Simply, genetics is the study of
genes.
Some also define genetics as the study of
heredity. However, heredity studies were of
interest to humans long before genetics as a
scientific discipline existed as we know it today.
The study of genetics began in the early part of
the 20th Century after advances were made in
CYTOLOGY and the discovery of the LAWS
OF HEREDITY in 1860’s.
Why study Genetics?
Genetics is an indispensable discipline that
occupies a pivotal position in the life sciences.
Genetic knowledge gives insight into the
mysteries of biology.
It helps us to explain mysteries such as
Why likes beget likes and dislikes (resemblance
and variation within a species)
The origin of the individual
Why certain diseases persist in a family
• To the agriculturist, a good knowledge of
genetics principles is a prerequisite for
conducting crop and animal improvements for
higher productivity through breeding.
What to Expect…..?
In this course, you will basically
learn about GENES
The nature of genes (where they are
found, their structure; both physical and
chemical structure)
How genes were discovered
How genes perform their biological roles
The science of genetics is studied at
the molecular (sub-cellular), cellular,
organismal, family and population
levels of life.
Cell Theory:
Cells are the basic units of organization, structure and
function in living organisms. All organisms are made up
of at least one cell.
Cells are derived from pre-existing cells (i.e. all cells
trace back to one original cell). Life progresses by
enlargement and division of cells.
Cell Structure and Organization
There are two basic types of cells:
1. Cells without a nucleus = Prokaryotes [Pro = before
evolution of karyotes] (e.g., bacteria, blue-green
algae)
Generally very small, unicellular, the earliest and still
most abundant life forms
2. Cells with a nucleus = Eukaryotes
Some are unicellular (protists – amoeba), some
multicellular forms (fungi, plants, animals)
Prokaryote versus Eukaryote
Similarities: Both are enclosed within a lipid
bilayer cell membrane – plasma membrane
Differences: Eukaryotes
bound organelles
contain
membrane
Prokayotic cell – DNA is concentrated into a
nucleoid, but no membrane system separates this
region from the rest of the cell
Eukayotic cell – has a true nucleus bound by a
membranous nuclear envelope
Viruses – no typical structure. E.g. a
Phage particle consists of a protein
coat surrounding a core of genetic
material which may be DNA or RNA.
They are not really living since they
cannot exist alone, but require cells to
infect
How do you see cells? – microscopes
(light, electron)
Eukaryotic Cells
Living material is Protoplasm
Protoplasm = Nucleus + Cytoplasm
Cytoplasm The part of a cell enclosed by the
plasma membrane but excluding the nucleus
Cytoplasm contains organelles - any of the
structures that occur within a cell e.g.,
mitochondria, lysosomes (ref organs)
Nucleus
The central structure (master control center ) of
eukaryotic cells. Concerned with replication or
reproduction
Structure:
Two unit membranes with a fluid-filled space
Nuclear pores present
Outer membrane may
endoplasmic reticulum.
be
continuous
with
Chromatin:
it is a complex of long DNA strands
wrapped around proteins. When condensed =
chromosomes
Function: contains instructions that control cell
metabolism and heredity
Nucleolus:non-membraneous
matrix
(ribonucleic acid) and protein
of
RNA
Function: instructions in DNA are copied here
(ribosomal RNA synthesis)
works with ribosomes in the synthesis of
protein
Mitochondrion (plural: mitochondria)
Structure: composed of modified double
unit membrane (protein, lipid)
Function:
centres
for
respiratory
catabolism, i.e. the release of
chemical energy from food
Physiology
Glucose
+
Oxygen
------> Carbon
Dioxide + Water + Energy (ATP)
Chloroplasts = Found only in plant cells.
Structure: composed of a double layer of modified
membrane (protein, chlorophyll, lipid)
- inner membrane invaginates to form
layers called "grana" (sing., granum) where
chlorophyll is concentrated
Function: Centre for photosynthetic anabolism
Carbon Dioxide + Water ---------------> Glucose +
Oxygen
radiant energy
Ribosomes:
Structure - non-membraneous, spherical bodies
composed of RNA and protein enzymes
Function: Sites for synthesis of protein from RNA
template
Lysosomes [Greek lysis dissolution + soma body]. Only in
animal cells.
Structure: membrane bound bag containing hydrolytic enzymes
- hydrolytic enzyme = (water split biological catalyst)
i.e. using water to split chemical bonds
Function: break large molecules into small molecules by inserting
a molecule of water into the chemical bond
Cytomembrane (endomembrane) system
This is a series of membranous vesicles involved in
coordinating protein production and secretion. Their structure
and organization depends very much on the cell and its
mission
Plasma membrane
Structure: the thin semi-permeable layer of protein and fat
that surrounds the cell, but is inside the cell wall in plants
Function: acts as a boundary layer to contain the protoplasm
- interlocking surfaces bind cells together
- selectively permeable to select chemicals that pass in
and out of cells
Cell Wall
Structure: - a thick, rigid membrane of cellulose
that surrounds a plant cell (a non-living secretion
of
the
cell
membrane)
- contains pits (openings) that make it totally
permeable
Function: - provides protection from physical
injury
- together with vacuole, provides skeletal
support
Endoplasmic reticulum (ER)
Structure: - sheets of unit membrane with ribosomes on the outside
- forms a tubular network throughout the cell
Function: - transports chemicals between cells and within cells
- provides a large surface area for the organization of
chemical reactions and synthesis
Golgi complex
Structure: stacks of flattened sacs of unit membrane (cisternae)
- vesicles pinch off the edges
Function: - modifies chemicals to make them functional
- secretes chemicals in tiny vesicles
- stores chemicals
- may produce endoplasmic reticulum
Vacuole
Structure: - a single layer of unit membrane
enclosing fluid in a sack
Function:
-produces turgor pressure against cell wall
for support, stores water and various
chemicals
- may store insoluble wastes
Cytoskeleton:
A network of fiber-like structures in the cytoplasm that provide
form for the cell and that may have other functions also
The contents of a cell are highly organized, rather than flopping
around randomly.
Cell structure is maintained by a cytoskeleton of microtubules
and microfilaments.
Microtubules are composed of primarily a single protein called
tubulin that stacks up into long filaments. They act like tiny
molecular “strings”, forming the basic skeleton of the cell,
maintaining the cell shape and providing a "highway system"
along which cell constituents are transported. (This is especially
important in nerve axons, which may be several feet in length.).
Cilia and flagella (both plural)
These structures are involved in many forms of motility, either of
the cell with respect to its environment (e.g. sperm with flagella
and paramecia with cilia) or to move substances across cell
surfaces, e.g. nasal cilia or pharyngeal cilia.
They are all based on microtubules that run the length of the
cilium or flagellum.
At the base of these microtubules is the centrosome which is
also involved in organizing microtubules during cell division. In
most species the centrosome is made up of a pair of centrioles.
Seed plants and a few other organisms do not have centrioles.
Structures specific to plant cells, called “basal bodies” seem to
take the place of centrioles.
Organization of Chromosomes
Chromo = Colour
Some = Body
Chromosome = A structure composed of DNA and proteins that
bears the genetic information of a cell
It is favourable to observe chromosomes during metaphase when both
chromatids are still joined
Chromosomes vary in structure
Karyotype [Greek karyon, kernel] is the depiction of the chromosomes
of an organism, normally from a mitotic cell in metaphase.
Chromosome size is one criteria used to construct karyotypes.
In addition, the position of the centromere that determines relative arm
lengths and presence or absence of satellites are important for
chromosome description
A typical chromosome has:
Centromere
[Latin centrum center + Greek
meros part.] The position on a chromosome at
which the spindle fibers attach in cell division. It
divides the chromosome into two arms
The centromere is
chromosome to divide
the
last
part
of
the
There is also a secondary constriction beyond
which is the knob or satellite. It also marks the
position of the nucleolus.
e
Classification of chromosome according to centromere position
Classification of chromosome according to centromere
position
Metacentric - about midway between arms giving similar but
not usually identical lengths – V shape at
anaphase. [Meta = middle]
Submetacentric - about midway between the centre and
the end of one arm – L shape at anaphase
Acrocentric - Very near the tip of one arm such that the
other is very short – ‘I’ shaped. [Greek akron
extremity + centric centre]
Telocentric -
Terminal so there is only one arm (telos = end)
Acentric -
A chromosome or, more commonly, a
chromosome fragment that lacks a centromere
Chromatin Structure/DNA
organization - Olins and Olins
used electron microscopy to
observe “beads on a string discussed under DNA structure
Condensation (super-coiling) of
DNA – discussed under DNA
structure
Chromosome theory of inheritance
Hereditary characters are carried and passed on
to offspring in discrete units in chromosomes
(Correlation between Mendelian inheritance and
chromosome behaviour)
Cytogenetics = The study of chromosome
number, structure, function and behaviour in
relation to gene inheritance, organization and
expression
The Cell Cycle:
The cell cycle is a series of stages through which the cell
passes between divisions and is composed of three
stages - Interphase, Nuclear division (Karyokinesis)
and Cytokinesis
A. Interphase is the period between divisions when nothing
seems to be happening (gap phase or resting nucleus). The
chromosomes are so decondensed (strung out) that they are
invisible. The chromatin (DNA and protein) that makes up the
chromosomes is still there but it’s so dispersed that only a few
dark blotches of chromatin (called nucleoli) can be seen. It is
abbreviated as G phase and dominates the cell cycle.
The Cell Cycle
S - Each chromosome is
replicated to form two sister
chromatids. The centrosome
is also duplicated.
G1 – GROWTH (cell gets food uses E,
grows in size) major period of cell growth
New organelles are synthesized
G2 - cell undergoes a period of rapid
growth to prepare for mitosis.
Microscopes were not very informative about G phase but its
chemistry enabled division into:
G1 (or Gap 1) – is “early interphase” and occurs after
cytokinensis, the last cell division, but before start of DNA
synthesis. Cell recovers from previous cell division and grows
larger. Cells that do not divide never move to S phase so they
never replicate their DNA e.g., most nerve cells (neurons). Cells
in G1 have only one centrosome
S phase (or Synthesis phase) is the time when DNA is
synthesized. Each single chromatid (inherited from the previous
nuclear division) is duplicated to give identical sister
chromatids. The chromatid now contains one parental and one
new strand (= semiconservative replication - one old strand is
completely conserved and the other strand is completely new).
G2 (or Gap 2) occurs after S phase but before the next M phase.
The cell prepares for mitosis and cytokinensis. A cell in G2 has
twice as much DNA as it had in G1 because of synthesis in the
S phase. During G2 the centrosome is duplicated so by late G2
the cell has two centrosomes. This tells us we are nearing M
phase. All cells must have 2 centrosomes to guide the
chromosomes during the M phase that follows.
Interphase = The part of the nuclear cycle following the
end of one division to the beginning of the next.
Interphase can be divided into three parts: G1, in which
the DNA has yet to replicate; S, the period in which DNA
replication occurs; and G2, the period between S and
the beginning of mitosis or meiosis
B.
Nuclear Division is when the genetic material is
dividing and chromosomes can be seen. There are two
types – mitosis and meiosis. It is called the M phase.
During this phase one mother nucleus becomes two
daughter nuclei.
Mitosis is the nuclear division associated with the
proliferation of somatic cells.
The main function of mitosis is to increase the number of
identical nuclei.
When followed by cytokinesis, as it usually is, mitosis
increases cell numbers. Each division produces two
identical daughter cells
During mitosis, each chromosome in the
duplicate longitudinally, into chromatids, and
double structure splits to become two
chromosomes, each going to a different
nucleus
nucleus
then the
daughter
daughter
Each chromosome consist of a single double helix DNA
molecule. During S phase DNA unwinds and duplicates
into 2 identical copies, thus the cell has twice as much
DNA in this phase, forming the sister chromatids
Mitosis is divided into four distinct stages: Prophase,
metaphase, anaphase and telophase
Prophase is the initial phase of mitosis and
meiosis. The chromosomes condense and
become visible. The nuclear membrane
disappears and spindle fibres start extending
from the poles of the cell. Prophase ends when
the chromosomes align to form metaphase
Metaphase is the phase of mitosis or meiosis in
which chromosomes are maximally condensed
and are aligned in a plane between the poles of
the spindle (metaphase plate). Metaphase marks
the end of prophase. It is followed by anaphase
Anaphase [Greek ana back + phase.] The phase
of nuclear division in which newly formed
chromosomes are pulled along the microtubules
of the spindle to the opposite poles.
In mitosis, former sister chromatids,
chromosomes, move to opposite poles
now
Telophase is the final phase of nuclear division.
The chromosomes uncoil and become very
extended, a nuclear membrane forms around
them, and the new nucleus enters interphase
C. Cytokinensis [kinesis = motion] is “proper” cell division. The
cytoplasm of the mother cell divides into two daughter cells (one
mother cell becomes two daughter cells). A cell in cytokinensis
has two nuclei formed by nuclear division during M phase. Most
cells (but not all) divide their cytoplasm pretty evenly.
Animal cells do not have a cell wall so they divide by a method
called furrowing. During furrowing the cell membrane puckers
inward along the cells “equator” as if an invisible thread were
tightening between the two parts. E
Eventually the furrowing pinches the cell into two. The “thread” is
actually fibres of proteins, microtubules, attached to the inside of
the cell membrane. Microtubules constict like a muscle.
Plant cells have rigid cell walls so they cannot divide by
furrowing. Instead, vesicles from the Golgi apparatus
appear along the “equator” roughly midway between the
daughter nuclei and with the help of microtubules, the
vesicles fuse to form new cell membrane and add to the
formation of a cell plate. The cell plate grows until it
becomes a proper cell wall.
Mitosis ensures that both nuclei have exactly equal
genetic information, but cytokinensis distributes the
organelles (mitochondria, ribosomes, etc) and cytoplasm
randomly. The cell will be viable as long as enough
organelles are present
Mitotic Division – phase 1
Time–lapse films of living,
dividing cells
mitosis is broken down
into five stages:
prophase,
prometaphase,
metaphase, anaphase,
telophase.
PROPHASE:
-Chromatin shows up under the
microscope as well defined chr’s
-Chromosomes seen as an X shape 2 sister chromatids connected by a
centromere
-Mitotic spindle begins to form and
Elongate from the centrosome region
Chromatin is the complex of DNA and protein that makes up
chromosomes
PROMETAPHASE:
-Nuclear membrane dissolves
-Spindle microtubules enter nucleus and some attach to the centromeric region of the chromosome
-those microtubules that do attach at the kinetochore and are called kinetochore microtubules
-the other microtubules are called non-kinetochore and polar
Mitotic Division – Phase 2
Overlapping with the latter stages of
mitosis, cytokinesis completes the
mitotic phase.
METAPHASE:
-kinetochore microtubules push from opposite
poles equally so that the chromosomes
are aligned in the middle of the cell
-this center area where the alignment
occurs is called the metaphase plate
ANAPHASE:
-paired sister chromatids separate as kinetochore
microtubules shorten rapidly
-polar microtubules lengthen as kinetochore
microtubules shorten, pushing poles of cell further
apart
TELOPHASE:
-separated sister chromatids group at opposite ends of
the cell, near the centrosome region, having been pulled
there by receding microtubules
-new nuclear envelope reforms around each group of
separated chromosomes
-Mitosis is over!
Mitotic
Spindle
• Segregates chromosomes during cell division (either
mitosis or meiosis) to the daughter cells
• Consists of a bundle of microtubules joined at the ends
but spread out in the middle
Image is of the mitotic spindle at
metaphase.
The kinetochores of a chromosome′s
two sister chromatids face in opposite
directions.
Here, each kinetochore is actually
attached to a cluster of kinetochore
microtubules extending from the
nearest centrosome.
Nonkinetochore microtubules overlap
at the metaphase plate (TEMs).
Kinetochore
•Each of the two sister chromatids of a
chromosome has a kinetochore = is a
proteins structure associated with specific
sections of chromosomal DNA at the
centromere.
•Kinetochore links the chromosome to
microtubule polymers from the mitotic
spindle during mitosis and meiosis
• Contains two regions: an inner
kinetochore, which is tightly associated
with the centromere DNA; and an outer
kinetochore, which interacts with
microtubules
However, experimental evidence
supports the hypothesis that the primary
mechanism of movement involves motor
proteins on the kinetochores that “walk”
a chromosome along the attached
microtubules toward the nearest pole.
Meanwhile, the microtubules shorten by
depolymerizing at their kinetochore ends
Mitosis is often called "copy division" because the genetic material is
copied.
Cytokinesis – animal vs plant
2. Cytokinesis in plant cells, which have
cell walls, is different.
There is no cleavage furrow. Instead,
during telophase, vesicles derived from
the Golgi apparatus move along
microtubules to the middle of the cell,
where they come together, producing a
cell plate (Figure12.9b ).
Cell wall materials carried in the vesicles
collect in the cell plate as it grows. The cell
plate enlarges until its surrounding
membrane fuses with the plasma
membrane along the perimeter of the cell.
Two daughter cells result, each with its own
plasma membrane. And a new cell wall
arising from the contents of the cell plate has
formed between the daughter cells.
1. In animal cells, cytokinesis occurs as cleavage.
The first sign of cleavage is the appearance of a cleavage furrow, a shallow groove in the cell surface near the
old metaphase plate (Figure 12.9a ). On the cytoplasmic side of the furrow is a contractile ring of actin
microfilaments associated with molecules of the protein myosin. (Actin and myosin are the same proteins that
are responsible for muscle contraction as well as many other kinds of cell movement.) The actin microfilaments
interact with the myosin molecules, causing the ring to contract. The cleavage furrow deepens until the parent
cell is pinched in two, producing two completely separated cells, each with its own nucleus and share of cytosol
and organelles.
DNA must Replicate before division can take palce
A model for DNA replication: the basic concept.
A short segment of DNA has been untwisted into a structure that resembles a ladder.
The rails of the ladder are the sugar–phosphate backbones of the two DNA
strands; the rungs are the pairs of nitrogenous bases.
Simple shapes symbolize the four kinds of bases.
Dark blue represents DNA strands present in the parent molecule; light blue
represents free nucleotides and newly synthesized DNA.
Replication begins at the DNA start site: the origin of replication
The reaction is catalyzed by an enzyme: DNA polymerase - An enzyme that catalyzes the
elongation of new DNA at a replication fork by the addition of nucleotides to the existing chain.
Meiosis [Greek meiosis diminution]
Upon fertilization two nuclei fuse, so that the number of chromosomes
does necessarily double. An exponential growth of the number of
chromosomes from generation to generation would thus have to be
expected. This is not the case, because the chromosomes are reduced to
half their normal number in germ cell production.
Meiosis is a two stage type of cell division in sexually reproducing
organisms that results in gametes with half the chromosome number of
the original cell.
It consists of two successive mitosis-like divisions: in the first division
the number of chromosomes is reduced to their half (reduction
division), the second is a normal mitosis (equational division)
Meiosis I - The first of two divisions in meiosis, often abbreviated MI.
In Prophase 1 the nuclear envelope disintegrates and chromosomes
become visible as in mitosis (1). Homologous chromosomes pair, and
crossing over occurs. It is divided into 5 stages:
Leptotene: The chromosomes have replicated but individual chromatids
are not visible.
Zygotene. Instead of lining up on a metaphase plate, as in mitosis,
chromosomes come together in pairs (2). Each chromosome in a pair is
similar in structure (homologous), but would have come originally from
different parents. The pairing of homologous chromosomes is also called
synapsis and the resulting structure synaptic complex. Directly after
initiation of the process the pairing spreads like a zipper across the whole
length of the chromosome.
Pachytene. During pachytene the pairing stabilizes. The number of
synaptic complexes corresponds to the number of chromosomes in a
haploid set of the respective species. The pairs are also called tetrad or
bivalents. This state is marked by twisting of homologous pairs twist
round each other and chromatids may cross over (3).
Diplotene: The bivalents separate again. During this process it emerges
that each chromosome is built of two chromatids, so that the whole
complex harbours four strands during the separation. Normally the
separation is not into 4, but the homologous chromosomes stick together
at certain points, the chiasmata (sing. chiasma). Breaks occur at these
cross-overs (or chiasmata, singular chiasma) and pieces of chromatid are
exchanged (4). The chiasmata move towards the end of the chromatids in
a process called Terminilization which may be viewed as a closed
zipper which is being opened from points in the middle to either end.
Diakinesis is the continuation of diplotene. The chromosomes condense
and become more compact. It is usually difficult to demarcate both
states.
Metaphase I: The paired homologues align to form the metaphase plate
Anaphase I: The members of a homologous pair separate and move to
opposite poles. The two daughter cells thus have a haploid set of
chromosomes, each of which has two chromatids and an undivided
centromere. It is followed by the telophase, then by interkinesis (this
state corresponds to the so-called quiescence or interphase state)
MI begins with one diploid cell and ends with two haploid cells
Meiosis II: The second of two divisions in meiosis, often abbreviated
MII. It is similar in many respects to mitosis. After the alignment of the
chromosomes at metaphase (metaphase II), the centromeres divide, the
chromatids are separated from each other, and the new sister
chromosomes move to opposite poles during anaphase (anaphase II).
Next the chromatids are pulled apart in anaphase 2 to form four clusters
of chromosomes in telophase 2. The nuclear envelopes reform around
four haploid nuclei that will give rise to the micro- or megagametophyte.
MII begins with two haploid cells and ends with four haploid cells
As a result of the meiosis of a diploid cell, four haploid cells (gones)
form, of which one (at egg cell formation) or all (at pollen formation) can
develop into gametes
Show animation of mitosis and meiosis from Freeman Genetics 2.0
Overview of Meiosis – for just 1 pair
of chromosomes
the two chromosomes of a homologous pair are
individual chromosomes that were inherited from
different parents; they are not usually connected to
each other.
both members of this single homologous pair of
chromosomes in a diploid cell are replicated and the
copies then sorted into four haploid daughter cells.
sister chromatids are two copies of one
chromosome, attached at the centromere; together
they make up one duplicated chromosome
Overview of meiosis: how meiosis reduces
chromosome number. After the chromosomes replicate
in interphase, the diploid cell divides twice, yielding four
haploid daughter cells. This overview tracks just one pair
of homologous chromosomes, which for the sake of
simplicity are drawn in the condensed state throughout
(they would not normally be condensed during interphase).
The red chromosome was inherited from the female
parent, the blue chromosome from the male parent.
Mitosis vs Meiosis
Meiosis I is called the
reductional division
because it halves the
number of chromosome
sets per cell—a reduction
from two sets (the diploid
state) to one set (the
haploid state).
The sister chromatids then
separate during the
second meiotic division,
meiosis II, producing
haploid daughter cells.
The mechanism for
separating sister
chromatids is virtually
identical in me
iosis II and mitosis.
Unique Events in Meiosis
Three events are unique to meiosis, and all three occur during meiosis I:
1. Synapsis and crossing over. During prophase I, duplicated
homologous chromosomes line up and become physically connected
to form the synaptonemal complex ; this process is called synapsis .
Genetic rearrangement between nonsister chromatids, known as
crossing over , also occur during prophase I.
The four chromatids of a homologous pair are visible in the light
microscope as a tetrad .
Each tetrad normally contains at least one X–shaped region called a
chiasma (plural, chiasmata ), the physical manifestation of crossing
over. Synapsis and crossing over normally do not occur during
mitosis.
2. Tetrads on the metaphase plate. At metaphase I of meiosis,
paired homologous chromosomes (tetrads) are positioned on the
metaphase plate, rather than individual replicated chromosomes, as
in mitosis.
Crossing Over
• Process by which two
chromosomes exchange some
portion of their DNA
during prophase 1 of meiosis
• Initiated before the synaptonemal
complex develops in zygotene. Is
completed near the end of
prophase 1
• Crossover usually occurs when
matching regions on matching
chromosomes break and then
reconnect to the other
chromosome
• Results in genetic recombination
(an exchange of genes)
Meiosis is often called "reduction division" because the genetic material
is reduced - by half.
Meiosis is extremely important not only for sexual reproduction, but also
for creating the diversity upon which natural selection operates
Life Cycle of Organisms
The life cycle is the span of the life of an organism from the moment of
fertilization to the time it reproduces. Don't confuse this with "life span"
which extends beyond the time of reproduction
Gamete formation in Mammals
The entire process of producing gametes is called Gametogenesis. In
males it is called Spermatogenesis and in females, Oogenesis. The
organ in which Gametogenesis takes place is called the gonad. The male
gonad is the testis; the female gonad the ovary.
Spermatogenesis
The diploid initial or primordial cells in the testis are called
spermatogonia. A spermatogoium may develop into a primary
spermatocyte which undergoes meiosis to produce four haploid
spermatids. At maturation, the cytoplasm of each spermatid would have
been pulled into a whip-like structure and is now called the
spermatozoon. Each primary spermatocyte produces four spermatozoa.
Oogenesis
The diploid primordial cells in the ovary are called oogonia. An
oogonium grows and stores a lot of food in its cytoplasm (yolk) to be
used as food for the zygote when it is formed. This cell is the primary
oocyte and it is this which undergoes meiosis.
Two haploid nuclei are produced at the end of the first meiotic division.
There is unequal distribution of cytoplasm during cytokinensis, and the
larger cell is called secondary oocyte while the smaller one is called a
polar body. The polar body may undergo the second meiotic division
producing two polar bodies.
The secondary oocyte also undergoes the second meiotic division, but
again there is unequal distribution of cytoplasm in the cytokinensis
which follows.
The result is that the smaller cell becomes a polar body whilst the bigger
one becomes the Ootid. By further growth and differentiation, the ootid
becomes the mature female gamete called ovum or egg cell. The three
polar bodies eventually degenerate.
Therefore for every primary oocyte that enters meiosis, only one egg cell
or ovum is produced in contrast to the four spermatozoa in males.
Fusion (fertilization)
causes two haploid
cells (gametes) to
create a unique diploid
cell (zygote).
The haploid stage is
merely a requirement
to make a zygote.
Our haploid cells, once
created, do "nothing".
They just hang around
waiting to fertilize
something or to be
fertilized!
Our diploid (2n) cells undergo mitosis but our haploid (n) cells NEVER
undergo mitosis. However, this isn't true of all organisms
Reproduction in Plants
Floral structure
Terminology
 Reproduction can be asexual (from vegetative
parts--non-gametic/ non-fertilized) or by sexual
(requiring
effective
fertilization/
hybridization
forming botanic seed) methods
 Alternation of sporophytic (2n) and gametophytic
(n) generations
 In order to change from the sporophytic (2n) to
gametophytic (n) generation, meiosis must take
place.
 Among vascular plants, the diploid (2n) phase
dominates the gametophyte (pollen or embryo sac
– n) phase.
Types of flowers
Complete flowers - have sepals,
petals, stamen, and pistil
Incomplete flowers—lacking one
of the above parts
Perfect
flowers--stamens
and
pistils are in the same floral
structure - wheat
Imperfect flower--stamen and
pistil not in the same floral
structure
Monoecious
("one
house")-stamens and pistils on the same
plant (eg. maize, cassava)
Dioecious
("two
houses")-stamens and pistils on different
plants. Ex. hemp, hops, buffalo
grass, pawpaw, kiwi, nutmeg
Flowers may either be solitary or
may be grouped together to form
an inflorescence
Gametogenesis in Plants
Formation of
higher plants
male and female gametes in
Pollination and Fertilisation
ANTHESIS: Maturation of the anther accompanied by the
extension of the filament
POLLINATION: Transfer of pollen grains from anther to
stigma.
• Method of transfer varies with crop
• Pollen germinates on the stigma and the pollen tube
enters the ovule via the micropyle
• The generative nucleus divides -----> 2 male germ cells
(gametes). These male nuclei enter the embryo sac
FERTILIZATION:
• One male gamete(sperm) fuses with the egg ---> zygote.
The other male gamete unites with the two polar nuclei.
This triple fusion -----> the primary endosperm nucleus.
Mechanisms that promote Self
Pollination
• Cleistogamy
• Stigma closely surrounded by anthers
• Very few species are completely self
pollinated
• Rice, oats, wheat, barley, cowpea,
soyabean, peanut, tomato, eggplant,
okra etc
Mechanisms that promote Cross
Pollination
• Dioecy
• Monoecy
• Dichogamy (protoandry and protogyny)
• Self incompatibility
• Male sterility
• Heterostyly (pin and thrum flowers)
Heterostyly
Asexual Reproduction
Vegetative Propagation
No meiosis
No genetic recombination
New plants can be formed from
–
–
–
–
–
–
–
Stolons
Rhizomes
Tubers
Offset buds on corms and bulbs
Suckers
Bulbils [bulb-like propagules in inflorescence]
Vivipary [tiny plantlets growing on the parent plant]
Tissue culture cloning
Tissue Culture Cloning
– Growth of a plantlet from
a few meristem cells
cultured on a chemical
medium
– A single plant can be
cloned into thousands of
copies that will continue
to grow when planted in
soil
– Orchids and certain pine
trees used in mass
plantings
are
propagated this way
Apomixis
• Reproduction in plants where meiosis and fertilization do not
occur
– Normal seed is set although no sexual fusion of gametes takes place
– Genotypes of the progeny are very similar, if not identical, to the (female)
parent.
– Embryo sac is unreduced i.e. it contains diploid nuclei and so there is no
need for fertilization to restore diploidy
• Example – citrus trees
– In one form, an egg is formed with 2N chromosomes and develops
without being fertilized
– In another form, the cells of the ovule (2N) develop into an embryo
instead of, or in addition to, the fertilized egg
Mendelian Inheritance
Mendel published a small
work
with
the
title:
Experiments
in
Plant
Hybridization in 1866
This
work
remained
obscured, and was rediscovered in 1900
Gregor Mendel (1822-1884)
Mendel’s Experiments
1. Mendel developed pure lines of
pea
Pure Line - a population that
breeds true for a particular trait e.g.,
all seeds are either round or
wrinkled, flowers purple or white for
many generations. This was an
important innovation because any
non-pure (segregating) generation
would and did confuse the results
of genetic experiments.
2. Counted his results and kept
statistical notes – this is essential
for data analysis
Mendel had pure parental lines (P) that differed in single characters or
traits
Flower colour: Purple vrs white
Seed colour: Green vrs yellow
Seed shape: Round vrs wrinkled
Plant height: Tall vrs dwarf
Mendel crossed parents differing in these characteristics and
obtained the following in the first offspring (F1 or first filial
generation):
P1 = Purple; P2 = white flowers
P1 = yellow; P2 = green seeds
F1 hybrids = All purple
F1 hybrids = All yellow
P1 = Round
P2 = wrinkled seeds
P1 = Short
P2 = Tall plants
F1 hybrid = All tall
Purple, white, yellow, green, round, wrinkled,
tall, short etc are what the eye sees, and is
termed the phenotype.
Phenotype - literally means "the form that is
shown"; it is the outward, physical appearance
of a particular trait. The phenotype is the
appearance of an individual that is based on an
underlying genotype and on the influence that
the environment exerts
F1 hybrids = All round
A genotype is the specific combination of the
alleles of a cell. The term means either the whole
genome or (the sense it usually has) certain genes
We always see only one of the two parental
phenotypes in the F1 generation
The Allele Concept
Allele - one alternative form of a given allelic pair; purple and white are the alleles
for the flower colour of a pea plant; more than two alleles can exist for any specific
gene, but only two of them will be found within any diploid individual
Allelic pair - the combination of two alleles which comprise the gene pair
Homozygote - an individual which contains only one allele at the allelic pair; for
example DD is homozygous dominant and dd is homozygous recessive; pure lines
are homozygous for the gene of interest
Dominant - the allele that expresses itself at the expense of
an alternate allele; an allele that determines the phenotype
in a heterozygous condition
Recessive - an allele whose expression is suppressed in the
presence of a dominant allele; the phenotype that
disappears in the F1 generation from the cross of two pure
lines and reappears in the F2 generation. A recessive allele
displays no influence on the phenotype in heterozygous
individuals
Homozygote - an individual which contains only one allele
at the allelic pair; for example DD is homozygous
dominant and dd is homozygous recessive; pure lines are
homozygous for the gene of interest
Heterozygote - an individual which contains one of each
member of the gene pair; for example the Dd heterozygote
Monohybrid cross - a cross between parents that differ at a
single gene pair (usually AA x aa)
Monohybrid - the offspring of two parents that are homozygous
for alternate alleles of a gene pair
Remember --- a monohybrid cross is not the cross of two
monohybrids
The phenotype is the appearance of an individual that is
based on an underlying genotype and on the influence that
the environment exerts
Mendel then crossed the F1 to themselves (selfed the F1)
He observed that white flowers that was absent in the F1 appeared in the F2 in a ratio of
3 purple flowers to one white flower i.e., a phenotypic ratio of 3:1
MENDEL's first law is the principle of
segregation. It states that during gamete
formation each member of the allelic pair
separates from the other member to form
the genetic constitution of the gamete.
The individuals of the F2 generation are
therefore not uniform because the traits
segregate (separate out - different types
are visible).
The characteristics of the parental
generation do always occur at a certain
ratio. Depending on a dominant-recessive
or an intermediate crossing, they
segregate in the ratio 3:1 or 1:2:1
Law of Segregation
Genotype vs. Phenotype
= appearance
= the allele combination
Confirmation of Mendel’s first law
The Testcross
This is the cross of any
individual to a
homozygous recessive
individual; used to
determine if the
individual is
homozygous dominant
or heterozygous
The F1 phenotypic ratios tell whether the dominant phenotype is homozygous (no
segregation) or heterozygous ( ratio of 1:1)
Confirmation of Mendel’s first law: The F3
Mendel’s second law
Mendel also performed crosses in which he followed the segregation of two genes e.g.,
Yellow and round seeds x Green and wrinkled seeds.
The dominance relationship between alleles for each trait was already known to Mendel
when he made this cross
Dihybrid cross - a cross between two parents that differ by two pairs of alleles (AABB
x aabb)
Dihybrid - an individual heterozygous for two pairs of alleles (AaBb)
Parental Cross: Yellow, Round Seed x Green, Wrinkled Seed
F1 Generation: All yellow, round
F2 Generation: 9 Yellow, Round, 3 Yellow, Wrinkled, 3 Green, Round, 1 Green,
Wrinkled
Let's now look at the cross using gene symbols
Mendel selfed the F1 and obtained individuals as shown in Punett Square below:
Female Gametes
gW
GW
Gw
GW
GGWW
GGWw
GgWW
GgWw
Gw
Yellow,
round
GGWw
Yellow, round
GGww
Yellow,
round
GgWW
Yellow, round
Ggww
gW
Yellow,
round
GgWW
Yellow,
wrinkled
GgWw
Yellow,
round
ggWW
Yellow,
wrinkled
ggWw
gw
Yellow,
round
GgWw
Yellow, round
Ggww
Green,
round
ggWw
Green, round
ggww
Yellow,
round
Yellow,
wrinkled
Green,
round
Green,
wrinkled
Male
Gametes
gw
The phenotypes and general genotypes from this cross can be represented in the
following manner:
Phenotype
General Genotype
9 Yellow, Round Seed
G_W_
3 Yellow, Wrinkled Seed
G_ww
3 Green, Round Seed
ggW_
1 Green, Wrinkled Seed
ggww
The results of this experiment led Mendel to formulate his Third law.
Mendel's Second Law - the law of independent assortment; during gamete formation
the segregation of the alleles of one allelic pair is independent of the segregation of the
alleles of another allelic pair
It does inevitably cover the case that new combinations of genes, that were not existing
before can arise. In MENDEL's experiment these are the combinations: Yellow
wrinkled seeds; Green round seeds
PUNNETT-Square: The
scheme shows the
genotypes of the P-, F1and F2-generation of a
dihybrid hereditary path.
This kind of representation
was introduced by the
British geneticist R. C.
PUNNETT at the
beginning of 20th century
Law of Independent Assortment
Note:
MENDEL's fundamental work was forgotten for 35 years. It became known in 1900.
The German C. CORRENS, the Dutchman HUGO de VRIES and the Austrian
ERICH von TSCHERMAK-SEYSENEGG are regarded as its rediscoverers.
Their articles were all published at nearly the same time in 1900. They heard first of
MENDEL's work, when their own work was nearly finished. H. de VRIES writes
apologetically:
"This important work is hardly cited, so that I myself did not get to know it before I
had finished most of my own experiments and had concluded the same laws as are
mentioned in the text."
C. CORRENS recognized furthermore that not all characters can be freely combined,
but that some of them are coupled and are thus always inherited together
Mendel’s work is today viewed as the fundament of modern genetics.
The chromosome theory confirmed Mendel’s work
Complications to Mendelian Genetics
1.
Gene actions
• Intra-allelic interactions
» Incomplete or partial dominance
» Codominance
» Over-dominance
•
Inter-allelic interactions
» Epistasis
» Pleiotrophy
2. Sex linked inheritance
3.
Linkage
Mendel’s Dominance
• Mendel’s rule of dominance was complete
dominance
– Homozygous dominant and heterozygous
individuals had indistinguishable phenotypes
– Example: Both PP and Pp plants have the
dominant PURPLE phenotype (P=purple and
p=white flowers)
Incomplete Dominance
• Offspring have an appearance somewhat in
between the phenotypes of the two parents
– “Mixed”
– Blended
R
R
r
Rr
Rr
F1 generation
r
Rr
Rr
All Rr = pink
(heterozygous pink)
Incomplete Dominance
• Incomplete dominance occurs when one allele
is partially dominant over the other – thus, the
two alleles have unequal influence on the
phenotype
Codominance
• BOTH alleles are expressed equally in
heterozygous individuals
• Neither allele is dominant over the other
– Example: blood type
• Determined by whether or not you have A or B
proteins
• IA = A protein
• IB = B protein
• I = no protein
Codominance
Codominance Problem
• Example:homozygous male Type B (IBIB)
•
x
heterozygous female Type A (IAi)
IB
IB
IA
IAIB
IAIB
i
IBi
IBi
1/2 = IAIB
1/2 = IBi
Another Codominance Problem
Example: male Type O (ii)
x
female type AB (IAIB)
IA
IB
i
IAi
IBi
i
IAi
IBi
1/2 = IAi
1/2 = IBi
Codominance
• Question:
If a boy has a blood type O and his sister
has blood type AB, what are the genotypes
and phenotypes of their parents?
boy - type O (ii) X girl - type AB (IAIB)
Codominance
• Answer:
IA
IB
i
i
IAIB
ii
Parents:
genotypes
= IAi and IBi
phenotypes = A and B
Sex-linked Inheritance
• Traits (genes) located on the
sex chromosomes
• Sex chromosomes are X and Y
–XX genotype for females
–XY genotype for males
• Many sex-linked traits carried
on X chromosome
Sex – Linked Traits
• Example: Colour blindness
– If the mother carries the colour blindness gene
on her X chromosome, her son could get it.
– As long as one X chromosome
is ok, a female will not
X
y
express the trait
cX
X
X
y
C
X
X
XX
Xy
Sex-linked Traits
Example: Colorblindness
Sex Chromosomes
Colorblindness
XX chromosome - female
Xy chromosome - male
Epistasis
Epistatic genes override or mask the phenotype of a second gene.
Epistasis is not dominance.
Compare the definitions:
Epistasis
One gene masks the expression of a different gene for a different trait
Dominance
One allele masks the expression of another allele of the same gene
Classical Epistatic Ratios
• About 6 different epistatic gene actions
have been observed
1. Complementary gene action (9:7):
also known as duplicate recessive
epistasis
2. Duplicate gene action (15:1): a.k.a
duplicate dominant epistasis
3. Recessive suppressors (13:3): a.k.a
dominant and recessive epistasis
4. Additive gene action (9:6:1)
5. Dominant epistasis (12:3:1)
6. Recessive epistasis (9:3:4)
Pleiotropy
One gene causes multiple effects on a phenotype, i.e.
the control of two or more characters by a single
gene
Sickle cell anemia: one mutant gene, many symptoms
Single amino acid
substitution in the
hemoglobin protein
Pain, stroke, leg ulcers, bone damage, jaundice, gallstones,
lung damage, kidney damage, eye damage, anemia, delayed
growth
LINKAGE
• T. H. MORGAN’S LAWS (1911):
• Genes occur
chromosomes
• Linked
genes
chromosome
in
a
are
linear
on
order
the
on
same
• Genes can be exchanged between
homologous chromosomes during meiosis
• The closer genes are located on a
chromosome, the less likely they will
separate and recombine in meiosis
Genes on the same chromosome are
linked
Gene loci
Dominant
a
P
P
Genotype:
PP
b
a
aa
Homozygous
Homozygous
for the
for the
dominant allele
recessive allele
allele
B
Bb
Recessive
allele
Heterozygous
Figure 9.9
GENETIC RECOMBINATION
• If two genes are close
together,
they
will
not
independently
enough
assort
• If they are not close together,
recombination or crossing over may
occur to separate them
• Linkage types
– Two possible configurations
• cis:
• trans:
A B // a b
A b // a B
MOLECULAR GENETICS:
THE CHEMICAL BASIS OF
HEREDITY
Discovery of DNA as the Hereditary Material
• Nucleic Acids (DNA and RNA)
were discovered in 1869 by
Friedrich
Mieschner
as
a
substance contained within cells
• During the ’30s & 40’s proteins
rather than DNA was thought to
hold genetic information
Griffith’s Transformation Experiment

1928

Attempting to develop a vaccine

Isolated two strains of Streptococcus
pneumoniae
 Rough
strain was harmless
 Smooth
strain was pathogenic
Transformation
1. Mice injected with
live cells of harmless
strain R.
2. Mice injected with live
cells of killer strain S.
3. Mice injected with
heat-killed S cells.
4. Mice injected with
live R cells plus heatkilled S cells.
Mice live. No live R cells
in their blood.
Mice die. Live S cells in
their blood.
Mice live. No live S cells in
their blood.
Mice die. Live S cells in
their blood.
Transformation
What happened in the fourth experiment?
 The
harmless R cells had been
transformed by material from the dead
S cells
 Descendents
of the transformed cells
were also pathogenic
 Why?
Oswald & Avery’s Experiment
What is the transforming material?
 Cell
extracts treated with proteindigesting enzymes could still transform
bacteria
 Cell
extracts treated with DNA-digesting
enzymes lost their transforming ability
 Concluded
that DNA,
transforms bacteria
not
protein,
Bacteriophages

Viruses that infect
bacteria

Consist of protein and
DNA

Inject their hereditary
material into bacteria
bacterial
cell wall
cytoplasm
plasma
membrane
Hershey & Chase’s Experiments
• Created labeled bacteriophages
– Radioactive sulfur – Labels Proteins
– Radioactive phosphorus – Labels Nucleic
Acids
• Allowed labeled viruses to infect bacteria
• Asked: Where are the radioactive labels after
infection?
What is DNA?
• Deoxyribonucleic acid (DNA) is a Nucleic Acid
• Nucleic acids are polymers of Nucleotides
• A nucleotide consists of three molecules
– A Pentose or 5-carbon sugar
– A nitrogenous base
– Phosphate group
• There are four N-bases in DNA
– Adenine, Guanine, Thymine, Cytosine
Composition of DNA
• Chargaff showed:
– Amount of adenine relative to guanine
differs among species
– Amount of adenine always equals
amount of thymine and amount of
guanine always equals amount of
cytosine
A=T and G=C
Rosalind Franklin’s Work
• Was an expert in X-ray crystallography
• Used this technique to examine DNA fibers
• Concluded that DNA was some sort of helix
Structure of DNA by J. Watson & F. Crick
(1953)
• Carbon 1 (C1) is where the base is attached.
• Carbon 2 (C2) tells you if it is a ribose or
deoxyribose. In deoxyribose, oxygen at C2 is
missing.
• Carbon 3 (C3) is the point of attachment for
more nucleotides through a phospho-diesther
bond
• Carbon 4 (C4) completes the ring via an
oxygen (O) which bridges to the carbon 1 (C1).
Carbon 5 (C5) hangs away from the ring and
is the point of attachment for its phosphate(s).
KNUST
137
• DNA is a double stranded helix
• The two strands are Antiparallel
• Strands are held together
hydrogen bonds between bases
• A pairs with T, and C with G
by
Nucleotide Structure
DNA is Antiparallel
Base-pairing rule
The four bases of DNA are:
Adenine (A) Guanine (G) Thymine
(T) Cytosine (C)
Adenine always hydrogen bonds with
Thymine (A-T)
Guanine always hydrogen bonds with
Cytosine (G-C)
These bonding patterns are called base
pairings (bp)
DNA Replication
• Before mitosis and meiosis, all of
the DNA in the cell must be copied
or replicated during the Synthesis
phase of Interphase
• How does this happen?
DNA Replication
What is a gene?
• A gene is a piece of DNA consisting of
coding (exons) and non-coding (introns) base
sequences with the inherent ability to be
transcribed and translated to produce a
protein
KNUST
144
• Thus, a gene locus for any character or trait
(eg. Flower colour, seed coat colour, disease
resistance, dwarfism, etc) on any chromosome,
can be viewed as a code of genetic information
written with the four bases; A, C, G, T.
• Alleles actually emanate from differences in
base sequences on homologous chromosomes
caused by mutations, resulting in different
proteins being formed, hence different
phenotypes.
How are Genes Expressed?
• Gene expression involves four important
processes
–Transcription
–RNA processing
–Translation
–Protein processing
• Transcription precedes translation during
gene expression, and takes place in the
nucleus, whereas translation occurs on the
ribosomes, in the cytoplasm
Transcription
• It is the first step in the expression of genes
• It is the process by which information on the DNA is
copied by a related chemical bearer RNA
• Genes must remain on chromosomes for replication,
repairs and transmission, but at the same time the
genes must be able to direct all cell activities notably
protein synthesis
• Transcription of genes is superficially similar to DNA
replication
• For, transcription to take place, an enzyme called DNA
dependent RNA Polymerase binds to one of the strands of the
DNA at a starting point referred to as PROMOTER SEQUENCE
• Only one strand of the DNA double helix serves as a template
for RNA
• The RNA polymerase then matches complementary
nucleotides along the DNA template according to the base
pairing rules
• The difference however is that Uracil replaces Thymine in the
matching of complementary bases
• The paired bases are then polymerised to form a single
stranded RNA molecule

Overview of transcription

The RNA formed (transcript) then peels off from
the DNA, and exits the nucleus through the
nuclear pore into the cytoplasm for translation to
proceed

In molecular terms, a gene is therefore a unit of
Translation (Protein Synthesis)
• Three types of RNA are mainly found in living cells,
and all these three are produced via transcription
– Messenger RNA (mRNA)
– Transfer RNA (tRNA)
– Ribosomal RNA (rRNA)
• However, it is ONLY mRNA that is translated during
protein synthesis
• mRNA undergoes a post-transcriptional processing
known as SPLICING, prior to translation
• During splicing, all non-coding sequences (introns) in
the mRNA transcript are removed by the enzyme
spliceosome, leaving only coding sequences (Exons)
• Translation involves the conversion of the message carried by
the mRNA to polypeptides (proteins)
•
when the mRNA exits the nucleus after transcription, it enters
the cytoplasm and attaches itself to the ribosome
• The nitrogenous bases on the mRNA are picked in groups of
three bases by the ribosome.
• Each group of three bases is known as a CODON
• Each codon species an amino acid
• There is an interaction between mRNA, tRNA and rRNA during
protein synthesis
• tRNA interacts with amino acids and influences their correct
insertion into the polypeptide chain
• The tRNA molecule also carries a group of three bases
known as ANTICODON, and each anticodon complements a
codon on the mRNA
• As the ribosome picks the codons on the mRNA, the tRNA
molecule with the corresponding anticodon moves into
position, carrying the amino acid specified by the codon
• As the next codon is picked by the ribosome, the tRNA
molecule with the complementing anticodon also moves into
position with the specific amino acid for the codon.
• A peptide bond joins the both amino acid molecules, and by
this process the polypeptide chain grows longer until a STOP
codon (UGA, UAG and UAA) is reached on the mRNA
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
THE GENETIC CODE


Special codons:

AUG (which specifies methionine) = start codon

UAA, UAG and UGA = termination, or stop, codons
The code is degenerate

More than one codon can specify the same amino acid


For example: GGU, GGC, GGA and GGG all code for lysine
The code is nearly universal

Only a few rare exceptions have been noted

An overview of gene expression
PEPTIDE BONDS
MUTATIONS AND
CHROMOSOMAL VARIATION
MUTATIONS
• A mutation is a sudden heritable change in the
genome of an organism that can not be accounted for
by segregation and recombination
• It is the ultimate source of new alleles in the
populations of living organisms; it creates new alleles
that could be acted upon by segregation and
recombination to increase variability in the population
• Mutations can occur spontaneously under natural
conditions or could be deliberately induced artificially
using mutagenic agents such as irradiation and
chemicals
• The new alleles created by mutations could be either
dominant or recessive, resulting in dominant and
recessive mutations respectively
• Most mutations are however recessive and sometimes
lethal or deleterious eg. Sickle cell anaemia (a
recessive lethal mutation)
• Mutations can also be classified based on the type of
cell involved, producing somatic or germinal mutations
• Mutations can be broadly grouped into two types:
–Micro/point/gene mutations
–Macro mutations
Micro/Point/Gene Mutations
• These are mutations that involve
changes in the chemical structure
(coding sequences) of a gene via
additions, substitutions or deletions
of nitrogenous base sequences
Types of Point Mutations
Missense mutation – changes amino acid
Nonsense mutations – creates stop codon
Frameshift mutation– alters
remainder of reading frame
results in completely different
amino acid sequence.
Base Substitutions
• Transitions
–
–
–
–
pyrimidine replaces pyrimidine - C to T or T to C
purine replaces purine – G to A or A to G
GC changed to A=T or vice versa
Most common base change
• Transversion
– purine replaces pyrimidine or vice versa
– G to C or T
– A to C or T
– Rare but classical example is the sickle cell
anaemia – caused by a point mutation in the gene
for producing haemoglobin. A transversion base
substitution of ‘T’ with ‘A’ in the sixth amino acid,
changed it from glutamic acid to valine in sicklers
MACRO OR CHROMOSOMAL
MUTATIONS
1. Variation in chromosome number
1.1. Euploidy/Polyploidy
1.2. Aneuploidy
2. Variation in chromosome structure
(chromosomal aberrations)
2A. Change in the amount of genetic
information
EUPLOIDY
EUPLOID: Chromosome number is changed to exact multiple of the basic set
Polyploids are euploids in multiple of basic set of chromosome
–
–
–
–
–
–
–
•
Diploid
Triploid
Tetraploid
Pentaploid
Hexaploid
Septaploid
Octoploid
2x
3x
4x
5x
6x
7x
8x
EUPLOIDS may be
– AUTOPLOIDS: Having Duplicate genome of same species
– Autotetraploid: Having Duplicate genome of same diploid species
– ALLOPLOIDS: Having Duplicate genome of different species
Allotetraploid or amphidiploid: Having Duplicate genome of different
species
Ploidy Levels in Different crops
Species
Crop
Basic
Haploid
Chromosom (Gametic)
e Number Number (n)
(x)
Somatic
(Diploid)
Chromosome
number (2n)
Avena strigosa
Oats
7
7
2n = 2x= 14
Avena barbata
Oats
7
14
2n = 4x= 28
Avena sativa
Oats
7
21
2n = 6x= 42
Gossypium arboreum
Cotton
13
13
2n = 2x= 26
Gossypium hirsutum
Cotton
13
26
2n = 4x= 52
Triticum monococum
Einkorn
Wheat
7
7
2n = 2x= 14
Triticum turgidum
Durum
Wheat
7
14
2n = 4x= 28
Triticum aestivum
BreadW
heat
7
21
2n = 6x= 42
ANEUPLOIDY
Chromosome number is changed by addition or
deletion of specific chromosomes
Nondisjunction
• Chromosomes fail to separate
• Results in gametes and zygote with an
abnormal chromosome number
• Most aneuploidy result from errors in
meiosis
Nondisjunction during
meiosis
Chromosome
number in gametes:
Extra
chromosome
(n + 1)
Extra
chromosome
(n + 1)
Missing
chromosome
(n – 1)
Missing
chromosome
Chromosomes
align at metaphase I
Nondisjunction
at anaphase I
Alignments at
metaphase II
Anaphase II
(n – 1)
Fig. 3-2, p. 45
Effects of Changes in Chromosome
Numbers
• May cause birth defects or fetal
death
• Monosomy of any autosome is
fatal
• Only a few trisomies result in live
births
AUTOSOMAL TRISOMIES
1. Trisomy 13: Patau Syndrome
(47,+13)
• 1/15,000
• Survival: 1–2 months
• Facial, eye, finger, toe, brain, heart, and
nervous system malformations
Patau Syndrome
2. Trisomy 13: Edwards Syndrome
(47,+18)
• 1/11,000, 80% females
• Survival: 2–4 months
• Small, mental disabilities, clenched fists,
heart, finger, and foot malformations
• Die from heart failure or pneumonia
Edwards Syndrome
3. Trisomy 21: Down Syndrome
(47,+21)
• 1/800 (changes with age of mother)
• Survival up to age 50
• Leading cause of childhood mental
retardation and heart defects
• Wide, flat skulls; eyelid folds; large tongues;
physical, mental, development retardation
• May live rich, productive lives
Down Syndrome
Aneuploidy in Sex
Chromosomes
• Turner syndrome (45,X):
monosomy of X chromosome
• Klinefelter syndrome (47,XXY)
• Jacobs syndrome (47,XYY)
Sex Chromosome Trisomies
Sex Chromosome Trisomies
Sex Chromosome Trisomies
Turner Syndrome (45,X)
• Survival to adulthood
• Female, short, wide-chested, undeveloped
ovaries, possible narrowing of aorta
• Normal intelligence
• 1/10,000 female births, 95–99% of 45,X
conceptions die before birth
Turner Syndrome
Klinefelter Syndrome (47,XXY)
• Survival to adulthood
• Male
• Features do not develop
until puberty, usually
sterile, may have
learning disabilities
• 1/1,000 males
XYY or Jacobs Syndrome
(47,XYY)
• Survival to adulthood
• Average height, thin, personality disorders,
some form of mental disabilities, and
adolescent acne
• Some may have very mild symptoms
• 1/1,000 male births
XYY Syndrome
Structural Changes in
Chromosomes
DUPLICATIONS
p. 47
DELETIONS OR
DEFICIENCIES
p. 47
INVERSIONS
p. 47
TRANSLOCATIONS
p. 47
STATISTICS AS APPLIED IN
GENETICS
PROBABILITY AND STATISTICS
• The laws of inheritance can be used to
predict the outcomes of genetic crosses
• For example
– Animal and plant breeders are concerned with
the types of offspring produced from their
crosses
– Parents are interested in predicting the traits
that their children may have
• This is particularly important in the case of families
with genetic diseases
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2-52
PROBABILITY AND STATISTICS
• Of course, it is not possible to definitely
predict what will happen in the future
• However, genetic counselors can help
couples by predicting the likelihood of
them having an affected child
– This probability may influence the couple’s
decision to have children or not
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2-53
Probability
• The probability of an event is the chance that the
event will occur in the future
Number of times an event occurs
• Probability =
Total number of events
• For example, in a coin flip
Pheads = 1 heads
(1 heads + 1 tails) = 1/2 = 50%
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2-54
• The accuracy of the probability prediction
depends largely on the size of the sample
• Often, there is deviation between observed and
expected outcomes
• This is due to random sampling error
– Random sampling error is large for small samples
and small for large samples
• For example
– If a coin is flipped only 10 times
• It is not unusual to get 70% heads and 30% tails
– However, if the coin is flipped 1,000 times
• The percentage of heads will be fairly close to the
predicted 50% value
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2-55
• Probability calculations are used in genetic
problems to predict the outcome of crosses
• To compute probability, we can use three
mathematical operations
– Sum rule
– Product rule
– Binomial expansion equation
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2-56
Sum rule
• The probability that one of two or more mutually
exclusive events will occur is the sum of their
respective probabilities
• Consider the following example in mice
• Gene affecting the ears • Gene affecting the tail
– De = Normal allele
– Ct = Normal allele
– de = Droopy ears
– ct = Crinkly tail
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2-57
• If two heterozygous (Dede Ctct) mice are crossed
• Then the predicted ratio of offspring is
– 9 with normal ears and normal tails
– 3 with normal ears and crinkly tails
– 3 with droopy ears and normal tails
– 1 with droopy ears and crinkly tail
• These four phenotypes are mutually exclusive
– A mouse with droopy ears and a normal tail cannot have
normal ears and a crinkly tail
• Question
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2-58
• Applying the sum rule
– Step 1: Calculate the individual probabilities
P(normal ears and a normal tail) = 9 (9 + 3 + 3 + 1) = 9/16
P(droopy ears and crinkly tail) = 1
(9 + 3 + 3 + 1) = 1/16
– Step 2: Add the individual probabilities
9/16 + 1/16 = 10/16
• 10/16 can be converted to 0.625
– Therefore 62.5% of the offspring are predicted to have
normal ears and a normal tail or droopy ears and a
crinkly tail
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2-59
Product rule
• The probability that two or more
independent events will occur is equal to
the product of their respective probabilities
• Note
– Independent events are those in which the
occurrence of one does not affect the
probability of another
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2-60
• Consider the disease congenital analgesia
– Recessive trait in humans
– Affected individuals can distinguish between
sensations
• However, extreme sensations are not perceived as painful
– Two alleles
• P = Normal allele
• p = Congenital analgesia
• Question
– Two heterozygous individuals plan to start a family
– What is the probability that the couple’s first three
children will all have congenital analgesia?
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2-61
• Applying the product rule
– Step 1: Calculate the individual probabilities
• This can be obtained via a Punnett square
P(congenital analgesia) = 1/4
– Step 2: Multiply the individual probabilities
1/4 X 1/4 X 1/4 = 1/64
• 1/64 can be converted to 0.016
– Therefore 1.6% of the time, the first three offspring of a
heterozygous couple, will all have congenital analgesia
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2-62
Binomial Expansion Equation
• Represents all of the possibilities for a
given set of unordered events
P=
n!
x! (n – x)!
px qn – x
• where
– p = probability that the unordered number of events will occur
– n = total number of events
– x = number of events in one category
– p = individual probability of x
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2-63
• Note:
– p+q=1
– The symbol ! denotes a factorial
• n! is the product of all integers from n down to 1
– 4! = 4 X 3 X 2 X 1 = 24
– An exception is 0! = 1
• Question
– Two heterozygous brown-eyed (Bb) individuals have five
children
– What is the probability that two of the couple’s five
children will have blue eyes?
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2-64
• Applying the binomial expansion equation
– Step 1: Calculate the individual probabilities
• This can be obtained via a Punnett square
P(blue eyes) = p = 1/4
P(brown eyes) = q = 3/4
– Step 2: Determine the number of events
• n = total number of children = 5
• x = number of blue-eyed children = 2
– Step 3: Substitute the values for p, q, x, and n in the
binomial expansion equation
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2-65
n!
P=
x! (n – x)!
P=
P=
5!
2! (5 – 2)!
px qn – x
(1/4)2 (3/4)5 – 2
5X4X3X2X1
(2 X 1) (3 X 2 X 1)
P = 0.26
(1/16) (27/64)
or 26%
• Therefore 26% of the time, a heterozygous couple’s
five children will contain two with blue eyes and three
with brown eyes
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2-66
The Chi Square Test
• A statistical method used to determine
goodness of fit
– Goodness of fit refers to how close the
observed data are to those predicted from a
hypothesis
• Note:
– The chi square test does not prove that a
hypothesis is correct
• It evaluates whether or not the data and the
hypothesis have a good fit
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2-67
The Chi Square Test
• The general formula is
c2 = S
(O – E)2
E
• where
– O = observed data in each category
– E = observed data in each category based on the
experimenter’s hypothesis
 S = Sum of the calculations for each category
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2-68
• Consider the following example in Drosophila
melanogaster
• Gene affecting wing shape
– c+ = Normal wing
– c = Curved wing
• Note:
• Gene affecting body color
– e+ = Normal (gray)
– e = ebony
– The wild-type allele is designated with a + sign
– Recessive mutant alleles are designated with lowercase
letters
• The Cross:
– A cross is made between two true-breeding flies (c+c+e+e+ and
ccee). The flies of the F1 generation are then allowed to mate
with each other to produce an F2 generation.
2-69
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• The outcome
– F1 generation
• All offspring have straight wings and gray bodies
– F2 generation
• 193 straight wings, gray bodies
• 69 straight wings, ebony bodies
• 64 curved wings, gray bodies
• Applying
the chi
square
test
• 26 curved
wings,
ebony
bodies
– Step
1: total
Propose
• 352
fliesa hypothesis that allows us to calculate the
expected values based on Mendel’s laws
• The two traits are independently assorting
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2-70
– Step 2: Calculate the expected values of the four
phenotypes, based on the hypothesis
• According to our hypothesis, there should be a
9:3:3:1 ratio on the F2 generation
Phenotype
Expected
Expected number
probability
straight wings,
9/16
9/16 X 352 = 198
gray bodies
straight wings,
ebony bodies
curved wings,
gray bodies
3/16
3/16 X 352 = 66
3/16
3/16 X 352 = 66
curved wings,
ebony bodies
1/16
1/16 X 352 = 22
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2-71
– Step 3: Apply the chi square formula
c2 =
(O1 – E1)2
+
E1
(193 – 198)2
2
c =
198
(O2 – E2)2
+
E2
+
(69 – 66)2
66
(O3 – E3)2
+
E3
+
(64 – 66)2
66
(O4 – E4)2
E4
+
(26 – 22)2
22
c2 = 0.13 + 0.14 + 0.06 + 0.73
c2 = 1.06
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2-72
• Step 4: Interpret the chi square value
– The calculated chi square value can be used to obtain
probabilities, or P values, from a chi square table
• These probabilities allow us to determine the likelihood that the
observed deviations are due to random chance alone
– Low chi square values indicate a high probability that the
observed deviations could be due to random chance alone
– High chi square values indicate a low probability that the
observed deviations are due to random chance alone
– If the chi square value results in a probability that is less than
0.05 (ie: less than 5%)
2-73
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• Step 4: Interpret the chi square value
– Before we can use the chi square table, we have to determine
the degrees of freedom (df)
• The df is a measure of the number of categories that are
independent of each other
• df = n – 1
– where n = total number of categories
• In our experiment, there are four phenotypes/categories
– Therefore, df = 4 – 1 = 3
– Refer to Table 2.1
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2-74
1.06
2-75
• Step 4: Interpret the chi square value
– With df = 3, the chi square value of 1.06 is slightly greater than
1.005 (which corresponds to P= 0.80)
– A P = 0.80 means that values equal to or greater than 1.005 are
expected to occur 80% of the time based on random chance
alone
– Therefore, it is quite probable that the deviations between the
observed and expected values in this experiment can be
explained by random sampling error
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2-76
• For quantitative characters, we
can also calculate measures of
central tendency like mean, mode
and median, as well as measures
of dispersion such as range,
variance,
standard
deviation,
coefficient of variation, range etc.