Module 1
Module 1
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REFERENCES:
Annunziato, A. (2008). DNA Packaging: Nucleosomes and Chromatin.
Nature Education 1(1):26
Verma, P.S. and V.K. Agarwal. (2004). Cell Biology, Genetics, Molecular
Biology, Evolution and Ecology. Multicolour Edition. S. Chand &
Company, Ltd.
All sessions are self-directed, which requires you to take full control of the
learning process. You need to take initiative, with or without the
assistance of your teacher, to complete all learning and assessment
activities. You have to develop and sustain your motivation to succeed in
this course.
Housekeeping Rules:
1. You need to study all reading materials and complete all activities.
2. Be mindful of the schedule of activities. If circumstance/s will not
allow you to take the quiz/exam, inform your teacher within 24 hrs
through email to your teacher or through private message in FB.
3. For any inquiry/clarification related to the topics, post the question
in Google Classroom. There may be changes regarding this. Just
wait for announcements from your teacher. For concerns which are
not related to the course topics but which you feel can affect your
performance, send a message through FB messenger. Questions
will be answered right away if they are asked during the agreed real-
time online consultation. If questions are asked at other times,
answers might be delayed but you will really get answers. Inquiries
done during the weekend will be answered on Monday.
4. Extension for submission would only be allowed if the reason is valid.
What is valid? Power interruption, internet connectivity problem,
real emergencies.
5. Each topic will be good for a certain duration and that will serve as
your guide in managing your schedule so that you can finish
everything within the allowable time. Schedule is posted in MOLE.
INTRODUCTION
In this module, we will review on how everything starts with the behavior
of chromosomes during cell division. It is important to understand these
cell division processes because they will help us understand how we got
traits from the generations ahead of us, how we may have gotten some
unique traits out of the combinations that we got from our parents, what
we may be able to contribute to the next generation and a deeper look at
some aspects of inheritance that still need to be studied deeply.
Why do you need to learn these things? Of course, you have to have a way
to explain how some traits come to be, how some diseases can be
hereditary while some are not, how it is not just the nucleus that governs
heredity and how you can appreciate the fact that there is variation.
Another thing that you should already know by this time is the basic cell
structure and what functions each of the cellular parts perform. If you
have forgotten these things, time to review on them so that you can fully
appreciate the process of learning this module.
Learning Outcomes:
At the end of this module, you should be able to:
1. describe the chromatin structure before and during cell division.
2. describe the changes that happen during cell division and discuss
how these can affect gene segregation.
3. compare and contrast the types of meiosis and life cycles.
4. define and explain the significance of “crossing over” and “random
assortment” during meiosis.
5. differentiate mitosis and meiosis and describe the changes that
happen during cell division.
6. name at least 6 important people who contributed greatly to the
science of genetics and your reasons for considering them most
important.
7. summarize and describe the common applications of genetics.
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Activating Prior Knowledge (Individual)
This should be accomplished before you start studying the
module. Reflect on the seven learning outcomes above. To
complete the Table below, use the downloadable file (in document
format) that is posted in our MOLE classroom. Name and save the file
using this format: your family name (section) – APK1. E-mail the
completed document to your professor.
Any questions/clarifications
Learning
What do you know? in relation to learning
Outcomes
outcomes
1
2
3
4
5
6
7
1. G1 Phase. After the M phase of previous cell cycle, the daughter cells
begin G1 of interphase of new cell cycle. G1 is a resting phase. It is called
first gap phase, since no DNA synthesis takes place during this stage;
currently, G1 is also called first growth phase, since it involves synthesis
of RNA, proteins and membranes which leads to the growth of nucleus
and cytoplasm of each daughter cell towards their mature size.
During G1 phase, chromatin is fully extended and not distinguishable
as discrete chromosomes. This is a time of resumption of normal cell
metabolism which has slowed down during the previous cell division.
Thus, G1 involves transcription of three types of RNAs, namely rRNA,
tRNA and mRNA; rRNA synthesis is indicated by the appearance of
nucleolus in the interphase (G1 phase) nucleus. Proteins synthesized
during G1 phase are (a) regulatory proteins which control various events
of mitosis; (b) enzymes (e.g., DNA polymerase) necessary for DNA
synthesis of the next stage; and (c) tubulin and other mitotic apparatus
proteins.
G1 phase is most variable as to duration; it either occupies 30 to 50
per cent of the total time of the cell cycle or entirely lacking or absent in
rapidly dividing cells (e.g., blastomeres of early embryo of frog and
mammals). Terminally differentiated somatic cells (i.e., end cells such
as neurons and striated muscle cells) that no longer divide, are arrested
usually in the G1 stage; such a type of G1 phase is called G0 phase.
2. S phase. During the S phase or synthetic phase of interphase,
replication of DNA and synthesis of histone proteins occur. New
histones are required in massive amounts immediately at the beginning
of the S period of DNA synthesis to provide the new DNA with
nucleosomes. Thus, at the end of S phase, each chromosome has two
DNA molecules and a duplicate set of genes. S phase occupies roughly
35 to 45 per cent of cell cycle.
3. G2 phase. This is a second gap or growth phase or resting phase of
interphase. During G2 phase, synthesis of RNA and proteins continues
which is required for cell growth. It may occupy 10 to 20 per cent time
Aside from the intact nuclear envelope, the chromosomes occur in the
form of diffused, long, coiled and indistinctly visible chromatin fibers. The
DNA amount becomes double during this time.
Due to accumulation of ribosomal RNA (rRNA) and ribosomal proteins in
the nucleolus, the size of the latter is greatly increased. In animal cells, a
daughter pair of centrioles originates near the already existing centriole
and, thus, an interphase cell has two pairs of centrioles which are
positioned perpendicular to each other.
In animal cells, net membrane biosynthesis increases just before cell
division (mitosis). This extra membrane seems to be stored as blebs on the
surface of the cells about to divide.
Before we proceed to the next stage, the M phase, let us first examine the
structure of chromosome (fig. 2).
Loose DNA is coiled around histones to form nucleosomes, which look like
beads on a string. Linker DNA can be seen extending from one
nucleosome to the next.
Nucleosomes coil to
form a thicker solenoid
fiber and the solenoid
fiber is organized tighter
by protein scaffold to
form the condensed
chromosome charac-
teristic of metaphase
chromosome (fig. 3).
CHROMATIN STRUCTURE
There are several levels of structure of chromatin. Let us differentiate
them.
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Chromatin Primary Structure. This refers to the nucleosome (fig. 4) which
is the first order of DNA packaging in the nucleus. A nucleosome is a
histone octamer composed of 2 copies of H2A, H2B, H3 and H4. Histones
are proteins which are rich in lysine and arginine residues and are thus
positively-charged, the main reason that they can bind tightly to the
negatively-charged phosphates in DNA. There are actually 5 kinds of
histones that can be found in eukaryotic chromosomes. H1, which is not
included in the nucleosome, is not part of the binding histones. They are
responsible for tightening the binding of the DNA for the histone octamer.
The nucleosome is composed of 146 base pairs (bp) of superhelical DNA.
Between nucleosomes is linker DNA approximately 20 to 90 bp and varies
among different species, tissues, and even fluctuates within a single
cellular genome.
Chromatin Secondary Structure. The formation of the secondary
structure of chromatin (solenoid fiber) is driven by salt and intrinsic
nucleosome-nucleosome and nucleosome-
DNA interactions and is stabilized by linker
histones. In physiological salt (100-150 mM
NaCl or 2-5 mM Mg2+), chromatin compacts
into the maximally folded structure,
comparable to the “30 nm fiber. See
structure of the solenoid fiber in fig. 4.
Chromatin Tertiary Structure. This is
formed from interactions between discreet
secondary chromatin structures (also
referred to as fiber-fiber interactions). See
structure of the condensed chromosome in
fig. 4.
2. submetacentric –
centromere is near the
middle and the
chromosome arms slightly
vary in length. When
pulled to one pole, this
type of chromosomes
appeared L-shaped.
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3. acrocentric – centromere is near one end and the arms clearly vary in
length; thus, p and q arms are easily distinguishable. When a
chromosome of this type is pulled to one pole during cell division, it
appears J-shaped.
Can you prepare a karyotype from a cell that is in interphase? Why or why not?
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If karyotyping is done prenatally, samples for karyotyping can be taken
from the amniotic fluid, fetal blood, chorionic villi, umbilical cord and other
embryonic or fetal tissues. If done postnatally, samples can be taken from
peripheral blood, one marrow, skin and other tissues.
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Now that we have finished characterizing chromosomes, let us continue
with the cell cycle.
To ensure that cells that enter any part of the cell cycle are ready and
equipped to do so, there are established checkpoints at certain phases
(fig. 10).
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this stage the chromosomes are violently rotated and oscillated back
and forth between the spindle poles (like tug-of-war) because their
kinetochores are capturing the plus ends of microtubules growing from
one or the other spindle pole and are being pulled by the captured
microtubules. The kinetochores thereby act as a “cap” that tends to
protect the plus end from depolymerizing, just as the centrosome at the
spindle pole tends to protect the minus end from depolymerizing. Thus,
sister chromatids become attached by their kinetochores to opposite
poles; balanced bipolar forces hold chromosomes on the metaphase
plate.
c. Metaphase (fig. 13). During metaphase (Gr., meta = after; phasis =
appearance), the chromosomes are shortest and thickest. Their
centromeres occupy the plane of the equator of the mitotic apparatus
(a region known as the equatorial or metaphase plate), although the
chromosomal arms may extend in any direction. At this stage, the sister
chromatids are still held together by centromere and the kinetochores
of the two sister chromatids face opposite poles; this would permit
proper separation in the next phase (anaphase).
Metaphase occupies a substantial portion of the mitotic phase, as if
the cells pause until all their chromosomes are lined up appropriately
on the metaphase plate. At metaphase, subunits (tubulin dimers) are
added to the plus end of a microtubule at
the kinetochore and are removed from
the minus end at the spindle pole. Thus, a
poleward flux of tubulin subunits occurs,
with the microtubules remaining
stationary and under tension.
Can you imagine how chromosomes align
without spindle fibers? Would it be
successful? Would you expect it to be
Fig. 13. A cell at metaphase. accurate?
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d. Anaphase (fig. 14). Anaphase (Gr., ana=up; phasis=appearance)
begins abruptly with the synchronous splitting of each chromosome
into its sister chromatids, called daughter chromosomes, each with one
kinetochore. Synchronous splitting of
each centromere during prophase is due
to an increase in cytosolic Ca2+. In fact,
Ca2+-containing membrane vesicles
accumulate at spindle poles and release
calcium ions to initiate anaphase.
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Cytokinesis
Both DNA synthesis and mitosis are coupled to cytoplasmic division, or
cytokinesis—the constriction of cytoplasm into two separate cells. During
cytokinesis, the cytoplasm divides by a process, called cleavage. The
mitotic spindle plays an important role in determining where and when
cleavage occurs. Cytokinesis usually begins in anaphase and continues
through telophase and into interphase. The first sign of cleavage in animal
cells is puckering and furrowing of the plasma membrane during
anaphase. The furrowing invariably occurs in the plane of the metaphase
plate, at right angles to the long axis of the mitotic spindle. A cleavage
furrow tends to form midway between asters originating from two
centrosomes.
Cleavage is accomplished by the contraction of a ring composed
mainly of actin filaments. This bundle of filaments, called contractile ring,
is bound to the cytoplasmic face of the plasma membrane by attachment
proteins. The contractile ring assembles in early anaphase. Once
assembled, it develops a force large enough to bend a fine glass needle
inserted into the cell.
Evidently, this force is generated due to muscle-like sliding of actin
and myosin filaments in the contractile ring. The actin-myosin interaction
pulls the plasma membrane down into a furrow. During a normal
cytokinesis, the contractile ring does not get thicker as the furrow
invaginates, suggesting that it continuously reduces its volume by losing
filaments. When cleavage ends, the contractile ring is finally dispensed
with altogether and the plasma membrane of the cleavage furrow narrows
to form the midbody, which remains as a tether (tether means a rope for
confining a beast within certain limits) between two daughter cells. The
midbody contains the remains of the two sets of polar microtubules,
packed tightly together with dense matrix material.
Cytokinesis greatly increases the total cell-surface area as two cells
form from one. Therefore, the two daughter cells resulting from
cytokinesis require more plasma membrane than in the plant cell.
Lastly, prior to cytokinesis, in M phase, large membrane-bounded
organelles such as Golgi apparatus and the endoplasmic reticulum break
up into smaller fragments and vesicles; this may ensure their even
distribution into daughter cells during cytokinesis.
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Significance of Mitosis
Mitosis has the following significance for living organisms:
1. helps the cell in maintaining proper size.
2. helps in the maintenance of an equilibrium in the amount of DNA and
RNA in the cell.
3. provides the opportunity for the growth and development to organs and
the body of the organisms.
4. replacement of old and dead cells
5. In certain organisms, it is involved in asexual reproduction.
6. The gonads and the sex cells depend on mitosis for the increase in their
number (before the cells undergo meiosis).
7. The cleavage of egg during embryogenesis and division of blastomeres
both occur through mitosis.
Follow the links given in MOLE for further information on cell division. Do
the worksheets for your self-check and review only. DO NOT submit.
MEIOSIS
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of chromosomes, no exchange of the genetic material and reduction of the
chromosome number do not occur.
Both the meiotic divisions occur continuously and each includes the usual
stages of the meiosis: prophase, metaphase, anaphase and telophase.
The prophase of first meiotic division is very significant phase because the
most cytogenetical events such as synapsis and crossing over occur
during this phase. The prophase is the longest meiotic phase; it is divided
into substages: leptonema (leptotene), zygonema (zygotene), pachynema
(pachytene), diplonema (diplotene) and diakinesis. The successive
meiotic substages can be represented as follows:
Meiosis starts after an interphase which is not very different from that of
an intermitotic interphase. During the premeiotic interphase DNA
duplication has occurred at the S phase. The cell passed G2 phase of
interphase and directed toward meiosis. Further, in the beginning of the
first meiotic division the nucleus of the meiocyte starts to swell up by
absorbing the water from the cytoplasm and the nuclear volume increases
about three folds. After these changes the cell passes to the first stage of
first meiotic division which is known as prophase.
Prophase I
The first prophase (fig. 16) is the longest stage of the meiotic division. It
includes following substages:
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4. Pachytene or Pachynema. (Gr., pachus = thick). In this stage, the pair
of chromosomes continue to coil and shorten and further development
of the synaptonemal complex occurs between the two members of
each bivalent. This leads to synapsis, a more intimate pairing.
Compared to the rough-pairing characteristic of zygonema, homologs
are now separated by only 100 nm.
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Metaphase I (fig. 17)
During this stage, the microtubules of the spindle are attached to the
kinetochores at the centromeres of the homologous chromosomes of
each tetrad, aligning chromosomes at the equator. The centromere of
each chromosome is directed towards the opposite poles. The repulsive
forces between the homologous chromosomes increase greatly and the
chromosomes become ready to separate.
Homologues are freed from each other and due to the shortening of
chromosomal fibers or microtubules, each homologous chromosome with
its two chromatids and undivided centromere moves towards the opposite
poles of the cell. The chromosomes with single or few terminal chiasmata
usually separate more frequently than the longer chromosomes
containing many chiasmata. The actual reduction and disjunction occur
at this stage. It should be emphasized that the homologous chromosomes
which move towards the opposite poles are the chromosomes of either
paternal or maternal origin. Moreover, because during the chiasma
formation out of two chromatids of a chromosome, one has changed its
counterpart, the two chromatids of a chromosome do not resemble each
other genetically.
The arrival of a haploid set of chromosomes at each pole defines the onset
of telophase I, during which nuclei are reassembled. The endoplasmic
reticulum forms the nuclear envelope around the chromosomes and the
chromosomes become uncoiled. The nucleolus reappears and, thus, two
daughter nuclei are formed. After the karyokinesis (nuclear division),
cytokinesis (cytoplasmic division) occurs and two haploid cells are
formed. Both cells pass through a short resting phase of interphase.
During interphase, no DNA replication occurs, so that chromosomes at
the second prophase are the same double-stranded structures that
disappeared at the first telophase. In case of some flowering plants,
telophase I and interphase I do not occur and the anaphase I is followed
by prophase II directly.
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Fig. 17. The transition of meiosis I from metaphase to telophase and from
telophase until prophase II. (source: Klug, Cummings, Spencer and
Palladino, 2012)
If meiosis ends after 1 round (meaning there is no
second round), what are some possible implications
in organisms which reproduce sexually?
The second meiotic division is actually when each haploid meiotic cell
divides into two haploid cells. It includes following four stages:
Each centriole divides into two and, thus, two pairs of centrioles are
formed. Each pair of centrioles migrates to the opposite pole. The
microtubules get arranged in the form of spindle at the right angle of the
spindle of meiosis I. The nuclear membrane and the nucleolus disappear.
The chromosomes with two chromatids become short and thick.
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Metaphase II (fig. 18)
The daughter chromosomes move towards the opposite poles due to the
shortening of chromosomal microtubules and stretching of interzonal
microtubules of the spindle.
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Telophase II (fig. 18)
The chromatids migrate to the opposite poles and are now known as
chromosomes. The endoplasmic reticulum forms the nuclear envelope
around the chromosomes and the nucleolus reappears due to synthesis of
ribosomal RNA (rRNA) and also due to accumulation of ribosomal
proteins. After karyokinesis in each haploid meiotic cell, cytokinesis
occurs and, thus, four haploid cells are formed. These cells have different
types of chromosomes due to the crossing over in prophase I.
Significance of Meiosis
1. It maintains a definite and constant number of chromosomes in the
organisms.
2. By crossing over, it provides an opportunity for the exchange of the
genes and, thus, causes the genetic variations among the species,
variation being a raw material of the evolutionary process.
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Table 2 continuation.
Basis MITOSIS MEIOSIS
Prophase Short duration; no Longer prophase I, which has
substage these successive stages:
leptotene, zygotene,
pachytene, diplotene,
diakinesis
No pairing of homologous Pairing of homologous
chromosomes or chromosomes (prophase I)
synapsis
No chiasma formation or Chiasma formation or crossing
crossing over over takes place (prophase I)
no exchange of genetic Exchange of genetic materials
materials between between the non-sister
homologous chromatids of the homologous
chromosomes chromosomes
Prophase Chromatids occur in the Chromatids of 2 homologous
(cont’d) form of dyads chromosomes occur as
tetrads
Metaphase The centromeres of the The centromeres of the
chromosomes remain chromosomes remain directed
directed towards the towards the poles and the
equator and the arms of chromosomal arms remain
the chromosomes remain directed towards the equator.
directed towards the
poles.
Anaphase The chromosomes are The chromosomes are the
the monads, i.e., having dyads, i.e., having two
single chromatid. chromatids and single
centromere.
Telophase Always occurs Telophase I is sometimes
omitted
Results 1 diploid parent cell 1 diploid parent cell produces
produces 2 diploid 4 haploid daughter cells
daughter cells
Significance Maintaining Maintaining chromosomal
chromosomal number number (fertilization combines
haploid sperm and haploid
oocyte)
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Kinds of Meiosis and Life cycles
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The tiny gametophyte is nurtured in
specialized tissues of sporophyte. Male
and female haploid cells called spores,
are produced by meiosis in the diploid
(sporophyte) organism. Spores grow into
multicellular male and female haploid
(gametophyte) structures, which through
meiosis produce haploid cells
corresponding to the actual gamete.
In the seed-producing plants,
development is arrested at an early
multicellular stage as a seed, which may
remain stable for long time before
germination permits a continuation of
growth. Thus, reproductive cycle
includes alternation of two generations:
haploid and diploid and involves meiosis.
Fig. 20. Sporic Life Cycle.IPLOBIONTIC
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EXERCISE 1. Cell Division
To continue your learning, the activity below is designed to
compare and contrast mitosis and meiosis. This is your first group output.
3. Assume that it takes, on the average, 24 hours (or 1,440 minutes) for
Allium cepa root tip cells to complete a cycle. Calculate the amount of
time spent by the cell in each phase (relative duration) using the
following formula:
Percent of cells in a stage X 1,440 minutes = ____ minutes of the cell
cycle spent in that stage
Values for % & relative duration should be rounded off to the nearest
thousandth.
Compute the mitotic index from the presumed single root tip using this
formula:
B. History of Genetics
Some of us do not like history but if we think about it, there are a lot of
things that the pioneers of genetics have contributed to the science. So,
we will start this course with a tribute to the famous names behind
genetics. This will be part of your Learning activity 1. Instructions will
follow after the next topic.
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C. Applications of Genetics
There are a lot of applications that genetics has on our daily lives. Maybe
those things may not seem obvious right now but all along they have been
making our lives easier.
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explained by genetics. The examination of chromosomes in
karyotyping can shed light on possible lack or excess of
chromosomes or segments of chromosomes. Production of
vaccines, antibodies, vitamins, insulin (as mentioned in number 2).
Gene therapy which corrects the defective gene and, in the future,
we are hoping to get access to personalized medicine, with our
genetic makeup as the basis for our treatment.
4. Legal applications. This includes the use of gathering samples and
doing DNA testing on them to identify the possible perpetrators of a
crime, or to check parentage of a child.
5. In industries. Genetics has provided some synthetically produced
raw materials for industries. For example, the brewing industry may
use geneticists to improve the strains of yeast that product the
alcohol. The pharmaceutical industry has developed strained of
molds, bacteria and other microorganisms which have high antibiotic
yield.
6. In humans. All of the benefits mentioned above benefit humans. In
addition, if we apply the knowledge of genetics to our choice of mate,
then we can have the possibility of making children with only the
desirable traits, those children who have higher resistance to
diseases that they do not get sick easily or maybe never even get sick
at all. Gene therapy can also address deficiencies by having
corrections done to the baby’s genetic structure. Life span of
humans have also been increased due to availability of vaccines,
medications and vitamins, among others.
7. Environment. The environment has benefited from the availability of
genetically modified microorganism which have the capability to
degrade waste materials rapidly. The process of bioremediation
which refers to the use of either naturally occurring or deliberately
introduced microorganisms or other forms of life to consume and
break down environmental pollutants, in order to clean up a polluted
site. Example is the rehabilitation of polluted waterways or cleaning
up oil spills. Another use of genetics is in the protection of valuable
wildlife populations. This can be done by genetic monitoring using
genetic markers which could probably solve problems causing the
reduction of populations in their natural habitats.
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Learning Activity 1
This is your 2nd group output. It should be realistic.
1. Read on history of genetics. Name 6 persons who you consider has
contributed most importantly to this science. Give your reasons for
choosing them each of them. Use your own words for your reasons.
Do not just lift words from your sources. Impressive words do not
guarantee more points. Just write an honest evaluation of what you
feel you benefited or will benefit from each name you chose.
2. Make a table containing the list of benefits that each of you have
enjoyed, are enjoying and sure to enjoy out of the applications of
genetics mentioned.
You can present your output as infographics or posters with this
filename: your family names (Section) – LA1
E-mail your group output to your professor.
D. Scope of Genetics
Genetics is a big field. It operates on many different levels. The scope
that is referred to here is the scope of this course. Basic aspects of the
following branches of genetics will be covered in this course:
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aspects of individuals as well as molecular markers from those
individuals.
Developmental Genetics: studies how genes control the developmental
processes especially in cell migration and differentiation. It emphasizes
on how genes control the growth and development of an organism
throughout its life-cycle.
Behavioral Genetics: studies the influence of varying genetics on animal
behavior, the effects of human disorders as well as its causes; has yielded
some very interesting questions about the evolution of various behaviors,
and even some fundamental principles of evolution in general
Fill in the downloadable version of this table. Save as your family name
(section) – ROYL1 and e-mail to your professor. Be sure to follow basic e-
mail etiquette.
Example:
Subject: BIO105 ROYL1
Type a short note in the body of the e-mail. And DO NOT FORGET to attach
the file.
What are your key learnings/highlights of
Learning Outcomes
your learning?
1.
2.
3.
4.
5.
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