Knes 259

Human
Anatomy and Physiology

Cell Division and Genetics

Suggested Readings
McKinley
Chapter 4 – Biology of the Cell
• Section 4.9 – Cell Division (pages 143-146)
• Chapter 28 – Reproductive system
• Section 28.2 – Meiosis (pages 1098-1101)
Chapter 29
• Section 29.9 - Heredity and Genetics (pages 1169-
1174)
Suggested Readings
Tortora
Chapter 3 – Biology of the Cell
• Section 3.7 – Cell Division (pages 92-98)
Chapter 29
• Section 29.12 - Heredity and Genetics (pages 1136-
1142)
Genes
Genes Chromosomes

units of heredity (for traits)

segments of DNA
Centromere
Each gene has a specific
locus (point) on a specific
chromosome
Sister chromatids
Human Chromosomes
Somatic cell
46 chromosomes (diploid)
• two sets of 23
Pair of homologous
chromosomes 5 µm

• One set from each parent

Centromere

Sister
chromatids

Gametes (sperm and egg cells)

haploid Figure 13.3

• 1 set of chromosomes (23)

• Result of Meiosis
Cell Division
Process by which cells reproduce themselves
Cell cycle

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
Cell Division
Some cells divide repeatedly
Use stem cells
Eg. Skin, Blood cells, cheek cells

Some cells stay alive but don’t divide

Eg. Muscle and nerve (called G0 cells)

Other cells divide infrequently

Eg. bone
 Chromosomes
To prepare for cell division
DNA is replicated
chromosomes condense

Each duplicated chromosome

Has two sister chromatids
Cell Division by Mitosis
Interphase
Chromosomes
INTERPHASE
duplicate
G1
Cell parts are made
S
(DNA synthesis)
Mitosis
G2
Chromatids splits
2 equal cells
Interphase
G1 phase
Cell grows, multiplies organelles, is active
S phase
Cell synthesizes DNA
G2 phase
Cell grows, centrioles replicate

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
 Mitosis – 5 Phases

G2 OF INTERPHASE PROPHASE PROMETAPHASE

Centrosomes Aster
Early mitotic Fragments Kinetochore
(with centriole pairs) Chromatin
spindle Centromere of nuclear
(duplicated) envelope Nonkinetochore
microtubules

Nucleolus Nuclear Plasma Chromosome, consisting Kinetochore

Figure 12.6 of two sister chromatids microtubule
envelope membrane
 Mitosis

METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS

Metaphase
plate Cleavage Nucleolus
furrow forming

Nuclear
envelope
Spindle Centrosome at Daughter forming
Figure 12.6 one spindle pole chromosomes
Mitotic Phase: Prophase
Chromatin condenses into chromosomes
Nuclear wall degenerates
Centrosomes start to move apart

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
 Prometaphase
Nuclear envelope
disappears
PROMETAPHASE Spindles from
Fragments
of nuclear
envelope
Kinetochore chromatids to
centrosomes
Kinetochore proteins
appear
Spindle
microtubules
Mitotic Phase: Metaphase
Centromeres of chromosomes line up at the
metaphase plate
Mitotic spindles start to form

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
Mitotic Phase: Anaphase
Centromeres of chromosomes split
Sister chromatids move toward opposite
poles of the cell

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
 Kinetochore microtubules move chromatids toward
opposite ends of the cell

Nonkinetechore microtubules
Overlap and push against each other, elongating the cell

1 The microtubules of a cell in early anaphase were labeled with a fluorescent dye
that glows in the microscope (yellow).

Kinetochore

Spindle
pole

Figure 12.8
Mitotic Phase: Telophase
Mitotic spindles
dissolve
Chromosomes
become chromatin
New nuclear
membrane forms

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
 Cytokinesis
Division of cytoplasm
Occurs with telophase
Cleavage
Cleavage furrow
SEM 140
furrow

pinches cell in two

Cleavage furrow Contracting ring
of
(actin-myosin
microfilaments
drawstring)

Daughter cells
Cytokinesis

After cytokinesis,
new cells enter
interphase

Copyright © 2014 John Wiley & Sons, Inc. All rights reserved.
 The Cell Cycle Control System
Events of the cell cycle are directed by a
control system
Specific checkpoints
G1 checkpoint

G0

Control G1 checkpoint
system S
G1

G2 G1 G1
M
(a) If a cell receives a go-ahead (b) If a cell does not receive a go-
signal at ahead
the G1 checkpoint, the cell signal at the G1checkpoint, the cell
continues exits the cell cycle and goes into
M checkpoint on in the cell cycle. G0, a
G2 checkpoint nondividing state.
Checkpoints
G1 Passed if
Nutrients sufficient
Cell size big enough
DNA undamaged
G2 Checkpoint – before mitosis
Two regulatory proteins involved
in cell cycle control
Cyclins and cyclin-dependent M G1 S G2 M
MPF activity
G1 S G2 M

kinases (Cdks) Cyclin

Tim
e

Cyclins and Cdks form MPF

Maturation promoting factor
• Triggers mitosis
Cdk

Degraded
Cyclin G2
Cdk
checkpoint
Cyclin is
degraded Cyclin
MPF
 External Factors
External cell factors can also trigger cell
division
Eg. Growth factor
Growth factor
Plasma membrane

Relay
Receptor proteins G1 checkpoint
protein
Signal
transduction Control
G1 S
pathway system

M G2
Density-dependent Inhibition
• Crowded cells stop dividing

Anchorage dependence
• Cells must be attached to substratum to divide

(a) Normal mammalian cells. The Cells anchor to dish surface and
availability of nutrients, growth divide (anchorage dependence).
factors, and a substratum for
attachment limits cell
density to a single layer. When cells have formed a complete single layer, they
stop dividing
(density-dependent inhibition).

If some cells are scraped away, the remaining cells divide

to fill the gap and then stop (density-dependent inhibition).

Figure 12.18 A 25 µm
Cancer cells
No density-dependent inhibition
Do not respond to body’s control mechanisms

No anchorage dependence
Cancer cells do not exhibit
Form tumours anchorage dependence or
density-dependent inhibition.

(b) Cancer cells. Cancer cells usually

continue to divide well beyond a
single layer, forming a clump of
overlapping cells.

Figure 12.18 B
25 µm
Meiosis
Sexual reproduction
Produces a haploid set of chromosomes
Eg. Eggs and sperm

Chromosomes replicate once

2 cell divisions (meiosis I and meiosis II)
 Interphase
Homologous pair

Meiosis of chromosomes
in diploid parent cell

Meiosis I Chromosomes
replicate
Reduces Homologous pair of replicated chromosomes

chromosomes from
diploid to haploid Sister
chromatids
Diploid cell with
replicated
chromosomes

Meiosis I

Meiosis II 1 Homologous
chromosomes
separate

Produces four Haploid cells with

replicated chromosomes

haploid daughter Meiosis II

2 Sister chromatids

cells separate

Haploid cells with unreplicated chromosomes

Figure 13.7
 Crossing Over
Prophase I

Increases genetic

TEM 2,200
variability
Chiasma
Tetrad

Produces
chromosomes that
carry genes from
two different parents Centromere
 Interphase and meiosis I

INTERPHASE MEIOSIS I: Separates homologous chromosomes

PROPHASE I METAPHASE I ANAPHASE I

Centrosomes Centromere Sister chromatids

(with centriole pairs) (with kinetochore) remain attached
Chiasmata Metaphase
Sister
chromatids Spindle plate

Nuclear Homologous
Microtubule
envelope Tetrad chromosomes
Chromatin attached to
kinetochore separate
Chromosomes duplicate Tertads line up Pairs of homologous
Homologous chromosomes chromosomes split up
(red and blue) pair and exchange
Figure 13.8
segments; 2n = 6 in this example
 Telophase I, cytokinesis, and meiosis II

MEIOSIS II: Separates sister chromatids

TELOPHASE I AND PROPHASE II METAPHASE II ANAPHASE II TELOPHASE II AND
CYTOKINESIS CYTOKINESIS

Cleavage Haploid daughter cells

furrow Sister chromatids forming
separate

Two haploid cells

form; chromosomes During another round of cell division, the sister chromatids finally separate;
Figure 13.8 are still double four haploid daughter cells result, containing single chromosomes
Mitosis vs Meiosis
MITOSIS MEIOSIS
Parent cell Chiasma (site of
MEIOSIS I
(before chromosome replication) crossing over)

Prophase I
Prophase
Chromosome Chromosome
replication replication Tetrad formed by
Duplicated chromosome synapsis of homologous
2n = 6
(two sister chromatids) chromosomes

Chromosomes Tetrads
positioned at the positioned at the Metaphase I
Metaphase
metaphase plate metaphase plate

Anaphase Sister chromatids Homologues

separate during separate Anaphase I
Telophase
anaphase during Telophase I
anaphase I;
sister Haploid
chromatids Daughter n=3
remain together cells of
meiosis I
2n 2n
Daughter cells MEIOSIS II
of mitosis

n n n n

Daughter cells of meiosis II

Sister chromatids separate during anaphase II

In independent assortment
Each pair of chromosomes sorts its maternal and paternal homologues
into daughter cells independently of the other pairs

Key

Maternal set of
chromosomes Possibility 1 Possibility 2
Paternal set of
chromosomes
Two equally probable
arrangements of
chromosomes at
metaphase I

Metaphase II

Daughter
cells

Figure 13.10 Combination 1 Combination 2 Combination 3 Combination 4

Genetic variability
Independent Prophase I
of meiosis
Nonsister
chromatids

assortment, random
Tetrad
fertilization and Chiasma,
site of
crossing over crossing
over
Metaphase I

produce a zygote Metaphase II

with any of about 64
trillion diploid Daughter
cells
combinations
Recombinant
Figure 13.11 chromosomes
Meiosis Malfunction
Abnormal chromosome count
• The failure of homologous pairs to separate during
meiosis I
• The failure of sister chromatids to separate during meiosis
II

Nondisjunctio
n in meiosis I Normal
meiosis I

Normal Nondisjuncti
meiosis on in meiosis
II II

Gametes
Gametes n+1 n −1 n n
n+1 n+1 n −1 n −1 Number of chromosomes
Number of chromosomes
 Egg cell

n+1

Zygote
Sperm cell 2n + 1
n (normal)

Birth defect depends on chromosome affected

XXY (Klinefelter’s syndrome), XO- Turner’s
Syndrome
Trisomy 18 – Edward’s syndrome
 Down syndrome is caused by trisomy 21
• An extra copy of chromosome 21

• Karyotype

5,000

Figure 8.20A Figure 8.20B

 Other Genetic Malformations
Reciprocal
translocation
Deletion

Nonhomologous
chromosomes

Chromosome 9

Duplication

Homologous
chromosomes Reciprocal
Chromosome 22 translocation

Inversion

“Philadelphia chromosome”

Activated cancer-causing gene

Gregor Mendel 1 Removed stamens
from purple flower
Transferred sperm-
2
bearing pollen from
stamens of white
Studied inheritance using flower to egg-
bearing carpel of

true breeding pea plants purple flower

Parental
generation
(P)
Stamens
Carpel
(male)
Discovered basic laws of 3 Pollinated carpel
matured into pod
(female)

heredity 4 Planted seeds

from pod

5 Examined
First offspring:

tracked characteristics that generation

offspring
all purple
flowers

varied in an “either-or” (F1)

manner
Experiment
P Generation


Only the purple factor (true-breeding

parents) Purple White
flowers flowers
was affecting flower
color F1 Generation
(hybrids)
All plants had
purple flowers
~3:1, purple to white
flowers in the F2 Generation

F2 generation
Mendel’s hypothesis
4 concepts
There are alternative versions of genes
• called alleles
An organism inherits two alleles, one from
each parent
Allele for purple flowers

Homologous
Locus for flower-color gene pair of
chromosomes

Allele for white flowers

3. If the two alleles at a locus differ
The dominant allele determines appearance
The recessive allele has no noticeable effect on
appearance

4. The law of segregation

The two alleles for a heritable character separate
during gamete formation and end up in different
gametes
 F1 generation All round yellow seeds
(RrYy)
R
r y

Y
R r r R

Metaphase I
Y y of meiosis Y y
(alternative arrangements)
R r r R

Anaphase I
Y y of meiosis Y y
R r r R
Metaphase II
of meiosis
Y y Y y

Y y
Y Y Y y y
Gametes y
R R r r r r R R

1 1 1 1
4
RY 4
ry rY 4 4
Ry
Fertilization among the F1 plants

F2 generation 9 :3 :3 :1
(See Figure 9.5A)
 Each true-breeding plant of the


parental generation has identical P Generation
Purple alleles, PP or pp.
Appearance: Purple flowers White flowers
Gametes (circles) each contain only Genetic makeup: PP pp
Dominant trait one allele for the flower-color gene.
In this case, every gamete produced
by one parent has the same allele.
Gametes: P p

White Union of the parental gametes

produces F1 hybrids having a Pp
combination. Because the purple- F1 Generation
flower allele is dominant, all

recessive these hybrids have purple flowers. Appearance:

Genetic makeup: Purple flowers
When the hybrid plants produce Pp
gametes, the two alleles segregate, Gametes: 1/ 1/ p
2 P 2
half the gametes receiving the P
allele and the other half the p allele.
This box, a Punnett square, shows F1 sperm
all possible combinations of alleles
P p
in offspring that result from an
F1  F1 (Pp  Pp) cross. Each square F2 Generation
represents an equally probable product P
of fertilization. For example, the bottom PP Pp
left box shows the genetic combination
F1 eggs
resulting from a p egg fertilized by p
a P sperm. Pp pp
Random combination of the gametes
results in the 3:1 ratio that Mendel
observed in the F2 generation.
3 :1
Phenotype (shown trait) and genotype (alleles)
Phenotype Genotype

Purple PP
1
(homozygous)

Pp
3 Purple (heterozygous)

2
Pp
(heterozygous)
Purple

pp
1 White 1
(homozygous)

Figure 14.6 Ratio 3:1 Ratio 1:2:1

Homozygous
Same genes
Either dominant or recessive

Heterozygous
Differing genes
Dominant trait is
displayed
Most traits are determined by allele pairs
Ear lobe shape
Taste sensations
Rolling tongue
freckles
Human Traits
Punnett Square
Determines probability Dad
of inheriting a trait Allele 1 Allele 2

Allele 1

Mom
Compare alleles
From both parents Allele 2
Dominant traits
TT x TT
100% with trait
TTxTt
100% with trait
50% heterozygous
TTxtt
100% with trait
100% heterozygous
tt x tt
Trait not shown
Heterozygous Parents
Tt x Tt
If dominant
75% with trait
• Homozygous dominant and
heterozygous
25% no trait
50% heterozygous
Recessive Disorders
Most disorders are recessive
Normal Normal
Parents
Dd  Dd
Recessive disorders
Sperm
D d
Show up only in individuals
homozygous for the allele
Dd
D DD
Normal
Normal
Carriers Eggs
(carrier)

heterozygous individuals
Dd dd
• carry the recessive allele d Normal Deaf
(carrier)
but are phenotypically normal
Examples of Recessive Disorders

Cystic Fibrosis
Sickle Cell Anemia
Tay-Sach’s Disease
Gaucher’s Disease
Phenylketonuria
Dominant Genetic Disorders
Disorder is expressed if dominant gene is
present
Seen in heterozygous individuals

Examples
Huntington’s disease
• Neurodegenerative
• effects seen after age 40
Marfan’s syndrome
• Affects connective tissue
Pedigree Analysis
A pedigree
family tree that describes the interrelationships of
parents and children across generations
Inheritance patterns of traits can be traced
Pedigree Analysis
Can trace dominant or recessive traits

First generation
Ww ww ww Ww (grandparents) Ff Ff ff Ff

Second generation
(parents plus aunts
Ww ww ww Ww Ww ww FF or Ff Ff ff Ff Ff ff
and uncles)

Third
WW ww generation ff FF
or (two sisters) or
Ww Ff

Widow’s peak No Widow’s peak Attached earlobe Free earlobe

(a) Dominant trait (widow’s peak)
(b) Recessive trait (attached earlobe)
Royal Pedigree - Hemophilia
 Codominance
Two dominant alleles
each distinctly affect the
phenotype
More than 2 allele forms

E.g. Human blood

groups
Both A and B phenotypes
are dominant
Incomplete Dominance
P Generation White
Red

Phenotype of F1 CRCR
CWCW

offspring is between the Gametes CR CW

phenotypes of the two F1 Generation

Pink
CRCW

parental varieties 1⁄
2 1⁄
2
Gametes CR CR

Human example Eggs

1⁄
2 CR 1⁄2 CR Sperm
F2 Generation
1⁄
CR
Eye/hair/skin colour? 2
CR CR CR CW
1⁄
2 Cw
CR CW CW CW
Sickle-cell anemia
• Heterozygous people can
show mild symptoms
Pleiotropy
Where one gene has multiple phenotypic
effects Individual homozygous
for sickle-cell allele

Sickle-cell (abnormal) hemoglobin

Abnormal hemoglobin crystallizes,

causing red blood cells to become sickle-shaped

Sickle cells

Breakdown of Clumping of cells

Accumulation of
red blood cells and clogging of
sickled cells in spleen
small blood vessels

Physical Heart Pain and Brain Damage to Spleen

Anemia
weakness failure fever damage other organs damage

Impaired Pneumonia
Paralysis Rheumatism Kidney
mental and other
failure
function infections
Polygeny
When traits are determined by two or more
genes

AaBbCc AaBbCc

Many human characters

aabbcc Aabbcc AaBbcc AaBbCc AABbCc AABBCc AABBCC

Vary along a continuum 20⁄

64

called quantitative characters 15⁄

64

6⁄
64

1⁄
64
Sex-Linked Genes
The X chromosome carries genes unrelated to
sex
Males have one X and one Y chromosome
Females have two X chromosomes
Sex-linked Traits
If mother is heterozygous for a recessive
X-linked trait
50% of the daughters will be carriers
50% of sons will show recessive trait
Sex-linked
Disorders
Most are recessive
Affect males more

A male
Has a single X-linked allele from his mother
Will have disorder if has allele

A female
Has two X alleles
• Needs recessive allele from both parents for disease
• If only one allele- carrier
Sex-linked Traits

Colour-Blindedness
9 % of males / 0.03% of females
Hemophilia
Male pattern Baldness
Gene Expression
Having a gene doesn’t mean it’s expressed
Epigenetic effects
Histones and methylation
Can turn on or turn off gene expression
Environmental factors determine epigenetics
 Human Diseases
Have both genetic and environment
components

Eg. Heart disease and cancer

Lifestyle choices matter

Genetics may increase risk
Definitions
Phenotype - its physical appearance of a
specific character

Genotype - the genetic makeup (alleles) that

determine the physical appearance
Definitions
Character: a heritable feature, such as eye colour
or hair colour
Trait: a variant of a character, such as blue eyes or
brown eyes

P generation – the true-breeding parents

F1 generation - hybrid offspring of the P
generation
F2 generation –when F1 individuals self-pollinate
Definitions
Alleles – inherited character on the genes (get
one from each parent)

Locus – location on the gene

Dominant allele - determines the organism’s

appearance

Recessive allele - has no noticeable effect on

the organism’s appearance
Definitions
Homozygous
Has a pair of identical alleles for that gene
Either dominant or recessive

Heterozygous
Has a pair of alleles that are different for that
gene
Definitions
Pleiotropy – one gene, many effects
Polygeny – Many genes affecting one trait
Co-dominance – more than one dominant
gene can be displayed
Incomplete dominance – intermediate trait
is seen with heterozygous genotypes