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Unit 4
Cell Biology for Biomedical Engineers
UNIT 4 - BME101
Chromosomes
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What is a Chromosome?
Chromosome is the highly condensed
form of DNA
Wrapped into nucleosomes
Wrapped into chromatin fiber
Condensed during metaphase into
the familiar shape
Humans have 22 autosomal pairs
And one pair of sex chromosomes
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Chromosome Parts:
Heterochromatin:
More condensed
Silenced genes (methylated)
Gene poor (high AT content)
Stains darker
Euchromatin:
Less condensed
Gene expressing
Gene rich (higher GC content)
Stains lighter
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Chromosome Parts:
Telomeres chromosome tips
Repeats
Act as sort of biological clock
Being whittled down at each Mitosis
Centromeres middle
Highly condensed
Also repetitive sequence
Region where spindle fibers attach
Pulling chromatids apart during Mitosis
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Chromosome Parts:
p arm the smaller of the two arms
p stands for petite
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Chromosome Types
There are four types of chromosomes:
1. Telocentric
2. Acrocentric
3. Submetacentric
4. Metacentric
Divided based on the position of the
centromere
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Chromosome Types:
1. Telocentric no p arm; centromere is
on end
2. Acrocentric very small p arm;
centromere is very near end
3. Submetacentric p arm just a little
smaller than q arm; centromere in
middle
4. Metacentric p and q arms are
exactly the same length; centromere
in exact middle of chromosome
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Chromosome Types:
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10
Things to remember
Homologous chromosomes are not
identical
Can have different alleles of genes
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11
What is DNA?
It's a history book - a narrative of the
journey of our species through time.
It's a shop manual, with an incredibly
detailed blueprint for building every
human cell.
And it's a transformative textbook of
medicine, with
insights that will give health care
providers immense
new powers to
treat, prevent and cure disease."
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13
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14
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Karyotype
Lung cell
Toe cell
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17
18
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Mutant Protein
Inheritance of Genes
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Gregor Mendel
1822-1884
MENDELS LAWS
22
MENDELS LAWS
MENDELS LAWS
Principle
of
Independent
Assortment: Genes for different
traits assort independently of one
another in gamete production
What it means: different genes are
inherited separately.
For example, the gene which codes for
eye color is inherited separately from
the gene which codes for nose shape.
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Mendelian Concepts
Dominant = only one allele of a gene
necessary to express the trait
Recessive = both alleles of a gene must
be identical to express the trait
Heterozygous = alleles of a particular gene
are non-identical
Homozygous = alleles of a particular gene
are identical
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25
Al lele 1
Allele 1
Allele 2
A1/A1
A1/A2
A2/A1
A2/A2
Parent 1
Al lele 2
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Homozygous dominant +
Homozygous dominant
Homozygous dominant +
Heterozygous
A
A
AA
AA
AA
A
AA
AA
AA
Aa
Aa
A
Homozygous dominant +
Homozygous recessive
a
a
A
A
Aa
Aa
Aa
Aa
Heterozygous + Heterozygous
AA
Aa
Aa
aa
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28
More information
What if you knew something about Kims
parents?
How could that help?
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Kims Parents
As it turns out, Kims father has dimples in
both cheeks, while her mother does not
Her mother must have the recessive trait
and therefore has to have the genotype
dd
Kims father has the dominant trait, but we
dont know if he is a homozygote or
heterozygote. He could be DD or Dd
just like Kim!
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30
But we still know
what Kims genotype
Kims genotype is Dd
Kim must have a recessive allele (d), since
that is all she could have inherited from
her mother
Since Kim has dimples, we know she
inherited a dominant allele (D) from her
father
It doesnt matter if Kims father is DD or
Dd; whichever it is, he passed on a D to
his daughter
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d
Dan
d
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D
Dd
Kim
d
dd
Dan
Dd
dd
50% chance the baby will have the genotype Dd and have
dimples
50% chance the baby will have the genotype dd and not have
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dimples
Chromosomal Anomalies or
Chromosomal Abnormalities
Unit 4
Cell Biology for Biomedical
Engineers
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34
Introduction
Teratology : The branch of biology
concerned with the development of
malformations or serious deviations from
the normal type of organism
Causes of congenital (Present at birth but not
necessarily hereditary; acquired during foetal
) malformations:
(a) Genetic factors: chromosomal
abnormalities
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BME101
(b) Environmental
drugs,
development
35
36
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37
38
Mechanism of Polyploidy
of
dissolving
chromosomes
of
nuclear
membrane.
UNIT 4 - BME101 division.
(c)Failure of cytoplasmic
39
Types of Polyploidy
1. Autopolyploidy:
even-numbered
40
Types of Polyploidy
Pentaploidy
chromosomes)
(23x5
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or
115
41
Mechanism of Aneuploidy
of
either
of
these
abnormal
42
nd
NormalUNIT
1st &
meiotic
4 -2BME101
division
43
abnormal
gametes
Zygotic Ploidy
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Zygotic Ploidy
44
Trisomies of Chromosomes
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Trisomy of Autosomes
46
48
Patau syndrome
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Patau syndrome
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51
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Edward syndrome
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54
Down Syndrome
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Down syndrome
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Down syndrome
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Down syndrome
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Deficiencies/Deletions
Duplications
Inversions
Translocations
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Translocation Deletion
Derivative
chromosome
Inversion
Insertion
Isochromosome
Ring
chromosome
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Figure 8.3
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Deficiencies
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Cri-du-chat Syndrome
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Duplications
Figure 8.5
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Duplications
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A gene family consists of two or more genes that are similar to each other
derived from a common gene ancestor
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Genes derived
from a single
ancestral gene
Figure 8.9
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Inversions
Centromere lies
within inverted
region
Figure 8.11
Centromere lies
outside inverted
region
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Inversions
Position effect
Gene is repositioned in a way that alters its
gene expression
separated from regulatory sequences, placed
next to constitutive heterochromatin
71
Inversion Heterozygotes
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Translocations
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Fig. 8.13b(TE
Art)
Nonhomologous
chromosomes
1 1
7 7
Crossover between
nonhomologous
chromosomes
Reciprocal
translocation
Nonhomologous
crossover
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
22
2
Reactive ends
78
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display
79
8-38
Breaks occur at the extreme ends of the short arms of two non-homologous
acrocentric chromosomes
The small acentric fragments are lost
The larger fragments fuse at their centromeic regions to form a single
chromosome
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display
80
8-39
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display
81
8-40
Figure 8.15
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8-42
1. Alternate segregation
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display
83
8-41
Figure 8.26
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display
84
8-71
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86
Mother
Father
XX
XY
Meiosis
Sex cells
Fertilisation
XX
XY
XX
XY
Possible
children
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Sex chromosomes
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HOMOGAMETIC
SEX
HETEROGAMETIC
SEX
SEX DETERMINATION
Female XX
Male XY
Male ZZ
Female ZW
Female XX
Male Xo
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Birds, amphibians,
reptiles, butterflies,
moths.
Grasshoppers
89
Sex Determination
Some mechanisms of sex determination
include:
a. Genotypic sex determination, in which
sex is governed by genotype.
b. Genic sex determination, in which sex
chromosomes are not involved.
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91
Sex Determination in
Mammals
1. Mammals use the Y-chromosome mechanism
of sex-determination, in which the Y
chromosome determines sex by conferring
maleness.
2. Sex of mammals is determined by a gene on
the Y chromosome, testis-determining factor. In
the absence of this gene, gonads develop into
ovaries.
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e. Higher numbers of
X and/or Y
chromosomes are
sometimes found,
including XXXY,
XXXXY, and XXYY.
The effects are
similar to Klinefelter
syndrome.
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Chapter 11 slide
Pedigree Analysis
The technique of looking through a family tree (of humans or other organisms)
for the occurrence of a particular characteristic in one family over a number of
generations.
Can be used to determine the likely mode of inheritance:
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
When looking at pedigrees, incomplete penetrance is occasionally observed.
Incomplete penetrance describes the situation where a proportion of a
population with a particular genotype does not show the expected
phenotype.
Complete penetrance of a phenotype means that all individuals with a
particular genotype will show the affected phenotype.
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Examples include:
Huntington disease
Achondroplasia (a form of
dwarfism)
Familial form of Alzheimer
disease
Defective enamel of the teeth
Neurofibromatosis (the Elephant
man disease)
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Chapter 11 slide
Examples include:
Albinism
Cystic fibrosis
Thalassaemia
Tay-Sachs disease
Phenylketonuria
Red hair colour
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Chapter 11 slide
Examples include:
Chapter 11 slide
Examples include:
Ichthyosis, an inherited skin disorder
One form of redgreen colour-blindness
One form of severe combined
immunodeficiency disease
Haemophilia
Fragile X syndrome
Duchenne muscular dystrophyUNIT 4 - BME101
Chapter 11 slide
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102
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103
P.17
7
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Normal
allele
Recessive
allele
106
trait
will
be
107
109
XX
B
**Carrier
XX
b
Female
Expresse
s RGCB
XY
b
XY
B
Normal
Male
Male
Express
es
RGCB
110
Sample Problem:
What is required?
Possibility of son possessing
RGCB
What is given:
Mother X X
Father X Y
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Solution:
X Y
X X
X X
X Y
112
Hemophilia A
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H normal expression
h hemophilia
H
X X
X X
Female with
**Carrier hemophilia
X Y
X Y
Male with
hemophilia
Normal
Male
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Sample Problem:
A man that
expresses
hemophilia
marries a woman
that does not
express this
disease. What is
the possibility of
their son
expressing
hemophilia?
What is required?
Possibility of son with
hemophilia
What is given?
XhY
H
H
Mom X X
Dad
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Solution:
X
X
X X
X Y
XY
X X
X
H
The son has no possibility of expressing hemophilia.
The daughter will be a carrier
the disease.
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- BME101
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MUTATION
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Mutation
Mutationsare
changes
in
a
genomic sequence: theDNA sequence
of
a
cell's
genome the DNA
orRNAsequence of a virus.
They can be defined as sudden and
spontaneous changes in the cell.
Mutations are caused byradiation,
viruses and mutagenic chemicals, as
well as errorsthat occur duringmeiosis
or DNA Replication. They can also be
TYPES OF MUTATIONS
The sequence of a gene can be altered in a
number of ways. Gene mutations have varying
effects on health depending on where they
occur and whether they alter the function of
essential proteins.
Mutations in the structure of genes can be
classified as:
Types of gene mutation:
1. Point mutation(substitution)
2. Insertion mutation
3. Deletion mutation
4. Frame shift mutation
G)
or
apyrimidinefor a pyrimidine, (C T). A
transition can be caused bynitrous acid, base
mis-pairing, or mutagenic base analogs
Less
common
is
atransversion,
which
exchanges a purine for a pyrimidine or a
pyrimidine for a purine (C/T A/G). An
example of a transversion isadenine(A) being
converted into acytosine(C).
Point
mutations
that
occur
within
theproteincoding region of a gene may be
classified into three kinds, depending upon
what the erroneous(wrong)codon codes for:
Silent Mutations
Missense Mutations
Nonsense Mutations
Nonsense Mutations:
A nonsense mutation is
also a change in one DNA base pair. Instead of
substituting one amino acid for another, however, the
altered DNA sequence prematurely signals the cell to
stop building a protein. This type of mutation results
in a shortened protein that may function improperly
or not at all.
Deletions:remove one or
more nucleotides from the DNA.
Like insertions, these mutations
can alter thereading frameof the gene.
They are generally irreversible: though
exactly the same sequence might
theoretically be restored by an insertion,
transposable elements able to revert a
very short deletion (say 12 bases)
inanylocation are either highly unlikely to
exist or do not exist at all. Note that a
deletion is not the exact opposite of an
insertion: the former is quite random while
the latter consists of a specific sequence
inserting at locations that are not entirely
random or even quite narrowly defined.
Aframeshift
Mutationsinchromosomal structure,
including
1.Deletion
2.Inversion
3.Translocation
4.Duplication
5.Non Disjunction
INVERSION
Chromosome segment breaks of
Segment flips around backwards
Segment reattaches
Translocations:
Interchange of genetic
parts from non homologous chromosomes.
Involves two chromosomes that are not
homologous.
Part of one chromosome is transferred to
another chromosomes
Duplications:
Nondisjunction
Failure of chromosomes to
separate during meiosis
Causes gamete to have too many
or too few chromosomes
Disorders:
Down Syndrome Turner syndromeKlinefelters syndrome-