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Human Genetics

Unit 4
Cell Biology for Biomedical Engineers

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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

q arm the longer of the two arms


Bands are numbered from centromere
outward

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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

Sister chromatids are identical


Form as cells go through S phase (replication)
Attached to each other by centromere
Until Anaphase of Mitosis
Once separated each is again referred
to as a chromosome

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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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What Does DNA Look Like?

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13

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14

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15

Every cell in our body has the


same DNA.
Eye cell

Karyotype

Lung cell

Toe cell
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How much DNA is in one cell?


Genome = 46 chromosomes
Genome = approx. 3 billion
base pairs
One base pair is
0.00000000034 meters
DNA sequence in any two
people is 99.9% identical
only 0.1% is unique!
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What makes one cell different from another?


DNA = the life
instructions of the
cell
Gene = segment of
DNA that tells the
cell how to make a
certain protein.
Allele = one of two
or more different
versions of a gene
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Sequence for normal adult hemoglobin:

Sequence for mutant hemoglobin:

Wild-type Hemoglobin Protein

Normal Red Blood Cell

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Mutant Protein

Abnormal Red Blood Cell 19

Inheritance of Genes
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Gregor Mendel
1822-1884

Picture from www.nih.nlm.gov

Augustinian monk who


cross-bred pea plants with
different characteristics
Observations led to laws
regarding the transmission
of hereditary
characteristics from
generation to generation
Many of the concepts from
his observations still hold
true
today!
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MENDELS LAWS

1. Unit factors in pairs


Genetic characters are controlled by unit
factors that exist in pairs in individual
organisms
2. Dominance/Recessiveness
When two unlike unit factors are
responsible for a single character are
present in a single individual, one unit
factor is dominant to the other which is
said to be recessive.
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MENDELS LAWS

Principle of Segregation: Two


members of a gene pair segregate
from each other in the formation of
gametes; half the gametes carry one
allele, and the other half carry the
other allele
What it means: each gene has two copies
(alleles) and a parent will give only one
copy to a child.
The other
parent will give another copy, and thus
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the child willUNITreceive
two copies23

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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Applying Mendelian Concepts:


The Punnett Square
Parent 2

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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We know Dan and Kims


phenotypes (no dimples/dimples),
but what are their genotypes?
Dan has the recessive trait (no dimples)
He must have two recessive alleles
Dans genotype can be represented as dd

Kim has the dominant trait (dimples)


But Kim could be homozygous dominant OR
heterozygous dominant
Kims genotype can be either DD or Dd
Which one is it?
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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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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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What are the chances Kim and Dans baby


will have dimples?
Kim

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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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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(b) Environmental
drugs,
development

35

Normally, humans have 23 pairs of


chromosomes - making 46 in total.
This
includes
one
pair
of
chromosomes which are the sex
chromosomes. The ova and the
sperm each carry 23 chromosomes.
Types of chromosomal abnormalities:
(a) Numerical
(b) Structural
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Causes of congenital malformations

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Numerical Chromosomal Abnormalities

Changes in the number of


chromosomes:
Polyploidy
Somatic cells contain multiples of
haploid number of chromosomes
3n, 4n, 5n etc.
Aneuploidy (Heteroploidy)
Deviation from the diploid number of
chromosomes
2n + 1, 2n -1 etc.
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Mechanism of Polyploidy

(a)Failure of pulling apart of 2


chromatids to opposite ends
after metaphase stage of mitosis.
(b)Reduplication
without

of

dissolving

chromosomes
of

nuclear

membrane.
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(c)Failure of cytoplasmic

39

Types of Polyploidy

1. Autopolyploidy:

even-numbered

multiples of haploid number of


chromosomes. e.g.(a) Tetraploidy (23x4 or 92
chromosomes)
(b) Hexaploidy (23x6 or 138
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chromosomes)

40

Types of Polyploidy

2. Allopolyploidy: odd-numbered multiples


of haploid number of chromosomes.
e.g.(a) Triploidy (23x3 or 69 chromosomes)commonest
(b)

Pentaploidy

chromosomes)

(23x5

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or

115
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Mechanism of Aneuploidy

Non-dysjunction: failure of separation of


chromosomes during cell division.
Formation of 2 types of gametes (both
abnormal)
Fusion

of

either

of

these

abnormal

gametes with a normal gamete can


UNIT or
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result in trisomy
monosomy

42

nd
NormalUNIT
1st &
meiotic
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division

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Meiotic Nondisjunction Generates Aneuploidies

abnormal
gametes

Zygotic Ploidy

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Zygotic Ploidy

44

Trisomies of Chromosomes

Presence of 3 copies of a chromosome


Trisomy of Autosomes (13,18,21)
Trisomy of Sex Chromosomes (XXX,
XXY)

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Trisomy of Autosomes

Trisomy 13 or D-trisomy (Patau


syndrome)
Trisomy 18 or E-trisomy (Edward
syndrome)
Trisomy 21 or G-trisomy (Down
syndrome)
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Trisomy 13 (Patau Syndrome)


1st described by Bartholin (1657) &
redefined by
Patau (1960).
Chromosomal complement: 47,XX,+13
(female) or
47,XY,+13
(male)
Phenotype: Male or female
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Incidence: 1:12,000
(increases with the 47

Features of Patau Syndrome


Mental deficiency
Low birth weight
Abnormal development of frontal lobe
Absence of corpus callosum
Hypoplasia of cerebellum
Sloping forehead
Scalp defects
Malformed ears
Congenital heart defects
Renal tract anomalies
Microphthalmia
Bilateral cleft lip/palate
Polydactyly with rudimentary digits
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Rocker-bottom heel

48

Patau syndrome

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Patau syndrome

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Trisomy 18 (Edward Syndrome)

Chromosomal complement: 47,XX,+18


(female) or
47,XY,+18
(male)
Phenotype: Male or female
Incidence: 1:8000
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Features of Edward Syndrome


Mental deficiency
Growth retardation
Prominent occiput with elongated head
Webbing of the neck
Short sternum
Micrognathia-abnormmal small jaw
Low-set malformed ears
Ventricular septal defects
Renal anomalies
Clenched fists with overlapping of fingers
Hypoplastic nails

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Edward syndrome

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Trisomy 21 (Down Syndrome)

Chromosomal complement: 47,XX,+21


(female) or
47,XY,+21
(male)
Phenotype: Male or female
Incidence: 1:800 (increases with the age
of
mother)
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Features of Down Syndrome


Short height
Severe mental deficiency with decline in the IQ
with age
Brachycephaly with flat face and occiput
Flat and low nasal bridge
Upward slant to palpebral fissures
Malformed large ears
Epicanthal folds of the eyes
Brushfield spots in iris
Renal anomalies
Prominent and protruding tongue (scrotal
tongue)
Simian crease
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th

Down Syndrome

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Down syndrome

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Down syndrome

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Down syndrome

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Variation In Chromosome Structure

Amount of genetic information in the chromosome


can change

Deficiencies/Deletions
Duplications

The genetic material remains the same, but is


rearranged

Inversions
Translocations

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Chromosome Structure Abnormalities

Translocation Deletion

Derivative
chromosome

Inversion

Insertion

Isochromosome

Ring
chromosome

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Deficiencies (aka Deletions)

A chromosomal deficiency occurs when a


chromosome breaks and a fragment is lost

Figure 8.3

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Deficiencies

Phenotypic consequences of deficiency depends on

Size of the deletion


Functions of the genes deleted

Phenotypic effect of deletions are usually detrimental


(harmful)

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Cri-du-chat Syndrome

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Duplications

A chromosomal duplication is usually caused by


abnormal events during recombination

Figure 8.5

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Duplications

Phenotypic consequences of duplications are


correlated to size & the genes involved

Duplications tend to be less detrimental

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Bar-Eye Phenotype in Drosophila

Phenotype: reduced number of ommatidia


Ultra-bar (or double-bar) is a trait in which flies have
even fewer facets than the bar homozygote
Both traits are X-linked and show intermediate
dominance

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Duplications and Gene Families

Majority of small duplications have no phenotypic


effect

However, they provide raw material for evolutionary


change

Lead to the formation of gene families

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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Duplications Generate Gene Families

Genes derived
from a single
ancestral gene

Figure 8.9

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Inversions

A segment of chromosome that is flipped relative to


that in the homologue

Centromere lies
within inverted
region

Figure 8.11

Centromere lies
outside inverted
region

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Inversions

No loss of genetic information


Many inversions have no phenotypic
consequences

Break point effect


Inversion break point is within regulatory or
structural portion of a gene

Position effect
Gene is repositioned in a way that alters its
gene expression
separated from regulatory sequences, placed
next to constitutive heterochromatin

~ 2% of the human population carries


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karyotypically detectable
inversions

71

Inversion Heterozygotes

Individuals with one copy of a normal chromosome and one copy of an


inverted chromosome

Usually phenotypically normal

Have a high probability of producing gametes that are


abnormal in genetic content
Abnormality due to crossing-over within the inversion
interval

During meiosis I, homologous chromosomes synapse with each other

For the normal and inversion chromosome to synapse


properly, an inversion loop must form
If a cross-over occurs within the inversion loop, highly
abnormal chromosomes are produced

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Crossing Over Within Inversion Interval


Generates Unequal Sets of Chromatids

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Crossing Over Within Inversion Interval


Generates Unequal Sets of Chromatids

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Inversions Prevent Generation of Recombinant


Offspring Genotypes
Only parental chromosomes (nonrecombinants) will produce normal
progeny after fertilization

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Translocations

When a segment of one chromosome becomes


attached to another

In reciprocal translocations two non-homologous


chromosomes exchange genetic material

Usually generate so-called balanced translocations

Usually without phenotypic consequences

Although can result in position effect

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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.

Fig. 8.13a(TE Art)


22
Environmental agent
causes 2 chromosomes
to break.

DNA repair enzymes


recognize broken ends
and connect them.

22
2

Reactive ends

Chromosomal breakage and DNA repair


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In simple translocations the transfer of genetic


material occurs in only one direction

These are also called unbalanced translocations

Unbalanced translocations are associated with


phenotypic abnormalities or even lethality
Example: Familial Down Syndrome

In this condition, the majority of chromosome 21 is attached to chromosome


14 (Figure 8.14a)

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79
8-38

Familial Down Syndrome is an example of


Robertsonian translocation

This translocation occurs as such

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

This type of translocation is the most common type


of chromosomal rearrangement in humans

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8-39

Balanced Translocations and Gamete


Production

Individuals carrying balanced translocations have a


greater risk of producing gametes with unbalanced
combinations of chromosomes

This depends on the segregation pattern during meiosis I

During meiosis I, homologous chromosomes


synapse with each other

For the translocated chromosome to synapse properly, a translocation cross


must form

Refer to Figure 8.15

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81
8-40

Figure 8.15

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8-42

Meiotic segregation can occur in one of three ways

1. Alternate segregation

Chromosomes on opposite sides of the translocation cross


segregate into the same cell
Leads to balanced gametes

Both contain a complete set of genes and are thus viable


2. Adjacent-1 segregation

Adjacent non-homologous chromosomes segregate into the


same cell
Leads to unbalanced gametes

Both have duplications and deletions and are thus inviable


3. Adjacent-2 segregation

Adjacent homologous chromosomes segregate into the same


cell
Leads to unbalanced gametes

Both have duplications and deletions and are thus inviable


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83
8-41

Consider a fertilized Drosophila egg that is XX

One of the Xs is lost during the first mitotic division


This produces an XX cell and an X0 cell

The XX cell is the


precursor for this side of
the fly, which developed
as a female

The X0 cell is the


precursor for this side of
the fly, which developed
as a male

Figure 8.26

This peculiar and rare individual is termed a bilateral gynandromorph

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8-71

Sex Determination and


Sex Linkage

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The inheritance of gender

Is it going to be a boy or a girl?

University of New Mexico

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The inheritance of gender

Mother

Father

XX

XY
Meiosis

Sex cells

Fertilisation

XX

XY

XX

XY

Possible
children

Chance of a girl 50%


Chance of a boy 50%

2007 Paul Billiet ODWS

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Sex chromosomes

The sex of many animals is determined


by genes but on chromosomes called
sex chromosomes
The other chromosomes are called
autosomes
One sex is homogametic
The other sex is heterogametic

2007 Paul Billiet ODWS

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Sex determination in different animals

HOMOGAMETIC
SEX

HETEROGAMETIC
SEX

SEX DETERMINATION

Female XX

Male XY

Presence of Ychromosome = maleness


(mammals and fish)
Presence of second Xchromosome =
femaleness (Drosophila,
the fruit fly)

Male ZZ

Female ZW

Female XX

Male Xo

2007 Paul Billiet ODWS

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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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Genotypic Sex Determination


Systems

Genotypic sex determination may occur two


different ways:

a. In the Y-chromosome mechanism of sex-determination


(e.g., in mammals), the Y chromosome determines sex,
conferring maleness.
b. In the X chromosome-autosome balance system (e.g.,
Drosophila, Caenorhabditis elegans) the ratio between
number of X chromosomes and number of sets of
autosomes determines sex. Y is required for male fertility,
but does not determine sex.
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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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Evidence for the Y Chromosome Mechanism


of Sex Determination
Understanding of the Y chromosome mechanism of sex
determination came from the study of individuals with unusual
chromosome complements. In humans these aneuploidies include:
a. XO individuals, who are sterile females exhibiting Turner
syndrome. Most XO fetuses die before birth. Surviving Turner syndrome
individuals become noticeable at puberty, when secondary sexual
characteristics fail to develop. Other traits include:
i. Below average height.
ii. Weblike necks.
iii. Poorly developed breasts.
iv. Immature internal sexual organs.
v. Reduced ability to interpret spatial relationships.
1.

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Evidence for the Y Chromosome


Mechanism of Sex Determination
b. XXY individuals, who are male and have Klinefelter syndrome. Other traits include:

i. Above average height.


ii. Breast development in about 50% of XXY individuals.
iii. Subnormal intelligence in some cases.
c. XYY individuals are male, and tend to be taller than
average. Fertility is sometimes affected.
d. XXX individuals are usually normal women, although they
may be slightly less fertile and a few have below average
intelligence.

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Evidence for the Y Chromosome Mechanism


of Sex Determination

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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Symbols used in drawing pedigrees

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Autosomal Dominant Pattern


An idealised pattern of inheritance of an autosomal dominant trait includes the following
features:
both males and females can be affected
all affected individuals have at least one affected parent
transmission can be from fathers to daughters and sons, or from mothers to
daughters and sons
once the trait disappears from a branch of the pedigree, it does not reappear
in a large sample, approximately equal numbers of each sex will be affected.

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

Autosomal Recessive Pattern


An idealised pattern of inheritance of an autosomal recessive trait includes the following features:
both males and females can be affected
two unaffected parents can have an affected child
all the children of two persons with the condition must also show the condition
the trait may disappear from a branch of the pedigree, but reappear in later generations
over a large number of pedigrees, there are approximately equal numbers of affected
females and males.

Examples include:
Albinism
Cystic fibrosis
Thalassaemia
Tay-Sachs disease
Phenylketonuria
Red hair colour

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Chapter 11 slide

X linked Dominant Pattern


An idealised pattern of inheritance of an X-linked dominant trait includes the following
features:
a male with the trait passes it on to all his daughters and none of his sons
a female with the trait may pass it on to both her daughters and her sons
every affected person has at least one parent with the trait
if the trait disappears from a branch of the pedigree, it does not reappear
over a large number of pedigrees, there are more affected females than males

Examples include:

Vitamin D resistant rickets


Incontinentia pigmenti, a
rare disorder that results in
the death of affected
males before birth
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Chapter 11 slide

X linked Recessive Pattern


An idealised pattern of inheritance of an X-linked recessive trait includes the following features:
all the sons of a female with the trait are affected
all the daughters of a male with the trait will be carriers of the trait and will not show the trait; the trait
can appear in their sons
none of the sons of a male with the trait and an unaffected female will show the trait, unless the mother
is a carrier
all children of two individuals with the trait will also show the trait
in a large sample, more males than females show the trait.

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

Sex Linked Traits


In 1910, Scientist
Thomas Morgan
studied eye colour in
fruit flies (Drosophila
melanogaster)

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He crossed 2 red-eyed parent flies


Result?
Produced white-eyed
male fly
Morgan thought this
outcome followed
Mendels Law of
Dominance :
R Dominant (red eye
colour)
r Recessive (white eye
colour)

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So he then crossed White-eyed


male and Red-eyed female
Morgan was not able
to obtain a whiteeyed offspring, so
he concluded that
eye colour was
associated with the
X chromosome

P.17
7

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Human Sex Linked Traits

X chromosome carries a great variety


of traits that are called X-linked
Y chromosome only carries a few
known traits that are called Y-linked
**unless specified, assume the sex-linked traits discussed are Xlinked.

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Many X-linked disorders or diseases


are recessive, therefore we use the
following:
X

Normal
allele

Recessive
allele

Note: Y stands alone


UNIT 4 - BME101

106

In females, the recessive


n n
expressed if X X is present.

trait

will

be

If the female is heterozygous for the trait,


X Xn, then the trait is not expressed but is
present and will be passed on This female
is called a GENETIC CARRIER
N

In males, the recessive trait will be


n
expressed if X Y is present. (**Notice, only
one recessive allele needs to be
inherited in order to be expressed)
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107

Example 1: Red-Green Colour


blindness (RGCB)
Person
that
expresses
(RGCB),
cannot
distinguish
shades of red and
green.
Their ability to see
remains normal.
Red
and
Green
pigments
called
opsins are found in
specific cells called
UNIT 4 - BME101
108
cones in the retina.

Example 1: Red-Green Colour


blindness (RGCB)
People with RGCB,
either have
A defective allele for
red pigment OR
A defective allele for
Green pigment
When one allele is
defective, then the
person cannot
distinguish between
Red and green.
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109

RGCB is a recessive X-linked trait

XX
B

**Carrier

XX
b

Female
Expresse
s RGCB

XY
b

XY
B

Normal
Male
Male
Express
es
RGCB

** The woman is a heterozygous carrier because


she carries one allele that will be passed on but
will not express RGCB
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110

Sample Problem:

A man with RGCB


marries a woman
that is a carrier
for
RGCB.
Determine
the
possibility of their
son being born
with RGCB.

What is required?
Possibility of son possessing
RGCB

What is given:
Mother X X
Father X Y

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111

Solution:

X Y

X X

X X

X Y

The son will have a 50% UNIT


chance
being born with RGCB
4 -of
BME101

112

Hemophilia A

Genetic disease where blood cannot


clot properly at the site of an injury
Coagulation proteins are involved in
the clotting of blood and become
active at a wound.
People with Hemophilia lack one of
these coagulation proteins.

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People with hemophilia also:


Bruise easily
May experience internal bleeding into their joints
and muscles
And are at risk of dying even from minor cuts

Frequency: 1 in 10,000 males

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114

Recessive X-linked disease

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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115

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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116

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.
UNIT 4 of
- BME101

117

MUTATION

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118

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

Mutation can result in several


different
types
of
change
in
sequences; (DNA) these can either
have no effect, alter theproduct of the
gene, or prevent the gene from
functioning properly or completely
Due to the damaging effects that
mutations can have on genes,
organisms have mechanisms such as
DNA repairto remove mutations.
Viruses that useRNAas their genetic
material
have
rapid
mutation

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

Point Mutations, often caused by chemicals or


malfunction of DNA replication, exchange a

Most common is thetransition that exchanges


apurinefor
a
purine
(A

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

Silent Mutations: which code for the sameamino acid.


Missense Mutations: This type of mutation is a change in
one DNA base pair that results in the substitution of one amino acid
for another in the protein made by a gene.

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.

Insertions add one or more extra nucleotides into the


DNA. They are usually caused bytransposable
elements, or errors during replication of repeating
elements (e.g. AT repeats). Insertions in the coding
region of a gene may
alterslicingof
themRNA(splice site mutation), or cause a shift in the
reading frame(frameshift), both of which can
significantly alter the gene product. Insertions can be
reverted by excision of thetransposable element.

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.

Frame shift mutation:


mutation

Aframeshift

is a mutation caused byinsertion


ordeletion of a number of nucleotides that is not
evenly divisible by three from a DNA sequence. Due to
the triplet nature of gene expression bycodons, the
insertion or deletion can disrupt thereading frame, or
the grouping of the codons, resulting in a completely
different translationfrom the original.

Mutationsinchromosomal structure,
including

Changing the structure of chromosome.


Loss or gain part of a chromosome.
Chromosomal Mutation five types exist:

1.Deletion
2.Inversion
3.Translocation
4.Duplication
5.Non Disjunction

Deletions of large chromosomal


regions, leading to loss of the genes
within those regions

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:

leading to multiple copies of


all chromosomal regions, increasing the
dosage of the genes located within them.

Nondisjunction
Failure of chromosomes to
separate during meiosis
Causes gamete to have too many
or too few chromosomes
Disorders:
Down Syndrome Turner syndromeKlinefelters syndrome-

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