Human Genetics

Concepts and Applications

Tenth Edition
RICKI LEWIS

13 Chromosomes

PowerPoint® Lecture Outlines

Prepared by Johnny El-Rady, University of South Florida

Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
 Cytogenetics
Cytogenetics is a subdiscipline within
genetics
Deals with chromosome variations
In general, excess genetic material has
milder effects on health than a deficit
Still, most large-scale chromosomal
abnormalities present in all cells disrupt
or halt prenatal development

2
 Portrait of a Chromosome

A chromosome consists primarily of DNA

and protein
Distinguished by size and shape
Essential parts are:
- Telomeres
- Origins of replication sites
- Centromere

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 Portrait of a Chromosome

Figure 13.1 4
 Portrait of a Chromosome

Heterochromatin is darkly staining

- Consists mostly of repetitive DNA
Euchromatin is lighter-staining
- Contains most protein-encoding genes
Telomeres are chromosome tips composed
of many repeats of TTAGGG
- Shorten with each cell division

5
 Centromeres
The largest constriction of the chromosome
and where spindle fibers attach
The bases that form the centromere are
repeats of a 171-base DNA sequence
Replicated at the end of S-phase
- Facilitated by centromere protein A
CENP-A is passed to next generation
- An example of an epigenetic change
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 Subtelomeres
The chromosome region between the
centromere and telomeres
Consists of 8,000 to 300,000 bases
Near telomere the repeats are similar to the
telomere sequence
Contains at least 500 protein-encoding
genes
- About 50% are multigene families that
include pseudogenes
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 Subtelomeres

Figure 13.2

Figure 13.2

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 Karyotype
A chromosome chart

Displays chromosomes arranged by size

and structure

Humans have 24 chromosome types

- Autosomes are numbered 1-22 by size
- Sex chromosomes are X and Y

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 Karyotype

Figure 13.3
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 Centromere Positions
At tip – Telocentric
Close to end – Acrocentric
Off-center – Submetacentric
At midpoint – Metacentric

Figure 13.4

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 Karyotype
Karyotypes are useful at several levels

1) Can confirm a clinical diagnosis

2) Can reveal effects of environmental

toxins

3) Can clarify evolutionary relationships

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 Visualizing Chromosomes
Tissue is obtained from person
- Fetal tissue: Amniocentesis
Chorionic villi sampling
Fetal cell sorting
Chromosome microarray analysis
- Adult tissue: White blood cells
Skinlike cells from cheek swab
Chromosomes are extracted
Then stained with a combination of dyes and DNA
probes
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 Amniocentesis
Detects about 1,000 of the more than 5,000 known
chromosomal and biochemical problems
Ultrasound is used to follow needle’s movement
Figure 13.6
Figure 13.5a

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 Chorionic Villi Sampling
Performed during 10-12th week of pregnancy
Provides earlier results than amniocentesis
However, it does not detect metabolic problems
- And has greater risk of spontaneous abortion

Figure 13.5b

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Figure 13.7
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 Fetal Cell Sorting
Fetal cells are distinguished from maternal
cells by a fluorescence-activated cell sorter
- Identifies cell-surface markers

Figure 13.5c
A new technique
detects fetal
mRNA in the
bloodstream of
the mother
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 Viewing Chromosomes
1882 Figure 13.8 Now

Drawing by German biologist Micrograph of actual stained

Walther Flemming human chromosomes
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 Staining Chromosomes

In the earliest karyotypes, dyes were used to stain

chromosomes a uniform color
Chromosomes were grouped into decreasing size
classes, designated A though G
In the 1970s, improved staining techniques gave
banding patterns unique to each chromosome
Then researchers found that synchronizing the
cell cycle of cultured cells revealed even more
bands per chromosome

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 FISH
Fluorescence in situ hybridization
DNA probes labeled with fluorescing dye
bind complementary DNA

Fluorescent dots
correspond to
three copies of
chromosome 21

Figure 13.9 20
Chromosomal Shorthand

21
 Ideogram
A schematic
chromosome map

Indicates chromosome
arms (p or q) and
delineates major
regions and
subregions by
numbers
Figure 13.10 22
 Chromosome Abnormalities

A karyotype may be abnormal in two ways:

1) In chromosome number
2) In chromosome structure
Abnormal chromosomes account for at least
50% of spontaneous abortions
Due to improved technology, more people
are being diagnosed with chromosomal
abnormalities
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24
 Polyploidy
Cell with extra chromosome sets is polyploid
Triploid (3N) cells have three sets of
chromosomes
- Produced in one of two main ways:
- Fertilization of one egg by two sperm
- Fusion of haploid and diploid gametes
Triploids account for 17% of all spontaneous
abortions and 3% of stillbirths and newborn
deaths
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 Triploidy

Figure 13.11

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 Aneuploidy
A normal chromosomal number is euploid
Cells with extra or missing chromosomes
are aneuploid
Most autosomal aneuploids are
spontaneously aborted
Those that are born are more likely to have
an extra chromosome (trisomy) rather
than a missing one (monosomy)

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 Nondisjunction
The failure of chromosomes to separate
normally during meiosis
Produces gamete with an extra chromosome
and another with one missing chromosome

Nondisjunction during Meiosis I results in

copies of both homologs in one gamete
Nondisjunction during Meiosis II results in
both sister chromatids in one gamete
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Nondisjunction
at Meiosis I

Figure 13.12

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Nondisjunction
at Meiosis II

Figure 13.12

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 Aneuploidy
Aneuploidy can also arise during mitosis,
producing groups of somatic cells with the
extra or missing chromosomes
An individual with two chromosomally-distinct
cell populations is called a mosaic
A mitotic nondisjunction event that occurs
early in development can have serious
effects on the health of the individual

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 Trisomies
Most autosomal aneuploids cease developing as
embryos or fetuses
Most frequently seen trisomies in newborns are
those of chromosomes 21, 18, and 13
- Carry fewer genes than other autosomes

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 Trisomy 21
Down syndrome
Most common trisomy
Figure
among newborns 13.13

Distinctive facial and

physical problems
Varying degrees of developmental disabilities
Individuals more likely to develop leukemia
Link with one form of Alzheimer disease
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Table 13.6
Table 13.5 34
 Trisomy 18
Figure 13.14a
Edwards syndrome

Most due to nondisjunction

in meiosis II in oocyte
and do not survive

Serious mental and physical disabilities

A distinctive feature: Oddly-clenched fists
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 Trisomy 13
Figure 13.14b
Patau syndrome

Very rare and generally

do not survive 6 months

Serious mental and physical disabilities

A distinctive feature: Eye fusion
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Table 13.7 37
 Turner Syndrome

Called the XO syndrome

1 in 2,500 female births
99% of affected fetuses die in utero
Features include short stature, webbing at
back of neck, incomplete sexual
development (infertile), impaired hearing
Individuals who are mosaics may have
children
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 Triplo-X
Called the XXX syndrome
1 in 1,000 female births
Few modest effects on phenotype include
tallness, menstrual irregularities, and
slight impact on intelligence
X-inactivation of two X chromosomes
occurs and cells have two Barr bodies
May compensate for presence of extra X
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 Klinefelter Syndrome
Called the XXY syndrome
1 in 500 male births
Phenotypes include:
- Incomplete sexual development
- Rudimentary testes and prostate
- Long limbs, large hands and feet
- Some breast tissue development
Most common cause of male infertility
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 XXYY Syndrome
Likely arises due to unusual oocyte and
sperm
Associated with more severe behavioral
problems than Klinefelter syndrome
- AAD, obsessive compulsive disorder,
learning disabilities
Individuals are infertile
Treated with testosterone
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 XYY Syndrome
Also known as Jacobs syndrome
1 in 1,000 male births
96% are phenotypically normal
Modest phenotypes may include great
height, acne, speech and reading
disabilities
Studies suggesting increase in aggressive
behaviors are not supported
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 Chromosome Structural
Abnormalities

Figure 13.15
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Figure 13.16
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 Deletions
A deletion refers to a missing genetic
segment from a chromosome
Deletions are often not inherited
- Rather they arise de novo
Larger deletions increase the likelihood that
there will be an associated phenotype
Cri-du-chat (cat cry) syndrome
- Deletion 5p–
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 Duplications
A duplication refers to the presence of an
extra genetic segment on a chromosome
Duplications are often not inherited
- Rather they arise de novo
The effect of duplications on the phenotype
is generally dependent on their size
- Larger duplications tend to have an
effect, while smaller one do not
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Duplications in Chromosome 15

Figure 13.17

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 Translocations
In a translocation, two nonhomologous
chromosomes exchange segments

There are two major types:

1) Robertsonian translocation

2) Reciprocal translocation

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Robertsonian Translocations
Two nonhomologous acrocentric
chromosomes break at the centromere
and their long arms fuse
- The short arms are often lost
Affect 1 in 1,000 people
Translocation carriers have 45
chromosomes
- Produce unbalanced gametes
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Translocation Down Syndrome
About 5% of Down syndrome results from a
Robertsonian translocation between
chromosomes 21 and 14
Tends to recur in families, which also have
more risk of spontaneous abortions
One of the parents is a translocation carrier
- They may have no symptoms
- However, the distribution of the unusual
chromosome leads to various imbalances
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Figure 13.18

Figure 13.19 51
 Reciprocal Translocations
Two nonhomologous chromosomes
exchange parts
About 1 in 500 people are carriers
- Are usually healthy because they have
the normal amount of genetic material
(but it is rearranged)
However, if the translocation breakpoint
interrupts a gene, there may be an
associated phenotype
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 Figure 13.19

Figure 13.19 53
 Inversions
An inversion is a chromosome segment
that is flipped in orientation
5-10% cause health problems probably due
to disruption of genes at the breakpoints
Paracentric inversion = Inverted region
does NOT include centromere
Pericentric inversion = Inverted region
includes centromere
Inversions may impact meiotic segregation
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 Segregation of a Paracentric Inversion

Figure 13.20

Figure 13.21 55
 Segregation of a Pericentric Inversion

Figure 13.21

Figure 13.21 56
 Isochromosomes

Chromosomes with Figure 13.22

identical arms

Form when
centromeres divide
along the incorrect
plane during meiosis

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 Ring Chromosomes
Occur in 1 in 25,000 conceptions
May arise when telomeres are lost and sticky
chromosome ends fuse
Genes can be lost or disrupted causing symptoms

Figure 13.23

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 59
Table 13.8
 Uniparental Disomy
Inheritance of two chromosomes or
chromosome parts from the same parent

UPD requires the simultaneous occurrence

of two rare events
1) Nondisjunction of the same
chromosome in both sperm and egg
2) Trisomy followed by chromosome loss
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 Uniparental Disomy

Figure 13.24

Figure 13.24
61