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CYTOGENETICS

•Hybrid science which attempts to correlate cellular

events, especially those of the chromosomes, with
genetic phenomena

•Marriage between CYTOLOGY (study of cells) and

genetics

CHROMOSOME STRUCTURE & BEHAVIOR DURING

THE CELL AND REPRODUCTIVE CYCLES

The Cell Cycle

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Mitosis

Meiosis

More elaborate
than in mitosis

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Different stages of Prophase I

Leptotene Zygotene Pachytene

•Chromosomes •Homologous •Homologous

condense & become chromosomes start to chromosomes are closely
visible pair paired and crossing over
takes place
Diplotene Diakinesis

•Homologous •Chromosomes condense at

chromosomes start to their greatest extent;
move away nucleolus disappears &
fragments of nuclear
envelope disperse

Crossing over during Prophase I

Leads to shuffling of alleles

More variations
of genes

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Different stages of Prophase I

Leptotene Zygotene Pachytene

•Chromosomes •Homologous •Homologous

condense & become chromosomes start to chromosomes are closely
visible pair paired and crossing over
takes place
Diplotene Diakinesis

•Homologous •Chromosomes condense at

chromosomes start to their greatest extent;
move away nucleolus disappears &
fragments of nuclear
envelope disperse

Meiosis

More elaborate
than in mitosis

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Comparison Between Mitosis and Meiosis

Mitosis Meiosis

•One division
•2 daughter cells per division
•Daughter cells genetically identical

•Chromosome # of daughter cell is

the same as the parent cell
•Occurs in somatic cells
•Occurs throughout life cycle
•Used for growth, repair and asexual
reproduction

•Note: review difference between plant and animal mitosis

Parts of a Chromosome

Chromatid

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Detailed Parts of a Chromosome

telomere

knob
20 constriction

heterochromatin

centromere (10 constriction)

euchromatin

stalk
satellite

Centromeric DNA
•Where proteins of the
spindle fibres bind

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Attachment of spindle fibre to kinetochore

•KINETOCHORE –
transient protein formed
on top of centromeres and
where spindle fibres bind

Telomeric DNA
•Ends of chromosomes that form hairpin loops to facilitate DNA
replication

•The ends of the chromosomes get shorter every time the cells divide,
because part of the bases are used to template off of themselves

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Telomeric DNA
•TELOMERASE – ribozyme that makes the telomeres longer
– contains a necessary piece of RNA which serves
as the template for synthesizing the new strand

•Some cancer cells have overexpressed telomerases that make

cancer  cells  live  “forever”

Synaptonemal Complex
•Formed during Pachytene stage of
Prophase I between two homologs

•Resembles a zipper
•Made of:
•CENTRAL ELEMENTS
•Less dense

•LATERAL ELEMENTS
•More dense
•Intimately associated with the
chromatin of the synapsed
homologs in either side

•Found in most plants and animals

but not in D. melanogaster (no
crossing over takes place)

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Specialized Chromosomes
1. Polytene Chromosomes
•Giant chromosomes found in larval
stages of Dipteran insects

•Found in:
•Salivary glands
•Midgut
•Malpighian tubules

•Formed by repeated chromosome

synthesis without cell division

•“Puffs”  are  actively  transcribed  

regions

Specialized Chromosomes
2. Lampbrush Chromosomes

•Appearance is similar to brushes

used to clean street lamps in 19th
century Europe

•Isolated from the diplotene stage of

prophase I of meiosis in most
animals, particularly amphibians

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Specialized Chromosomes
2. Lampbrush Chromosomes

•Consists of the following:

•CHROMOMERE
•Condensed area that is repeated
along the main axis

•LATERAL LOOPS
•Extended, less coiled DNA
emanating from the chromomeres

•DNA in these loops are actively

transcribed

Types of Chromosomes

1. Based on the number of sister chromatids

a. monad
•consists of only one sister chromatid

b. dyad
•consists of two sister chromatids

c. tetrad
•consists of two homologs during synapsis pairing
•With four sister chromatids (2 from each homolog)

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Types of Chromosomes

1. Based on the number of centromeres

a. univalent
•consists of only one centromere
•may be a monad or dyad

b. bivalent
•consists of two centromeres
•MUST be a tetrad

Chromosome conditions at different stages of mitosis

and meiosis

Monad Dyad Tetrad

Univalent Univalent Bivalent

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Types of Chromosomes Based on Centromere Location

Metacentric Submetacentric Acrocentric Telocentric

•Which chromosome types are present in humans?

Reproductive Cycles
1. Spermatogenesis and Oogenesis in Animals

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Reproductive Cycles
2. Generalized Life Cycle of Plants

Angiosperm Life Cycle

Key
Haploid (n)
Diploid (2n) Microsporangium
Anther
Mature flower on Microsporocytes (2n)
sporophyte plant
(2n) MEIOSIS

Microspore Generative cell

Ovule (2n) Tube cell
(n)
Male gametophyte
Ovary (in pollen grain) Pollen
Germinating MEIOSIS (n) grains
Stigma
seed Megasporangium
(2n) Pollen
tube
Embryo (2n)
Endosperm (3n) Sperm
Seed Megaspore
Seed coat (2n) (n)
Style
Antipodal cells
Female gametophyte
Central cell Pollen
(embryo sac)
Synergids tube
Egg (n) Sperm
Nucleus of
developing (n)
endosperm
(3n) FERTILIZATION

Zygote (2n)
Egg
nucleus (n) Discharged sperm nuclei (n)

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Genetic Implications of Mitosis and Meiosis

1. Mitosis

•Daughter cells will have the same number (2N or N) and

kinds of chromosomes as the parent cell
•Necessary for:
•Asexual reproduction
•Replacement of dead or damaged cells
•However, brain cells do NOT divide

Genetic Implications of Mitosis and Meiosis

2. Meiosis

•Provides additional mechanisms for producing variations

a. Crossing over during Prophase I of Meiosis I

b. Random segregation of homologous chromosomes

c. Independent assortment of non-homologous

chromosomes

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Genetic Implications of Mitosis and Meiosis

2. Meiosis

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Chromosome Number

•The nucleus of each somatic cell contains a fixed number of

chromosomes typical of the particular species

•This number varies tremendously among species and bears

little relation to the complexity of the organism

Chromosome Number

Organism Chromosome # Organism Chromosome #

Field horsetail 216 Yeast 32

Bracken fern 116 Fruit fly 8

Giant sequioa 22 Caenorhabditis elegans 11 ♂, 12 ♀

Macaroni wheat 28 House fly 12

Bread wheat 42 Scorpion 4

Fava bean 12 Geometrid moth 224

Garden pea 14 Common toad 22

Mustard cress 10 Chicken 78

Corn 20 Mouse 40

Lily 24 Gibbon 44

Snapdragon 16 Human 46

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44 + 44 +
Chromosomal Basis XY
Parents
XX

of Sex Determination
22 + 22 + 22 +
X or Y + X
Sperm Egg

44 + 44 +
XX or XY

Zygotes (offspring)
(a) The X-Y system

22 + 22 +
XX X

(b) The X-0 system

76 + 76 +
ZW ZZ

(c) The Z-W system

32 16
(Diploid) (Haploid)

(d) The haplo-diploid system

Chromosomal Basis
of Sex Determination

44 + 44 +
Parents
XY XX

22 + 22 + 22 +
X or Y + X
Sperm Egg

44 + 44 +
XX or XY

Zygotes (offspring)
(a) The X-Y system

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Chromosomal Basis
of Sex Determination

(a) The X-Y system

•In mammals, the Y chromosome contains factors that

trigger male development

•In fruit flies, the number of X chromosomes determine

sex.

Chromosomal Basis
of Sex Determination

22 + 22 +
XX X

(b) The X-0 system

•Males produce gametes with either an X chromosome

or with no sex chromosome

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Chromosomal Basis
of Sex Determination

76 + 76 +
ZW ZZ

(c) The Z-W system

•In birds, the default gender is male.

•The W chromosome triggers female development.

•Also present in many bees and moths

Chromosomal Basis
of Sex Determination

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(Diploid) (Haploid)

(d) The haplo-diploid system

•Peculiar to the Hymenoptera

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Chromosomal Basis
of Sex Determination

32 16
(Diploid) (Haploid)

(d) The haplo-diploid system

•Males develop from an unfertilized egg, making them

haploid; they therefore have no fathers

Chromosomal Basis
of Sex Determination

(d) The haplo-diploid system

•In bees, gender is actually determined by a single gene

•If there is only one copy of the gene, because the

animal is haploid, then the animal develops as a male.

•If there are two copies (representing two chromosomes)

and they differ in their DNA sequences, then the animal is
female.
•A homozygous diploid honeybee develops as a sterile male
and is usually killed.

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Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• Gene dosage varies between the sexes in mammals

• females have two copies of X while males have one.
• Early in development, gene expression from the X
chromosome must be equalized to avoid death.

•X-chromosome inactivation
•Random inactivation of one of the X chromosomes
•Expressed as a BARR body

Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• BARR body
• Condensed and (mostly) inactivated X chromosome (Xi).
• Lyonization/heterochromatization of one chromosome
leaves one transcriptionally active X, equalizing gene dose
between the sexes.
• An X is randomly chosen in each cell for inactivation early
in development (in humans, day 16 postfertilization).
• Characteristics:
• High levels of DNA methylation
• Low levels of histone acetylation

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Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• Number of Barr bodies:

• n-1, where n=number of X chromosomes

Dosage Compensation Mechanism for X-Linked Genes

in Mammals

•Other attributes of X inactivation:

•Generally random

•Generally irreversible, although female germ line cells that

give rise to gametes will have both X-chromosomes active

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Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• X inactivation center (XIC)

•Region in the X chromosome crucial for inactivation

•Contain genes that code for non-translated RNA sequences

that are involved in X chromosome inactivation

Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• Mechanism of X inactivation: Xist and Tsix genes

•Xist gene
•Encodes an RNA that binds to a specific site on one of
the X chromosomes
•After RNA binding, inactivation takes place, one gene at
a time

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Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• Mechanism of X inactivation: Xist and Tsix genes

•Tsix gene
•Also encodes an RNA that binds to the X chromosome

•Overlaps with the Xist gene but is complementary or

opposite to it

•Believed to be an antagonist of the Xist gene in that X

chromosomes lacking the Tsix gene are inactivated more
easily and quickly

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Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• Consequences of non-X inactivation in mouse embryos:

•Ectodermal cell death

•Absence of mesoderm
•Embryonic death at day 10 of gestation

Dosage Compensation Mechanism for X-Linked Genes

in Mammals

• Coat color in cats

•Black, brown, and orange fur color are X-linked genes, with
orange as the recessive

•Females who are heterozygous will exhibit different patches

of fur color (calico cats)

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X chromosomes
Allele for
orange fur
Early embryo:
Allele for
black fur

Cell division and

X chromosome
Two cell inactivation
populations
in adult cat: Active X
Inactive X
Active X

Black fur Orange fur

Dosage Compensation Mechanism for X-Linked Genes

in Mammals

•Manifesting heterozygote condition (Manifesting carrier)

•Exhibited by carriers for an X-linked recessive trait

•E.g. hemophilia carriers that become hemophiliacs

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X-Y Pairing and the Pseudoautosomal Regions in

Mammals

• In mammalian males, X and Y chromosomes pair off during

Prophase I

• This is facilitated by the PSEUDOAUTOSOMAL REGIONS

X-Y Pairing and the Pseudoautosomal Regions in

Mammals

• Characteristics of pseudoautosomal regions:

• present as homologous copies in X and Y chromosomes

• they are not inactivated in the X chromosome

• crossing over takes place in X and Y in male cells

• genes in this region are not linked to either X or Y

chromosome

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SRY Region of the Y Chromosome in Mammals

• Sex-determining region of the Y (SRY)

• Found in placental and marsupial mammals
• Intronless
• Code for the transcription factor protein for male sex
determination
• member of the high mobility group (HMG)-box family of DNA-
binding protein

SRY Region of the Y Chromosome in Mammals

• XX Male Syndrome (de la Chapelle syndrome)

•translocation of part of the SRY region to the X chromosome

•4-5 individuals in 100,000

•With small testis and varying degrees of gynecomastia

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• Case report of a four-month old boy in India with XX male

syndrome

Ambiguous genitalia with

microphallus, penoscrotal
hypospadias, bifid scrotum
and bilateral palpable
gonads
Karyotype showing two X chromosomes

SRY Region of the Y Chromosome in Mammals

• XX Male Syndrome (de la Chapelle syndrome)

•Controversial in athletic competitions

•Caster Semenya is a world
champion, but questions about her
gender was raised, which prompted
the IAAF to request her to undergo
gender testing. She was withdrawn
from competitions from 2009-2011

South African distance runner Caster

Semenya

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Variation in Chromosome Number and Structure

Karyotyping
•Cytological technique that demonstrates chromosomal
variations
•Makes use of cultured cells at late prophase or metaphase
•Chromosomes are arranged from largest to smallest and
according to centromere location

Variation in Chromosome Number and Structure

Karyotyping
Cells (fetal, blood, bone marrow, etc.) are cultured

Cells are arrested at metaphase using COLCHICINE

Cells placed in hypotonic solution

Cells are fixed in CARNOY’S fixative

Cell suspension is dropped onto a slide

Cells are stained

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•Humans have 23 pairs of chromosomes distributed among 8

groups (A-G and sex chromosomes)

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•Human chromosome description (Giemsa Stain)

Chromosome 1 (Group A): The longest chromosome, metacentric; p arm fading at distal end,
with at least two dark bands above centromere; q arm with a dark area just below centromere, a
light band below, followed by four dark bands of which the middle two are often more intense.

Chromosome 2 (Group A): Almost as long as chromosome 1, submetacentric; p arm without light
distal end, with four dark bands; q arm with more than four dark bands.

Chromosome 3 (Group A): Metacentric; both p and q arms with a large light band in the middle;
dark area (consisting of two or three close dark bands) distal to the light band of q arm thicker than
its counterpart in p arm.

Chromosome 4 (Group B): Very submetacentric; p arm with a thick dark band which may
sometimes be resolved as double; q arm with a distinct, prominent dark band below centromere.

Chromosome 5 (Group B): Very submetacentric; p arm with a single dark band; q arm without a
prominent dark band below centromere, with three close dark bands in the middle.

Chromosome 6 (Group C): Submetacentric; p arm with a distinct, large light band in the middle; q
arm with several dark bands.

•Human chromosome description (Giemsa Stain)

Chromosome 7 (Group C): Submetacentric; p arm with a prominent flat dark band at the top; q
arm with two distinct dark bands followed by a much less intense dark band.

Chromosome 8 (Group C): Very submetacentric; p arm with two dark bands (sometimes unclear);
q arm with two (sometimes three) dark bands, the distal dark band characteristically more intense.

Chromosome 9 (Group C): Varying from slightly submetacentric to very submetacentric; p arm
with a broad (often square in shape ) dark band (which may be resolved as double); q arm with a
variable, proximal light area (from as long as the p arm to almost non-existent) followed by two
distinct, equally intense broad dark bands with a light band between them; these three bands (two
dark and one light) equal in thickness.

Chromosome 10 (Group C): Submetacentric; p arm with a dark band; q arm with three distinct
dark bands, the proximal dark band most intense.

Chromosome 11 (Group C): Submetacentric; p arm with one or occasionally two dark bands; q
arm with a very large light area followed by a dark band which may be resolved into two dark
bands.

Chromosome 12 (Group C): Very submetacentric; p arm with a dark band; q arm with a proximal
light band (which is relatively thinner than the counterpart of chromosome 11) followed by a dark
area in the middle which may be resolved into two, or more often three, bands.

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•Human chromosome description (Giemsa Stain)

Chromosome 13 (Group D): Acrocentric; p arm with satellites (visible or invisible); q arm with
several dark bands.

Chromosome 14 (Group D): Acrocentric; p arm with satellites (visible or invisible); q arm with a
distal dark band which is more intense than other dark bands.

Chromosome 15 (Group D): Acrocentric; p arm with satellites (visible or invisible); q arm with
dark proximal half and light distal half.

Chromosome 16 (Group E): Metacentric or occasionally submetacentric; p arm light or slightly

dark; q arm with a prominent dark band just below centromere, followed by one or two lesser dark
bands.

Chromosome 17 (Group E): Submetacentric or very submetacentric; p arm with a thin dark band
(may be invisible); centromere dark followed by a distinct, large light band occupying a large part
of q arm, q arm with one or two distinct dark bands near the terminal end.

Chromosome 18 (Group E): Submetacentric or very submetacentric; p arm often uniformly dark;
q arm with two distinct dark bands, one proximal and one distal; the light band between these two
dark bands slightly smaller than the counterpart of chromosome 17.

•Human chromosome description (Giemsa Stain)

Chromosome 19 (Group F): Metacentric; p and q arms both light; centromere dark.

Chromosome 20 (Group F): Metacentric; p arm dark; q arm light, with two narrow, less intense
dark bands.

Chromosome 21 (Group G): Acrocentric; p arm with satellites (visible or invisible); q arm with
intense dark area proximally, fading out toward distal end.

Chromosome 22 (Group G): Acrocentric; p arm with satellites (visible or invisible); centromere
dark; q arm with a narrow, less intense dark band.

X Chromosome (sex chromosome): Submetacentric; p arm with distinct, strong dark band at the
middle; q arm with a proximal dark band about the same distance from the centromere as the p arm
dark band, with two less intense dark bands near distal end.

Y Chromosome (sex chromosome): Very submetacentric; p arm very short or invisible; q arm
dark throughout.

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Variation in Chromosome Number and Structure

Karyotyping
•Chromosomes are identified based on the banding patterns
revealed by stains

•Types of banding
1) G-banding
2) Q-banding
3) C-banding
4) T-banding
5) R-banding

1) G-banding (Giemsa) – alternating dark and light bands

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The bands on each chromosome arm

divide it up into regions. The regions are
numbered starting at the centromere and
progressing to the end of the
chromosome arm.

Regions for Chromosome 18

2) Q-banding (Quinacrine) – fluorescent

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3) C-banding (Giemsa) – centromeres

4) T-banding (Acridine orange) - telomeres

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5) R-banding (Giemsa) – reverse of G-banding

G-banding R-banding

Variation in Chromosome Number and Structure

FISH
•Fluorescent in-situ hybridization

•Rapid technique to identify the different chromosomes

•Does not require cell culturing

•Makes use of DNA probes that are complementary to DNA
sequences found only on one chromosome type
•Probes are attached to molecules that fluoresce when
illuminated
•Chromosome painting – shows a karyotype where each
chromosome type is fluoresced by a unique color

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FISH

Whole chromosome painting (WCP)

FISH

Locus-specific Probes

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Karyotyping at the fetal stage

1) Amniocentesis
•Sampling fetal cells shed into the amniotic fluid
•Used on fetuses at 15-16 weeks of gestation

Karyotyping at the fetal stage

2) Chorionic villus sampling
•Uses cells from the chorionic villi, whose chromosomes
match those of the fetus because they all descend from
the fertilized ovum
•Used on fetuses at 10 weeks of gestation

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Karyotyping at the fetal stage

3) Fetal cell sampling

•Makes  use  of  fetal  cells  separated  from  the  woman’s  

blood stream

•A device called fluorescence-activated cell sorter

(FACS) separates fetal cells by identifying surface
characteristics  that  differ  from  those  on  the  mother’s  
cells

•Safer than the other 2 techniques because it reduces

the risk of a miscarriage while fetal cells are being
sampled

Chromosomal aberrations based on number

1) Euploidy
•Change in chromosome number involving whole
sets of chromosomes

2) Aneuploidy
•Change in chromosome number involving single
whole chromosomes

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Chromosomal aberrations based on number

1) Euploidy
•Change in chromosome number involving whole
sets of chromosomes

•Polyploids are euploids whose chromosome number

is more than the diploid condition by multiples of the
haploid (n) chromosome number

Triploid chromosome
number in humans

Chromosomal aberrations based on number

1) Euploidy

•Polyploids are produced when cytokinesis is interfered

either during mitosis or meiosis

•MITOSIS

•Chromosomes remain dyads

•Failure of separation of sister chromatids

•MEIOSIS
•Gametes produced are unreduced
•Failure of separation of homologous chromosomes

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Chromosomal aberrations based on number

1) Euploidy

•Viable polyploids are rare in animals because self-

fertilization of unreduced gametes seldom takes place

•Polyploidy more common in plants

•Can be induced by the addition of colchicine, which
prevents normal spindle fiber formation
•Tetraploids (4N) are usually fertile because chromosome
pairing is possible during meiosis
•Tetraploids are more fit than their diploid counterparts

Chromosomal aberrations based on number

1) Euploidy
•New species of plants arise through polyploidy
•Autotetraploidy
•Self-fertilization of unreduced gametes

•Allotetraploidy
•Sterile hybrids from different species double their
chromosomes so as to undergo regular meiosis

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Chromosomal aberrations based on number

1) Euploidy
•Some examples
•Raphanobrassica (Rabbage)
•A cross between the radish Raphanus (2N=18) and
cabbage Brassica (2N=18)

•An allotetraploid (4n = 36) was produced by

Karpechenko from the sterile hybrid of these two
genera using the diploid gametes

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Radish Cabbage

Rabbage

Chromosomal aberrations based on number

1) Euploidy
•Some examples
•Polyploidy in humans
•Very rare
•Responsible for 17% of all spontaneous abortions
(triploids and tetraploids) and 3% of stillbirths
•Some survive up to a few
hours only

Triploid chromosome
number in humans

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Chromosomal aberrations based on number

2) Aneuploidy
•Change in chromosome number involving single
whole chromosomes

•The chromosome number is not an exact

multiple of the haploid number of the species

•Results in non-disjunction of one or more

homologous chromosome pairs either during
meiosis I or meiosis II

NULLISOMY

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Chromosomal aberrations based on number

2) Aneuploidy
•Aneuploidy in jimsonweed (Datura stramonium)
•2N=24
•12 primary trisomic
(24 + 1) conditions
possible, each
producing a unique
fruit capsule

Aneuploidy in Humans
Aneuploidy in the Sex Chromosomes
•Turner Syndrome (45, X0)
•Women lacking an X
chromosome
•1 in 2000 females
•Short, stocky
•Flat-chested
•With folds of skin at the back of the
neck (50% of affected individuals)
•Wide-set nipples
•Has undeveloped ovaries
•Verbal IQ normal
•Performance IQ lower than average
•Sterile
•Not correlated with age of the mother

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Aneuploidy in Humans
Aneuploidy in the Sex Chromosomes
•Metafemale Syndrome (47, XXX)
•1 in 1000 females
•Phenotypically female
•Rarely mentally retarded, although they may be less intelligent
than their siblings
•Mental IQ reduces as the number of X chromosomes increases
•Irregular menstrual cycle
•May be tall or short
•Others are flat-chested
•May be fertile, although may produce eggs with two X
chromosomes
•Incidence of offspring increases with maternal age
Non-disjunction of X chromosomes in aging oocytes

Aneuploidy in Humans
Aneuploidy in the Sex Chromosomes
•Klinefelter Syndrome
•1 in 500 males
•With female-like breast
development (Gynecomastia)
•However, it only occurs in 25% of
those with 47-XXY
•With rudimentary testis
•With long arms and legs
•Large hands and feet
•No pubic or facial hair
•Usually sterile
•Slow to learn, but not mentally
retarded
•Mental retardation sets in as more X
chromosomes are added
Incidence also increases with
maternal  age  (mid  to  late  30’s)

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Aneuploidy in Humans
Aneuploidy in the Sex Chromosomes
•Jacobs Syndrome
•1 in 1000 males
•Patricia Jacobs studied 197 inmates in Carstairs, a high-security
mental hospital in Scotland
•7 out of 12 men with unusual chromosomes had an extra Y
•attributed  to  “congenital  criminals”  due  to  these  patients’  violent  or  
aggressive behavior
•no clear correlation between extra Y and aggressive behavior
•great height
•acne
•speech and reading problems
•may be mentally retarded

Aneuploidy in Humans
Aneuploidy in the Autosomes
•Down Syndrome (Trisomy 21)

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Aneuploidy in Humans
Aneuploidy in the Autosomes
•Down Syndrome (Trisomy 21)
•1 in 800 to 1000 births
•Studied by Dr. Langdon Down in 1886
•Patients resembled people of Mongolian
heritage
•Poor muscle tone
•Flat face
•Eyes slant upward
•Abnormally shaped ears
•Single deep crease across palms
•Joints extremely flexible
•Underdeveloped fifth fingers
•With epicanthal folds (skin folds at inner corners of the eyes)
•Gap between first and second toes
•Large tongue
•People affected with Down syndrome has increased risk of getting
affected  with  Alzheimer’s  disease  beyond  40  years  old

•Down Syndrome (Trisomy 21)

•Incidence increases dramatically with age of mother
Age of mother Frequency of Down Syndrome
20 1 in 1667
25 1 in 1250
30 1 in 952
35 1 in 378
36 1 in 289
37 1 in 224
38 1 in 173
39 1 in 136
40 1 in 106
41 1 in 82
42 1 in 63
43 1 in 49
44 1 in 38
45 1 in 30

Source: The American College of Obstetrics and Gynocology (based on data published in the Journal of
the American MedicalAssociation 1981;58:282-285 and 1983;249:2034-2038).

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•Down Syndrome (Trisomy 21)

•Incidence increases dramatically with age of mother

•An oocyte can be stored in an ovary for 40-50 years or more before
becoming an ovum. During that time, environmental contamination
theoretically can render it defective.

•The female meiosis process resulting in ova actually begins before

birth and is completed usually one or a few cells at a time later in life
before each ovulation.

Aneuploidy in Humans
Aneuploidy in the Autosomes
•Edward Syndrome (Trisomy 18)
•1 in 6000 individuals
•heart defects
•displaced liver
•growth retardation
•oddly clenched fists
•narrow and flat skull
•abnormally shaped and low-set ears
•small mouth and face
•unusual or absent fingerprints
•short large toes
•“rocker-bottom”  feet
90% of newborns do not survive the first 6 months

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Aneuploidy in Humans
Aneuploidy in the Autosomes
•Edward Syndrome (Trisomy 18)

Aneuploidy in Humans
Aneuploidy in the Autosomes
•Patau Syndrome (Trisomy 13)
•1 in 15000 individuals
•fusion of the eyes during development, forming one large eye-like
structure in the center of the face (CYCLOPIA)
•malformed nose
•cleft lip/palate present
•extra fingers or toes may appear
•some with extra spleen
•abnormal liver structure
•rotated intestines
•abnormal pancreas
•more than 80% die during the first month
•some survive up to adulthood, but they do not progress
developmentally beyond the six-month level

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Aneuploidy in Humans
Aneuploidy in the Autosomes
•Patau Syndrome (Trisomy 13)

Aneuploidy in Humans
Aneuploidy in the Autosomes
•Warkany Syndrome (Trisomy 8)
• causes severe effects on the developing fetus and is almost
always perinatal lethal

• accounts for 0.8% of

pregnancy losses

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Aneuploidy in Humans
Aneuploidy in the Autosomes
•Mosaic Warkany Syndrome (T8mS)
• 1 in 2500 – 1 in 5000
• occurs when only a portion of these cells contains three copies
of chromosome 8, while others contain the usual two copies of
that chromosome.
• people with mosaic trisomy 8 may have cells in their blood and
other tissues with the normal chromosome number, but may
have cells in their skin with trisomy 8.
• with low-set or abnormally shaped ears and a bulbous-tipped
nose, eye abnormalities like strabismus and corneal clouding,
bone and tissue abnormalities, various structural heart
problems, palate abnormalities, hydronephrosis (swelling of
urine), cryptorchidism (undescended testes), mild to moderate
mental delays, and deep hand and feet creases.
• characteristics tend to vary widely from person to person.

Chromosomal aberrations based on structure

Types
1) Deletion
•A segment is lost

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Chromosomal aberrations based on structure

Types
2) Duplication
•A segment is repeated or duplicated

Chromosomal aberrations based on structure

Types
3) Paracentric Inversion
•A segment that does not include the centromere
breaks in two places and is reinserted in reversed
orientation

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Chromosomal aberrations based on structure

Types
4) Pericentric Inversion
•Inversion that includes the centromere

Chromosomal aberrations based on structure

Types
5) Simple Translocation
•A segment of one chromosome is transferred to a
non-homologous chromosome

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Chromosomal aberrations based on structure

Types
7) Reciprocal Translocation
•Exchange of segments between non-homologous
chromosomes
•May be:
•Balanced – no genetic material is gained or lost

•Unbalanced – some genetic material is gained or lost

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Chromosomal aberrations based on structure

Types
7) Robertsonian Translocation
•Fusion of acrocentric chromosomes

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Some Examples
A. Deletions
1. Cri du chat syndrome (5p-)
•Results in the deletion of a segment of the short arm
of chromosome 5

Some Examples
A. Deletions
1. Cri du chat syndrome (5p-)
•Affected individuals have a
high-pitched cry similar to
the mewing of a cat
•Low birth weight
•Poor muscle tone
•Small head
•Impaired language skills
•Mentally retarded
•Rarely survives to teens

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Some Examples
A. Deletions
2. Prader Willi syndrome (15q-) or PWS
•deletion of segments q11 and q12 in chromosome 15
•affected chromosome from the father

Some Examples
A. Deletions
2. Prader Willi syndrome (15q-)
•mentally retarded
•obese
•eats uncontrollably
•small hands and feet
•does not develop signs of
puberty
•Poor muscle tone, resulting
in floppy infants

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Some Examples
A. Deletions
2. Prader Willi syndrome (15q-)
•Can be treated with growth hormones

Some Examples
A. Deletions
3. Angelman syndrome (15q-) or AS

•deletion of same segments in chromosome 15 as

in PWS
•affected chromosome from the mother
•Developmental delay
•Speech impairment
•Movement or balance disorder
•Frequent laughter or smiling
•Easily excitable
•Frequent flapping of arms
•Jerky movements
•Also known as the happy puppet syndrome

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Genetic imprinting and AS/PWS

Genetic imprinting
• the turning off of one parent's gene is thought to occur
during the formation of an egg or a sperm cell.

• part of the mechanism that turns off the parent's gene

is methylation (the attachment of a methyl group) of that
parent's DNA.

• For a specific region of chromosome 15, only one copy of

specific genes is needed; hence, the other copies from the
other chromosome must be turned off

Genetic imprinting and AS/PWS

Genetic imprinting
• In Angelman syndrome, a deletion occurred in a region of
chromosome 15 that included a gene of the ubiquitin
pathway (UBE3A) of the maternal chromosome while the
same region in the paternal chromosome is silenced.

• In Prader-Willi syndrome, a deletion occurred in the same

region of chromosome 15 that included the SNRPN gene
(encodes a component of the mRNA splicing system) of the
paternal chromosome while the same region in the maternal
chromosome is silenced.

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Some Examples
B. Duplications
1. Facet number in the compound eyes of Drosophila
•Can result in Bar eyes

Some Examples
B. Duplications
2. X chromosome duplication in humans
•Duplication of segments q13 1 to q21 1
•Developmental delays
•Seizures
•Webbed neck
•Short stature
•Microcephaly – small head
•Mental retardation and learning disabilities
•Non-functional gonads

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Some Examples
C. Translocations
1. Translocation/Familial Down Syndrome
•Still with 3 copies of
chromosome 21s
•Extra 21 is attached to
Group D chromosome
(14 or 15)
•With 46 chromosomes
•Phenotypically identical
with trisomy Down
•Inherited from
translocation carrier

Some Examples
C. Translocations
2. Bipolar Affective Disorder (Manic Depression)

•Associated with reciprocal translocation between

chromosomes 9 and 11

•Leads to disruption of the DIBD 1 gene in chromosome 11

•People exhibit manic episodes sometimes with extreme

depressive episodes

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“Starry  Night”  by  Vincent  van  Gogh

Other Chromosomal Aberrations Based on Structure

A. Isochromosomes
•Chromosomes with identical arms
•Formed when, during anaphase, the centromeres part in the wrong
plane
•Result in loss of some genes and duplication of other genes
•May be genetically or environmentally induced

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Other Chromosomal Aberrations Based on Structure

B. Dicentric Chromosomes
•Abnormal fusion of two fragments from non-homologous
chromosomes, each with a centromere

Other Chromosomal Aberrations Based on Structure

C. Ring Chromosomes
•Occur when the ends of a chromosome are broken and
the subsequent new ends fuse to form a ring

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Other Chromosomal Aberrations Based on Structure

C. Ring Chromosomes

•Exemplified in humans by the Cat Eye Syndrome

•People affected have an extra chromosome 22 in the
form of a ring

•An extra copy of the q11 region leads to the disorder

•Vertical pupils
•Mentally retarded
•Have heart and urinary tract anomalies
•Have skin growing over their anus

Cat Eye Syndrome

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Other Chromosomal Aberrations Based on Structure

D. Fragile X Chromosomes
•X-chromosomes in humans where one tip dangles from the
rest by a thin thread
•When cells with this chromosome are cultured in media
w/o folic acid, the region is prone to breakage

Other Chromosomal Aberrations Based on Structure

D. Fragile X Chromosomes
•1 in 1000 individuals
•Affected individuals:
•Apparent in adults
•Ears protrude
•Jaw is long
•Testicles are very large
•Mental impairment varies
•Mental retardation
•Learning disabilities
•Poor speech
•Hyperactivity
•Shyness
•Social anxiety
•Short attention span

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Other Chromosomal Aberrations Based on Structure

D. Fragile X Chromosomes
•Trait is not 100% penetrant
•Fragile site caused by CGG repeats
•6 to 49 normal
•50 to 200 asymptomatic
•230 – 1000+ w/ symptoms
•The fragile site expands from generation to generation
(GENETIC ANTICIPATION)

Other Chromosomal Aberrations Based on Structure

D. Fragile X Chromosomes

•Expansion of trinucleotide repeat affects the fragile X

mental retardation 1 (FMR1) gene
•The protein translated, fragile mental retardation
protein (FMRP) is needed for normal neural development

•Only men are affected

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The evolution of the human chromosome number (46)

•Chimpanzees, our closest relatives, have a chromosome

number of 48.

• Evolutionary biologists account for this difference by

suggesting that two chimp chromosomes (2A and 2B) fused.
This fusion could have generated what is now human
chromosome 2.

The evolution of the human chromosome number (46)

•Evidence for fusion close similarity of the banding

patterns for human chromosome 2 and chimp chromosomes
2A and 2B when these two are oriented end-on-end

• two centromeres in human chromosome 2, one

functional, the other inactive

• an internal telomere sequence within human

chromosome 2

• The location of the two centromeres and internal

telomere sequences correspond to the expected
locations if, indeed, human chromosome 2 arose as
a fusion event.

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Genes and the Environment

• hazardous chemicals are increasingly being

discharged to the environment

• need to identify compounds that react with DNA

• development of cytotoxicity and genotoxicity assays

Allium Test
• short-term test

• indicator of cytotoxicity and

mutagenicity

• low cost

• ease of handling

• comparable to other test systems

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Root Growth Inhibition Test

• obtain red onion bulbs from the same batch

• remove loose outer scales and old roots

• place onion on bottle with tap water for 2 days

• use onions that produced roots for experiment

Root Growth Inhibition Test

• expose 6 onions to 6 – 9 concentrations of test
chemical

• measure root length of 5 onions per concentration

• compute for 50% effective concentration (EC50)

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Genotoxicity Assay
• expose onions to treatments for 24-48 hrs

• cut root tips (2-3 mm)

• place in vial with aceto-ethanol

• store in ref until further use

Genotoxicity Assay
• hydrolyze roots tips with 1 N HCl for 3 mins

• stain with Carbol fuchsin for 3 min

• stain with aceto-orcein for 3 min

• squash root tips under the cover glass

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Genotoxicity Assay
• examine 1000 cells from 2-3 root tips/replicate

• compute mitotic index

• record chromosomal aberrations

• photograph

Chromosomal Aberrations

sticky anaphase

vagrant chromosomes

vagrant chromosomes

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Chromosomal Aberrations

chromosome bridge chromosome fragment

chromosome fragment

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