Download Chromosome Wrap-up

Chromosome “Wrap-up”
How does so much DNA fit in
Nucleus?
 Even the shortest human chromosome
contains more DNA than would fit into the
nucleus (46 b. base pairs)
 If it weren’t condensed, it would take up 1.5
cm of length
 Chromosomes must condense to fit in
nuclei
“Packing” a punch!
 The smallest chromosome DOESN’T take
up 1.5 cm, it only takes up 2 micrometers
during its condensed state of
mitosis/meiosis
 How?
 DNA is organized into a hierarchy of
“packing”
Levels of DNA Packing in
Chromosomes
 Level 1
– 4 nm DNA is wound around a protein
core to look like a bead called a
“nucleosome” 10 nm thick
Levels of DNA Packing in
Chromosomes
 Level 2
– Further coiling results in 30 nm
nucleoprotein fibers
– Looped addtionally to form metaphase
chromosomes 700nm
DNA coiling
The Coils of Chromosomes
Basic chromosome structure
P arm
kinetochore
Q arm of
chromosome
chiasmata
nucleosome
Telomere
Recombinant
DNA
Nucleo
protein
fiber
Chromosomes Carry Genes
CHROMOSOMES
Human chromosomes are
stored in the nucleus
Chromosomes have DNA wrapped
around special histone proteins.
“Beads on string”: nucleosomes
organize DNA in human genome
DNA
Base-Pairs:
DNA
Helix
A-T
G-C
How Many Chromosomes Are There?
Bacteria usually have one circular
chromosome and no nucleus
Organisms with nuclei have
variable numbers of chromosomes
depending on the species:
• Mosquito 6
• Chimpanzees 48
• Goldfish 94
http://gnn.tigr.org/whats_a_genome/Chp1_3_1.shtml
You Inherited Two Copies of Each Chromosome,
One from Mom and One from Dad
You inherited two copies of
each gene, one from Mom
and one copy from Dad.
One copy of
chromosome
#3 from Mom
All 46 Human chromosomes
together is called a human
karyotype.
The X and Y chromosomes
are the sex chromosomes.
The 22 chromosomes (not the sex
chromosomes) are called autosomes.
One copy of
chromosome
#3 from Dad
Human Cells Have 22 Sets of Paired Chromosomes
22 SETS OF PAIRED AUTOSOMES EACH
2 sex
chromosomes
2 sex
chromosomes
Almost every cell in your body (except RBC, eggs,
sperm) has two sets of genes carried on 22 sets of
paired chromosomes, plus 2 sex chromosomes.
What is the Relationship Between DNA
and Chromosomes?
?
Each Chromosome Contains Hundreds of Genes!
DNA
CELL
CHROMOSOMES
DNA
G
E
N
E
NUCLEUS
DNA Helix
DNA
GENE 1
GENE 6...
A
GENE 2
GENE 5
GENE 3
GENE 4
DNA is Packaged Into Chromosomes
DNA double helix
GENE (blue)
Several GENES
along a length of DNA
DNA is coiled around proteins
(more on this later)
Small region of
“unwrapped”
chromosome
Loosely wrapped DNA
in chromosome
Tightly wrapped
chromosome
Adapted from
Alberts et al.
Molecular Cell Biology
Chromosomes are Dynamic Structures
Human Chromosomes
CONDENSED
EXTENDED
Metaphase
Chromosome
Fruit Fly
One Human Chromosome
Contains One ds DNA Helix
Short arm
(‘p’)
Centromere
Long arm
(‘q’)
ONE double-stranded
(ds) DNA molecule
extends from one end
of the chromosome to
the other end of the
chromosome.
The chromosome on
the left has duplicated
(replicated). How many
ds DNA helices does it
contain?
Human Chromosomes Have Two Ends
and a Middle!
The ends of a linear
chromosome are
called telomeres.
Telomeres play a
special role when
the chromosome
DNA duplicates
during cell division.
Centromeres are
usually in the middle
of the chromosome,
but can be near one
end. What essential
role do centromeres
play in cell division?
Telomere
Centromeres are
Stained
Centromere
Telomeres are
Stained
Telomere
Human Chromosome Karyotypes
1
2
3
4
6
7
8
9
10 11
Which gender
results from
inheriting these
chromosomes?
Banding patterns on
chromosomes represents
different staining of A-T
and G-C rich regions in
the DNA
What Happens to Chromosomes and Genes
When Cells Divide?
CENTROMERE
ONE
DOUBLESTRANDED
DNA HELIX
DNA Replication
(Duplication)
DNA Replication
(Duplication)
TWO DOUBLESTRANDED
DNA HELICES
CENTROMERE
Telomeres are
needed to
duplicate the
very ends of the
chromosomes
Before A Cell Can Divide To Make Two Cells, It Must
Duplicate It’s Genes, Chromosomes and DNA
46
chr
Chromosomes duplicate and
line-up on metaphase plate
[46 x 2 = 92]
Start
here
Chromosomes
move to
opposite poles
chromosomes
attach to
spindle fibers
46 chromosomes In
each daughter cell
Centromeres are Critical for Chromosome (Gene) Inheritance
Spindle fibers attach to
centromeres on the
Metaphase chromosomes.
Spindle
Pole
Spindle
Microtubule
Centromeres
Molecular motors at
centromere move the
chromosome along the
spindle fiber to the pole.
Anaphase
Down Syndrome: A Consequence of Centromere Failure
and Incorrect Chromosome Inheritance
A special type of cell division
(meiosis) generates germ
cells: eggs and sperm
46
46
A mistake in meiosis during egg
production creates an egg with one
additional chromosome (#21)
Chromosome
number
46
46
46
46
meiosis
meiosis
23
23
germ
cells
24
23
germ
cells
23
23
fertilization
24
23
fertilization
46
fertilized
zygote
47
fertilized
zygote
How Does Down Syndrome Affect People Who Inherit
an Extra Copy of Chromosome 21?
Down Syndrome identified by John
Langdon Down (1866) who noticed
that some people looked similar
although they were not biologically
related.
Down Syndrome features: a
broad flat face, small nose and
variable levels of mental
impairment. Called “Mongolism”
in 1866 but now properly called
Down Syndrome.
Down Syndrome is caused by
Trisomy 21 (3 copies of chr 21)
Extra copy of chromosome 21 causes the “Down” characteristics.
Most Down people have 47 chromosomes in every cell. Others
have 46 chromosomes in some cells and 47 chromosomes in other
cells (mosaic) and have less severe Down symptoms.
http://www.genetics.com.au Genetics Fact Sheet #24A
Down Syndrome Risk Increases with Age of Mother
Down Syndrome occurs more
frequently in women over age
35 years.
Down Syndrome can also be
caused by inheriting an extra
chromosome 21 from the
father’s sperm. Risk does not
increase with age.
Age of Mother:
20-24 yrs risk is 1 in 1474
35 yrs risk is 1 in 384
40 yrs risk is 1 in 112
45 yrs risk is 1 in 28
There is no cure for a child with
Down Syndrome.
Note: Risk of having child with a
chromosome abnormality also
increases with age of mother:
There are pre-natal screening
tests available for Down
Syndrome. Discuss this in unit
on genetic testing.
20-24 yrs 1 in 506
35 yrs 1 in 179
40 yrs 1 in 64
45 yrs 1 in 19
Scientists are looking for the
regions of chromosome 21 that
are most likely to be involved in
causing Down Syndrome.
Other Genetic Disorders Caused by
Chromosome Abnormalities
Klinefelter Syndrome: 46,XXY
(“Normal” is 46,XY)
Klinefelter affects only boys with
risk of 1 in 500 to 1 in 1000 males
born. (fairly common)
Symptoms include sparse facial
hair, inability to form sperm
(infertility but sexuality is
“normal”), learning difficulties
Klinefelter caused by a mistake in
segregation of the X chromosome
at or soon after conception.
When the mistake occurs after
conception, Klinefelter boys can be
mosaic (have some 46,XY cells and
some 46,XXY cells)
Klinefelter is not related to the
age of the mother or father at
conception.
There is no cure although
treatment with testosterone can
reduce symptoms.
There are pre-natal screening
tests available. Discuss this in
unit on genetic testing.
Klinefelter occurs sporadically
for unknown reasons.
http://www.genetics.com.au
Genetics Fact Sheet #24B