PORTLAND STATE BI 341

CHAPTER 5: HUMAN CHROMOSOMES AND

CHROMOSOME BEHAVIOR

Kim H Brown, PhD

Royal Institute Chromosome Videos:

https://www.youtube.com/watch?v=_I
L-cHlVcKc#t=217
 Objectives
1) Human karyotypes
2) Centromeres
3) The X & Y chromosome: linkage, inactivation, and
lessons learned
4) Example chromosomal abnormalities:
i) Down’s Syndrome
ii) Trisomy
iii)Trisomy of the sex chromosomes
iv) Nondisjuction
5) Chromosomal Rearrangements: deletions, duplications,
inversions, reciprocal translocations.
6) Polyploidy: The grass family
 Human Chromosomes
• Humans contain 46
Human
chromosomes, including 22 chromosome
pairs of homologous painting.
autosomes and two sex
chromosomes.

• Karyotype = stained and

photographed preparation
of metaphase Human
chromosome
chromosomes arranged painting.
according to their size and
position of centromeres
 A karyotype of a typical human male.
The chromosomes as seen in the cell by The chromosomes have been cut out of the
microscopy. photograph and paired with their homologs

Giesma Stain: specific for the phosphate groups of DNA and attaches itself to regions
of DNA where there are high amounts of adenine-thymine bonding.
The human chromosome complement at
metaphase of mitosis

.
 Centromeres
1. Centromeres: constricted
region of the chromosome
where two identical sister
chromatids are most closely
in contact
2. Sister chromatids are linked
all along their length by
cohesion
3. Cohesion is released from
chromosome arms during
prophase
4. Last place where they are
Chromosomal components:(1) Chromatid (2)
linked with one another is in Centromere (3) short arm (4) Long arm
the chromatin in and around http://en.wikipedia.org/wiki/Centromere

the centromere
 Centromeres
• Chromosomes are classified
according to the relative
position of their centromeres
• In metacentric it is located in
middle of chromosome
• In submetacentric — closer to
one end of chromosome
• In acrocentric — near one end
of chromosome
• Telocentric if joined at end of
chromosome, acentric (no
centromere) or dicentric (two
centromeres) chromosomes,
are genetically unstable.
Exception: if 2 centromeres are
very close together
Human ancestors had 24 pairs of chromosomes. Two acrocentric
chromosomes fused, creating human chromosome 2.

Video: Human vs. Chimp and Chromosome 2:

http://www.youtube.com/watch?v=8FGYzZOZxMw
How do we know this?
 Human Chromosomes
• Each chromosome in the
karyotype is divided into
two regions (arms)
separated by the
centromere
• p = short arm (petit); q =
long arm
• p and q arms are divided
into numbered bands and
interband regions based on
pattern of staining
• Within each arm the regions
are numbered.
Designations of the bands and interbands in
the human karyotype.
Beneath each
chromosome is the
lettered group (A–G,
based on size,
centromere position)
 Dosage compensation balances the dose of X
chromosome gene expression in females and males
• Dosage compensation prevents excessive expression of
X-linked genes in humans and other mammals

http://www.bozemanscience.com/x-inactivation
 Barr Bodies
• The inactive X is highly condensed, can be observed in
stained interphase cells, and is referred to as Barr bodies
• Random inactivation of either the maternal or paternal
chromosome
• Occurs early in embryonic development, and all cellular
descendants have the same inactivated chromosome
Inactivation of X
chromosome is
random
Occurs in somatic cells
at an early stage of
embryonic development
and is then passed on to
progeny cells by mitosis
 The mechanism of inactivation

• The X-inactivation center

(Xic) is active on the
inactive X
• It consists of the X-
inactive specific
transcript (XIST) gene
• Expression of Xic leads
to inactivation of
chromosome expressing
the Xist locus

http://genes.atspace.org/
 Y chromosome determines genetic
maleness in humans
The Y chromosome determines maleness in humans
The human karyotype revealed that one pair of
chromosomes differs in males and females:
• Typical females have two X chromosomes
• Typical males have one X and one Y chromosome
 Y chromosome has at least 75 genes
• The pseudoautosomal regions (PARs) present on both ends of
the Y chromosome that share homology with regions on the X
chromosome and synapse and recombine with it during meiosis
• The presence of such a pairing region is critical to segregation of
the X and Y chromosomes during male gametogenesis
The non-recombining region of Y chromosome is
called the male specific region of the Y
• It has euchromatic and heterochromatic regions
• The SRY (sex determining region) is located adjacent to PAR of
the short arm of the Y chromosome
 The Y chromosome and male development
• At 6-8 weeks of development, the SRY genes become active in
XY embryos
• The testis-determining factor (TDF) is a protein encoded by a
gene in the SRY that triggers testes formation
The pseudoautosomal region of the X and Y chromosomes
has gotten progressively shorter in evolutionary time

http://news.discovery.com/human/videos/are-men-going-
extinct-video.htm
 Human Y Chromosome
Y chromosome does not undergo recombination along most of its
length
• Genetic markers in the Y are completely linked
• Y genes degenerate over time as in the absence of
recombination, mutations accumulate
• The set of alleles at two or more loci present in a particular
chromosome is called a haplotype
• The history of human populations can be traced through studies
of the Y chromosome

Genetic Adam and Eve:

http://www.huffingtonpost.com/2013/
08/01/genetic-adam-eve-
chromosome-men-
man_n_3691084.html

http://www.radiolab.org/story/91519-
genghis-khan/
 Abnormal Chromosome Number
Euploid = balanced
chromosome abnormality
(example: tetraploids have 4 of
each chromosome)

Aneuploid = unbalanced set of

chromosomes (example:
trisomy of chromosome 21)
• Monosomic = loss of a
single chromosome copy
• Polysomic = extra copies of
single chromosomes

Chromosome abnormalities are

frequent in spontaneous
abortions.
 Nondisjunction
• Chromosomal variation can arise from nondisjunction, in
which chromosomes or chromatids fail to disjoin and move to
opposite poles during meiosis I or II
 Sex Chromosome Aneuploidies
An extra X or Y chromosome
usually has a relatively mild effect
due to single-active-X principle
and relatively few genes in Y
chromosome

Trisomy-X = 47, XXX (female)

Double-Y = 47, XYY (male,
Jacob’s Syndrome)
Klinefelter Syndrome = 47, XXY
(male, sterile)
Turner Syndrome = 45, X
(female, sterile)
Jacob’s Syndrome
 Abnormal Chromosome Number
Monosomy or trisomy of most
human autosomes is unviable.
There are three exceptions:
trisomies of 13, 18, and 21

• Down Syndrome is a
genetic disorder due to
trisomy 21, the most
common autosomal
aneuploidy in humans
• Frequency of Down
Syndrome increases with
mother’s age
• CNV’s increase with paternal
age
 Monosomy
The loss of one chromosome to produce
a 2n – 1 complement is called
monosomy
• The loss of a single chromosome may
have severe phenotypic effects
• Monosomy for the X chromosome
occurs in humans geneticdisordersp7.wikispaces.com

• Monosomy for any of the autosomes

is usually not tolerated in humans and
other animals
Monosomy usually results in more
harmful effects than trisomy
 Trisomy (2n + 1 chromosomes)

• Trisomies for autosomes are

often lethal
• For the sex chromosomes
has a less dramatic impact
on the phenotype
• When three copies of a
chromosome are synapsed, the
configuration is called a
trivalent
• In some cases, prior to the first
meiotic division, one bivalent
and one univalent (an
unpaired chromosome) may be
present instead of a trivalent
 Down syndrome: nondisjunction of the maternal
chromosome 21 during meiosis
• Down syndrome has 12 to 14 characteristics, and affected
individuals express 6 to 8 on average
 Chromosomal Abberations
• There are two primary ways in which the structure of
chromosomes can be altered
• The total amount of genetic information in the
chromosome can change
• Deletions
• Duplications
• The genetic material remains the same, but is
rearranged
• Inversions
• Translocations

McGraw Hill Animation Chromasomal Mutations:

https://highered.mheducation.com/sites/9834092339/student_
view0/chapter15/changes_in_chromosome_structure.html
 Chromosome Deletions
Terminal deletion: near one end
Intercalary deletion of the chromosome ()
• Deletions can be formed by spontaneous double stranded
breaks, or ectopic recombination
 Cri-du-chat
Cri-du-chat results from a segmental deletion of a small
terminal portion of the short arm of chromosome 5
 Gene Duplications
Duplication are genetics rearrangements in which chromosome
segment present in multiple copies.
Tandem duplications: repeated segments are adjacent
• Tandem duplications often result from unequal crossing-
over due to mispairing of homologous chromosomes during
meiotic recombination

Figure 05.17: Unequal crossing-over of tandem duplications.

 Red-Green Color Vision Genes
• Genes for red and green pigments
are close on X-chromosome
• Green-pigment genes may be
present in multiple copies on the
chromosome due to mispairing and
unequal crossing-over
• Unequal crossing-over between
these genes during meiotic
recombination can also result in
gene deletion and color-blindness “green blindness”
• Crossing-over between red- and
green-pigment genes results in
chimeric (composite) gene
 CNV with Reciprocal Risks of Autism and
Schizophrenia
• CNV= Copy Number Variation
• Can result from
homologous recombination
in which the chromosomes
have misaligned along
flanking repeat sequences
Autism and schizophrenia
 Chromosome Inversions
• Inversions are genetic
rearrangements in which
the order of genes in a
chromosome segment is
reversed
• Inversions do not alter the
genetic content
• In an inversion
heterozygote,
chromosomes twist into a
loop in the region in which
the gene order is inverted
 Chromosome Inversions
• Paracentric inversion does not include centromere
• Crossing-over within a paracentric inversion loop
during recombination produces one acentric
(no centromere) and one dicentric (two centromeres)
chromosome
 Chromosome Inversions
• Pericentric inversion includes centromere
• Crossing-over within a pericentric inversion loop during
homologous recombination results in duplications and
deletions of genetic information.

Figure 05.26: Synapsis between homologous chromosomes.

 Reciprocal Translocation
Translocation: Recombination
between nonhomologous
chromosomes

Reciprocal Translocations:
https://www.youtube.com/w
atch?v=MLDCJ2gUC84
 Robertsonian Translocation
• A special case of nonreciprocal translocation is a
Robertsonian translocation – fusion of two
acrocentric chromosomes in the centromere
region
• Translocation results in apparent loss of one
chromosome in karyotype analysis
• Genetic information is lost in
the tips of the translocated
acrocentric chromosomes

Robertsonian Translocation:
https://www.youtube.com/watch?v=vbGw4VanNjk
 Robertsonian Translocation
• When chromosome 21 is one of the acrocentrics
in a Robertsonian translocation, the
rearrangement leads to a familial type of Down
syndrome
• The heterozygous carrier is phenotypically
normal, but a high risk of Down syndrome results
from aberrant segregation in meiosis

• Approximately 3 percent of children with Down

syndrome have one parent with such a
translocation
 Polyploidy
• Polyploid species have multiple complete
sets of chromosomes
• The naming of polyploids is based on the number
of sets of chromosomes found:
• a triploid has 3n chromosomes
• a tetraploid has 4n chromosomes
• a pentaploid has 5n chromosomes
• and so forth
• The basic chromosome set, is called the
monoploid set
• The haploid chromosome set is the set of
chromosomes present in a gamete
 Polyploidy
Autopolyploids have all chromosomes in the polyploid
species derive from a single diploid ancestral
Allopolyploids have complete sets of chromosomes from
two or more different ancestral species
• Chromosome painting: chromosomes hybridized with
fluorescent dye to show their origins
• The crocus flower has 7 pairs of chromosomes

DNews Seedless Fruit:

http://news.discovery.com/
earth/plants/how-do-
farmers-make-seedless-
fruit-150511.htm
AUTOPOLYPOIDS HAVE CHROMOSOME SETS FROM A SINGLE SPECIES;
ALLOPOLYPOIDS HAVE CHROMOSOME SETS FROM DIFFERENT SPECIES
 Polyploidy
Two mechanisms of asexual polyploidization:
 the increase in chromosome number takes place in
meiosis through the formation of unreduced gametes that
have double the normal complement of chromosomes
 the doubling of the chromosome number takes place in
mitosis. Chromosome doubling through an abortive
mitotic division is called endoreduplication

Endoreduplication:
Production of a diploid from a
monoploid by treatment with
colchicine, which disrupts
spindle and prevents
separation of chromatids
 Polyploidy
• The grass family illustrates the importance of
polyploidy and chromosome rearrangements in
genome evolution
• The cereal grasses (rice, wheat, maize, millet,
sugar cane, sorghum, and other cereals) are our
most important crop plants
• Their genomes vary enormously in size: from 400
Mb found in rice to 16,000 Mb found in wheat
 Polyploidy
• In spite of the large variation in chromosome
number and genome size, there are a number of
genetic and physical linkages between single-
copy genes that are remarkably conserved in all
grasses amid a background of rapidly evolving
repetitive DNA
• Each of the conserved regions (synteny groups)
can be identified in all the grasses and referred to
a similar region in the rice genome.
Conserved linkages (synteny groups) between rice genome and other
grass species.