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Chapter 5
Human
Chromosomes and
Chromosome
Behavior
Human Chromosomes
• Humans contain 46 chromosomes, including 22
pairs of homologous autosomes and two sex
chromosomes
• Karyotype = stained and photographed preparation
of metaphase chromosomes arranged according to
their size and position of centromeres
Figure 05.01A: Human chromosome
painting.
Parts A and B Courtesy of Johannes Wienberg,
Ludwig-Maximillians-University, and Thomas Ried,
National Institutes of Health
Figure 05.01B: Human chromosome
painting.
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
• Chromosomes with no centromere, or with two
centromeres, are genetically unstable
Figure 05.F05: Three possible shapes of monocentric chromosomes in
anaphase as determined by the position of the centromere (shown in dark
blue).
Figure 05.F06: Human ancestors had 24 pairs of chromosomes. In the
evolution of the human genome, two acrocentric chromosomes fused,
creating human chrosome 2.
Human Chromosomes
• Each chromosome in 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.
Figure 05.03: Designations of the bands and interbands in the human karyotype.
Figure 05.F04: The human chromosome complement at metaphase of
mitosis.
Sequence data from International Human Genome
Sequencing Consortium, Nature 409 (2001): 860-921, and
J.C. Venter, et al., Science 291 (2001): 1304-1351.
Chromosome image courtesy of Michael R. Speicher.
Institute of Human Genetics, Medical University of Graz.
Human X Chromosome
• Females have two copies of X chromosome.
• One copy of X is randomly inactivated in all somatic
cells.
• Females are genetic mosaics for genes on the X
chromosome; only one X allele is active in each cell.
• Barr body = inactive X chromosome in the nucleus of
interphase cells.
• Dosage compensation equalizes the number of active
copies of X-linked genes in females and males.
Figure 05.07: Schematic diagram of somatic cells of a normal female.
The calico cat shows visible evidence
of X-chromosome inactivation.
Figure 05.08: Female cat heterozygous for the orange and black coat color alleles.
Human Y Chromosome
• Y chromosome is largely heterochromatic.
• Heterochromatin is condensed inactive chromatin.
• Important regions of Y chromosome:
– pseudoautosomal region: region of shared X-Y
homology
– SRY – master sex controller gene that encodes
testis determining factor (TDF) for male
development
The pseudoautosomal region of the X and Y
chromosomes has gotten progressively shorter
in evolutionary time.
Figure 05.09: Progressive shortening of the mammalian X-Y pseudoautosomal region
through time.
Data from B.T. Lahn and D.C. Page,
Science 286 (1999): 964-967
Human Y Chromosome
• Y chromosome does not undergo recombination
along most of its length, genetic markers in the Y are
completely linked and remain together as the
chromosome is transmitted from generation to
generation
• 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
Abnormal Chromosome Number
• Euploid = balanced chromosome abnormality = the same
relative gene dosage as in diploids (example: tetraploids)
• Aneuploid = unbalanced set of chromosomes = relative
gene dosage is upset (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.
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
• Monosomy usually results in more harmful effects
than trisomy
Figure 05.F11: Risk of Down syndrome in the absence of prenatal
screening as related to mother’s age. Note that the scale on the vertical
axis is logarithmic.
Data from J. K. Morris, D. E. Mutton, and E.
Alberman, J. Med. Screen. 9 (2002): 2-6
Abnormal Chromosome Number
Table 05.01 Chromosome Abnormalities per 100,000 Recognized Human Pregnancies.
Abnormal Chromosome Number
• Trisomic chromosomes undergo abnormal segregation
• Trivalent = abnormal pairing of trisomic chromosomes
in cell division
• Univalent = extra chromosome in trisomy is unpaired
in cell division
Figure 05.12: Meiotic synapsis in a trisomic.
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)
• Klinefelter Syndrome = 47, XXY (male, sterile)
• Turner Syndrome = 45, X (female, sterile)
Abnormal Chromosome Number
• Aneuplody results from nondisjunction: a failure of
chromosomes to separate and move to opposite
poles of the division spindle
• The rate of nondisjunction can be increased by
chemicals in the environment.
Chromosome Deletions
• Deletions: missing chromosome segment
• Polytene chromosomes of Drosophila can be used to
map physically the locations of deletions
• Any recessive allele that is uncovered by a deletion
must be located inside the boundaries of the deletion:
deletion mapping
• Large deletions are often lethal
Figure 05.F13: Ectopic recombination between direct repeats in the same
DNA molecules results in deletion of the material between the repeats.
Figure 05.F14: Mapping of a deletion by testcrosses. The F1
heterozygotes with the deletion express the recessive phenotype of all
deleted genes.
Figure 05.F15: Polytene chromosomes from a larval salivary gland cell of
Drosophila melanogaster.
© Andrew Syred/Photo Researchers, Inc.
Figure 05.16: Part of the X chromosome in polytene salivary gland nuclei and the
extent of six deletions (I–VI) in a set of chromosomes.
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 Xchromosome
• 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
• Crossing-over between red- and green-pigment genes
results in chimeric (composite) gene
Figure 05.19: Red-pigment and green-pigment genes.
Figure 05.F18: A standard color chart used in initial testing for color
blindness. The pattern tests for an inability to distinguish red from green.
© Steve Allen/Brand X Pictures/Alamy Images
Figure 05.F19: (A) Organization of genes in three wildtype X
chromosomes. (B) Origin of multiple green-pigment genes by unequal
crossing-over.
Figure 05.F19: (A) Organization of genes in three wildtype X
chromosomes. (B) Origin of multiple green-pigment genes by unequal
crossing-over.
CNV with Reciprocal Risks of
Autism and Schizophrenia
Figure 05.21: Origin of chromosomes bearing a duplication or deletion of a genomic region
by means of unequal crossing-over between repeated sequences.
Figure 05.22: Comparison of some of the major symptoms of autism spectrum disorder and
schizophrenia highlighting those that resemble polar opposits.
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
Figure 05.24: Loop in the region in
which the gene order is inverted.
Figure 05.F23: Ectopic recombination between inverted repeats results in
an inversion.
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
Figure 05.25: Crossover within the inversion loop.
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 Translocations
• A chromosomal aberration resulting from the
interchange of parts between nonhomologous
chromosomes is called a translocation
• There is no loss of genetic information, but the
functions of specific genes may be altered
• Translocations may produce position effects: changes
in gene function due to repositioning of gene
• Gene expression may be elevated or decreased in
translocated gene
Reciprocal Translocation
• In heterozygous translocation, one pair of
chromosomes interchanged their segments and one
pair is normal
• In homozygous translocation, both pairs interchanged
their segments
Figure 05.27: Two pairs of nonhomologous chromosomes in a diploid organism.
Reciprocal Translocations
• Synapsis involving heterozygous reciprocal
translocation results in pairing of four pairs of sister
chromatids – quadrivalent
• Chromosome pairs may segregate in several ways
during meiosis, with three genetic outcomes:
adjacent-1 segregation, homologous centromeres
separate at anaphase I, and gametes contain
duplications and deletions
Reciprocal Translocation
• Adjacent-2 segregation: homologous centromeres
stay together at anaphase I; gametes have a
segment duplication and deletion
• Alternate segregation: half the gametes receive
both parts of the reciprocal translocation and the
other half receive both normal chromosomes; all
gametes are euploid, i.e. have normal genetic
content, but half are translocation carriers
Reciprocal Translocation
• The duplication and deficiency of gametes produced
by adjacent-1 and adjacent-2 segregation results in the
semisterility of genotypes that are heterozygous for a
reciprocal translocation
• The frequencies of each outcome is influenced by the
position of the translocation breakpoints, by the
number and distribution of chiasmata, and by whether
the quadrivalent tends to open out into a ring-shaped
structure on the metaphase plate
Figure 05.28: A quadrivalent formed in the synapsis of a heterozygous reciprocal
translocation.
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
Figure 05.29: Formation
of a Robertsonian
translocation by fusion.
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 basic chromosome set, from which
all the other genomes are formed, is
called the monoploid set
• The haploid chromosome set is the set
of chromosomes present in a gamete,
irrespective of the chromosome
number in the species.
Figure 05.31: Chromosome
numbers in diploid and
polyploid species of
Chrysanthemum.
Polyploidy
• Polyploids can arise from genome duplications
occurring before or after fertilization
• 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
Figure 05.F32: Formation of a tetraploid organism by (A) sexual
polyploidization and (B) asexual polyploidization.
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
• Plant cells with a single set of chromosomes can be
cultured
Figure 05.33: Autopolyploids have chromosome sets from a single species;
allopolyploids have chromosome sets from diffrerent species.
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.
Figure 05.37: Conserved linkages (synteny groups) between rice genome and
other grass species.
Data from G. Moore, Curr. Opin. Genet. Dev.
5 (1995): 717-724.
Figure 05.F36: Production of a diploid from a monoploid by treatment
with colchicine.