Transcript Ch. 7: Presentation Slides

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
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Figure 5.1A: Human chromosome
painting
Figure 5.1B: Human chromosome
painting
Parts A and B Courtesy of Johannes Wienberg, Ludwig-MaximilliansUniversity, and Thomas Ried, National Institutes of Health
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Figure 5.2: A karyotype of a normal human male
Courtesy of Patricia A. Jacobs, Wessex Regional Genetics Laboratory,
Salisbury District Hospital
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
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Figure 5.5: Three possible shapes of monocentric chromosomes in
anaphase
Figure 5.6: Evolution of the human genome
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.
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Figure 5.3: Designations of the bands and interbands in the human
karyotype.
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Figure 5.4: The human chromosome complement
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.
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Figure 5.7: Schematic diagram of somatic cells of a normal female
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The calico cat shows visible evidence of
X-chromosome inactivation.
Figure 5.8: Female cat heterozygous for the orange and black coat color
alleles
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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
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The pseudoautosomal region of the X and
Y chromosomes has gotten progressively
shorter in evolutionary time.
Figure 5.9: 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
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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
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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.
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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
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Figure 5.11: Risk of Down syndrome in the absence of prenatal screening
as related to mother’s age
Data from J. K. Morris, D. E. Mutton, and E. Alberman, J. Med. Screen. 9
(2002): 2-6
Abnormal Chromosome Number
Table 5.1 Chromosome Abnormalities per 100,000 Recognized Human 20
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
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Figure 5.12: Meiotic synapsis in a trisomic
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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)
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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.
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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
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Figure 5.13: Ectopic recombination
Figure 5.14: Mapping of a deletion by testcrosses
Figure 5.16: Part of the X chromosome in polytene salivary gland nuclei
and the extent of six deletions (I–VI) in a set of chromosomes
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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 5.17: Unequal crossing-over of tandem duplications
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Figure 5.18: A standard color chart used in initial testing for color blindness
© Steve Allen/Brand X Pictures/Alamy Images
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
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Figure 5.19: Red-pigment and green-pigment genes
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Figure 5.20: Genetic basis of absent or impaired red–green color vision
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 but change the
linear sequence of genetic
information
• In an inversion heterozygote,
chromosomes twist into a loop
in the region in which the gene
order is inverted
Figure 21: recombination between
inverted repeats results in an inversion
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Figure 5.21: Loop in the region in which the gene order is inverted
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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 5.23: Crossover within the
inversion loop
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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 5.24: Synapsis between homologous chromosomes
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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
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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 5.25: Two pairs of nonhomologous chromosomes in a diploid organism
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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
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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
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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
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Figure 5.26: A quadrivalent
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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 5.27: Formation of a Robertsonian
translocation by fusion
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Robertsonian Translocation
• Robertsonian translocations are an important risk
factor to be considered in Down syndrome. 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 are found to have one parent with such
a translocation
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Figure 5.28: A karyotype of a child with Down syndrome
Courtesy of Viola Freeman, Associate Professor, Faculty of Health
Sciences, Department of Pathology and Molecular Medicine, McMaster
University
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 5.29: Chromosome numbers in diploid and
polyploid species of Chrysanthemum
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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
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Figure 5.30: Formation of a tetraploid organism
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
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Figure 5.31: Chromosome sets
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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
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Figure 5.32: Repeated hybridization and polyploidization in the origin of
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.
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Figure 5.35: Conserved linkages (synteny groups)
Data from G. Moore, Curr. Opin. Genet. Dev. 5 (1995): 717-724.
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Figure 5.34: Production of a diploid from a monoploid