Transcript 2. Sex-linked genes have unique patterns of inheritance

CHAPTER 15
THE CHROMOSOMAL BASIS OF
INHERITANCE
生物醫學暨環境生物學系
張學偉
助理教授
Section A: Relating Mendelism to Chromosomes
1. Mendelian inheritance has its physical basis in the behavior of
chromosomes during sexual life cycles
2. Morgan traced a gene to a specific chromosome
3. Linked genes tend to be inherited together because they are located on the
same chromosome
4. Independent assortment of chromosomes and crossing over produce genetic
recombinants
5. Geneticists use recombination data to map a chromosome’s genetic loci
Introduction
• Mendel’s hereditary factors are the genes
located on chromosomes.
•  chromosomes theory of inheritance.
1. Mendelian inheritance has its physical
basis in the behavior of chromosomes
during sexual life cycles
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Chromosomal basis of
Mendel’s laws.
Fig. 15.1
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2. Morgan traced a gene to a specific
chromosome
• Thomas Hunt Morgan was the first to associate
a specific gene with a specific chromosome.
•Morgan choice an experimental animal,
Drosophila melanogaster
•fruit fly species that eats fungi on fruit
•prolific breeders
•generation time of two weeks.
•Fruit flies have three pairs of autosomes and a pair of sex
chromosomes (XX in females, XY in males). 3+1
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• The normal character phenotype is the wild type (red).
• Alternative traits are mutant phenotypes.
female
male
Fig. 15.2
Genes located on a sex chromosome are called sex-linked genes.
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Morgan concluded that a fly’s
eye color was linked to its sex (x).
Fig. 15.3
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3. Linked genes tend to be inherited
together because they are located on the
same chromosome
• Results of crosses with linked genes deviate from those
expected according to independent assortment.
• Morgan reasoned that
body color and wing
shape are usually
inherited together
because their genes
are on the same
chromosome.
(b+vg+
Or b vg+)
(b vg)
Fig. 15.4
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4. Independent assortment of chromosomes
and crossing over produce genetic
recombinants
The production of offspring with new
combinations of traits inherited from two parents
is genetic recombination.
 result from:
• (1) independent assortment of genes located on
nonhomologous chromosomes
(2) or crossing over of genes located on
homologous chromosomes.
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•The physical basis of recombination between
unlinked genes is the random orientation of
homologous chromosomes at metaphase I of
meiosis.  leads to the independent assortment of alleles.
• linked genes, genes located on the same
chromosome, tend to move together through
meiosis and fertilization. [Don’t assort
independently]
• Under normal Mendelian genetic rules, we would
not expect linked genes to recombine into
assortments of alleles not found in the parents.
• But in fact, recombination between linked genes
does occur. (see Morgan)
•A 50% frequency of recombination is observed
for any two genes located on different
chromosomes.
• This switched alleles between homologous chromosomes.
Fig. 15.5a
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Fig. 15.5b
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• The results of Morgan’s testcross for body
color and wing shape did not conform to either
independent assortment or complete linkage.
• Most of the offspring had parental phenotypes,
suggesting linkage between the genes.
• However, 17% of the flies were recombinants,
suggesting incomplete linkage.
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5. Geneticists can use recombination data
to map a chromosome’s genetic loci
• One of Morgan’s students, Alfred Sturtevant,
used crossing over of linked genes to develop a
method for constructing a chromosome map.
• This map is an ordered list of the genetic loci
along a particular chromosome.
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• Sturtevant hypothesized :
that the frequency of recombinant offspring
reflected the distances between genes on a
chromosome.
The farther apart two genes are, the higher the
probability that a crossover will occur between
them and therefore a higher recombination
frequency.
Sturtevant used recombination frequencies
from fruit fly crosses to map the relative
position of genes along chromosomes, a
linkage map.
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Using recombination frequencies to construct a genetic map
One map unit (sometimes called a centimorgan) is
equivalent to a 1% recombination frequency.
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Fig. 15.6
• Some genes on a chromosome are so far
apart, the frequency of recombination reaches
is its maximum value of 50% and the genes
act as if found on separate chromosomes and
are inherited independently.
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More than one gene can affect
a given phenotypic characteristic
(eye color)
Partial genetic map
Fig. 15.7
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• Map units (linkage map) indicate relative
distance and order, not precise locations of
genes.  The frequency of crossing over is not actually uniform
over the length of a chromosome.
•Combined with other methods like
chromosomal banding, geneticists can develop
cytological maps.  the positions of genes with
respect to chromosomal features.
•More recent techniques show the absolute
distances between gene loci in DNA
nucleotides.
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CHAPTER 15
THE CHROMOSOMAL BASIS OF
INHERITANCE
Section B: Sex Chromosomes
1. The chromosomal basis of sex varies with the organism
2. Sex-linked genes have unique patterns of inheritance
1. The chromosomal basis of sex varies with the
organism
• In human and other mammals, there are two
varieties of sex chromosomes, X and Y.
•In humans, the anatomical
signs of sex first appear when
the embryo is about two
months old.
Avoid confusion with XY system
Male develop from unfertilized eggs
(they have no father)
Fig. 15.8
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• In individuals
 with the SRY gene (sex determining region of the
Y chromosome), the generic embryonic gonads are
modified into testes.
lacking the SRY gene, the generic embryonic gonads
develop into ovaries.
• Activity of the SRY gene triggers a cascade of
biochemical, physiological, and anatomical
features because it regulates many other genes.
• In addition, other genes on the Y chromosome are
necessary for the production of functional sperm.
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2. Sex-linked genes have unique
patterns of inheritance
• the sex chromosomes, especially the X
chromosome, have genes for many characters
unrelated to sex.
• E.g., white-eye locus in Drosophila.
Fig. 15.9
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Because males have only one X chromosome
(hemizygous), any male receiving the
recessive allele from his mother will express
the trait.
males are far more likely to inherit sex-linked
recessive disorders than are females.
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human sex-linked disorders
• Duchenne muscular dystrophy.
•
due to the absence of an X-linked gene for a key
muscle protein, called dystrophin.
• characterized by a progressive weakening of the
muscles and loss of coordination.
• Hemophilia is a sex-linked recessive trait
defined by the absence of one or more clotting
factors.
• Individuals can be treated with intravenous injections of the missing
protein.
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2. Sex-linked genes have unique
patterns of inheritance
Although female mammals inherit two X
chromosomes, only one X chromosome is active
and one X chromosome condenses into a
compact object, a Barr body
•  involves the attachment of methyl (CH3) groups to
cytosine nucleotides on the X chromosome (inactivates
most of its genes).
•  After Barr body formation, all descendent cells have
the same inactive X.
• The condensed Barr body chromosome is
reactivated in ovarian cells that produce ova.
• Barr body occurs randomly and independently in embryonic cells at
the time of X inactivation.
• As a consequence, females consist of a mosaic of cells, some with an
active paternal X, others with an active maternal X.
Fig. 15.10
•If a female human is heterozygous for a sex-linked trait, will
have patches of normal skin and skin patches lacking sweat
glands.
CHAPTER 15
THE CHROMOSOMAL BASIS OF
INHERITANCE
Section C: Errors and Exceptions in Chromosomal
Inheritance
1. Alterations of chromosome number or structure cause some genetic
disorders
2. The phenotypic effects of some mammalian genes depend on whether they
are inherited from the mother or the father (imprinting)
3. Extranuclear genes exhibit a non-Mendelian pattern of inheritance
1. Alterations of chromosome number or
structure cause some genetic disorders
Nondisjunction
problems with
the meiotic
spindle
Fig. 15.11 Meiotic nondisjunction
• after nondisjunction cells will have an abnormal
chromosome number or aneuploidy.
 Trisomic = 2n + 1; Monosomic = 2n - 1.
• Although the frequency of aneuploid zygotes may be quite high in
humans, most of these alterations are so disastrous that the embryos
are spontaneously aborted long before birth.
• Organisms with more than two complete sets of
chromosomes polypoidy. (nondisjunction) e.g,
triploid (3n). tetraploid (4n)
• e.g., both fishes and amphibians have polyploid species.
• Polyploidy is relatively common among plants and
much less common among animals.
• Polyploids are more nearly normal in phenotype than
aneuploids.
• Down syndrome: three copies of chromosome
21 aneuploid (nondisjunction)
Fig. 15.14
•The frequency of Down syndrome correlates with the age of
the mother. age-dependent abnormality
Breakage of a chromosome can lead to four types of
changes in chromosome structure.
common in meiosis
Typically harmful
chronic myelogenous leukemia
(CML).[ch9/ch22]
Fig. 15.13
2. The phenotypic effects of some mammalian
genes depend on whether they were inherited
from the mother or the father (imprinting)
• For most genes it is a reasonable assumption that a specific
allele will have the same effect regardless of whether it was
inherited from the mother or father.
• However, for some traits in mammals, it does
depend on which parent passed along the alleles
for those traits.
The imprinting genes involved are not sex linked
and may or may not lie on the X chromosome.
• . a deletion of a specific segment of chromosome 15
• Prader-Willi syndrome  abnormal chromosome from father.
• Angelman syndrome  from the mother.
•  same alleles may have different effects on offspring,
depending on whether they arrive in the zygote via
ovum or sperm.
•  The imprinting status of a given gene
• In genomic imprinting process, a gene on one
homologous chromosome is silenced, while the
other is expressed.
• cp: barr body is for x chromosome inactivation.
Fig. 15.15
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• In many cases, genomic imprinting occurs when
methyl groups are added to cytosine nucleotides
on one of the alleles.
• Fragile X syndrome, which leads to various
degrees of mental retardation, also appears to be
subject to genomic imprinting.
(inherited from the mother)
• This disorder is named for an abnormal X chromosome
with extra CGG repeat.
3. Extranuclear genes exhibit a nonMendelian pattern of inheritance
Not all of a eukaryote cell’s genes are located in the nucleus.
Extranuclear genes are found on small circles of DNA in
mitochondria and chloroplasts.
These organelles reproduce themselves.
Their cytoplasmic genes do not display Mendelian inheritance.
• They are not distributed to offspring during meiosis.
 phenotype of the offspring was determined only by the
maternal parent (maternal inheritance).
summary
Mendel didn’t include:
•
Sex-linked traits
•
Major chromosomal aberrations
•
imprinting & extranuclear genes