Transcript The Chromosomal Basis of Inheritance

The Chromosomal
Basis of Inheritance
Chapter 15
Genes and Chromosomes

Genes
 Are

located on chromosomes
Can be visualized using certain
techniques
Figure 15.1
Introduction
In 1875 process of Mitosis and in 1890
Meiosis was worked out
 But not until 1900 did biology finally
catch up with Gregor Mendel
 Independently, Karl Correns, Erich von
Tschermak, and Hugo de Vries all found
that Mendel had explained the same
results 35 years before
 But there was still resistance


Around 1900, cytologists and geneticists
began to see parallels between the
behavior of chromosomes and the
behavior of Mendel’s factors
 Chromosomes
and genes are both present in
pairs in diploid cells
 Homologous chromosomes separate and
alleles segregate during meiosis
 Fertilization restores the paired condition
for both chromosomes and genes.
Chromosomal Theory of
Inheritance

In 1902, Walter
Sutton, Theodor
Boveri, and others
noted these parallels
and a chromosome
theory of
inheritance began to
take form
Chromosomal Theory of
Inheritance


Researchers proposed in the early 1900s that
genes are located on chromosomes
The chromosome theory of inheritance states
that
 Mendelian
genes have specific loci on chromosomes
 Chromosomes undergo segregation and independent
assortment

Behavior of chromosomes during meiosis was
said to account for Mendel’s laws of
segregation and independent assortment
Evidence that Genes Associated
to Chromsomes



Thomas Hunt Morgan was the first to
associate a specific gene with a specific
chromosome
He provided convincing evidence that
chromosomes are the location of Mendel’s
heritable factors
Experimental animal, Drosophila melanogaster,
a fruit fly species that eats fungi on fruit.
 Fruit
flies  prolific breeders  generation time
of two weeks.
 Fruit flies  three pairs of autosomes and a pair
of sex chromosomes (XX in females, XY in males).
Wild Type and Mutant Phenotypes
After a year of research Morgan
discovered a mutant /variant (traits
alternative to the wild type)male fly
with White eyes
 Wild type Red eyes

Figure 15.3
Correlating Behavior of a Gene’s Alleles
with Behavior of a Chromosome Pair

In one experiment Morgan mated male flies
with white eyes (mutant) with female flies with
red eyes (wild type)
 The
F1 generation all had red eyes
 The F2 generation showed the 3:1 red:white eye
ratio



The white-eyed trait appeared only in males.
All the females and half the males had red
eyes
Morgan concluded that a fly’s eye color was
linked to its sex
Morgan concluded that a fly’s eye
color was linked to its sex


Females (XX) may have
two red-eyed alleles and
have red eyes or may be
heterozygous and have
red eyes.
Males (XY) have only a
single allele and will be
red eyed if they have a
red-eyed allele or whiteeyed if they have a whiteeyed allele.
Morgan’s Discovery

That transmission of the X chromosome
in fruit flies correlates with inheritance
of the eye-color trait

Was the first solid evidence indicating that
a specific gene is associated with a specific
chromosome
Figure 15.3
Linkage of Genes Affects Inheritance

Each chromosome



Has hundreds or thousands of genes
Genes located on the same chromosome,
linked genes, tend to be inherited
together because the chromosome is
passed along as a unit
Morgan did other experiments with
fruit flies

To see how linkage affects the inheritance
of two different characters
Inheritance of Characters for
Body Color and Wing Size
The wild-type body color is gray (b+) and
the mutant black (b)
 The wild-type wing size is normal (vg+) and
the mutant has vestigial wings (vg)
 P Generation b+b+vg+vg+ (gray, normal
wing) X bbvgvg (black, vestigeal wings)
 Crossed F1 heterozygous females
(b+bvg+vg) with homozygous recessive
males (bbvgvg).

Fig. 15.4
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Results
According to independent assortment,
this should produce 4 phenotypes in a
1:1:1:1 ratio
 Observed a large number of wild-type
(gray-normal) and double-mutant (blackvestigial) flies among the offspring
 These phenotypes correspond to those
of the parents

Morgan Reasoned

That body color and wing shape are usually
inherited together because their genes are on
the same chromosome


The other two
phenotypes (grayvestigial and blacknormal) were fewer
than expected from
independent
assortment (and totally
unexpected from
dependent assortment).
These new phenotypic
variations must be the
result of crossing over
Genetic Recombination and
Linkage
Recombination of Unlinked Genes:
Independent Assortment of Chromosomes
 When Mendel followed the inheritance of
two characters
 He
observed two parental phenotypes and
two non parental phenotypes (Recombinants)
Gametes from yellow-round
heterozygous parent (YyRr)
YR
Gametes from greenwrinkled homozygous
recessive parent (yyrr)
yr
Yr
yR
Yyrr
yyRr
yr
YyRr
yyrr
Parentaltype offspring
Recombinant
offspring
 Recombinant
offspring
Are those that show new
combinations of the parental
traits
 When 50% of all offspring are
recombinants
Geneticists say that there is a
50% frequency of recombination
Recombination of Linked Genes: Crossing Over

Morgan discovered that genes can be
linked


But due to the appearance of recombinant
phenotypes, the linkage appeared incomplete
Morgan proposed that
Some process must occasionally break the
physical connection between genes on the
same chromosome
 Crossing over of homologous chromosomes
was the mechanism

Linkage Mapping
Morgan’s student 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



Sturtevant hypothesized  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.
 The
greater the distance between two genes, the
more points between them where crossing over can
occur.

He used recombination frequencies from fruit
fly crosses to map the relative position of genes
along chromosomes, a linkage map (the actual
map of a chromosome based on recombination
frequencies)
Map of Fruit Fly Genes
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The test cross design to map the relative position of
three fruit fly genes, body color (b), wing size (vg), and
eye color (cn).
The recombination frequency between cn and b is 9%.
The recombination frequency between cn and vg is 9.5%.
The recombination
frequency between
b and vg is 17%.
The only possible
arrangement of these
three genes places
the eye color gene
between the other two.
Map Units
Sturtevant expressed the distance
between genes, the recombination
frequency, as map units.
 One map unit (sometimes called a
centimorgan) is equivalent to a 1%
recombination frequency

Genetic Map of a Drosophila
Chromosome
Cytological Maps





A linkage map provides an imperfect picture of
a chromosome
Map units  relative distance and order, not
precise locations of genes.
The frequency of crossing over is not actually
uniform over the length of a chromosome.
Geneticists can develop cytological maps 
indicates the positions of genes with respect to
chromosomal features.
More recent techniques show the absolute
distances between gene loci in DNA nucleotides.
The Chromosomal Basis of Sex

The Chromosomal basis for determining
sex is rather simple
 The
X-Y System
 The X-O System
 The Z-W System
 The haploid-diploid System
The X-Y System
Female homogameticXX
 Male heterogametic XY
 Sex of offspring depends on whether
the sperm has an X

The X-Y System

The Y and X chromosomes behave as
homologous chromosomes during meiosis.
 In
reality, they are only partially homologous and
rarely undergo crossing over.

In both testes (XY) and ovaries (XX), the two
sex chromosomes segregate during meiosis
and each gamete receives one.
 Each
egg receives an X chromosome.
 Half the sperm receive an X chromosome and half
receive a Y chromosome.

Because of this, each conception has about a
fifty-fifty chance of producing a particular
sex.
The X-Y System
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

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In humans, the anatomical signs of sex  the embryo is
about two months old,
before that the gonads can develop into either ovaries or
testes, depending on the hormonal conditions within the
embryo
Also,which of these two occurs depends on the Y
chromosome
Researchers have found the SRY gene (sex determining
region of the Y chromosome
In individuals with the SRY gene the generic embryonic
gonads are modified into testes,



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.
In individuals lacking the SRY gene, the generic embryonic
gonads develop into ovaries.
The X-O System
In insects Only one type of
chromosome
 Females  XX, Males XO
 Sex of off spring sperm has X or O

The Z-W System
In birds, some fishes and some insects
 Females ZW, Males ZZ
 Sex chromosome is in the ovum

The haploid-diploid System
No sex chromosomes inmost species of
ants and bees
 Females fertilized ova diploid
 Males unfertilized ova haploid

Inheritance of Sex Linked Genes
The sex chromosomes have genes for
many characters unrelated to sex
 A gene located on either sex
chromosome a sex-linked

• A father with the
disorder will transmit
the mutant allele to all
daughters but to no
sons. When the mother
is a dominant
homozygote, the
daughters will have the
normal phenotype but
will be carriers of the
mutation.
If a carrier mates with
a male of normal
phenotype, there is a
50% chance that
each daughter will be
a carrier like her
mother, and a 50%
chance that each son
will have the
disorder.
If a carrier mates with a
male who has the
disorder, there is a 50%
chance that each child
born to them will have
the disorder, regardless
of sex. Daughters who
do not have the disorder
will be carriers, where
as males without the
disorder will be
completely free of the
recessive allele.
Human Sex linked Disorders

Some recessive alleles found on the X
chromosome in humans cause certain
types of disorders
 Color
blindness
 Duchenne muscular dystrophy
 Hemophilia
Color blindness
 Sex
linked disorder due to several
X-linked genes(recessive)
 Normal Vision 150 colors
 Colorblind fewer than 25 colors
Affected People
RED & GREEN  Gray
RED & GREEN Weak confuse
shades
Color Blindness
Normal Female  XX
Color Blind XcXc
Normal,Carrier  XcX
Normal Male  X Y
c
Color Blind Male X Y
Normal Father &
Color Blind Mother

All daughters are carriers, sons are color
blind
X
Y
Xc
X Xc
X Xc
Xc
X Xc
Xc Y
Normal Mother &
Color Blind Father
 All
daughters are carriers,
sons are normal
Xc
Y
X
X Xc
XY
X
X Xc
XY
Duchenne’s Muscular Dystrophy
Affects 1/ 3,500 males born in the US
 Affected individuals rarely live past
their early 20s
 Due to absence of X-linked gene that
makes a protein  dystrophin
 Disease progressive weakening of
muscles & loss of coordination

Hemophilia
 Sex
linked recessive trait
 Absence of one or more clotting factors
in the blood
 Gene that controls formation of
clotting factors are recessive and
present on the X chromosome
 Individuals bleed excessively when
injured
 Approx. 1/10,000 males are affected
Hemophilia
 Female
Hemophiliacmust have
this trait on both the XX
 Male only one X chromosome
from mother, will be a
hemophiliac if mother has this
trait
Ex: Queen Victoria’s genes
Queen Victoria & Hemophilia
Victoria
Albert
Alexandra
Alexandra & Hemophilia
Czar Nicholas II
Alexandra
Alexis
X Inactivation


Although female mammals inherit two X
chromosomes, only one X chromosome is active.
Therefore, males and females have the same
effective dose (one copy ) of genes on the X
chromosome.
 During
female development, one X chromosome per
cell condenses into a compact object, a Barr body.
 This inactivates most of its genes.

The condensed Barr body chromosome is
reactivated in ovarian cells that produce ova.
Barr Bodies


Mary Lyon, a British geneticist the selection of
which X chromosome to form the Barr body occurs
randomly and independently in embryonic cells at the
time of X inactivation
Females consist of a mosaic of cells, some with an
active paternal X, others with an active maternal X.




After Barr body formation, all descendent cells have the
same inactive X.
If a female is heterozygous for a sex-linked trait,
approximately half her cells will express one allele and the
other half will express the other allele.
In humans, this mosaic pattern is evident in women
who are heterozygous for a X-linked mutation that
prevents the development of sweat glands.
A heterozygous woman will have patches of normal
skin and skin patches lacking sweat glands.
Barr Bodies

Similarly, the orange and black pattern on
tortoiseshell cats is due to patches of cells
expressing an orange allele while others have a
nonorange allele.
X Inactivation


X inactivation involves the attachment of methyl
(CH3) groups to cytosine nucleotides on the X
chromosome that will become the Barr body.
One of the two X chromosomes has an active
XIST gene (X-inactive specific transcript).
 This
gene produces multiple copies of an RNA molecule
that almost cover the X chromosome where they are
made.
 This initiates X inactivation, but the mechanism that
connects XIST RNA and DNA methylation is unknown.

What determines which of the two X
chromosomes will have an active XIST gene is
also unknown.
Alteration of Chromosome
Number and Genetic Disorders




Sex-linked traits are not the only notable
deviation from the inheritance patterns
observed by Mendel
Also, gene mutations are not the only kind of
changes to the genome that can affect
phenotype
Physical and chemical disturbances, errors in
meiosis damage chromosomes and alter #s
Large-scale chromosomal alterations lead to
spontaneous abortions or cause a variety of
developmental disorders
Abnormal Chromosome Numbers

Members of the pair of homologous
chromosomes do not move apart
 Aneuploidy offspring have an abnormal number
of a particular chromosome
 Trisomy
 three copies of a particular
chromosome
 Monosomy
 only one copy of a particular
 Polyploidy
Is a condition in which there are
chromosome
more than two complete sets of chromosomes
(3n,4n)
Nondisjunction



Occurs when problems
with the meiotic spindle
cause errors in daughter
cells.
If tetrad chromosomes
do not separate
properly during
meiosis I.
Or sister chromatids
may fail
to separate during
meiosis II
Alterations of Chromosome Structure

Breakage of a chromosome can lead to
four types of changes in chromosome
structure
 Deletion
 Duplication
 Inversion
 Translocation
Deletion

A deletion occurs when a chromosome
fragment lacking a centromere is lost during
cell division.
 This
chromosome will be missing certain genes.
Duplication

A duplication occurs when a fragment
becomes attached as an extra segment to a
sister chromatid
Inversion

Occurs when a chromosomal fragment
reattaches to the original chromosome but in
the reverse orientation.
Translocation

a chromosomal fragment joins a
nonhomologous chromosome.
 Some
translocations are reciprocal, others
are not.
Human Disorders Due to
Chromosomal Alterations


Several serious human disorders are due to
alterations of chromosome number and structure.
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.


These developmental problems results from an imbalance
among gene products.
Certain aneuploid conditions upset the balance less,
leading to survival to birth and beyond.

These individuals have a set of symptoms - a syndrome characteristic of the type of aneuploidy.
Trisomy 21




Abnormal
Chromosome number
If not drastic
individuals carrying it
can be born
Results from an
error during meiosis
Affects 1/700
children born in the
US
Downs Syndrome



Extra chromosome on # 21
This affects phenotype
Facial features
 Broad
round face
 Flattened nose
 Small irregular teeth





Stature usually short
Heart defects
Susceptible to infection, leukemia, Alzheimer’s
Life span shorter
Varying degrees of mental retardation
Aneuploidy of Sex Chromosomes

Klinefelter’s syndrome, an XXY male,
occurs once in every 2000 live births.
 These
individuals have male sex organs, but
are sterile.
 There may be feminine characteristics, but
their intelligence is normal

Males with an extra Y chromosome
(XYY) tend to somewhat taller than
average
Aneuploidy of Sex Chromosomes
Trisomy X (XXX),  occurs once in
every 2000 live births, produces
healthy females.
 Monosomy X or Turner’s syndrome (X0),
occurs once in every 5000 births,
produces phenotypic, but immature
females.

Disorders due to Structurally
Altered Chromosomes


Deletions, even in a heterozygous state, cause
severe physical and mental problems.
One syndrome, cri du chat, results from a
specific deletion in chromosome 5.
 These
individuals are mentally retarded, have a
small head with unusual facial features, and a cry
like the mewing of a distressed cat.
 This syndrome is fatal in infancy or early childhood
Structurally Altered Chromosomes

Chromosomal translocations between
nonhomologous chromosome are also associated
with human disorders.
 Chromosomal
translocations have been implicated in
certain cancers, including chronic myelogenous
leukemia (CML).
 CML occurs when a fragment of chromosome 22
switches places with a small fragment from the tip
of chromosome 9
Normal chromosome 9
Reciprocal
translocation
Translocated chromosome 9
Philadelphia
chromosome
Normal chromosome 22
Translocated chromosome 22
Inheritance Patterns that are
exceptions to the standard
chromosome theory

Two normal exceptions to Mendelian
genetics include
Genes located in the nucleus
 Genes located outside the nucleus

Genomic Imprinting


In this process, a gene on one
homologous chromosome is silenced,
while its allele on the homologous
chromosome is expressed.
The imprinting status of a given gene
depends on whether the gene resides in
a female or a male.

The same alleles may have different
effects on offspring, depending on whether
they arrive in the zygote via the ovum or
via the sperm.
Genomic imprinting

Involves the silencing of certain genes that are
“stamped” with an imprint during gamete
production
Normal Igf2 allele
(expressed)
Paternal
chromosome
Maternal
chromosome
Normal Igf2 allele
Wild-type mouse
with imprint
(normal size)
(not expressed)
(a) A wild-type mouse is homozygous for the normal igf2 allele.
Normal Igf2 allele
Paternal
Maternal
Mutant
lgf2 allele
Normal size mouse
Mutant
lgf2 allele
Paternal
Maternal
Figure 15.17a, b
Dwarf mouse
Normal Igf2 allele
with imprint
(b) When a normal Igf2 allele is inherited from the father, heterozygous mice grow to normal size.
But when a mutant allele is inherited from the father, heterozygous mice have the dwarf
phenotype.
Inheritance of Organelle Genes

Extranuclear genes

Are genes found in organelles in the
cytoplasm

The inheritance of traits controlled by
genes present in the chloroplasts or
mitochondria

Depends solely on the maternal parent
because the zygote’s cytoplasm comes
from the egg
Figure 15.18

Some diseases affecting the muscular
and nervous systems

Are caused by defects in mitochondrial
genes that prevent cells from making
enough ATP
Genomic Imprinting