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THE CHROMOSOMAL BASIS OF INHERITANCE
Unit 3- Chapter 15
Non-linked vs. Linked Genes
Primordial Germ Cells
Gametes
A
A
B
B
•If the genes in question are on
different chromosome pairs,
they are considered non-linked.
•This PGC will give rise to only
one kind of gamete with respect
to the genes A and B., because
it is homozygous for both traits.
•If the genes in question are on
the same chromosome pair,
they are considered linked.
A
B
A
B
•This PGC will also give rise to
only one kind of gamete, with
respect to the genes A and B,
because it is homozygous for
both traits.
Non-linked vs. Linked Genes
Primordial Germ Cell
A
A
B
a
A
B
b
b
•In this case, the PGC is
heterozygous for both traits, and the
genes are non-linked, so after
meiosis, it can produce 4 different
types of gametes.
a
B
a
b
A
B
a
b
•In this PGC however, the genes in
question are lined. So even though
the PGC is heterozygous for both
traits, after meiosis, it can only
produce 2 different types of gametes.
What is the outcome of this cross?
P generation
A
A
B
a
X
a
b
B
b
Gametes
A
a
F1 generation
B
b
Phenotype = 100% dominant
Genotype = 100% heterozygous
The F2 Generation in non-linked genes
P2 generation
A
A
a
B
b
a
X
B
b
Gametes
A
A
A
b
b
B
A
B
a
a
a
B
B
a
b
b
F2 generation
The phenotypes of the F2 generation in a dihybrid
cross of non-linked genes always results in a
9:3:3:1 ratio
What is the outcome of this cross?
P generation
A
B
A
B
a
X
b
a
b
Gametes
F1 generation
A
B
a
b
Phenotype = 100% dominant
Genotype = 100% heterozygous
The F2 Generation in linked genes
P2 generation
A
B
A
a
b
X
B
a
b
Gametes
F2 generation
AB
ab
AB
AABB
AaBb
ab
AaBb
aabb
Genotype = 1:2:1
Phenotype = 3:1 dominant
Recombination in non-linked genes – involves
independent assortment of chromosomes
In nonlinked genes, the following test cross:
YyRr X yyrr
Would yield a phenotypic ratio of 1:1:1:1
Recombination in linked genes –
involves crossing over
Thomas Morgan, noticed something strange when working with linked genes.
Crossing over created more types of
gametes than what Morgan expected
Linkage maps
Recombination frequencies can be used to create linkage
maps, which indicate the distance between various genes on
the same chromosome. The distance is measured in
“centimorgans” or “map units”. The recombination frequency cannot
exceed 50%, because after that, one cannot tell linked from nonlinked genes.
Linked Genes
• Genes located on the same
chromosomes
• They tend to be inherited
together - are not sorted
independently like unlinked
genes usually are
• However, they can be
“shuffled” through crossing
over or recombination
• The farther apart the genes
are from each other in a
chromosome, the greater the
likelihood that they will be
unlinked as a result of
crossing-over.
In this example, the "A" and "E"
genes have the highest likelihood of
being unlinked because they are at
opposite ends of their chromosome.
Recombination of linked genes
HUMAN KARYOTYPE
Sex
Determination in
Organisms
SEX-LINKED inheritance
This involves genes which are found only on the X chromosome. The pattern of
inheritance differs from somatic genes, because males have only one X
chromosome.
Genes on the X and Y
Chromosomes
The SRY gene
Sex-Linked Inheritance, cont’d.
• In humans and fruit flies,
– females have two X chromosomes
– males have one X and one Y (HEMIZYGOUS – only one copy of a
gene on the XY chromosomes)
– females get an X from the mother and another X from the father
– males get an X from the mother and a Y from the father
• In humans, the Y chromosome is relatively small and contains only a
few genes, among them the important "SRY" gene, which contains
the instructions for turning on genes on other chromosomes to
activate the signals for making male hormones and male anatomical
peculiarities. The SRY gene and some other "Y" chromosome
genes are not present on the X chromosome
• In humans and also fruit flies, the X chromosome contains many
genes which are not present on the Y chromosome. For these
genes males have only one allele.
Hemophilia
Perhaps the most well-known disease related to
plasma is hemophilia. An inherited change in one of
the clotting proteins (called factor VIII) leaves it
dysfunctional. This single change disrupts the entire
sequence of chemical reactions necessary for
clotting. As a result, people with hemophilia can
suffer severe swelling, bruising and bleeding from
simple day to day events that the rest of the
population take for granted.
Hemophilia
The child shown above has a severe swelling on the
forehead from a bump to the head. This was caused
by a failure of his clotting system to stop the bleeding
from a bruise. Hemophilia can be controlled with the
infusion of factor VIII collected from donated blood or
plasma.
X-Inactivation n Females
• One X chromosome condenses into a
compact object visible as a dark spot
against the inner nuclear envelope -this is
called the Barr Body
• This happens during early embryonic
development
• Therefore, males and females have in
reality, only one active X chromosome
Mosaicism
Barr Bodies
Hemophilia in Females
Hemophilia B is an X-linked bleeding disorder resulting from
factor IX (F.IX) deficiency, caused by a wide range of
mutations on the F.IX gene.
Hemophilia B in girls is extremely rare and results from
different mechanisms, the most common of which is
skewed inactivation of the normal X chromosome in
heterozygous girls. In some cases, the inactivation process
does not seem to be random and occurs by either selection
in favor of the activity of an X chromosome involved in a
balanced X:autosome translocation or as a result of genetic
differences affecting the X chromosome inactivation itself.
More rarely, the phenotypic expression of the disease can
be related to compound heterozygosity for hemophilic
mutations or Turner syndrome.
CHROMOSOMAL ABERRATIONS
MUTATIONS
NON-DISJUNCTION
NORMAL DISJUNCTION
NON-DISJUNCTION
Results of non-disjunction: Aneuploidy - Trisomy, Monosomy, Polyploidy
Down Syndrome, Trisomy 21
Down Syndrome can also be caused by the
translocation of chromosomes (most often
chromosome 14 or 21).
Frequency of Down Syndrome increases with the
mother’s age.
Turner Syndrome
Turner Syndrome
• The most common characteristics of Turner
syndrome include short stature and lack of
ovarian development. A number of other
physical features, such as webbed neck, arms
that turn out slightly at the elbow, and a low
hairline in the back of the head are sometimes
seen in Turner syndrome patients. Individuals
with Turner syndrome are also prone to
cardiovascular problems, kidney and thyroid
problems, skeletal disorders such as scoliosis
(curvature of the spine) or dislocated hips, and
hearing and ear disturbances.
Turner Syndrome
Klinefelter's Syndrome
Klinefelter’s
Jacob’s Syndrome
Alterations of Chromosomal Structure
Alterations of Chromosome Structure,
cont’d.
Deletion
Cri du chat
•
•
•
•
•
•
•
•
•
•
•
Major identifying characteristics
Monotone, weak, cat-like cry
Small head (microcephally)
High palate
Round face
Small receding chin
(micrognathia)
Widely spaced eyes
(hypertelorism)
Low set ears
Low broad nasal ridge
Folds of skin over the upper eyelid
(epicanthic folds)
Distinctive creases on the palms
of the hands
Cri du Chat
Chromosome 5
Cri Du Chat Syndrome results from the loss or deletion of a
significant portion of the genetic material from the short arm of
one of the pair of number five chromosomes.
Cri Du Chat Syndrome is also known as 5P Minus syndrome,
Le Jeune's syndrome and Cat's-cry syndrome.
It is possible to detect Cri du Chat Syndrome with
amniocentesis or CVS (Chorionic Villus Sampling) in the first
trimester of pregnancy. An ultrasound may lead the doctor to
suspect a disorder of this type and carry out further
investigations but it is not possible to diagnose it solely by this
means.
The critical region of the chromosome containing genes which
are responsible for the main features of the syndrome appears
to be located in band 5p15.2.
The gene causing the cry has been located in band 15.3. This
would explain why some babies with other features of the
syndrome do not have the characteristic cry and some babies
have the cry but not the other characteristics.
Genomic Imprinting
• Genes remember?
• Alleles that come from mother (ovum) may have a
different effect on the individual than alleles that come
from father (sperm)
• This pattern continues for all future generations.
• Example: Prader-Willi / Angelman
Prader-Willi- mutation in gene on Ch.15: If inherited from
father, child gets the disease. The mother’s genes in this
area are “turned off” through DNA methylation
• If inherited from mother, child gets Angelman’s
syndrome. Father’s gene is methylated and inactive.
Prader-Willi Syndrome
• characterized by
– severe hypotonia and feeding difficulties in early
infancy, followed in later infancy or early childhood
by excessive eating and gradual development of
morbid obesity.
– Motor and language development are delayed.
– All individuals have some degree of cognitive
impairment.
– A distinctive behavior (with temper tantrums,
stubbornness, manipulative behavior, and
obsessive-compulsive characteristics) is common.
– Hypogonadism is present in both males and
females and manifests as genital hypoplasia,
incomplete pubertal development, and, in most,
infertility.
– Short stature is common; characteristic facial
features, strabismus, and scoliosis are often
present, and
– non-insulin-dependent diabetes mellitus often
occurs in obese individuals.
Angelman Syndrome
• characterized by
– Developmental delay,
functionally severe
– Speech impairment, none or
minimal use of words;
receptive and non-verbal
communication skills higher
than verbal ones
– Movement or balance
disorder, usually ataxia of gait
and/or tremulous movement
of limbs
– Behavioral uniqueness: any
combination of frequent
laughter/smiling; apparent
happy demeanor; easily
excitable personality, often
with hand flapping
movements; hypermotoric
behavior; short attention span
How does the cell express only certain genes?
• The cell uses 2 techniques in order to
have certain genes (or alleles) expressed
and others silenced.
– Methylation of cysteines in gene (DNA
segment)
– Acetylation of histones in the region of the
gene
DNA methylation
• Enzymes (DNA methyl transferases) add a
methyl group (--CH3) to the number 5
carbon of the cytosine pyrimidine ring.
• This causes that segment of DNA to
become compact – it is inaccessible to
enzymes and cannot be transcribed into
mRNA.
• So the gene is silent. This compact DNA
stains dark and is called heterochromatin.
Histone Acetylation
• Acetyl groups (COCH3) are added by
enzymes to the tails of histone proteins
• This prevents the DNA from “hugging” the
histones, making that segment of DNA
more accessible to transcription enzymes.
• So this gene is expressed
• Opposite effect of DNA methylation
• "CpG" stands for
cytosine and
guanine separated
by a phosphate
• (C-phosphate-G-),
which links the two
nucleosides
together in DNA.
•
The "CpG"
notation is used to
distinguish a
cytosine followed
by guanine, from a
cytosine basepaired to a
guanine.
Inheritance of mDNA* and pDNA*
• Mitochondria are always inherited from the
mother (In animals and plants)
• Daughters will pass them on to their progeny
• Sons will not pass them on to their offspring
• Plastids are always inherited from the plant ova
(egg) and not from the pollen
*mDNA=mitochondrial DNA
*pDNA=plastid DNA
mDNA mutations
• mDNA contains genes for proteins used in
the electron transport chain
• Defects in these genes will cause
problems with ATP production
• Less ATP = decreased muscle and neuron
function, because muscle cells and
neurons have high energy (ATP)
requirement.
THE END