Transcript X- Linked Inheritance

Molecular Genetics
The Objective :
To give information about :
1- Mendelian genetics and how Gregor Mendel proved that
transmission genetics is the general process by which
traits controlled by factors ( genes on chromosome ) are
transmitted through gametes from generation to
generation .
2- What crossing over means and how it occurs in meiosis .
3- What X- linked inheritance means and how X- linked
conditions are inherited through recessive or dominant
mutations .
4- Types of X- linked genetic diseases caused by X- linked
mutations .
Definition :
Genetics : The study of inherited variation .
Gene : A sequence of DNA that instructs a cell to produce a
particular protein .
Allele : An alternate Forms of a gene that occur at a given locus
in chromosome .Allele are symbolized with the same basic
symbol ( eg. T for tall peas and t for dwarf ) .
Homozygous : Having two identical alleles of a gene . TT or tt .
Heterozygous : Having two different alleles of a gene . Tt .
Genotype : The alleles combinations in an individual that cause
particular traits or disorders .
Phenotype : The expression of a gene in traits or symptoms .
Dominant : A gene variant expressed when present in even one copy.
TT , T t .
Recessive : An allele whose expression is masked by another allele .
tt .
Diploid : A cell containing two sets of chromosomes .
Haploid : A cell containing one sets of chromosomes .
Gamete : A sex cell sperm or ovum .
Mendelian Genetics :
Mendel’s Experiments:
Mendel is called the Father of Genetics ( 1822 – 1884 ) . His
precedent setting experiments with garden peas ( Pisum sativum ) .
1- The First Experiment :
Mendel took Tall plants and crossed them with dwarf plants .
Mendel found that first generation offspring or F1 were all Tall ( Tt )
We will specifically refer to the offspring of Tall and dwarf
peas as Monohybrids because they are Hybrid for only one
characteristics (height ) .
Since all the F1 offspring plants were Tall Tt , Mendel
referred to Tallness as Dominant Trait . The alternative dwarfness ,
he referred to as Recessive .
When the F1 plants were self – fertilized to form F2
generation , both Tall and dwarf offspring occurred , the dwarf
characteristics reappeared .
Among the F2 offspring Mendel observed 3 Tall and 1
dwarf ,then the Ratio : 3 : 1 . ( Figure 1 ) .
Monohybrids Cross
Figure (1)
Mendel assumed the first Law of Inheritance : Law of Segregation :
Segregation : The distribution of alleles of a gene into separate
gametes during meiosis . ( Mendels first law ) .
The Genotype TT is called Homozygous Dominant .
The Genotype tt is called Homozygous Recessive .
The Genotype Tt is called Heterozygous .
Both Genotypes TT and Tt show dominant phenotype Tall
and Genotype tt shows recessive phenotype dwarf .
2- Second Experiment :
This Experiment involves crossing organisms that differ in
two Traits , shape and color of the seeds So it is called Dihybrid
Cross .
Mendel
crossed plants having Round, Yellow seeds with
plants having Wrinkled , Green seeds .
F1 offspring are Dihybrid Round and Yellow seeds ( Dominant
Trait) .
When F1 plants were self -fertilized , they produced an F2
generation that had all four possible combinations of the seeds
characteristics :
Round Yellow , Round Green , Wrinkled Yellow and
Wrinkled Green seeds with 9 : 3 : 3 : 1 ratio . ( Figure 2 ) .
Dihybrid Cross
Figure (2)
Therefore , Mendel formulated his second Law of Heredity
Mendels Law of Independent Assortment :
Independent Assortment : The random arrangement of
homologous chromosome pairs, in terms of maternal or
paternal origin, down the center of a cell in metaphase 1 of
meiosis . Inheritance of a gene on one chromosome does not
influence inheritance of a gene on a different chromosome .
(Mendels second law ) .
3- Trihybrid Cross :
Trihybrid : The offspring from Homozygous Parents differing in
three pairs of genes .
The Trihybrid cross is illustrated in ( Figure 3 ) .
Trihybrid Cross
Figure (3)
Crossing Over :
Crossing over : an event during prophase 1 of
meiosis when homologous chromosomes
exchange parts, that mixes up maternal and
paternal gene combinations .
Progeny that exhibit this mixing of maternal and
paternal alleles on single chromosome are
called recombinant .
Features of Crossing Over :
1. The probability that crossing over will occur between two Loci
increase with increasing distance between the two Loci on the
chromosome .
2. Crossing Over involves the breakage of each of two Homologous
chromosomes by Endonuclease Enzymes and then exchange
parts and reunion by Ligase Enzymes .
3. Crossing Over occurs during Profase 1 of Meiosis in the post
Replication Tetrad stage ( 4 chromatids are present for each pair of
Homologous chromosomes ) . ( Figure 7 ) .
Crossing Over
Sex Determination:
Sex chromosome : A chromosome containing genes that specify
sex . X and Y chromosome .
Autosome : A chromosome that does not have a gene that
determine sex .
Eggs produced by the Female in Oogenesis have 23
chromosomes
( autosomes ( 22 ) plus an X chromosome) .
Sperm from the Male have the same autosomal number and either an
X or Y .
Eggs fertilized with sperm containing a Y chromosome result in
Zygotes that develop into Males ; those fertilized with sperm containing
an X develop into Females . ( Figure 4 ) .
Sex Determination
Figure (4)
Human cell include 46 chromosomes (( 44 autosomes and XX
( Homogametic in Female )) or (( 44 autosomes and XY ( Heterogametic)
in Male )) . X chromosome has many genes that are important for
growth and development . Y chromosome is much smaller and has
fewer genes . ( Figure 5 ) .
XX- XY Mechanism of Sex Determination :
XX- Zygote became Females and XY- Zygotes became
Males .
Figure (5)
Sex – Linked Inheritance :
Sex Linked : refers to aTrait determined by a gene Located
on Sex chromosome , usually the X chromosome .
Because of there location on the X chromosome as Sex determiners
they are said to be Sex Linked .
Sex-Linked Diseases are inherited through one of the sex chromosomes
the X or Y chromosomes .
Autosomally Inherited Diseases are inherited through the non-sex
chromosomes ( Autosomes ) , pairs 1 through 22 .
X- Linked Inheritance :
X- linked diseases are single gene disorders that reflect
the presence of defective genes on the X chromosome .
This chromosome is present as two copies in females
but only as one copy in males .
X- Linked inheritance are complicated by the fact
that :
1- Males ( XY ) always pass their X chromosome to their
daughters but never to their sons, whereas females (XX)
pass their X chromosomes to daughters and sons with
equil .
2- X- linked inheritance refers to the pattern of inheritance
of a condition caused by mutation on the X chromosome
. The mutation may be recessive or dominant .
3- Conditions that follow a pattern of X- Linked recessive
inheritance include Hemophilia , Colourblindness .
X- Linked Inheritance :
4- The chance that a child will inherit an X- Linked recessive
condition in every pregnancy is different for sons and
daughters and depends on whether the mother or father has a
mutation :
A - When the mother is a carrier of an X- linked recessive
mutation there is 1 chance in 2 ( 50% ) that a son will be
affected and a 1 chance 2 in ( 50% ) that a daughter will be a
carrier .
Since the normal gene on the second X chromosome counteracts
the defect , the daughters can only be carriers . Since the Y
chromosome of the son cannot offset the defective gene from
his X chromosome a son will be affected .
A- when the mother is a carrier of an X- linked recessive mutation
there is 1 chance in 2 ( 50% ) that a son will be affected and a 1
chance 2 in ( 50% ) that a daughter will be a carrier .
A
( Figure 7A and 8A)
A
X- Linked
Inheritance
B -When the father is affected by a condition due to an X- Linked
recessive mutation , non of his sons will be affected but all of his
daughters will be carriers . ( Figure 7 B and 8 B)
B
B
X- Linked Inheritance :
5- X- linked recessive diseases are much more common
in males than in females because 2 copies of the
mutant allele are required for the disease to occur in
females, while only one copy is required in males .
6- Affected males never pass the disease to their sons
because there is no male to male transmission of X
chromosome .
X- Linked Inheritance :
7- There are very few conditions that have been shown to follow a
pattern of X- linked dominant inheritance :
A - When the mother has the mutated X- linked dominant gene
and is affected : both daughters and sons will have 50%
probability to be affected . ( Figure 7 C and 8 C)
C
C
B - When the father has X- linked dominant condition :
all daughters will be affected and all sons are normal .
( Figure 7 D and 8 D)
D
D
X- Linked Inheritance :
8- X- Linked dominant inheritance Expressed in female in one
copy .
9- X- Linked dominant inheritance Much more severe effects in
males .
10- Conditions that follow a pattern of X- Linked dominant
inheritance incontinentia pigmenti . ( Figure 9 )
Sex Linked Recessive Traits in Humans :
1- Colour Blindness
1- Colour Blindness :
Is the redused ability to distinguish between certain colours . Its
usually inherited and is more common in men, affecting about one in 20 .
Far fewer women around one in 200 are affected .The gene for red-green
colourblindness lies on the X-chromosome .
Inheritance :
Colourblindness follow a pattern of X linked recessive
inheritance.
AA-
B-
Inheritance of Colour Blindness
Inheritance of Colour Blindness
Diagnosis :
Test for colourblindness : which consists of aseries of pictures of colored
spots, is the most often used to diagnose red-green color deficiencies .
Afigure is embedded in the picture as anumber of spots in aslightly
different color, and can be seen with normal color vision , but not with
aparticular color defect
2-Hemophilia :
Is a rare genetic disorder that almost always occurs in males . Aperson has
hemophilia when he or she inherits problems with certain blood- clotting factors,
making them unable to work properly . Blood clotting factors are needed to help
stop bleeding after acut or injury and to prevent spontaneous bleeding.
Hemophilia gene can contain many different errors, leading to different degrees
of abnormality in the amount of clotting factor produced . About 1 in every 5000
boys is born with Hemophilia ; girls are more rarely affected by this genetic
condition linked to gender .
There are two major types of Hemophilia :
1- Hemophilia A :
Is caused by adeficiency of active clotting factor V111 . Factor V111: a
protein that participates in acascade of reactions that result in formation of
blood clot ( Figure 9 ) . The disease arises from amutation in gene for Factor
V111 which located on X-chromosome . Is the cause of about 80% of cases .
2- Hemophilia B :
Is caused by alack of active
clotting Factor 1X .Which makes
up the majority of the remaining
20 % of cases .
A
Inheritance :
Hemophilia follow a pattern
of X- linked recessive
inheritance .
B
A
H
Inheritance of Hemophilia
Inheritance of
Hemophilia