2. Introduction
• A human female, has 23 pair of
chromosomes
• A human male, has 22 similar pairs and
one pair consisting of two chromosomes t
hat are dissimilar in size and structure.
• The 23 rd pair in both the sexes is called
sex chromosomes
• the female, XX. the male, XY
3. X-linked diseases
• X-linked diseases are those for which the gene is present
on the X chromosome.
• X-linked diseases show inheritance patterns that differ
from autosomal diseases.
• This occurs because males only have one copy of the X
chromosome (plus their Y chromosome) and females have
two X chromosomes.
• Because of this, males and females show different
patterns of inheritance and severity of manifestation. Whil
e there are both dominant and recessive X-linked diseases,
there are some characteristics that are common to X-linked
disorders in general
4. • X-linked genes are never passed from father
to son.
• The Y chromosome is the only sex
chromosome that passes from father to son.
• Males are never carriers – if they have a
mutated gene on the X chromosome, it will b
e expressed.
• Males are termed hemizygous for genes on
the X chromosome.
5. X-linked dominant
• hereditary pattern in which a dominant gene on the X chromosome
causes a characteristic to be manifested in the offspring.
• X-linked dominant diseases are those that are expressed in females
when only a single copy of the mutated gene is present.
• Very few X-linked dominant diseases have been identified (e.g.
hypophosphatemic rickets, Alport syndrome, diabetes insipidus)
hypophosphatemic rickets or vitamin D resistant rickets >>>low
serum phosphorus, skeletal abnormalities
• Alport syndrome, which involves progressive hearing loss and
progressive kidney problems.
6. Characteristics of X-linked
dominant diseases include:
• Never passed from father to son.
• Affected males produce only affected females. An affected
male only has one X chromosome to pass on to his daughters
• Affected females produce 50% normal and 50% affected
offspring.. >>>> heterozygous
• Males are usually more severely affected than females. Some
X-linked dominant traits may even be lethal to males.
• Females are more likely to be affected. Since females have 2 X
chromosomes, they have 2 “chances” to inherit the mutated
allele.
7. The pattern for the pedigree of X-
linked dominant inheritance
11. X-linked recessive
• hereditary pattern in which a recessive gene
on the X chromosome results in the manifest
ation of characteristics in male offspring and
a carrier state in female offspring
• X-linked recessive diseases are those in
which a female must have two copies of the
mutant allele in order for the mutant phenoty
pe to develop.
• Many X-linked recessive disorders are well-
known, including color blindness, hemophilia
, and Duchenne muscular dystrophy.
14. Hemophilia
• The blood fails to clot normally
• Lacking a blood clotting factor
VIII(antihemophilic globulin, AHG),IX
• bleeding from even minor cuts
• in 1,500 newborn males. Most (75%) have
hemophilia A, a lack of clotting factor VIII.
• Hemophilia B- "Christmas Disease" is a defect in
clotting factor IX.
• Transfusions of fresh whole blood or plasma or
factor concentrates control bleeding
20. Typical features of X-linked
recessive inheritance
• Never passed from father to son.
• Males are much more likely to be affected because they only
need one copy of the mutant allele to express the phenotype.
•
• Affected males get the disease from their mothers and all of
their daughters are obligate carriers.
• Sons of heterozygous females have a 50% chance of receiving
the mutant allele.
• These disorders are typically passed from an affected
grandfather to 50% of his grandsons.
21. The Marker X syndrome
• Fragile X syndrome (Marker X syndrome )
is a genetic condition involving changes in
the long arm of the X chromosome. It is ch
aracterized by mental retardation.
Alternative Names
Martin-Bell syndrome; Marker X syndrome
22. Causes, & Risk Factors
• Fragile X syndrome is the most common form of
inherited mental retardation in males and a significa
nt cause in females.
• The inheritance is different from common dominant
or recessive inheritance patterns.
• A fragile area on the X chromosome tends to repeat
bits of the genetic code.
• The more repeats, the more likely there is to be a
problem.
• Boys and girls can both be affected, but because
boys have only one X chromosome, a single fragile X
is more likely to affect them more severely.
23. Mental retardation
• Mental retardation is described as below-
average general intellectual function with associ
ated deficits in adaptive behavior that occurs bef
ore age 18.
• Causes of mental retardation are numerous, but
a specific reason for mental retardation is deter
mined in only 25% of the cases.
24. Mental retardation
• Failure to adapt normally and grow intellectually
may become apparent early in life or, in the case
of mild retardation, not become recognizable unt
il school age or later.
• An assessment of age-appropriate adaptive
behaviors can be made by the use of developme
ntal screening tests.
• The failure to achieve developmental milestones
is suggestive of mental retardation.
25. Fragile X Syndrome Symptoms & Signs
• Family history of fragile X syndrome, especially
a male relative
• Mental retardation
• Large testicles (macro-orchidism)
• Large size
• Tendency to avoid eye contact
• Hyperactive behavior
• Large forehead and/or ears with a prominent jaw
26. Fragile X Syndrome Symptoms
www.fragilexohio.org/ images/366_littleguy.gif
28. • In the F1 generation, a man hemizygous for an X-chromosome with
a 40-fold CGG repeat marries a woman heterozygous for X-
chromosomes with 10- and 30-fold CGG repeats. Their daughter inh
erits the 40 CGG repeat from her father, and the 30 CGG repeat fro
m her mother. In her germline, slipped-mispair recombination res
ults in production of eggs with 10- or 60-fold CGG repeats. Although
the threshold for expression of Fragile-X syndrome is ~55CGG rep
eats, because the event occurs only in her germline and not in the s
omatic tissues, she does not show the syndrome.
• In the F2 generation, the daughter marries a man with a 20-fold
CGG repeat. One-half of their sons will inherit the 60 CGG chromos
ome and will likely show the syndrome, and one-half of their daught
ers will be carriers. Further slippage of the repeat region may occur
in the F3 daughter's germlines. These daughters may or may not sh
ow the syndrome themselves: the phenotype is sex-influenced, wit
h higher penetrance in males (80%) than females (30%), which ma
y be due the presence of a 'standard' X-chromosome in heterozygo
us females.
29. Inheritance of Fragile-X syndrome.
www.sciencemuseum.org.uk/. ../genes/218.asp
An altered gene on the X-chromosome causes Fragile-X syndrome. A girl will
normally have a working gene on her other X-chromosome, which partially makes up
for the altered gene, so girls are usually less severely affected than boys. The geneti
c change in Fragile-X is very unusual; it tends to change between parent and child, s
o predicting the exact risk of having an affected child is complicated.
30. Inheritance of Fragile-X syndrome
• This picture shows affected men and
women in a fragile x pedigree. Solid
colored shapes are those that are
affected and dotted shapes are those
that may have mild symptoms, and
carry the disease. The percentages on
the pedigree show the disease rate as
the generations progress. The picture
was borrowed from Medical Genetics
by Carey, John C., Jorde, Lynn B., and
White, Raymond L.
www.ikm.jmu.edu/.../ shermananticipation.gif
31. Sex limited traits
• sex linked traits are generally expressed much
more often in males than in females.
• some traits which affect one sex more than
another are not necessarily sex linked.
• Examples are cases of sex limited expression
which might include genes affecting beard growt
h or breast size, and (in cattle), horn growth and
milk yield.
• These genes have no visible affect in one sex
because the necessary machinery to express th
em is not present.
32. • Sex-limited inheritance:
• A trait that appears in only one sex is called sex-limited
inheritance.
• Sex hormones and other physiologic differences between
males and females may alter the expressivity of a gene.
• For example, premature baldness is an autosomal dominant
trait, but presumably as a result of female sex hormones,
the condition is rarely expressed in the female, and then usu
ally only after menopause.
• Thus, sex-limited inheritance, perhaps more correctly called
sex-influenced inheritance, is a special case of limited expre
ssivity and penetrance
