Md2 Block3 Genetics Simple Gene Disorders Slide 69

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=

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info+

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Genetic Mosaicism:
is defined as a condition in which cells with different =

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genotypes
or
chromosome constitutions

are present in the same individual.

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It is random: in some cells of the female embryo, the X chromosome inherited from the father is inactivated,
and in others the X chromosome inherited from the mother is inactivated. Like coin tossing, this is a random process. Most women have their paternal X chromosome active in approximately 50% of their cells and the maternal X chromosome active in approximately 50% of their cells. Thus, females are said to be mosaics with respect to the active X chromosome.

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Mechanisms Associated with
X Inactivation:

X-chromosome inactivation is thought to be mediated by more than one mechanism.

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A gene called XlST =

has been identified as the primary gene that causes X inactivation.
XIST produces an RNA product that coats the chromosome, helping produce its inactivation.

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(X-inactive specific transcript)

Condensation into heterochromatin

►Methylation of gene regions on the X chromosome

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X-Linked Dominant Inheritance

There are relatively few diseases whose inheritance is classified as X-linked dominant.

an important example =

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Fragile X syndrome

females are differently affected than males, and whereas penetrance in males is __ %,
in females is approximately __ %

The typical fragile X patient is which sex =

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100

60

60

As in X-linked recessive inheritance, male-male transmission of the disease-causing mutation is not seen

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Penetrance in Genetic Diseases:
***

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a disease-causing mutation is the percentage of individuals who are known to have the disease-causing genotype .
who display the disease phenotype (develop symptoms).

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Recurrence Risks:

Affected male-homozygous normal female:
None of the

all of the =

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sons are affected;

daughters are affected.

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X-linked Dominant Diseases:
3ct

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Hypophosphatemic rickets
Fragile X syndrome
Alports’s syndrome

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Hypophosphatemic rickets

is *** caused by a mutation in the =

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fibroblast growth factor # =

Hypophosphatemic rickets affects men and women _______ ;

symptoms may become apparent at any point from

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23 (FGF23).

equally

childhood through early adulthood.

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*** Rickets is a disorder caused by = 3ct

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a lack of:

-vitamin D,
-calcium,
-phosphate

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*** Rickets
▼phosphate (hypophosphatemia)
S. calcium =
High urinary =

Inappropriately normal levels of =

X-ray: Cupped metaphysis with widening of epiphysis

Treatment consists of increasing phosphate intake and high doses of vitamin D.

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N, Alkaline phosphatase ▲

po4

vitamin D.

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Fragile X syndrome
Type of Mutation =

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X-Linked Dominate***

Males: __ % penetrance
Females: __ % penetrance

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100

60

Mental retardation
Large ears
Prominent jaw
Macro-orchidism
(usually postpubertal)

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Mitochondrial Inheritance

Mitochondria, which are cytoplasmic organelles involved in cellular respiration, have their own chromosomes, each of which contains 16,569 DNA base pairs (bp) arranged in a circular molecule.

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This DNA encodes 13 proteins that are subunits of complexes in the electron transport and oxidative phosphorylation processes .

In addition, mitochondrial DNA encodes
22 transfer RNAs and 2 =

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ribosomal RNAs

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Because a sperm cell contributes no mitochondria to the egg during fertilization,
mitochondrial DNA is inherited exclusively through =.

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females

Pedigrees for mitochondrial diseases thus display a distinct mode of inheritance:
Diseases are, transmitted only from affected =

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females to their offspring.

Both males and females are affected.

Transmission of the disease is only from a female.

All offspring of an affected female are affected.

None of the offspring of an affected male is affected.

Diseases are typically neuropathies and/or myopathies

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Heteroplasmy
A typical cell contains hundreds of mitochondria in its cytoplasm.
Sometimes a specific mutation is seen in only some of the mitochondria,
a condition known as =.

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Heteroplasmy

Variations in heteroplasmy can result in substantial variation in the severity of expression of mitochondrial diseases.

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Mitochondrial Diseases:
5ct

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-Kearns-sayre syndrome

-Leber’s hereditary optic neuropathy

-MELAS:
mitochondrial encephalomyopathy, lactic acidosis w stroke-like episodes

-(MERRF syndrome)
Myoclonic epilepsy w ragged red myo fibers

-Sensory neural hearing loss (Mitochondrial)

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