Javad Jamshidi Fasa University of Medical Sciences, November 2014 Session 5 Medical Genetics...

J a v a d J a m s h i d i

F a s a U n i v e r s i t y o f M e d i c a l S c i e n c e s , N o v e m b e r 2 0 1 4

S e s s i o n 5Medical Genetics

Patterns of

InheritancePart 2

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X-Linked Dominant Inheritance

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X-Linked Dominant Inheritance Specific Features

Affected females are more frequent than affected males

All daughters of a affected male, will be affected

Females are usually less severely affected than males

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X-Linked Recessive Inheritance

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X-Linked Recessive Inheritance Specific Features

The trait or disorder should affect males almost exclusively

Are transmitted through unaffected carrier females to their sons

Male-to-male transmission is not observed

Daughters of affected males are obligate carriers

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X-inactivation (lionization)

Occurs at around 15 to 16 days' gestation, when the embryo consists of approximately 5000 cells

Normally either of the two X chromosomes can be inactivated in any particular cell.

Thereafter the same X chromosome is inactivated in all daughter cells

The inactive X chromosome exists in a condensed form during interphase (bar body)

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Variable Expression in Heterozygous Females

Images from: Emery's Elements of Medical Genetics, 14th Edition, by Peter D. Turnpenny and Sian Ellard, (2012)

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Females with X-Linked Recessive Disorders

Occasionally a woman might manifest features of an X-linked recessive trait.

Homozygosity for X-Linked Recessive Disorders

Skewed X-Inactivation

Numerical X-Chromosome Abnormalities

X-Autosome Translocations

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Y-Linked Inheritance

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Y-Linked Inheritance Specific Features

Only males are affected.

An affected male transmits Y-linked traits to all of his sons but to none of his daughters.

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Multiple Alleles ( e.g. ABO blood groups)

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Sex Influence

Autosomal traits that express more frequently in one sex than in another

Gout and presenile baldness

Hemochromatosis

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Anticipation

In some autosomal dominant disorders, the onset of the disease occurs at an earlier age in the offspring or occurs with increasing severity

A result of the expansion of unstable triplet repeat sequences

Huntington disease and myotonic dystrophy

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Mosaicism

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Mitochondrial Inheritance

Each cell contains thousands of copies of mitochondrial DNA

Mitochondrial DNA has a higher rate of spontaneous mutation than nuclear DNA

Mitochondria, and therefore their DNA, are inherited almost exclusively from the mother

A number of rare disorders with unusual combinations of neurological and myopathic features

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Mitochondrial Inheritance

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Mitochondrial Heteroplasmy

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Mitochondrial Inheritance