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Mutatii Genetice

Baze fiziopatologice

DNA Model by J. Watson and F. Crick Cold Spring Harbor Laboratory Archives


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Exploring Our Molecular Selves

"Exploring Our Molecular Selves"is a 3D computer-animated videoillustrating the basic componentsand principles of molecularbiology. The video gives a senseof the scale of cells,chromosomes, and DNA andshows how the information inDNA is converted into the

molecules necessary for life.

http://www.genome.gov/Pages/EducationKit/online.htm

The National Human Genome Research

Institute with co-sponsorship of the

Office of Biological and Environmental

Research, US Department of Energy,Howard Hughes Medical Institute,

Pharmaceutical Research and

Manufacturers of America,Nature,

Science and the American Society of

Human Genetics.


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Human Genetic Disorders (I)

Chromosomal Disorders Alteration of number or structure of

chromosomes.

Contiguous Gene DeletionSyndromes Deletion of a large continuous section

of genetic material from a singlechromosome.

Single Gene Disorders

Mutation in a single gene.

Common Complex Disorders Influenced by multiple genetic and/or

environmental factors.

National Center of Biotechnology Information,

National Library of Medicine


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Mendelian Disorders (I)

Autosomal dominant inheritance A disorder appears in several

generations of a family.

Affected parents have a 50%

risk of an affected child witheach pregnancy.

Variability and reducedpenetrance can complicate

predictions of prognosis.


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Mendelian Disorders (III)

X-linked inheritance X-linked dominant disorders

are few in number.

Male to male transmission of

X-linked disorders is notseen.

Carrier females may showmild to moderate symptoms

of certain X-linked disorders.


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Maternal (Mitochondrial) Inheritance

Inheritance through the maternal lineage. Sperm do not contribute mitochondria to the embryo.


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Complex Mechanisms ofHereditary Disease (I)

Multifactorial

Common Complex Disorders

New Mutation

Found in the child, but not in eitherparent.

Imprinting

A form of gene silencing.

Anticipation

Progressive severity of a disorder insuccessive generations.

Fragile X syndrome

is an example of a

disorder involving acomplex mechanism

of inheritance called

anticipation and

results in a form of

mental retardation

known as Fragile Xsyndrome.

National Center for Biotechnology

Information,

National Library of Medicine


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Complex Mechanisms ofHereditary Disease (II)

Genetic Heterogeneity

Allelic different mutations in asingle gene result in the samedisorder.

Locus mutations in different genesproduce the same disorder.

Nonrandom X-inactivation

In females, genes on one of the X

chromosomes are turned off.

Barr Bodies

(indicated by the

arrows) are the

highly compactedinactive X

chromosomes.

Courtesy of

Dr. Steven M. Carr.


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The Molecular Basis of DNA Sequence Variations (III)

Missense mutations

Result in thesubstitution of oneamino acid foranother.

May or may notaffect a proteinsfunction.

Benign mutations

can becomeprevalent in apopulation.


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Polymorphisms

DNA sequence variations are part of the genetic makeup

of every species and every individual.

Not always associated with disease.

Polymorphisms can be used as markers to map disease

genes.


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Causes of Mutations

Errors during DNA replication The proofreading capability of

DNA polymerase corrects many,but not all errors.

Exposure to mutagens

Ultraviolet light

DNA damaging chemicals

RadioactivityDNA damage resulting in

multiple broken chromosomes
http://en.wikipedia.org/wiki/Image:Brokechromo.jpg


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Significance of DNA Sequence Variations

Normal variation: DNA sequence variations are part ofwhat makes each of us unique.

Adaptation: DNA sequence variations provide the rawmaterial for natural selection.

Speciation: DNA sequence variations are the basis forspeciation in reproductively isolated populations.

Genetic disease: DNA sequence variations can result ingenetic disorders.


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DNA Sequence Variations as aFossil Record

Understanding who we are. We are >99.9% genetically

identical.

Each of us is genetically unique,

except for identical twins(maternal).

Understanding where wecame from.

Africa

Group of 10,000-80,000

50,000-100,000 years ago

Human Genome Project,

U.S. Department of Energy


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