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8/13/2019 1Mutatii Genetice-baze Fiziopatologice
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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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www.BioEdOnline.org
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
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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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