DNA Model by J. Watson and F. Crick Cold Spring Harbor Laboratory Archives
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.
www.BioEdOnline.org
Chromosomal Disorders
Deletion of a large continuous section of genetic material from a single chromosome. Mutation in a single gene. Influenced by multiple genetic and/or environmental factors.
www.BioEdOnline.org
Pedigree Boxes represent males. Circles represent females. Diamond represents an individual of unspecified gender. Shading represents affected individuals. This example:
P
www.BioEdOnline.org
Autosomal dominant inheritance A disorder appears in several generations of a family. Affected parents have a 50% risk of an affected child with each pregnancy. Variability and reduced penetrance can complicate predictions of prognosis.
www.BioEdOnline.org
Disorders often appear in only one generation of a family. Carrier couples have a 25% risk of an affected child with each pregnancy.
www.BioEdOnline.org
X-linked inheritance X-linked dominant disorders are few in number. Male to male transmission of X-linked disorders is not seen. Carrier females may show mild to moderate symptoms of certain X-linked disorders.
www.BioEdOnline.org
Inheritance through the maternal lineage. Sperm do not contribute mitochondria to the embryo.
www.BioEdOnline.org
www.BioEdOnline.org
Genetic Heterogeneity Allelic different mutations in a single gene result in the same disorder. Locus mutations in different genes produce the same disorder.
Nonrandom X-inactivation
Barr Bodies (indicated by the arrows) are the highly compacted inactive X chromosomes.
Courtesy of Dr. Steven M. Carr.
www.BioEdOnline.org
Substitution: ACTGACCTGATT (Thr-Asp-Leu-Ile) Deletion: ACTCTGATT (Thr-Leu-Ile) Insertion: ACTGAACCTGAACTGATT (Thr-Glu-Pro-Gly-Leu-Ile) Frameshift: ACTGACTGATT (Thr-Asp-Stop) Inversion: ACTGGTCAAATT (Thr-Glu-Gln-Ile)
www.BioEdOnline.org
www.BioEdOnline.org
Result in the substitution of one amino acid for another. May or may not affect a proteins function. Benign mutations can become prevalent in a population.
www.BioEdOnline.org
Null mutations Result in the loss of a protein product from a gene. Repetitive elements Repeated sequences are found throughout the genome. Vary in size. Consequences depend on location.
www.BioEdOnline.org
Mutations
Can affect transcription, RNA processing, RNA stability, or amino acid sequence.
Can have a variety of consequences including:
www.BioEdOnline.org
Polymorphisms
DNA sequence variations are part of the genetic makeup of every species and every individual.
www.BioEdOnline.org
Causes of Mutations
Errors during DNA replication The proofreading capability of DNA polymerase corrects many, but not all errors. Exposure to mutagens
www.BioEdOnline.org
Cells have built-in mechanisms for DNA repair. These mechanisms protect against the consequences of errors during replication and exposure to mutagens.
G C
A
T
T A
C G
G C
A
T
T A
C G
G C
A
T
T A
C G
G C
G C
A T
T A
C G
G C T A G C T
T A
C G
G C
G C
A T
T A
C G
G C
A T
T A
C G
G C
A T
T A
C G
G C
Repair
Visiscience Corporation. (2005). ScienceSlides. All rights reserved.
www.BioEdOnline.org
Normal variation: DNA sequence variations are part of what makes each of us unique.
Adaptation: DNA sequence variations provide the raw material for natural selection.
Speciation: DNA sequence variations are the basis for speciation in reproductively isolated populations. Genetic disease: DNA sequence variations can result in genetic disorders.
www.BioEdOnline.org
Understanding who we are. We are >99.9% genetically identical. Each of us is genetically unique, except for identical twins (maternal). Understanding where we came from. Africa
Human Genome Project, U.S. Department of Energy
Summary
DNA sequence variation is a normal part of every species and is not always associated with disease.
DNA sequence variations provide a mechanism for mapping genes and tracing the genetic history of organisms. Understanding the genetic basis of diseases permits genetic testing and risk prediction, and research into treatments and cures.
www.BioEdOnline.org