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doc111
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HomeGrown&Smoked
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Howard Stern
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LOL that is what I was saying!Since we are having a riveting conversation about genetic mutations I figured I'd put up this gem here. I really enjoy science.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A1876
8.1 Mutations: Types and Causes
The development and function of an organism is in large part controlled by genes. Mutations can lead to changes in the structure of an encoded protein or to a decrease or complete loss in its expression. Because a change in the DNA sequence affects all copies of the encoded protein, mutations can be particularly damaging to a cell or organism. In contrast, any alterations in the sequences of RNA or protein molecules that occur during their synthesis are less serious because many copies of each RNA and protein are synthesized.
Geneticists often distinguish between the genotype and phenotype of an organism. Strictly speaking, the entire set of genes carried by an individual is its genotype, whereas the function and physical appearance of an individual is referred to as its phenotype. However, the two terms commonly are used in a more restricted sense: genotype usually denotes whether an individual carries mutations in a single gene (or a small number of genes), and phenotype denotes the physical and functional consequences of that genotype.
Mutations Are Recessive or Dominant
A fundamental genetic difference between organisms is whether their cells carry a single set of chromosomes or two copies of each chromosome. The former are referred to as haploid; the latter, as diploid. Many simple unicellular organisms are haploid, whereas complex multicellular organisms (e.g., fruit flies, mice, humans) are diploid.
Figure 8-1
For a recessive mutation to give rise to a mutant phenotype (more...)
Figure 8-1
.
For a recessive mutation to give rise to a mutant phenotype in a diploid organism, both alleles must carry the mutation
However, one copy of a dominant mutant allele leads to a mutant phenotype. Recessive mutations result in a loss of function, whereas dominant mutations often, but not always, result in a gain of function.
Different forms of a gene (e.g., normal and mutant) are referred to as alleles. Since diploid organisms carry two copies of each gene, they may carry identical alleles, that is, be homozygous for a gene, or carry different alleles, that is, be heterozygous for a gene. A recessive mutation is one in which both alleles must be mutant in order for the mutant phenotype to be observed; that is, the individual must be homozygous for the mutant allele to show the mutant phenotype. In contrast, the phenotypic consequences of a dominant mutation are observed in a heterozygous individual carrying one mutant and one normal allele (Figure 8-1
Recessive mutations inactivate the affected gene and lead to a loss of function. For instance, recessive mutations may remove part of or all the gene from the chromosome, disrupt expression of the gene, or alter the structure of the encoded protein, thereby altering its function. Conversely, dominant mutations often lead to a gain of function. For example, dominant mutations may increase the activity of a given gene product, confer a new activity on the gene product, or lead to its inappropriate spatial and temporal expression. Dominant mutations, however, may be associated with a loss of function. In some cases, two copies of a gene are required for normal function, so that removing a single copy leads to mutant phenotype. Such genes are referred to as haplo-insufficient. In other cases, mutations in one allele may lead to a structural change in the protein that interferes with the function of the wild-type protein encoded by the other allele. These are referred to as dominant negative mutations.
Some alleles can be associated with both a recessive and a dominant phenotype. For instance, fruit flies heterozygous for the mutant Stubble (Sb) allele have short and stubby body hairs rather than the normal long, slender hairs; the mutant allele is dominant in this case. In contrast, flies homozygous for this allele die during development. Thus the recessive phenotype associated with this allele is lethal, whereas the dominant phenotype is not.
Inheritance Patterns of Recessive and Dominant Mutations Differ
Recessive and dominant mutations can be distinguished because they exhibit different patterns of inheritance. To understand why, we need to review the type of cell division that gives rise to gametes (sperm and egg cells in higher plants and animals). The body (somatic) cells of most multicellular organisms divide by mitosis (see Figure 1-10), whereas the germ cells that give rise to gametes undergo meiosis. Like body cells, premeiotic germ cells are diploid, containing two of each morphologic type of chromosome. Because the two members of each such pair of homologous chromosomes are descended from different parents, their genes are similar but not usually identical. Single-celled organisms (e.g., the yeast S. cerevisiae) that are diploid at some phase of their life cycle also undergo meiosis (see Figure 10-54).
Figure 8-2
Meiosis
Figure 8-2
.
Meiosis
A premeiotic germ cell has two copies of each chromosome (2n), one maternal and one paternal. Chromosomes are replicated during the S phase, giving a 4n chromosomal complement. During the first meiotic division, each replicated chromosome (actually two sister chromatids) aligns at the cell equator, paired with its homologous partner; this pairing off, referred to as synapsis, permits genetic recombination (discussed later). One homolog (both sister chromatids) of each morphologic type goes into one daughter cell, and the other homolog goes into the other cell. The resulting 2n cells undergo a second division without intervening DNA replication. During this second meiotic division, the sister chromatids of each morphologic type separate and these now independent chromosomes are randomly apportioned to the daughter cells. Thus, each diploid cell that undergoes meiosis produces four haploid cells, whereas each diploid cell that undergoes mitosis produces two diploid cells (see Figure 1-10).
Figure 8-2
Figure 8-3
Segregation patterns of dominant and recessive mutations (more...)
Figure 8-3
.
Segregation patterns of dominant and recessive mutations
Crosses between genotypically normal individuals (blue) and mutants (yellow) that are heterozygous for a dominant mutation (a) or homozygous for a recessive mutation (b) produce different ratios of normal and mutant phenotypes in the F1 generation. Although all the F1 progeny from a cross between a normal individual and an individual homozygous for a recessive mutation will have a normal phenotype, one-quarter of the progeny from the intercross between F1 progeny will have a mutant phenotype. Observation of segregation patterns like these led Gregor Mendel (1822  1884) to conclude that each gamete receives only one of the two parental alleles, a conclusion known as Mendels first law.
Now, lets see what phenotypes are generated by mating of wild-type individuals with mutants carrying either a dominant or a recessive mutation. As shown in Figure 8-3a
Mutations Involve Large or Small DNA Alterations
Figure 8-4
Different types of mutations
Figure 8-4
.
Different types of mutations
(a) Point mutations, which involve alteration in a single base pair, and small deletions generally directly affect the function of only one gene. A wild-type peptide sequence and the mRNA and DNA encoding it are shown at the top. Altered nucleotides and amino acid residues are highlighted in green. Missense mutations lead to a change in a single amino acid in the encoded protein. In a nonsense mutation, a nucleotide base change leads to the formation of a stop codon (purple). This results in premature termination of translation, thereby generating a truncated protein. Frameshift mutations involve the addition or deletion of any number of nucleotides that is not a multiple of three, causing a change in the reading frame. Consequently, completely unrelated amino acid residues are incorporated into the protein prior to encountering a stop codon. (b) Chromosomal abnormalities involve alterations in large segments of DNA. Presumably these abnormalities arise owing to errors in the mechanisms for repairing double-strand breaks in DNA. Chromosomes (I or II) are shown as single thick lines with the regions involved in a particular abnormality highlighted in green or purple. Inversions occur when a break is rejoined to the correct chromosome but in an incorrect orientation; deletions, when a segment of DNA is lost; translocations, when breaks are rejoined to the wrong chromosomes; and insertions, when a segment from one chromosome is inserted into another chromosome.
A mutation involving a change in a single base pair, often called a point mutation, or a deletion of a few base pairs generally affects the function of a single gene (Figure 8-4a
Small deletions have effects similar to those of frameshift mutations, although one third of these will be in-frame and result in removal of a small number of contiguous amino acids.
- <LI id=A1883 class=reg>Missense mutation, which results in a protein in which one amino acid is substituted for another
<LI id=A1884 class=reg>Nonsense mutation, in which a stop codon replaces an amino acid codon, leading to premature termination of translation- Frameshift mutation, which causes a change in the reading frame, leading to introduction of unrelated amino acids into the protein, generally followed by a stop codon
The second major type of mutation involves large-scale changes in chromosome structure and can affect the functioning of numerous genes, resulting in major phenotypic consequences. Such chromosomal mutations (or abnormalities) can involve deletion or insertion of several contiguous genes, inversion of genes on a chromosome, or the exchange of large segments of DNA between nonhomologous chromosomes (Figure 8-4b
Mutations Occur Spontaneously and Can Be Induced
Mutations arise spontaneously at low frequency owing to the chemical instability of purine and pyrimidine bases and to errors during DNA replication. Natural exposure of an organism to certain environmental factors, such as ultraviolet light and chemical carcinogens (e.g., aflatoxin B1), also can cause mutations.
Figure 8-5
One mechanism by which errors in DNA replication produce (more...)
Figure 8-5
.
One mechanism by which errors in DNA replication produce spontaneous mutations
The replication of only one strand is shown; the other strand is replicated normally, as shown at the top. A replication error may arise in regions of DNA containing tandemly repeated sequences (in this case, GTC) when a portion of the newly synthesized strand (light blue) loops out into a single-stranded form. This slippage displaces the newly synthesized strand back along the template strand (dark blue), with its 3′ end still paired with the template. As a result, the DNA-synthesizing enzymes copy a region of the template strand a second time, leading to an increase in length of nine nucleotides (yellow) in this example. A subsequent round of DNA replication results in the production of one normal duplex DNA molecule and one mutant duplex containing the additional nucleotides.
A common cause of spontaneous point mutations is the deamination of cytosine to uracil in the DNA double helix. Subsequent replication leads to a mutant daughter cell in which a T·A base pair replaces the wild-type C·G base pair. Another cause of spontaneous mutations is copying errors during DNA replication. Although replication generally is carried out with high fidelity, errors occasionally occur. Figure 8-5
In order to increase the frequency of mutation in experimental organisms, researchers often treat them with high doses of chemical mutagens or expose them to ionizing radiation. Mutations arising in response to such treatments are referred to as induced mutations. Generally, chemical mutagens induce point mutations, whereas ionizing radiation gives rise to large chromosomal abnormalities.
Figure 8-6
Induction of point mutations by ethylmethane sulfonate (more...)
Figure 8-6
.
Induction of point mutations by ethylmethane sulfonate (EMS), a commonly used mutagen
(a) EMS alkylates guanine at the oxygen on position 6 of the purine ring, forming O6-ethylguanine (Et-G), which base-pairs with thymine. (b) Two rounds of DNA replication of a strand containing Et-G yields a mutant DNA in which a G·C base pair is replaced with an A·T pair. Cells also have repair enzymes that can remove the ethyl group from Et-G (Chapter 12).
Ethylmethane sulfonate (EMS), a commonly used mutagen, alkylates guanine in DNA, forming O6-ethylguanine (Figure 8-6a
Some Human Diseases Are Caused by Spontaneous Mutations
Many common human diseases, often devastating in their effects, are due to mutations in single genes. Genetic diseases arise by spontaneous mutations in germ cells (egg and sperm), which are transmitted to future generations. For example, sickle-cell anemia, which affects 1 in 500 individuals of African descent, is caused by a single missense mutation at codon 6 of the β-globin gene; as a result of this mutation, the glutamic acid at position 6 in the normal protein is changed to a valine in the mutant protein. This alteration has a profound effect on hemoglobin, the oxygen-carrier protein of erythrocytes, which consists of two α-globin and two β-globin subunits (see Figure 3-11). The deoxygenated form of the mutant protein is insoluble in erythrocytes and forms crystalline arrays. The erythrocytes of affected individuals become rigid and their transit through capillaries is blocked, causing severe pain and tissue damage. Because the erythrocytes of heterozygous individuals are resistant to the parasite causing malaria, which is endemic in Africa, the mutant allele has been maintained. It is not that individuals of African descent are more likely than others to acquire a mutation causing the sickle-cell defect, but rather the mutation has been maintained in this population by interbreeding.
Figure 8-7
Role of spontaneous somatic mutation in retinoblastoma, (more...)
Figure 8-7
.
Role of spontaneous somatic mutation in retinoblastoma, a childhood disease marked by retinal tumors
Tumors arise from retinal cells that carry two mutant Rb− alleles. (a) In hereditary retinoblastoma, a child receives a normal Rb+ allele from one parent and a mutant Rb− allele from the other parent. A single mutagenic event in a heterozygous somatic retinal cell that inactivates the normal allele will result in a cell homozygous for two mutant Rb− alleles. (b) In sporadic retinoblastoma, a child receives two normal Rb+ alleles. Two separate somatic mutations, inactivating both alleles in a particular cell, are required to produce a homozygous Rb−/Rb− retinal cell.
Spontaneous mutation in somatic cells (i.e., non-germline body cells) also is an important mechanism in certain human diseases, including retinoblastoma, which is associated with retinal tumors in children (see Figure 24-11). The hereditary form of retinoblastoma, for example, results from a germ-line mutation in one Rb allele and a second somatically occurring mutation in the other Rb allele (Figure 8-7a
In a later section, we will see how normal copies of disease-related genes can be isolated and cloned.
SUMMARY
- <LI id=A1893 class=reg> Diploid organisms carry two copies (alleles) of each gene, whereas haploid organisms carry only one copy.
<LI id=A1894 class=reg> Mutations are alterations in DNA sequences that result in changes in the structure of a gene. Both small and large DNA alterations can occur spontaneously. Treatment with ionizing radiation or various chemical agents increases the frequency of mutations.
<LI id=A1895 class=reg> Recessive mutations lead to a loss of function, which is masked if a normal copy of the gene is present. For the mutant phenotype to occur, both alleles must carry the mutation.
<LI id=A1896 class=reg> Dominant mutations lead to a mutant phenotype in the presence of a normal copy of the gene. The phenotypes associated with dominant mutations may represent either a loss or a gain of function.
<LI id=A1897 class=reg>
 In meiosis, a diploid cell undergoes one DNA replication and two cell divisions, yielding four haploid cells (Figure 8-2
 Dominant and recessive mutations exhibit characteristic segregation patterns in genetic crosses (see Figure 8-3
Copyright © 2000, W. H. Freeman and Company
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- SUMMARY
Howard Stern
Well-Known Member
oh yeah nice postSince we are having a riveting conversation about genetic mutations I figured I'd put up this gem here. I really enjoy science.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A1876
8.1 Mutations: Types and Causes
The development and function of an organism is in large part controlled by genes. Mutations can lead to changes in the structure of an encoded protein or to a decrease or complete loss in its expression. Because a change in the DNA sequence affects all copies of the encoded protein, mutations can be particularly damaging to a cell or organism. In contrast, any alterations in the sequences of RNA or protein molecules that occur during their synthesis are less serious because many copies of each RNA and protein are synthesized.
Geneticists often distinguish between the genotype and phenotype of an organism. Strictly speaking, the entire set of genes carried by an individual is its genotype, whereas the function and physical appearance of an individual is referred to as its phenotype. However, the two terms commonly are used in a more restricted sense: genotype usually denotes whether an individual carries mutations in a single gene (or a small number of genes), and phenotype denotes the physical and functional consequences of that genotype.
Mutations Are Recessive or Dominant
A fundamental genetic difference between organisms is whether their cells carry a single set of chromosomes or two copies of each chromosome. The former are referred to as haploid; the latter, as diploid. Many simple unicellular organisms are haploid, whereas complex multicellular organisms (e.g., fruit flies, mice, humans) are diploid.
Figure 8-1
For a recessive mutation to give rise to a mutant phenotype (more...)
Figure 8-1
.
For a recessive mutation to give rise to a mutant phenotype in a diploid organism, both alleles must carry the mutation
However, one copy of a dominant mutant allele leads to a mutant phenotype. Recessive mutations result in a loss of function, whereas dominant mutations often, but not always, result in a gain of function.
Different forms of a gene (e.g., normal and mutant) are referred to as alleles. Since diploid organisms carry two copies of each gene, they may carry identical alleles, that is, be homozygous for a gene, or carry different alleles, that is, be heterozygous for a gene. A recessive mutation is one in which both alleles must be mutant in order for the mutant phenotype to be observed; that is, the individual must be homozygous for the mutant allele to show the mutant phenotype. In contrast, the phenotypic consequences of a dominant mutation are observed in a heterozygous individual carrying one mutant and one normal allele (Figure 8-1
Recessive mutations inactivate the affected gene and lead to a loss of function. For instance, recessive mutations may remove part of or all the gene from the chromosome, disrupt expression of the gene, or alter the structure of the encoded protein, thereby altering its function. Conversely, dominant mutations often lead to a gain of function. For example, dominant mutations may increase the activity of a given gene product, confer a new activity on the gene product, or lead to its inappropriate spatial and temporal expression. Dominant mutations, however, may be associated with a loss of function. In some cases, two copies of a gene are required for normal function, so that removing a single copy leads to mutant phenotype. Such genes are referred to as haplo-insufficient. In other cases, mutations in one allele may lead to a structural change in the protein that interferes with the function of the wild-type protein encoded by the other allele. These are referred to as dominant negative mutations.
Some alleles can be associated with both a recessive and a dominant phenotype. For instance, fruit flies heterozygous for the mutant Stubble (Sb) allele have short and stubby body hairs rather than the normal long, slender hairs; the mutant allele is dominant in this case. In contrast, flies homozygous for this allele die during development. Thus the recessive phenotype associated with this allele is lethal, whereas the dominant phenotype is not.
Inheritance Patterns of Recessive and Dominant Mutations Differ
Recessive and dominant mutations can be distinguished because they exhibit different patterns of inheritance. To understand why, we need to review the type of cell division that gives rise to gametes (sperm and egg cells in higher plants and animals). The body (somatic) cells of most multicellular organisms divide by mitosis (see Figure 1-10), whereas the germ cells that give rise to gametes undergo meiosis. Like body cells, premeiotic germ cells are diploid, containing two of each morphologic type of chromosome. Because the two members of each such pair of homologous chromosomes are descended from different parents, their genes are similar but not usually identical. Single-celled organisms (e.g., the yeast S. cerevisiae) that are diploid at some phase of their life cycle also undergo meiosis (see Figure 10-54).
Figure 8-2
Meiosis
Figure 8-2
.
Meiosis
A premeiotic germ cell has two copies of each chromosome (2n), one maternal and one paternal. Chromosomes are replicated during the S phase, giving a 4n chromosomal complement. During the first meiotic division, each replicated chromosome (actually two sister chromatids) aligns at the cell equator, paired with its homologous partner; this pairing off, referred to as synapsis, permits genetic recombination (discussed later). One homolog (both sister chromatids) of each morphologic type goes into one daughter cell, and the other homolog goes into the other cell. The resulting 2n cells undergo a second division without intervening DNA replication. During this second meiotic division, the sister chromatids of each morphologic type separate and these now independent chromosomes are randomly apportioned to the daughter cells. Thus, each diploid cell that undergoes meiosis produces four haploid cells, whereas each diploid cell that undergoes mitosis produces two diploid cells (see Figure 1-10).
Figure 8-2
Figure 8-3
Segregation patterns of dominant and recessive mutations (more...)
Figure 8-3
.
Segregation patterns of dominant and recessive mutations
Crosses between genotypically normal individuals (blue) and mutants (yellow) that are heterozygous for a dominant mutation (a) or homozygous for a recessive mutation (b) produce different ratios of normal and mutant phenotypes in the F1 generation. Although all the F1 progeny from a cross between a normal individual and an individual homozygous for a recessive mutation will have a normal phenotype, one-quarter of the progeny from the intercross between F1 progeny will have a mutant phenotype. Observation of segregation patterns like these led Gregor Mendel (1822  1884) to conclude that each gamete receives only one of the two parental alleles, a conclusion known as Mendels first law.
Now, lets see what phenotypes are generated by mating of wild-type individuals with mutants carrying either a dominant or a recessive mutation. As shown in Figure 8-3a
Mutations Involve Large or Small DNA Alterations
Figure 8-4
Different types of mutations
Figure 8-4
.
Different types of mutations
(a) Point mutations, which involve alteration in a single base pair, and small deletions generally directly affect the function of only one gene. A wild-type peptide sequence and the mRNA and DNA encoding it are shown at the top. Altered nucleotides and amino acid residues are highlighted in green. Missense mutations lead to a change in a single amino acid in the encoded protein. In a nonsense mutation, a nucleotide base change leads to the formation of a stop codon (purple). This results in premature termination of translation, thereby generating a truncated protein. Frameshift mutations involve the addition or deletion of any number of nucleotides that is not a multiple of three, causing a change in the reading frame. Consequently, completely unrelated amino acid residues are incorporated into the protein prior to encountering a stop codon. (b) Chromosomal abnormalities involve alterations in large segments of DNA. Presumably these abnormalities arise owing to errors in the mechanisms for repairing double-strand breaks in DNA. Chromosomes (I or II) are shown as single thick lines with the regions involved in a particular abnormality highlighted in green or purple. Inversions occur when a break is rejoined to the correct chromosome but in an incorrect orientation; deletions, when a segment of DNA is lost; translocations, when breaks are rejoined to the wrong chromosomes; and insertions, when a segment from one chromosome is inserted into another chromosome.
A mutation involving a change in a single base pair, often called a point mutation, or a deletion of a few base pairs generally affects the function of a single gene (Figure 8-4a
Small deletions have effects similar to those of frameshift mutations, although one third of these will be in-frame and result in removal of a small number of contiguous amino acids.
- <LI id=A1883 class=reg>Missense mutation, which results in a protein in which one amino acid is substituted for another
<LI id=A1884 class=reg>Nonsense mutation, in which a stop codon replaces an amino acid codon, leading to premature termination of translation- Frameshift mutation, which causes a change in the reading frame, leading to introduction of unrelated amino acids into the protein, generally followed by a stop codon
The second major type of mutation involves large-scale changes in chromosome structure and can affect the functioning of numerous genes, resulting in major phenotypic consequences. Such chromosomal mutations (or abnormalities) can involve deletion or insertion of several contiguous genes, inversion of genes on a chromosome, or the exchange of large segments of DNA between nonhomologous chromosomes (Figure 8-4b
Mutations Occur Spontaneously and Can Be Induced
Mutations arise spontaneously at low frequency owing to the chemical instability of purine and pyrimidine bases and to errors during DNA replication. Natural exposure of an organism to certain environmental factors, such as ultraviolet light and chemical carcinogens (e.g., aflatoxin B1), also can cause mutations.
Figure 8-5
One mechanism by which errors in DNA replication produce (more...)
Figure 8-5
.
One mechanism by which errors in DNA replication produce spontaneous mutations
The replication of only one strand is shown; the other strand is replicated normally, as shown at the top. A replication error may arise in regions of DNA containing tandemly repeated sequences (in this case, GTC) when a portion of the newly synthesized strand (light blue) loops out into a single-stranded form. This slippage displaces the newly synthesized strand back along the template strand (dark blue), with its 3′ end still paired with the template. As a result, the DNA-synthesizing enzymes copy a region of the template strand a second time, leading to an increase in length of nine nucleotides (yellow) in this example. A subsequent round of DNA replication results in the production of one normal duplex DNA molecule and one mutant duplex containing the additional nucleotides.
A common cause of spontaneous point mutations is the deamination of cytosine to uracil in the DNA double helix. Subsequent replication leads to a mutant daughter cell in which a T·A base pair replaces the wild-type C·G base pair. Another cause of spontaneous mutations is copying errors during DNA replication. Although replication generally is carried out with high fidelity, errors occasionally occur. Figure 8-5
In order to increase the frequency of mutation in experimental organisms, researchers often treat them with high doses of chemical mutagens or expose them to ionizing radiation. Mutations arising in response to such treatments are referred to as induced mutations. Generally, chemical mutagens induce point mutations, whereas ionizing radiation gives rise to large chromosomal abnormalities.
Figure 8-6
Induction of point mutations by ethylmethane sulfonate (more...)
Figure 8-6
.
Induction of point mutations by ethylmethane sulfonate (EMS), a commonly used mutagen
(a) EMS alkylates guanine at the oxygen on position 6 of the purine ring, forming O6-ethylguanine (Et-G), which base-pairs with thymine. (b) Two rounds of DNA replication of a strand containing Et-G yields a mutant DNA in which a G·C base pair is replaced with an A·T pair. Cells also have repair enzymes that can remove the ethyl group from Et-G (Chapter 12).
Ethylmethane sulfonate (EMS), a commonly used mutagen, alkylates guanine in DNA, forming O6-ethylguanine (Figure 8-6a
Some Human Diseases Are Caused by Spontaneous Mutations
Many common human diseases, often devastating in their effects, are due to mutations in single genes. Genetic diseases arise by spontaneous mutations in germ cells (egg and sperm), which are transmitted to future generations. For example, sickle-cell anemia, which affects 1 in 500 individuals of African descent, is caused by a single missense mutation at codon 6 of the β-globin gene; as a result of this mutation, the glutamic acid at position 6 in the normal protein is changed to a valine in the mutant protein. This alteration has a profound effect on hemoglobin, the oxygen-carrier protein of erythrocytes, which consists of two α-globin and two β-globin subunits (see Figure 3-11). The deoxygenated form of the mutant protein is insoluble in erythrocytes and forms crystalline arrays. The erythrocytes of affected individuals become rigid and their transit through capillaries is blocked, causing severe pain and tissue damage. Because the erythrocytes of heterozygous individuals are resistant to the parasite causing malaria, which is endemic in Africa, the mutant allele has been maintained. It is not that individuals of African descent are more likely than others to acquire a mutation causing the sickle-cell defect, but rather the mutation has been maintained in this population by interbreeding.
Figure 8-7
Role of spontaneous somatic mutation in retinoblastoma, (more...)
Figure 8-7
.
Role of spontaneous somatic mutation in retinoblastoma, a childhood disease marked by retinal tumors
Tumors arise from retinal cells that carry two mutant Rb− alleles. (a) In hereditary retinoblastoma, a child receives a normal Rb+ allele from one parent and a mutant Rb− allele from the other parent. A single mutagenic event in a heterozygous somatic retinal cell that inactivates the normal allele will result in a cell homozygous for two mutant Rb− alleles. (b) In sporadic retinoblastoma, a child receives two normal Rb+ alleles. Two separate somatic mutations, inactivating both alleles in a particular cell, are required to produce a homozygous Rb−/Rb− retinal cell.
Spontaneous mutation in somatic cells (i.e., non-germline body cells) also is an important mechanism in certain human diseases, including retinoblastoma, which is associated with retinal tumors in children (see Figure 24-11). The hereditary form of retinoblastoma, for example, results from a germ-line mutation in one Rb allele and a second somatically occurring mutation in the other Rb allele (Figure 8-7a
In a later section, we will see how normal copies of disease-related genes can be isolated and cloned.
SUMMARY
- <LI id=A1893 class=reg> Diploid organisms carry two copies (alleles) of each gene, whereas haploid organisms carry only one copy.
<LI id=A1894 class=reg> Mutations are alterations in DNA sequences that result in changes in the structure of a gene. Both small and large DNA alterations can occur spontaneously. Treatment with ionizing radiation or various chemical agents increases the frequency of mutations.
<LI id=A1895 class=reg> Recessive mutations lead to a loss of function, which is masked if a normal copy of the gene is present. For the mutant phenotype to occur, both alleles must carry the mutation.
<LI id=A1896 class=reg> Dominant mutations lead to a mutant phenotype in the presence of a normal copy of the gene. The phenotypes associated with dominant mutations may represent either a loss or a gain of function.
<LI id=A1897 class=reg>
 In meiosis, a diploid cell undergoes one DNA replication and two cell divisions, yielding four haploid cells (Figure 8-2
 Dominant and recessive mutations exhibit characteristic segregation patterns in genetic crosses (see Figure 8-3
Copyright © 2000, W. H. Freeman and Company
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Help ǀ Contact Help Desk ǀ Copyright and Disclaimer
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Table of Contents
Browse on
- <LI class=nav-title>In this Page <LI class=nav-self-title>Molecular Cell Biology <LI class=navigation-parts>Mutations Are Recessive or Dominant <LI class=navigation-parts>Inheritance Patterns of Recessive and Dominant Mutations Differ <LI class=navigation-parts>Mutations Involve Large or Small DNA Alterations <LI class=navigation-parts>Mutations Occur Spontaneously and Can Be Induced <LI class=navigation-parts>Some Human Diseases Are Caused by Spontaneous Mutations
- SUMMARY
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Howard Stern
Well-Known Member
thanks for the infoSince we are having a riveting conversation about genetic mutations I figured I'd put up this gem here. I really enjoy science.
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A1876
8.1 Mutations: Types and Causes
The development and function of an organism is in large part controlled by genes. Mutations can lead to changes in the structure of an encoded protein or to a decrease or complete loss in its expression. Because a change in the DNA sequence affects all copies of the encoded protein, mutations can be particularly damaging to a cell or organism. In contrast, any alterations in the sequences of RNA or protein molecules that occur during their synthesis are less serious because many copies of each RNA and protein are synthesized.
Geneticists often distinguish between the genotype and phenotype of an organism. Strictly speaking, the entire set of genes carried by an individual is its genotype, whereas the function and physical appearance of an individual is referred to as its phenotype. However, the two terms commonly are used in a more restricted sense: genotype usually denotes whether an individual carries mutations in a single gene (or a small number of genes), and phenotype denotes the physical and functional consequences of that genotype.
Mutations Are Recessive or Dominant
A fundamental genetic difference between organisms is whether their cells carry a single set of chromosomes or two copies of each chromosome. The former are referred to as haploid; the latter, as diploid. Many simple unicellular organisms are haploid, whereas complex multicellular organisms (e.g., fruit flies, mice, humans) are diploid.
Figure 8-1
For a recessive mutation to give rise to a mutant phenotype (more...)
Figure 8-1
.
For a recessive mutation to give rise to a mutant phenotype in a diploid organism, both alleles must carry the mutation
However, one copy of a dominant mutant allele leads to a mutant phenotype. Recessive mutations result in a loss of function, whereas dominant mutations often, but not always, result in a gain of function.
Different forms of a gene (e.g., normal and mutant) are referred to as alleles. Since diploid organisms carry two copies of each gene, they may carry identical alleles, that is, be homozygous for a gene, or carry different alleles, that is, be heterozygous for a gene. A recessive mutation is one in which both alleles must be mutant in order for the mutant phenotype to be observed; that is, the individual must be homozygous for the mutant allele to show the mutant phenotype. In contrast, the phenotypic consequences of a dominant mutation are observed in a heterozygous individual carrying one mutant and one normal allele (Figure 8-1
Recessive mutations inactivate the affected gene and lead to a loss of function. For instance, recessive mutations may remove part of or all the gene from the chromosome, disrupt expression of the gene, or alter the structure of the encoded protein, thereby altering its function. Conversely, dominant mutations often lead to a gain of function. For example, dominant mutations may increase the activity of a given gene product, confer a new activity on the gene product, or lead to its inappropriate spatial and temporal expression. Dominant mutations, however, may be associated with a loss of function. In some cases, two copies of a gene are required for normal function, so that removing a single copy leads to mutant phenotype. Such genes are referred to as haplo-insufficient. In other cases, mutations in one allele may lead to a structural change in the protein that interferes with the function of the wild-type protein encoded by the other allele. These are referred to as dominant negative mutations.
Some alleles can be associated with both a recessive and a dominant phenotype. For instance, fruit flies heterozygous for the mutant Stubble (Sb) allele have short and stubby body hairs rather than the normal long, slender hairs; the mutant allele is dominant in this case. In contrast, flies homozygous for this allele die during development. Thus the recessive phenotype associated with this allele is lethal, whereas the dominant phenotype is not.
Inheritance Patterns of Recessive and Dominant Mutations Differ
Recessive and dominant mutations can be distinguished because they exhibit different patterns of inheritance. To understand why, we need to review the type of cell division that gives rise to gametes (sperm and egg cells in higher plants and animals). The body (somatic) cells of most multicellular organisms divide by mitosis (see Figure 1-10), whereas the germ cells that give rise to gametes undergo meiosis. Like body cells, premeiotic germ cells are diploid, containing two of each morphologic type of chromosome. Because the two members of each such pair of homologous chromosomes are descended from different parents, their genes are similar but not usually identical. Single-celled organisms (e.g., the yeast S. cerevisiae) that are diploid at some phase of their life cycle also undergo meiosis (see Figure 10-54).
Figure 8-2
Meiosis
Figure 8-2
.
Meiosis
A premeiotic germ cell has two copies of each chromosome (2n), one maternal and one paternal. Chromosomes are replicated during the S phase, giving a 4n chromosomal complement. During the first meiotic division, each replicated chromosome (actually two sister chromatids) aligns at the cell equator, paired with its homologous partner; this pairing off, referred to as synapsis, permits genetic recombination (discussed later). One homolog (both sister chromatids) of each morphologic type goes into one daughter cell, and the other homolog goes into the other cell. The resulting 2n cells undergo a second division without intervening DNA replication. During this second meiotic division, the sister chromatids of each morphologic type separate and these now independent chromosomes are randomly apportioned to the daughter cells. Thus, each diploid cell that undergoes meiosis produces four haploid cells, whereas each diploid cell that undergoes mitosis produces two diploid cells (see Figure 1-10).
Figure 8-2
Figure 8-3
Segregation patterns of dominant and recessive mutations (more...)
Figure 8-3
.
Segregation patterns of dominant and recessive mutations
Crosses between genotypically normal individuals (blue) and mutants (yellow) that are heterozygous for a dominant mutation (a) or homozygous for a recessive mutation (b) produce different ratios of normal and mutant phenotypes in the F1 generation. Although all the F1 progeny from a cross between a normal individual and an individual homozygous for a recessive mutation will have a normal phenotype, one-quarter of the progeny from the intercross between F1 progeny will have a mutant phenotype. Observation of segregation patterns like these led Gregor Mendel (1822  1884) to conclude that each gamete receives only one of the two parental alleles, a conclusion known as Mendels first law.
Now, lets see what phenotypes are generated by mating of wild-type individuals with mutants carrying either a dominant or a recessive mutation. As shown in Figure 8-3a
Mutations Involve Large or Small DNA Alterations
Figure 8-4
Different types of mutations
Figure 8-4
.
Different types of mutations
(a) Point mutations, which involve alteration in a single base pair, and small deletions generally directly affect the function of only one gene. A wild-type peptide sequence and the mRNA and DNA encoding it are shown at the top. Altered nucleotides and amino acid residues are highlighted in green. Missense mutations lead to a change in a single amino acid in the encoded protein. In a nonsense mutation, a nucleotide base change leads to the formation of a stop codon (purple). This results in premature termination of translation, thereby generating a truncated protein. Frameshift mutations involve the addition or deletion of any number of nucleotides that is not a multiple of three, causing a change in the reading frame. Consequently, completely unrelated amino acid residues are incorporated into the protein prior to encountering a stop codon. (b) Chromosomal abnormalities involve alterations in large segments of DNA. Presumably these abnormalities arise owing to errors in the mechanisms for repairing double-strand breaks in DNA. Chromosomes (I or II) are shown as single thick lines with the regions involved in a particular abnormality highlighted in green or purple. Inversions occur when a break is rejoined to the correct chromosome but in an incorrect orientation; deletions, when a segment of DNA is lost; translocations, when breaks are rejoined to the wrong chromosomes; and insertions, when a segment from one chromosome is inserted into another chromosome.
A mutation involving a change in a single base pair, often called a point mutation, or a deletion of a few base pairs generally affects the function of a single gene (Figure 8-4a
Small deletions have effects similar to those of frameshift mutations, although one third of these will be in-frame and result in removal of a small number of contiguous amino acids.
- <LI id=A1883 class=reg>Missense mutation, which results in a protein in which one amino acid is substituted for another
<LI id=A1884 class=reg>Nonsense mutation, in which a stop codon replaces an amino acid codon, leading to premature termination of translation- Frameshift mutation, which causes a change in the reading frame, leading to introduction of unrelated amino acids into the protein, generally followed by a stop codon
The second major type of mutation involves large-scale changes in chromosome structure and can affect the functioning of numerous genes, resulting in major phenotypic consequences. Such chromosomal mutations (or abnormalities) can involve deletion or insertion of several contiguous genes, inversion of genes on a chromosome, or the exchange of large segments of DNA between nonhomologous chromosomes (Figure 8-4b
Mutations Occur Spontaneously and Can Be Induced
Mutations arise spontaneously at low frequency owing to the chemical instability of purine and pyrimidine bases and to errors during DNA replication. Natural exposure of an organism to certain environmental factors, such as ultraviolet light and chemical carcinogens (e.g., aflatoxin B1), also can cause mutations.
Figure 8-5
One mechanism by which errors in DNA replication produce (more...)
Figure 8-5
.
One mechanism by which errors in DNA replication produce spontaneous mutations
The replication of only one strand is shown; the other strand is replicated normally, as shown at the top. A replication error may arise in regions of DNA containing tandemly repeated sequences (in this case, GTC) when a portion of the newly synthesized strand (light blue) loops out into a single-stranded form. This slippage displaces the newly synthesized strand back along the template strand (dark blue), with its 3′ end still paired with the template. As a result, the DNA-synthesizing enzymes copy a region of the template strand a second time, leading to an increase in length of nine nucleotides (yellow) in this example. A subsequent round of DNA replication results in the production of one normal duplex DNA molecule and one mutant duplex containing the additional nucleotides.
A common cause of spontaneous point mutations is the deamination of cytosine to uracil in the DNA double helix. Subsequent replication leads to a mutant daughter cell in which a T·A base pair replaces the wild-type C·G base pair. Another cause of spontaneous mutations is copying errors during DNA replication. Although replication generally is carried out with high fidelity, errors occasionally occur. Figure 8-5
In order to increase the frequency of mutation in experimental organisms, researchers often treat them with high doses of chemical mutagens or expose them to ionizing radiation. Mutations arising in response to such treatments are referred to as induced mutations. Generally, chemical mutagens induce point mutations, whereas ionizing radiation gives rise to large chromosomal abnormalities.
Figure 8-6
Induction of point mutations by ethylmethane sulfonate (more...)
Figure 8-6
.
Induction of point mutations by ethylmethane sulfonate (EMS), a commonly used mutagen
(a) EMS alkylates guanine at the oxygen on position 6 of the purine ring, forming O6-ethylguanine (Et-G), which base-pairs with thymine. (b) Two rounds of DNA replication of a strand containing Et-G yields a mutant DNA in which a G·C base pair is replaced with an A·T pair. Cells also have repair enzymes that can remove the ethyl group from Et-G (Chapter 12).
Ethylmethane sulfonate (EMS), a commonly used mutagen, alkylates guanine in DNA, forming O6-ethylguanine (Figure 8-6a
Some Human Diseases Are Caused by Spontaneous Mutations
Many common human diseases, often devastating in their effects, are due to mutations in single genes. Genetic diseases arise by spontaneous mutations in germ cells (egg and sperm), which are transmitted to future generations. For example, sickle-cell anemia, which affects 1 in 500 individuals of African descent, is caused by a single missense mutation at codon 6 of the β-globin gene; as a result of this mutation, the glutamic acid at position 6 in the normal protein is changed to a valine in the mutant protein. This alteration has a profound effect on hemoglobin, the oxygen-carrier protein of erythrocytes, which consists of two α-globin and two β-globin subunits (see Figure 3-11). The deoxygenated form of the mutant protein is insoluble in erythrocytes and forms crystalline arrays. The erythrocytes of affected individuals become rigid and their transit through capillaries is blocked, causing severe pain and tissue damage. Because the erythrocytes of heterozygous individuals are resistant to the parasite causing malaria, which is endemic in Africa, the mutant allele has been maintained. It is not that individuals of African descent are more likely than others to acquire a mutation causing the sickle-cell defect, but rather the mutation has been maintained in this population by interbreeding.
Figure 8-7
Role of spontaneous somatic mutation in retinoblastoma, (more...)
Figure 8-7
.
Role of spontaneous somatic mutation in retinoblastoma, a childhood disease marked by retinal tumors
Tumors arise from retinal cells that carry two mutant Rb− alleles. (a) In hereditary retinoblastoma, a child receives a normal Rb+ allele from one parent and a mutant Rb− allele from the other parent. A single mutagenic event in a heterozygous somatic retinal cell that inactivates the normal allele will result in a cell homozygous for two mutant Rb− alleles. (b) In sporadic retinoblastoma, a child receives two normal Rb+ alleles. Two separate somatic mutations, inactivating both alleles in a particular cell, are required to produce a homozygous Rb−/Rb− retinal cell.
Spontaneous mutation in somatic cells (i.e., non-germline body cells) also is an important mechanism in certain human diseases, including retinoblastoma, which is associated with retinal tumors in children (see Figure 24-11). The hereditary form of retinoblastoma, for example, results from a germ-line mutation in one Rb allele and a second somatically occurring mutation in the other Rb allele (Figure 8-7a
In a later section, we will see how normal copies of disease-related genes can be isolated and cloned.
SUMMARY
- <LI id=A1893 class=reg> Diploid organisms carry two copies (alleles) of each gene, whereas haploid organisms carry only one copy.
<LI id=A1894 class=reg> Mutations are alterations in DNA sequences that result in changes in the structure of a gene. Both small and large DNA alterations can occur spontaneously. Treatment with ionizing radiation or various chemical agents increases the frequency of mutations.
<LI id=A1895 class=reg> Recessive mutations lead to a loss of function, which is masked if a normal copy of the gene is present. For the mutant phenotype to occur, both alleles must carry the mutation.
<LI id=A1896 class=reg> Dominant mutations lead to a mutant phenotype in the presence of a normal copy of the gene. The phenotypes associated with dominant mutations may represent either a loss or a gain of function.
<LI id=A1897 class=reg>
 In meiosis, a diploid cell undergoes one DNA replication and two cell divisions, yielding four haploid cells (Figure 8-2
 Dominant and recessive mutations exhibit characteristic segregation patterns in genetic crosses (see Figure 8-3
Copyright © 2000, W. H. Freeman and Company
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- <LI class=nav-title>In this Page <LI class=nav-self-title>Molecular Cell Biology <LI class=navigation-parts>Mutations Are Recessive or Dominant <LI class=navigation-parts>Inheritance Patterns of Recessive and Dominant Mutations Differ <LI class=navigation-parts>Mutations Involve Large or Small DNA Alterations <LI class=navigation-parts>Mutations Occur Spontaneously and Can Be Induced <LI class=navigation-parts>Some Human Diseases Are Caused by Spontaneous Mutations
- SUMMARY
HomeGrown&Smoked
Active Member
Howard Stern
Well-Known Member
how late into flowering will a plant turn into a hermi?
doc111
Well-Known Member
Any time my friend.
Outdoorindica
Well-Known Member
I would have to agree, I never had a hermie outdoors, but indoors I have. And I did some brutal things to a few girls to experiment and still no hermies, and they were bag seed from mid grade commercial pot, no great genetics there. I think its the lights we are using. No matter what lights you use together they dont match the suns spectrum. And without the proper spectrum the plant will always be stressed in some way. Therefore you get hermies. The sun will always produce the best best pot, in my opinion. But I also agree that better genetics have less chance of going hermie. Thats why you should use regular seeds and not fems. Even they would have to be a from a strain that does not have the hermie trait in its lineage. So if you want no hermies, grow outdoors. Or use good genetics indoors, clones preferably since you would know what to expect from them.
mastakoosh
Well-Known Member
i think it is hard to mimic optimal outdoor conditions, although it can be done somewhat. i think a problem with some new growers will be dark interruptions and light leaks. it shows you its hard to beat mother nature.
danno48
Active Member
If you believe or think that genetics cannot be altered through stress, then you've a lot to learn about biology there scotty. You tend to read shit off the internet, improperly digest it, and like so many others just go off into a half-cocked frenzy of telling people how wrong they are. I suggest you "google" how stress effects genetically pre-disposed life forms to mutate.OOOOOOOOOOOOHHHHHHHHHHHHHH feeling the jealousy are we ????????
See you 2 trolls later.
hahahahahahahahahaha.
HomeGrown&Smoked
Active Member
reggaerican
Well-Known Member
dude i will bet my life on it that i can take a perfect female with all the best genetics, stress it so bad with heat, nutes, ph,light and it will turn hermie. i done it befor. but its not easy
freethoughexchange
Active Member
Agreed!!! All a plant needs to turn hermie is the belief that it will not survive, especially when it is near or has entered flowering, and it will mutate to protect its existence. (Indoor of course, I have no knowledge of outside growing).
