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Peptide Bond
Pe pt i d e Bo nd 1429 A `nonspecific' pedigree is the term used when a trait or disease affects more than one individual but where the pattern does not conform to any of the above three patterns. This might be caused by multifactorial inheritance, chance with common disorders, environmental factors, autosomal dominant inheritance with low penetrance, or a chromosomal translocation. In multifactorial inheritance the risks of recurrence are increased in close relatives above the general population risk and thus there is more likely to be a family history of other affected individuals. The pattern of involvement is, however, not typical or diagnostic. Similarly with common disorders there may be a family history by chance alone. One in three people develop cancer at some stage in their lives and thus it is not uncommon to see a family history of cancer on a purely chance basis. If the same type of cancer is involved and especially if there is a young age of onset or involvement of multiple sites or more than two relatives, then single gene forms of cancer need to be excluded. See also: Autosomal Inheritance; Consanguinity; Genetic Counseling; Genetic Diseases; Mitochondrial Inheritance; Mosaicism in Humans; Multifactorial Inheritance; Oncogenes; Penetrance; Sex Linkage; Vertical Transmission
Pedomorphosis W Fitch Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1494
The condition where sexual reproduction occurs in the immature (e.g., larval) organism; compare with neoteny. See also: Neoteny
Penetrance J A Fossella Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0968
Penetrance is the conditional probability of observing a corresponding phenotype given a specific genotype. Typically, it refers to the degree to which some individuals of a mutant genotype display the associated phenotype. Penetrance may vary from 0 to 1. When less than 100% of a population with the identical
mutant genotype display the associated phenotype, that mutation is said to be `incompletely penetrant.' Penetrance is similar in meaning to `expressivity' and the two terms are often used together when describing mutations. For example, certain weak alleles of the W locus seen in mice result in white coat color spots. These mutant alleles are said to show reduced penetrance and variable expressivity. The distinction between penetrance and expressivity is that penetrance refers to the genotype while expressivity refers to the phenotype. In this example, only some of the mice that carry the W / genotype show any spots at all. This is an example of reduced penetrance. Of the animals that show the spotted phenotype, however, some tend to show much spotting while others show very little spotting. This is an example of variable expressivity. Penetrance is sometimes used in a narrow sense to describe the probability of being affected by a disease, given the presence of a certain disease-predisposing allele. In principle, the penetrance of a diseasesusceptibility allele is the fraction of individuals that are affected among a population that carry the disease allele. In practice, it is often very difficult to estimate the penetrance of a disease-predisposing allele, since it is difficult to collect a population of susceptible individuals and determine the fraction that are affected in an unbiased way. This task is further confounded in cases of complex diseases by factors such as age, genetic background, and phenocopies, which are cases that resemble the affected state but are nongenetic in origin. The phenomena of reduced penetrance and variable expressivity have a similar root cause. The phenotypic effects of a specific gene are highly contingent on the environmental conditions that exist during the development of an organism and during maturity. The effects of a specific gene are also dependent on other modifier genes in the same developmental or physiological pathway. Hence, variation in the environment and in modifier loci among individuals in a population may alter the phenotypic effects of a specific gene or mutation resulting in reduced penetrance and variable expressivity. See also: Expressivity; W (White Spotting) Locus
Peptide Bond J Parker Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0969
A peptide bond is the amide bond which is formed when the carboxyl group of one amino acid becomes
1430
Pe r i n u c l e a r S p a ce
linked to the amino group of another to form a peptide. (The loss of a water molecule occurs during formation of the peptide bond and the basic amino acid unit in a protein chain is therefore referred to as an amino acid residue.) The oxygen atom of the carbonyl group involved in the bond is in the trans position with respect to the hydrogen on the bonded nitrogen atom. The peptide group (±CO±NH±) has a partially double-bond character which results from resonance and keeps these four atoms planar. Peptide bonds link all the amino acid residues together in a polypeptide chain and form the very regular backbone of the chain. This regular linkage means that every polypeptide has a free amino group on the amino acid residue at one end of the chain (the N-terminus) and a free carboxyl group on the amino acid residue at the other end (the C-terminus). See also: Amino Acids; Polypeptides
Perinuclear Space Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1953
The perinuclear space is the gap between the inner and outer membranes of the nuclear envelope (approx. 10± 40 nm wide). See also: Nucleus
Permissive Cells I Schildkraut Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0970
Permissive cells are cells that can support the growth of a virus. A number of factors must be met if a virus is to have the capacity to replicate successfully in a host cell. The cell must first have the correct proteins displayed on its outer surface to absorb the virus. If the cell has an altered receptor protein for a specific virus the virus will be unable to attach to the cell, although the cell may be permissive for other strains of viruses which use other means to enter the cell. Likewise departure of the newly replicated virus particles from the host cell can be affected by host cell mutations. See also: Virus
Petite Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1956
Petite strains of yeast lack mitochrondrial function. These mutants grow slowly and rely on anaerobic respiration. The mitochondria present have reduced cristae and are functionally defective. See also: Mitochondria
P-Glycoprotein M A Barrand Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1607
P-glycoprotein (Pgp) (now ABCB1) is one of the most extensively studied members of the superfamily of ATP-binding cassette (ABC) transporters found in prokaryotes and eukaryotes of plants and animals. By utilizing the energy released by ATP hydrolysis, ABC transporters bring about movement of substances such as ions, sugars, amino acids, phospholipids, peptides, toxins, and antibiotics. They thus can affect distribution of molecules at subcellular, cellular, and tissue levels. Pgp is remarkable in that it is able to transport a wide range of substrates with differing structures including many lipophilic anticancer drugs. Pgp was first identified by Juliano and Ling in 1976 in cultured mammalian tumor cells that had been exposed to a cytotoxic drug and over time developed resistance not just to the original selecting drug but to a range of different drugs, i.e., `multidrug resistance.' By comparing membranes obtained from the original sensitive cells with those from the resistant cells it was possible to observe a 170 kDa protein present only in the resistant cell membranes. Following cloning and sequencing of the gene, transfection experiments showed that the presence of this protein at the cell surface could bring about efflux of a number of different drugs, thus preventing access of these toxic agents to their intracellular target sites and so conferring resistance to the transfected cells. Since that time, orthologs of Pgp have been identified in many different species. Pgps are present not only in tumor cell lines but also in many normal tissues where their ability to expel toxic material not only affects the pharmacokinetics of many therapeutic drugs including anticancer agents and drugs used against AIDS but
Pedomorphosis W Fitch Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1494
The condition where sexual reproduction occurs in the immature (e.g., larval) organism; compare with neoteny. See also: Neoteny
Penetrance J A Fossella Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0968
Penetrance is the conditional probability of observing a corresponding phenotype given a specific genotype. Typically, it refers to the degree to which some individuals of a mutant genotype display the associated phenotype. Penetrance may vary from 0 to 1. When less than 100% of a population with the identical
mutant genotype display the associated phenotype, that mutation is said to be `incompletely penetrant.' Penetrance is similar in meaning to `expressivity' and the two terms are often used together when describing mutations. For example, certain weak alleles of the W locus seen in mice result in white coat color spots. These mutant alleles are said to show reduced penetrance and variable expressivity. The distinction between penetrance and expressivity is that penetrance refers to the genotype while expressivity refers to the phenotype. In this example, only some of the mice that carry the W / genotype show any spots at all. This is an example of reduced penetrance. Of the animals that show the spotted phenotype, however, some tend to show much spotting while others show very little spotting. This is an example of variable expressivity. Penetrance is sometimes used in a narrow sense to describe the probability of being affected by a disease, given the presence of a certain disease-predisposing allele. In principle, the penetrance of a diseasesusceptibility allele is the fraction of individuals that are affected among a population that carry the disease allele. In practice, it is often very difficult to estimate the penetrance of a disease-predisposing allele, since it is difficult to collect a population of susceptible individuals and determine the fraction that are affected in an unbiased way. This task is further confounded in cases of complex diseases by factors such as age, genetic background, and phenocopies, which are cases that resemble the affected state but are nongenetic in origin. The phenomena of reduced penetrance and variable expressivity have a similar root cause. The phenotypic effects of a specific gene are highly contingent on the environmental conditions that exist during the development of an organism and during maturity. The effects of a specific gene are also dependent on other modifier genes in the same developmental or physiological pathway. Hence, variation in the environment and in modifier loci among individuals in a population may alter the phenotypic effects of a specific gene or mutation resulting in reduced penetrance and variable expressivity. See also: Expressivity; W (White Spotting) Locus
Peptide Bond J Parker Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0969
A peptide bond is the amide bond which is formed when the carboxyl group of one amino acid becomes
1430
Pe r i n u c l e a r S p a ce
linked to the amino group of another to form a peptide. (The loss of a water molecule occurs during formation of the peptide bond and the basic amino acid unit in a protein chain is therefore referred to as an amino acid residue.) The oxygen atom of the carbonyl group involved in the bond is in the trans position with respect to the hydrogen on the bonded nitrogen atom. The peptide group (±CO±NH±) has a partially double-bond character which results from resonance and keeps these four atoms planar. Peptide bonds link all the amino acid residues together in a polypeptide chain and form the very regular backbone of the chain. This regular linkage means that every polypeptide has a free amino group on the amino acid residue at one end of the chain (the N-terminus) and a free carboxyl group on the amino acid residue at the other end (the C-terminus). See also: Amino Acids; Polypeptides
Perinuclear Space Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1953
The perinuclear space is the gap between the inner and outer membranes of the nuclear envelope (approx. 10± 40 nm wide). See also: Nucleus
Permissive Cells I Schildkraut Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0970
Permissive cells are cells that can support the growth of a virus. A number of factors must be met if a virus is to have the capacity to replicate successfully in a host cell. The cell must first have the correct proteins displayed on its outer surface to absorb the virus. If the cell has an altered receptor protein for a specific virus the virus will be unable to attach to the cell, although the cell may be permissive for other strains of viruses which use other means to enter the cell. Likewise departure of the newly replicated virus particles from the host cell can be affected by host cell mutations. See also: Virus
Petite Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1956
Petite strains of yeast lack mitochrondrial function. These mutants grow slowly and rely on anaerobic respiration. The mitochondria present have reduced cristae and are functionally defective. See also: Mitochondria
P-Glycoprotein M A Barrand Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1607
P-glycoprotein (Pgp) (now ABCB1) is one of the most extensively studied members of the superfamily of ATP-binding cassette (ABC) transporters found in prokaryotes and eukaryotes of plants and animals. By utilizing the energy released by ATP hydrolysis, ABC transporters bring about movement of substances such as ions, sugars, amino acids, phospholipids, peptides, toxins, and antibiotics. They thus can affect distribution of molecules at subcellular, cellular, and tissue levels. Pgp is remarkable in that it is able to transport a wide range of substrates with differing structures including many lipophilic anticancer drugs. Pgp was first identified by Juliano and Ling in 1976 in cultured mammalian tumor cells that had been exposed to a cytotoxic drug and over time developed resistance not just to the original selecting drug but to a range of different drugs, i.e., `multidrug resistance.' By comparing membranes obtained from the original sensitive cells with those from the resistant cells it was possible to observe a 170 kDa protein present only in the resistant cell membranes. Following cloning and sequencing of the gene, transfection experiments showed that the presence of this protein at the cell surface could bring about efflux of a number of different drugs, thus preventing access of these toxic agents to their intracellular target sites and so conferring resistance to the transfected cells. Since that time, orthologs of Pgp have been identified in many different species. Pgps are present not only in tumor cell lines but also in many normal tissues where their ability to expel toxic material not only affects the pharmacokinetics of many therapeutic drugs including anticancer agents and drugs used against AIDS but