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Pedigree Analysis
1428
pBR322
transcription factor of the winged helix family (forkhead FKHR). All these phenotypes point to a function of Pax genes in very early steps of cell differentiation. Analysis of Pax5-deficient mice support the hypothesis that Pax genes may have a dual function in this process: activating a certain differentiation potential and thereby inhibiting inappropriate lineages. It is conceivable that Pax genes act on cell proliferation and/or survival.
Further reading
Noll M (1993) Evolution and role of Pax genes. Current Opinion Genetics and Development 3: 595±605. Mansouri A, Hallonet M and Gruss P (1996) Pax genes and their roles in cell differentiation and development. Current Opinion in Cell Biology 8: 851±857. Mansouri A, St-Onge L and Gruss P (1999) Pax genes in endoderm-derived organs. Trends in Endocrinology and Metabolism 10: 164±167.
See also: Developmental Genetics; Embryonic Development of the Nematode Caenorhabditis elegans
pBR322 Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1952
pBR322 is one of the standard plasmid cloning vectors. See also: Cloning Vectors
PCR See: Polymerase Chain Reaction (PCR)
Pedigree Analysis J M Connor Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0964
Pedigree analysis describes the process of interpretation of information displayed as a family tree. The family tree or pedigree is constructed using a standardized set of symbols and will include information about the disease status of each individual. If only a single individual is affected within the family then the pedigree cannot in itself provide proof for a particular mode of inheritance and cannot distinguish inherited
from noninherited conditions. When more than one individual is affected then the pattern may provide important clues or even proof of the mode of inheritance. There are four main patterns of inheritance that may be seen in a pedigree. A `vertical' pedigree is the term used when a trait or disease is passed down through several generations, directly from an affected individual to affected descendants in successive generations. Such vertical transmission is typically seen in autosomal dominant inheritance but can also be seen in X-linked dominant inheritance, mitochondrial inheritance, inherited chromosomal imbalances and nongenetic situations (such as infective agents). In autosomal dominant inheritance both sexes can be affected and, in turn, transmit the trait to both males and females. In Xlinked dominant inheritance both sexes can be affected and females can transmit the trait to both sons and daughters but affected males transmit it to all daughters and no sons. In mitochondrial inheritance both sexes can be affected but males do not transmit the trait and females transmit it to all offspring (although not all may be clinically affected). A `horizontal' pedigree is the term used when a trait or disease only affects family members in the same generation. This type of pedigree pattern is typical of autosomal recessive inheritance but can also be seen in X-linked recessive disorders, autosomal dominant disorders with incomplete penetrance, chromosomal translocations and nongenetic situations. In autosomal recessive inheritance both sexes can be affected in a sibship (brothers and sisters) and the disease severity is similar in males and females. Parental consanguinity (parents who are blood relatives) would be a further clue to an autosomal recessive condition. In an X-linked recessive condition only brothers are affected and in the absence of other affected male relatives (see above) this would mimic an autosomal recessive pedigree. The situation of affected brothers and sisters with normal parents might also be seen if one parent has an autosomal dominant condition but is clinically unaffected due to nonpenetrance or gonadal mosaicism. A `knight's move' pedigree is the term used when a trait or disease only affects males in a family and where affected males are related via outwardly normal females. Thus, for example, an affected boy may have an affected maternal uncle or affected maternal male cousins. The intervening females are usually clinically normal but are carrying the faulty gene. This pedigree pattern is typical of X-linked recessive inheritance. Males have only a single X chromosome and thus are affected by mutations in genes on the X, whereas the intervening females have a normal copy of the gene on their other X chromosome and are not usually affected.
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
pBR322
transcription factor of the winged helix family (forkhead FKHR). All these phenotypes point to a function of Pax genes in very early steps of cell differentiation. Analysis of Pax5-deficient mice support the hypothesis that Pax genes may have a dual function in this process: activating a certain differentiation potential and thereby inhibiting inappropriate lineages. It is conceivable that Pax genes act on cell proliferation and/or survival.
Further reading
Noll M (1993) Evolution and role of Pax genes. Current Opinion Genetics and Development 3: 595±605. Mansouri A, Hallonet M and Gruss P (1996) Pax genes and their roles in cell differentiation and development. Current Opinion in Cell Biology 8: 851±857. Mansouri A, St-Onge L and Gruss P (1999) Pax genes in endoderm-derived organs. Trends in Endocrinology and Metabolism 10: 164±167.
See also: Developmental Genetics; Embryonic Development of the Nematode Caenorhabditis elegans
pBR322 Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1952
pBR322 is one of the standard plasmid cloning vectors. See also: Cloning Vectors
PCR See: Polymerase Chain Reaction (PCR)
Pedigree Analysis J M Connor Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0964
Pedigree analysis describes the process of interpretation of information displayed as a family tree. The family tree or pedigree is constructed using a standardized set of symbols and will include information about the disease status of each individual. If only a single individual is affected within the family then the pedigree cannot in itself provide proof for a particular mode of inheritance and cannot distinguish inherited
from noninherited conditions. When more than one individual is affected then the pattern may provide important clues or even proof of the mode of inheritance. There are four main patterns of inheritance that may be seen in a pedigree. A `vertical' pedigree is the term used when a trait or disease is passed down through several generations, directly from an affected individual to affected descendants in successive generations. Such vertical transmission is typically seen in autosomal dominant inheritance but can also be seen in X-linked dominant inheritance, mitochondrial inheritance, inherited chromosomal imbalances and nongenetic situations (such as infective agents). In autosomal dominant inheritance both sexes can be affected and, in turn, transmit the trait to both males and females. In Xlinked dominant inheritance both sexes can be affected and females can transmit the trait to both sons and daughters but affected males transmit it to all daughters and no sons. In mitochondrial inheritance both sexes can be affected but males do not transmit the trait and females transmit it to all offspring (although not all may be clinically affected). A `horizontal' pedigree is the term used when a trait or disease only affects family members in the same generation. This type of pedigree pattern is typical of autosomal recessive inheritance but can also be seen in X-linked recessive disorders, autosomal dominant disorders with incomplete penetrance, chromosomal translocations and nongenetic situations. In autosomal recessive inheritance both sexes can be affected in a sibship (brothers and sisters) and the disease severity is similar in males and females. Parental consanguinity (parents who are blood relatives) would be a further clue to an autosomal recessive condition. In an X-linked recessive condition only brothers are affected and in the absence of other affected male relatives (see above) this would mimic an autosomal recessive pedigree. The situation of affected brothers and sisters with normal parents might also be seen if one parent has an autosomal dominant condition but is clinically unaffected due to nonpenetrance or gonadal mosaicism. A `knight's move' pedigree is the term used when a trait or disease only affects males in a family and where affected males are related via outwardly normal females. Thus, for example, an affected boy may have an affected maternal uncle or affected maternal male cousins. The intervening females are usually clinically normal but are carrying the faulty gene. This pedigree pattern is typical of X-linked recessive inheritance. Males have only a single X chromosome and thus are affected by mutations in genes on the X, whereas the intervening females have a normal copy of the gene on their other X chromosome and are not usually affected.
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