The Pedigree

The change in the nature of causes in a sense reflects the changes in what the constituents of systems of work are, what they are made of, and the reliability of the various constituents. When there was no electricity, there could be no short circuits when there was no radio communication, there could be no transmission errors when there was no software, there could be no software errors, etc. From the very beginning, systems 

The realisation that things can go wrong is as old as civilisation itself. The first written evidence is probably found in the Code of Hammurabi, produced circa 1760 BC, which even includes the notion of insurance against risk ( bottomry ) by which the master of a ship could borrow money upon the bottom or keel of it, so as to forfeit the ship itself to the creditor, if the money with interest was not paid at the time appointed at the ship s safe return. 

One of the earliest examples of a collective concern for safety and risk was the US Railroad Safety Appliance Act of 1893, which argued for the need to combine safety technology and government policy control. The railway was one of the first conditions in which innocent bystanders - meaning train passengers - were 

In the civihan domain, the fields of communication and transportation were the first to witness the rapid growth in scope and performance as equipment manufacturers adapted 

Other methods such as Failure Mode and Effects Analyses (FMEA) and Hazard and Operability Analysis (HAZOP) were developed not just to analyse possible causes of hazards (and, later on, causes of accidents), but also systematically to identify hazards and risks before a system was taken into operation or when a major change was considered. 

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Figure 13, The pedigree of a Caucasian family with Hh AtUmta or atpt Leu Pro(E19)...

Note If transmission occurs only through affected mothers and never through affected sons, the pedigree is likely to reflect mitochondrial inhoritance. 

Examination of the offspring in generation 3 shows that our prediction is met in all cases but one the last son in the pedigree has a 1,1 genotype but is unaffected. We infer that a crossover occurred in the chromosome transmitted from the mother to this offspring. Thus, on the basis of the limited information provided by this family, we estimate the recombination frequency to be one sixth, or about 17%. In other words, we predict that, about 17% of the time, a crossover will occur between the marker locus and the disease locus. In practice, a much larger sample of families is used to provide a more accurate estimate of the recombination frequency. If the recombination frequency is estimated to be 50%, the two loci are unlinked and may be on different chromosomes. 

What is the genotype at the hemophilia A locus of individual II-7 in the pedigree shown above ... 

Cell lineage. The pedigree of cells resulting from binary fission. 

Martin ER, Monks SA, Warren LL, Kaplan NL. A test for linkage and association in general pedigrees the pedigree disequilibrium test. Am J Hum Genet 2000 67 146-154. 

What is the pedigree of the numbers used as input to an exposure assessment ... 

Structural uncertainties in models can be dealt with in a variety of ways, including (1) parameterization of a general model that can be reduced to alternative functional forms (e.g. Morgan Henrion, 1990), (2) enumeration of alternative models in a probability tree (e.g. Evans et al., 1994), (3) assessment of critical assumptions within a model, (4) assessment of the pedigree of a model and (5) assessment of model quality. The first two of these are quantitative methods, whereas the others are qualitative. In practice, a typical approach is to compare estimates made separately with two or more models. However, the models may not be independent of each other with respect to their basis in theory or data. Thus, an apparently favourable comparison of models may indicate only consistency, rather than accuracy. 

Analysts often refer to data as being limited . In common, practical usage, the term limited might refer to any of several deficiencies, such as small sample size, lack of precision, lack of accuracy or lack of knowledge of the pedigree of the data. These limitations are related to the data quality concepts of accuracy and integrity. Depending on the type of limitation, the data quality problems can translate into implications for uncertainty or can lead to a representativeness problem. 

What is the pedigree of the numbers used as input to an exposure assessment This question deals with issues of who developed the numbers, how they were developed and who has reviewed them. For example, have they been subject to scientific peer review Are the numbers based upon measurements, or are these preliminary estimates based... 

Once the inheritance pattern of the disorder is determined, the status of family members in the pedigree can be evaluated. By carefully observing the position of affected individuals, mutation carriers may be identified. From this data, the risk of carrier status for other family members or the chance that a couple may have an affected child can be estimated. 

A couple has three girls, the last of whom is affected with cystic fibrosis. The first-born daughter marries her first cousin—that is, the son of her mothers sister—and they have a son with cystic fibrosis. The father has a female cousin with cystic fibrosis on his mother s side. Select the pedigree that best represents this family history from the diagrams below. 

I. A family presents with an unusual type of footdrop and lower leg atrophy that is unfamiliar to their physician. The pedigree below is obtained. Based on the pedigree, what is the risk of individual III-3 having an affected child ... 

A different family with retinitis pigmentosa is encountered, and the pedigree shown below is documented. What is the risk that a son born to individual 111-3 would be affected ... 

The answer is a. (Murray, pp 812-828. Scriver, pp 3-45. Sack, pp 97-158. Wilson, pp 23-39.) Autosomal recessive conditions tend to have a horizontal pattern in the pedigree. Men and women are affected with equal frequency and severity. It is the pattern of inheritance most often seen in cases of deficient enzyme activity (inborn errors of metabolism). Autosomal recessive conditions tend to be more severe than dominant conditions and are less variable than dominant phenotypes. Both alleles are defective but do not necessarily contain the exact same mutation. All individuals carry 6 to 12 mutant recessive alleles. Fortunately, most matings involve persons who have mutations at different loci. Since related persons are more likely to inherit the same mutant gene, consanguinity increases the possibility of homozygous affected offspring. 

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