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When the nuclei fuse, a hybrid cell is formed, and this hybrid tends to lose human chromosomes preferentially through succeeding generations Upon stabilization, the result is a cell with one or more human chromosomes in addition to the original mouse or hamster chromosomal complement Banding techniques allow the observer to recognize the human chromosomes A geneticist looks for speci c human phenotypes, such as enzyme products, and can then assign the phenotype to one of the human chromosomes in the cell line When cells are mixed together for hybridization, some cells do not hybridize It is thus necessary to be able to select for study just those cells that are hybrids One technique, originally devised by J W Little eld in 1964, makes use of genetic differences in the way the cell lines synthesize DNA Normally, in mammalian cells, aminopterin acts as an inhibitor of enzymes involved in DNA metabolism.

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1 Any sinusoidal signal may be mathematically represented in one of two ways: a time-domain form, v(t) = A cos( t + ) and a frequency-domain (or phasor) form, V(j ) = Aej = A Note the j in the notation V(j ), indicating the ej t dependence of the phasor In the remainder of this chapter, bold uppercase quantities will be employed to indicate phasor voltages or currents (Continued)

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Two enzymes, hypoxanthine phosphoribosyl transferase (HPRT) and thymidine kinase (TK), can bypass aminopterin inhibition by making use of secondary, or salvage, pathways in the cell If hypoxanthine is provided, HPRT converts it to a purine, and if thymidine is provided, TK converts it to the nucleotide thymidylate (Purines are converted to nucleotides and nucleotides are the subunits of DNA see chapter 9) Thus, normal cells in the absence of aminopterin synthesize DNA even if they lack HPRT activity (HPRT ) or TK activity (TK ) In the presence of aminopterin, HPRT or TK cells die However, in the presence of aminopterin, HPRT TK cells can synthesize DNA and survive Using this information, the following selection system was developed Mouse cells that have the phenotype of HPRT TK are mixed with human cells that have the phenotype of.

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(Concluded) 2 A phasor is a complex number, expressed in polar form, consisting of a magnitude equal to the peak amplitude of the sinusoidal signal and a phase angle equal to the phase shift of the sinusoidal signal referenced to a cosine signal 3 When using phasor notation, it is important to make a note of the speci c frequency, , of the sinusoidal signal, since this is not explicitly apparent in the phasor expression

Techniques were developed around 1970 that make use of certain histochemical stains that produce repeatable banding patterns on the chromosomes. For example, Giemsa staining is one such technique; the resulting bands are called G-bands. More detail on these techniques is presented in chapter 15. Before these tech-

Compute the phasor voltage resulting from the series connection of two sinusoidal voltage sources (Figure 428)

Known Quantities:

The McGraw Hill Companies, 2001

Find: Equivalent phasor voltage vS (t)

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uman population geneticists can increase the accuracy of their linkage analysis by using a probability technique, developed by Newton Morton, called the lod score method (Log Odds). The geneticist asks what the probability is of getting a particular pedigree assuming a particular recombination frequency ( ), as compared with getting the same pedigree assuming independent assortment ( 0.50). In other words, he or she calculates the ratio of the probability of genotypes in a family given a certain crossover frequency compared with the probability of those genotypes if the loci are unlinked. Logarithms are used for ease of calculation, and the parameter is called z, the lod score. Using this method, a researcher can try different crossover frequencies until the one giving the highest lod score is found. For example, take the pedigree in gure 6.28. The father in generation

v2(t)

Analysis: Write the two voltages in phasor form:

(0.25)8. This is the denominator of the equation. Thus, z z log (0.4375)7(0.0625) (0.25)8 1.099

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