Classical genetic markers and DNA markers: A ... - Springer Link

PRIMATES,34(3): 365-376, July 1993

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Classical Genetic Markers and DNA Markers: A Commensal Marriage W. H. STONE, J. J. ELY, G. S. MANIS, Trinity University Southwest Foundation for Biomedical Research and J. L. VANDEBERG Southwest Foundation for Biomedical Research

ABSTRACT. In this paper, we present an overview of classical genetic markers in nonhuman primates and then contrast the discriminatory powers of these markers with DNA markers. We have restricted the scope of our discussion to genetic markers found in blood, since they have been studied most extensively over the past 30 years. For example, immunoglobulin allotypes, complement markers, transferrins, and other protein markers can be identified using serum or plasma. Lymphocytes carry the major histocompatibility complex (MHC) markers, which are very polymorphic in most nonhuman primates. Lymphocytes are also used as a source of DNA. Finally, red blood cells carry an enormous array of blood group as well as isozyme markers. Our discussion will be limited to three species: rhesus monkeys (Macaca mulatta), baboons (Papio hamadryas), and chimpanzees (Pan troglodytes), although the principles are applicable to all nonhuman primates. Key Words: Blood groups; Biochemical polymorphisms; Tandem repeats; Parentage determination. BLOOD G R O U P M A R K E R S The blood group markers were a m o n g the first genetic markers clearly defined in nonh u m a n primates (DOGCLEnY & STONE, 1971; STONE, 1967). Chimpanzees are polymorphic for the h u m a n ABO blood groups and can be typed for them using a simple agglutination test. However, the majority of reagents that detect polyrnorphic systems in humans do not detect genetic variation in n o n h u m a n primates (SocHA, 1989). To type Old World monkeys, it is necessary to use operationally monospecific alloimmune sera (FREOERICI~ et al., 1990). A polyspecific blood typing serum would detect the products of several unidentifiable loci and, in this respect, would be similar to a multi-locus D N A fingerprinting probe. We have produced monospecific reagents that detect polymorphisms at 13 independent blood group loci in rhesus monkeys. Using these reagents, almost two million possible genotypes can be differentiated (STONE et al., 1987). These blood groups have been used for parentage testing (SULLIVAN et al., 1977) as shown in Table I. The offspring clearly inherited factors G1, H2, I1, and M3 from its father, since these are absent in the mother. The only male with all of these factors is designated the true father. This case demonstrates the power of markers which define genotypes over those which only characterize phenotypes. Blood groups have been used to study the relationship between male social dominance and reproductive success in a captive troop o f rhesus monkeys (CURIE-COHENet al., 1983). In this troop, the social structure remained relatively stable over an eight-year period,

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Table 1. Example of a disputed parentage case in rhesus monkeys solved by blood group typing. Animal

Abbreviated Blood Type (Genotype)

Offspring Mother Listed father True father

61/63 G3/ G 4 64/G 4 GI / G 4

H 1 / H2 H1/ H 1 nl /n I H1/ H 2

I1/i I2/l I2/i I1/1

L1/1 L1/ I L 2/l 1/l

M3/m M1/ m MI / M 3 M3 / M 3

Table 2. Mating behavior of the dominant and subordinant males in a closed colony:*. Male Avg. copulation (%) Avg. duration (rain.) Offspringsired (%) Dominant Subordinant (2nd) Subordinant (3rd) Others ( > 3rd)

67 14 7 12

11.2 3.6 5.6 3.7

13a - 32 b 30-48 12 - 18 8 - 53

*Data from CURIE-COHEN et al., 1983. a: Minimum percentage of offspring sired (denotes percentage of cases actually solved); b: maximum percentage of offspring sired (denotes cases where sire could not be excluded).

although the number of adult males varied from 4 to 10. Using blood typing, we determined paternity for 48 of 77 offspring born into the colony. The 62~ success rate is remarkable given that this was a closed troop with considerable inbreeding. Our results (Table 2) indicated that the dominant male sired only 13- 32~ of the offspring, even though he participated in 67~ of the observed copulations. Surprisingly, the second ranking male sired 30-48~ of the offspring, despite the fact that he participated in only 14~ of the observed matings. This research project was one of the first to use genetic markers to study mating behavior and reproductive success in nonhuman primates. Similar results have been obtained in rhesus and Japanese macaques (Macaca fuscata) (SMITH, 1981; INOUE et al., 1992). These studies are important for understanding and managing the genetic structure of captive breeding colonies.

SERUM PROTEIN MARKERS The serum protein markers include the transferrins (TF), complement components (C), immunoglobulin allotypes (IG), lipoprotein types (LP), and many others. These are usually detected by electrophoresis or by gel precipitation techniques combined with a variety of specific staining techniques (HARRIS & HOPKINSON, 1976; SMITHIES, 1955). Our discussion of serum protein markers will be limited to TF, since it is highly polymorphic in most species, and hence useful for solving disputed parentage cases. For example, rhesus monkeys exhibit up to 13 different TF alleles. Recently, we have adapted the automatic, programmable Phastsystem (Pharmacia-LKB, Piscataway, New Jersey) for running TFs of nonhuman primates (MANIS et al., in press). The many advantages of this technique, as compared to standard acrylamide or starch gel electrophoresis, include convenience (use of precast gels, etc.) and electrophoretic times ( 1 - 2 hours). Figure 1 illustrates a disputed parentage case involving TF polymorphisms in rhesus monkeys. Since the mother is homozygous for the C allele, the D allele in both offspring must have been transmitted by the father. Only individual F1 has the D allele and thus must be the father of both offspring.

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Fig. 1. Protein electrophoresis demonstrating the use of serum transferrins (TF) for paternity determination. Lanes l, 4, and 8 contain a composite size standard of known TF phenotypes. Samples of the offspring (lanes 2 and 3), mother (lane 6), and possible fathers (lanes 5 and 7).

ISOZYMES OF E R Y T H R O C Y T E S Isozymes have been extremely useful to biologists in many disciplines because about 25~ o f the loci sampled in a particular species are likely to be polymorphic (VANDEBERG, 1992). Isozymes are easily and distinctly identified by gel electrophoresis or isoelectric focusing. We routinely type for three isozymes in rhesus monkeys (DIA, 6PGD, and G P I ) (Fig. 2). D I A and 6 P G D are monomers and exhibit only two protein bands in heterozygotes, whereas G P I is a dimer and exhibits three bands in heterozygotes (MEERAKHAN, 1987). In a recent study, protein markers coded for by six independent loci (five isozyme loci and the TF locus) were used to estimate the level of genetic variation in two captive and one wild population of rhesus monkeys (GILLet al., 1992). One of the captive groups had a harem breeding system, the other captive group had been maintained as a closed population at the Wisconsin Regional Primate Research Center for many generations since it was brought intact from North India. The wild population consisted of a

Fig. 2. Electrophoretic pattern of three different isozymes (DIA, 6-PGD, and GPI) in rhesus monkeys run on cellulose acetate gels. DIA and 6-PGD are monomers, while GPI is a dimers.

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random sample of monkeys trapped from several troops inhabiting the same geographic area as the progenitors of the Wisconsin group. We found considerable genetic variation among the populations. Also, we found that all three populations had approximately the same mean heterozygosities despite the diverse breeding practices. These kinds of data are invaluable for genetic management of captive colonies of nonhuman primates, since they compare the degree of genetic variability in captive populations with that in the original, presumed outbred population.

MAJOR HISTOCOMPATIBILITY COMPLEX MARKERS Finally, MHC markers are found on lymphocytes. The MHC system of nonhuman primates (BALNER, 1977; LAWLORet al., 1990) is remarkably similar to that found in humans and mice (KLEIN, 1986). The class I genes code for a large array of surface antigens (glycoproteins) that are detected by polyclonal sera, usually obtained from multiparous females who were immunized transplacentally by fetal cells. The class I markers are very highly polymorphic and function in allograft rejection and in the killing of virus-infected cells. The class II antigens (JONKERet al., 1982) are less polymorphic and are involved in immune regulation. Typing for these MHC markers can be extremely labor-intensive, time-consuming, and expensive (HEISE et al., 1987). At present, typing for MHC loci is carried out at the DNA level using the polymerase chain reaction (PCR). Different alleles can then be distinguished by allele-specific oligonucleotides (WORDSWORTH et al., 1990). These data have been useful for elucidating the evolutionary history of the MHC (GYLLENSTEN& ERLICH, 1989; LAWLORet al., 1990).

TANDEM REPEAT LOCI Restriction fragment length polymorphisms (RFLPs) which detect restriction site variation have been used extensively in human genetics, and have also been applied in nonhuman primates (DONIS-KELLERet al., 1987; ROGERS, 1992; ROGERS et al., 1992). Due to their limited variability, most recent interest in DNA markers focuses on tandem repeat loci. Polymorphisms of tandem repeat loci result from insertions or deletions of repetitive DNA elements. The advantages of studying such loci became clear when two tandem repeat loci near the myoglobin locus were cloned and characterized in humans (JEFFREYSet al., 1985a, b). These probes revealed extensive interindividual variability in humans, and have been used for DNA fingerprinting in many species (see ELY et al., 1991, Table III; REEVE et al., 1990, Fig. 3). They have also been used extensively for the identification and cloning of species-specific probes (BURKE et al., 1991; GEORGESet al., 1991). Unfortunately, tandem repeat polymorphisms have been given a bewildering variety of terms. Many of these terms emphasize unimportant details, including the technology of detection (e.g. Amp-FLPs, RAPDs), length of repeat units (VNTR, VNDR), complexity of repeat sequences (SSLPs, STRs), and presumed homologies to the classical repetitive DNAs originally identified by cesium chloride density gradient centrifugation (mini-, midi-, microsatellites). We propose a terminology which reflects the molecular basis of the variability. The essential feature of insertion/deletion polymorphisms is that they consist of DNA sequences organized as tandem repeats. This term emphasizes their repetitive, nondispersed nature, it does not require that a locus be characterized by high levels of


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variability, repeat units may be short or long, and the locus may be detectable by any appropriate technology. The primary distinction to be made is between single and multilocus characterizations. " D N A typing" is an appropriate term for the characterization of single tandem repeat loci. "Typing" suggests genotyping, indicating that the basis of the information is genetic. Thus, DNA typing corresponds to typing with the classical genetic markers, which also detect discrete, identifiable, Mendelizing units. These markers allow for genetic studies such as segregation and linkage analyses, quantification of heterozygosity, and estimation of allelic frequencies (HACKLEMAN et al., 1993). " D N A fingerprinting" refers to a multi-locus characterization or profile. The term "fingerprinting" is actually a misnomer. There is no a priori reason why tandem repeats should be hypervariable in any particular species. The variability of these loci depends upon the population genetics and the evolutionary history of the gene family detected and of the species studied. Because individual loci are very difficult to identify and characterize, no true genetic analyses are possible. Consequently, paternity determinations and other approximations of genetic parameters must be based on probability theory (JEFVREYS et la., 1991; YASSOURDIS& EPPLEN, 1991).

Multiple Tandem Repeat Loci The tandem repeat loci detected by multi-locus probes results in a pattern of many bands which may be polymorphic. Oddly enough, the very multiplicity of bands which promised to make DNA fingerprinting so informative is also the source of major shortcomings and analytical problems. For example, without segregation analysis involving known pedigrees, it is impossible to tell which bands represent which loci. Consequently, multi-locus probes are not useful in studies that require tracking genes across generations, as in linkage analysis or selection studies. An interesting exception has been described in cattle (GEORGES et al., 1990). The uncertainty resulting from the high mutation rates at tandem repeat loci (DEKA et al., 1991) is compounded by the use of multi-locus probes. When a dozen or more loci which can not be precisely identified are exhibited simultaneously, it may not be unusual to find one offspring band that is not present in either parent. Since neither loci nor allelic bands can be determined, the problem is somewhat more complicated than sequential use o f single tandem repeat loci. Furthermore, accurate paternity determinations are possible only if the offspring and both parents are run on the same gel, since the large number of bands typically precludes matching bands across different autoradiographs. For cases of individual identification, it is necessary to know the probability of finding another individual in the reference population with the same band. But the relevant population data do not exist, since specific alleles cannot be identified. Again, some interesting and notable exceptions exist (G~LBEgT, et al., 1990, 1991). Individual profiles can be difficult to reproduce, and often show variations in band intensity, band shifting, and other peculiarities that make interpretations unreliable or inaccurate. We reported earlier what appeared to be a mutant band revealed by M13 DNA fingerprinting in chimpanzees (ELY & FERRELL, 1990). Figure 3 compares that result to the same family fingerprinted after a longer electrophoretic run to allow greater separation o f fragments. The longer run clearly indicates that the presumed mutant band is of maternal origin. Curiously, a new and different band appeared on the second autoradiograph. The dilemma lies in deciding whether this second novel fragment is indeed a mutation, or

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Fig. 3. Possible mutation in a chimpanzee family fingerprinted with bacteriophage M13. (Right) A fragment of about 4Kb found in a chimpanzee (see arrow) is not clearly visible in the mother, yet could not be attributed to the presumed sire. (Left) After longer electrophoresis, the 4Kb fragment is clearly demonstrated to be of maternal origin. However, a novel fragment of about 6Kb, not present in either parent (see arrow) is now visible in the offspring.

merely an artifact of an inherently unreliable technique. Finally, the crucial role played by the conditions of stringency in determining the number of bands detected on a given filter should not be overlooked.

Single Tandem Repeat Locus Because of substantial limitations in the use o f multi-locus probes, we have turned our attention to single tandem repeat loci (ELy, DEKA, CHAKRABORTY,& FERRELL, 1992; ELY, SPONEYBARGER, MANIS, MORTON, & STONE, 1992). Tandem repeat loci characterized in humans, cattle, mice, and fish exhibit a high degree of heterozygosity with many alleles, and therefore are very efficient for parentage determination and for population genetic studies (BURKE et al., 1991). For example, Figure 4 depicts a disputed parentage case in chimpanzees resolved using a tandem repeat locus near the alpha globin gene cluster. Because of the high heterozygosity at this locus, and since alleles could be precisely attributed to each parent, the true sire was readily assigned. Only about 50O7oof the human tandem repeat probes cross-hybridized to great ape DNA (WOLFF et al., 1991). Furthermore, many of the probes which do cross-hybridize reveal monomorphic loci (ELY, DEKA, CHAKRABORTY, & FERRELL, 1992). For example, as shown in Figure 5, a tandem repeat locus which is highly variable in humans is monomorphic in chimpanzees. More distantly related species, such as macaques, require screening an even larger number of human probes to identify homologous polymorphic loci (ELY, SPONEYBARGER, MANIS, MORTON, & STONE, 1992). Figure 6 demonstrates that some tandem repeat loci which are variable in humans are also variable in rhesus monkeys. Much of the work faced by primate geneticists is to identify which human-derived tandem repeat loci have informative homologues in particular


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Fig. 4. Chimpanzee parentage case resolved with a probe that detects a tandem repeat locus near the alpha-globin gene cluster. The first sire is excluded, since he does not possess the fragment shown in the offspring that is not present in the mother.

Fig. 5. Human tandem repeat locus D17S5 is polymorphic in humans but monomorphic in chimpanzees.

n o n h u m a n primate species of interest and are appropriate for parentage determination and population genetics. When the alleles are small enough, tandem repeat loci can be studied using the PCR. Di-, tri-, and tetra-nucleotide repeats are scattered throughout h u m a n and other m a m m a l i a n genomes (EDWARDS et al., 1992; LOVE et al., 1990; WEBER & MAY, 1989). Their smaller repeat units are associated with somewhat lower heterozygosity compared to many larger tandem repeats, but they often exhibit multiple alleles (WEBER, 1990). Dinucleotide repeats appear to be associated with single-copy genes (HAMADAet al., 1982).

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Fig. 6. A highly variable tandem repeat locus in rhesus monkeys.

Because they detect single polymorphic loci which can be rapidly typed, these markers are likely to replace the multi-locus probes.

PROGRESSIVE PATERNITY EXCLUSION Before one can answer the question of whether or not there is a commensal marriage between classical markers and DNA markers, it is necessary to consider the specific aim of the study. If the aim is simply parentage testing (SMITH et al., 1984), one approach is to use the classical markers first. Despite their lower resolving power, they are unequivocal, simple, and economical in cost and time. If they do not resolve the case, the use of DNA markers is appropriate as a second approach (DE RUITER et al., 1992; SMITH et al., 1992). We call this approach to genetic typing Progressive Parentage Exclusion. Table 3 illustrates this progressive approach in a disputed parentage case in rhesus monkeys. The mother and her infant (Ego) plus the six putative fathers were typed initially for the TFs. From these results, males 01 and 17 were excluded, because neither had the TF D allele which was present in Ego's serum and had to be inherited from the father. The four remaining males, plus the mother-offspring pair, were then tested for the isozyme CA II. From this test, males 12 and 31 were excluded because neither had the paternal B allele. The two putative fathers remaining (30 and 32), as well as the mother and Ego, were tested for the isozyme DIA, but the results were inconclusive. Finally, male 30, the mother, and the infant were fingerprinted with M13 bacteriophage. (No DNA sample from male 32 was available at that time.) The fingerprint showed five paternal bands in Ego that were also present in male 30. We estimated the band-sharing probability in this colony and used a conservative method to estimate inclusion probabilities (GEORGES et al., 1988). The probability that male 30 was the true father among all possible fathers was 0.797, and we tentatively designated him as the father. We emphasize the probabilistic nature of this infer-

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Classical and DNA Genetic Markers Table 3. Progressive paternity exclusion in rhesus monkeys. Protein marker Animal ID "TF" CA H DIA Ego 40B DD BB 2- 3 Mother 14 DG BB 2- 3 Possible fathers 01 CC 17 CG 12 CD AA 31 DF AA 30 DG BB 2- 2 32 CD BB 2- 2 *M13 DNA fingerprinting indicated a 79.7070 probability that male 30 is corroborated using a single locus tandem repeat marker.

Bases of sire exclusion

TF TF CAII CAll None* None the sire. This conclusion was later

ence. We subsequently corroborated these M13 results using a single-locus t a n d e m repeat marker, which clearly excluded male 32 but not male 30. This case concisely demonstrated the utility o f combining classical and D N A markers for disputed parentage cases (MARTIN et al., 1992). A discussion o f genetic markers would be incomplete without considering their usefulness to colony m a n a g e m e n t (SMITH, 1980; DYKE et al., 1987). For assessing heterozygosity, gene diversity and inbreeding, the classical markers have been invaluable (MELNICK, 1988). Tandem repeat loci originally identified in h u m a n s can be very useful if they detect a high level o f variability in a n o n h u m a n primate species. They m a y be more useful t h a n the classical markers for determining parentage and estimating p o p u l a t i o n genetic parameters. As these loci are identified and characterized for each species, the application o f P C R will significantly reduce the labor and cost o f genotyping while providing data essential for genetic typing and m a n a g e m e n t o f primate colonies (ERLICH et al., 1991). The classical markers are standard and authoritative, while the D N A markers and their applications to n o n h u m a n primates are new and still evolving. We firmly believe that a c o m m e n s a l marriage exists between the two. Each type o f marker has its role. The challenge is to use each singly or together as appropriate.

Acknowledgements. We thank UT MD Anderson System Cancer Center, Bastrop, TX, NIH-NICHD Animal Center, Poolesville, Maryland and the Wisconsin Regional Primate Research Center, Madison, Wisconsin for supplying blood samples used in many of the results described here. We gratefully acknowledge MYRTLEJUELG for typing the manuscript. This work was supported in part by NIH grants RR04301 and RR05080 to WHS and HL28972, HL39890, and HG00336 to JLV.

REFERENCES

BALNER, H., 1987. The major histocompatibility system of subhuman primate species. In: The Major Histocompatibility Systems in Man and Animals, D. GOTZE (ed.), Springer-Verlag,

Berlin, pp. 79-127. BURKE, Z., G. DOLE, A. J. JEEEREYS, • R. WOLFF, 1991. DNA Fingerprinting: Approaches and Applications. Birkhauser Verlag, Basel. CURIE-COHEN, M., J. L. VANDEBERG,& W. H. STONE, 1983. Opportunities for genetics in research on non-human primates. Evolution, 12: 573-585.

374

W . H . STONEet al.

DEKA,R., R. CHAKRABORTY,• R. E. FERRELL,1991. A population genetic study of 6 VNTR loci in 3 ethnically defined populations. Genomics, ll: 8 3 - 92. DONIS-KELLER, H., P. GREEN, C. HELMS et al., 1987. A genetic linkage map of the human genome. Cell, 51: 319-337. DUGGLEBY,C. & W. H. STONE, 1971. Immunogenetic studies of rhesus monkeys: I. the G blood group system. Vox Sang., 20: 109- 123. DYKE, B., T. B. GAGE, J. L. VANDEBERG,R. H. KING, P. M. MAMELKA,M. L. CHENG,& W. J. GOODWlN, 1987. Decision making in genetic management of primate breeding colonies. Genetica, 73: 137-144. EDWARDS, A., H. A. HAMMOND, L. J~N, C. T. CASKEY,& R. CHAKRABORTY,1992. Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups. Genomics, 12:241-253. ELY, J., P. A. ALFORD, & R. E. FERRELL, 1991. DNA "fingerprinting" and the genetic management of a captive chimpanzee population (Pan troglodytes). Amer. J. Primatol., 24: 3 9 - 5 4 . - - - , R. DEKA, R. CHAKRABORTY,& R. E. FERRELL, 1992. Comparison of five tandem repeat loci between humans and chimpanzees. Genomics, 14: 692-698. & R. E. FERRELL, 1990. DNA "fingerprinting" and paternity ascertainment in chimpanzees. Zoo Biol., 9 : 9 1 - 9 8 . - - , K. SPONEYBARGER,G. S. MANIS, K. MORTON, & W. H. STONE, 1992. Characterization of single and multiple tandem repeat loci in rhesus monkeys (Macaca mulatta). Paper presented at the Second International Conference on DNA fingerprinting, Belo Horizonte, Brazil, November 1992. ERLICH, H. A., O. GELFAND,& J. J. SNINSKY, 1991. Recent advances in the polymerase chain reaction. Science, 252: 1643-1651. FREDERICK, D. L., N. K. SAMPLES,& W. H. STONE, 1990. Three new blood groups of rhesus monkeys. Amer. J. Primatol., 20: 127-131. GEORGES,M., A. GUNAWARDANA,D. W. THREADGILLet al., 1991. Characterization of a set of variable number of tandem repeat markers conserved in Bovidae. Genomics, 11: 2 4 - 32. - - , M. LATHROP,P. HILBERTet al., 1990. On the use of DNA fingerprints for linkage studies in cattle. Genomics, 6 : 4 6 1 - 4 7 4 . - - , A.-S. LEQUARRE, M. CASTELLI, R. HANSET, & G. VASSART, 1988. DNA fingerprinting in domestic animals using four different minisatellite probes. Cytogen. Cell Gen., 47: 127-131. GILBERT, D. A., N. LEHMAN, S. J. O'BR1EN, & R. K. WAYNE, 1990. Genetic fingerprinting reflects population differentiation in the California Channel Island fox. Nature, 344: 764-767. - - , C. PACKER, A. E. PUSEY, J. C. STEPHENS, & S. J. O'BRIEN, 1991. Analytical DNA fingerprinting in lions: parentage, genetic diversity, and kinship. J. Heredity, 82: 378-386. GILL, P. S., J. BLANGERO,G. S. MANIS, J. SCHEFFLER,M. E. KEEL1NG,& W. H. STONE, 1992. Genetic structure of three populations of rhesus macaques (Macaca mulatta): implications for genetic management. Amer. J. Primatol., 27: 8 5 - 92. GYLLENSTEN, U. B. & H. A. ERLICH, 1989. Ancient roots for polymorphism at the HLA-DQa locus in primates. Proc. Nat. Acad. Sci., 86: 9986-9990. HACKLEMAN, S. M., C. M. KAMMERER, S. MANIS, J. SCHEFFLER, B. DYKE, & W. H. STONE, 1993. Linkage between two blood group markers in rhesus monkeys (M. mulatta). Cytogen. Cell Genet., 62: 5 6 - 5 7 . HAMADA, H., M. G. PETR1NO, & Z. KAKUNAGA,1982. A novel repeated element with Z-DNA-forming potential is widely found in evolutionarily diverse eukaryotic genomes. Proc. Nat. Acad. Sci., 79: 6465 - 6469. HARRIS, H. & D. A. HOPKINSON, 1976. Handbook of Enzyme Electrophoresis in Human Genetics. North Holland Pub., Amsterdam. HEISE, E. R., D. J. BOOK, B. S. SCHEPART,C. H. MANNING,M. R. MCMAHON, M. CHEDID, t~ C. A. KEEVER, 1987. The major histocompatibility complex of primates. Genetica, 73: 5 3 - 6 8 . INOUE, M., F. MITSUNAGA, H. OHSAWA, A. TAKENAKA, Y. SUGIYAMA, A. G. SOUMAH, ~r O. TAKENAKA,1992. Paternity testing in captive Japanese macaques (Macaca fuscata) using DNA fingerprinting. In: Paternity in Primates." Genetic Tests and Theories, R. D. MARTIN, A. E DIXSON, t~r E. J. WICKINGS(eds.), Karger, Basel, pp. 131-140. -

-


375

JEFFREYS, A. J., M. TURNER, t~ P. DEBENHAM, 1991. The efficiency of multilocus DNA fingerprint probes for individualization and establishment of family relationships, determined from extensive casework. Amer. J. Human Genet., 48: 824-840. - - , V. WILSON,t~ S. L. THEIN, 1985a. Hypervariable "mini-satellite" regions in human DNA. Nature, 316: 6 7 - 7 3 . , & - - , 1985b. Individual-specific "fingerprints" of human DNA. Nature, 316: 7 6 - 7 9 . JONKER, M., G. MEURS, & H. BALNER, 1982. Typing for RhLA-D in Rhesus monkeys: II genetics of the D antigens and their association with DR antigens in a population of unrelated animals. Tissue Antigens, 19:69 - 78. KLEIN, J., 1986. Natural History o f the Major Histocompatibility Complex. Wiley, New York. LAWLOR, D. A., E. WARREN, /7. E. WARD, ~r P. PARHAM, 1990. Comparison of class I MHC alleles in humans and apes. Immunol. Rev., 113: 147-185. LOVE, J. M., A. M. KNIGHT,M. A. MCALEER, & J. A. TODD, 1990. Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Res., 18: 4123 - 4130. MAN1S, G. S., N. K. SAMPLES,• W. H. STONE,in press. A simple method for genetic typing of transferrins in nonhuman primates. Lab. Anita. Sci. MARTIN, R. D., A. F. D1XSON,& E. J. W1CKINGS(eds.), 1992. Paternity in Primates: Genetic Tests and Theories - - Implications o f Human DNA Fingerprinting. S. Karger, Basel. MEERA KHAN, P., 1987. Isozymes as bioprobes for genetic analysis of nonhuman primates. Genetica, 73: 2 5 - 36. MELNlCK, D. J., 1988. The genetic structure of a primate species: rhesus macaques and other cercopithecine monkeys. Int. J. Primatol., 9 : 1 9 5 - 2 3 1 . REEVE, H. K., D. F. WESTNEAT,W. A. NOON, P. W. SHERMAN,& C. F. AQUANDRO,1990. DNA fingerprinting reveals high Ievels of inbreeding in colonies of the eusocial naked mole-rat. Proc. Nat. Acad. Sci., 87: 2496-2500. ROGERS, J., 1992. Nuclear DNA polymorphisms in hominoids and cercopithecoids: applications to paternity testing. In: Paternity in Primates: Genetic Tests and Theories - - Implications o f Human D N A Fingerprinting, R. D. MARTIN, A. E DlXSON, & E. J. WICK1NCS(eds.), S. Karger, Basel, pp. 82-91. - - , G. RUANO, & K. K. KIDD, 1992. Variability in nuclear DNA among nonhuman primates: application of molecular genetic techniques to intra- and inter-species genetic analyses. Amer. J. Primatol., 27: 93-105. DE RUITER, J. R., W. SCHEFFRAHN,G. J. J. M. TROMMELEN,A. G. U1TTERLINDEN,R. D. MARTIN,& J. A. R. A. M. VANHOOFF, 1992. Male social rank and reproductive success in wild long-tailed macaques. In: Paternity in Primates." Genetic Tests and Theories - - Implications o f Human DNA Fingerprinting, R. D. MARTIN, A. E DlXSON, & E. J. WICK1NGS(eds.), Karger, Basel, pp. 175-191. SMITH, D. G., 1980. Potential for cumulative inbreeding and its effects upon survival in captive groups of nonhuman primates. Primates, 21: 430-436. - - , 1981. The association between rank and reproductive success of male rhesus monkeys. Amer. J. PrimatoL, 1 : 8 3 - 9 0 . - - , B. ROLFS, & J. LORENZ, 1992. A comparison of the success of electrophoretic methods and DNA fingerprinting for paternity testing in captive groups of rhesus macaques. In: Paternity in Primates: Genetic Tests and Theories - - Implications o f Human D N A Fingerprinting, R. D. MARTIN, A. E DIXSON, & E. J. WICKINGS(eds.), S. Karger, Basel, pp. 3 2 - 5 2 . , M. E SMALL, C. E. AHLFORS, E W. LOREY, B. R. STERN, & B. K. ROLVS, 1984. Paternity exclusions analysis and its applications to studies of nonhuman primates. Adv. Vet. ScL Comparat. Med., 2 8 : 1 - 2 4 . SMITHIES, O., 1955. Zone electrophoresis in starch gels: group variation in serum proteins of normal human adults. Biochem. J., 61: 629-641. SOCHA, S., 1989. Blood group serology of apes and monkeys. In: Perspectives in Primate Biology, Vol. 2, P. K. SETH & S. SETH (eds.), Today & Tomorrow's Printers & Publishers, New Delhi, pp. 145 - 165. STONE, W. H., 1967. Immunogenetics of type-specific antigens in animals. In: Advances in Immunogenetics, T. J. GREENWALT(ed.), Lippincott, Philadelphia, pp. 173-215.

376

W . H . STONEet al.

- - , R. C. S. TREICHEL, t~ J. L. VANDEBERG, 1987. Genetic significance of some common primate models in biomedical research. In: Animal Models: Assessing the Scope o f Their Use in Biomedical Research, Alan. R. Liss, New York, pp. 7 3 - 93. SULLIVAN, P. T., C. BLYSTAD,~; V~7, H. STONE, 1977. Immunogenetic studies of rhesus monkeys: XI. use of blood groups in problems of parentage. Lab. Anita. Sci., 47:348 - 351. VANOEBERG, J. L., 1992. Biochemical markers and restriction fragment length polymorphisms in baboons: their power for paternity exclusion. In: Paternity in Primates: Genetic Tests and Theories - - Implications o f Human DNA Fingerprinting, R. D. MARTIN,A. E DIXSON, & E. J. WICKINGS (eds.), S. Karger, Basel, pp. 1 8 - 31. WEBER, J. L., 1990. Informativeness of human (dC-dA)no(dG-dT)n polymorphisms. Genomics, 7: 524 - 530. & P. E. MAY, 1989. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Amer. J. Human Genet., 44: 388-396. WOLFF, R., Y. NAKAMURA,S. ODELBERG, R. SHIAN% & W. WHITE, 1991. Generation of variability at VNTR loci in human DNA. In: DNA Fingerprinting: Approaches and Applications, T. BURKE, G. DOLF, A. J. JEFFREYS, & R. WOLFF (eds.), Birchauser-Verlag, Basel, pp. 2 0 - 3 8 . WORDSWORTH, B. P., C. E. M. ALLSOPP, R. P. YOUNG, & J. I. BELL, 1990. HLA-DR typing using DNA amplification by the polymerase chain reaction and sequential hybridization to sequencespecific dinucleotide probes, lmmunogenetics, 32: 413- 418. YASSOURDIS, A. & J. T. EPPLEN, 1991. On paternity determination from multilocus DNA profiles. Electrophoresis, 12:221 - 226. -

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Received: December 29, 1992; Accepted: March 15, 1993

Authors' Names and Addresses: W. H. STONE,J. J. ELY,G. S. MANIS,Department of Biology, Trinity University, San Antonio, Texas 78212, U. S. A. and Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228, U. S. A.; J. L. VANDEBERG,Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228, U. S. A.