CHAPTER 18
MEASURES OF GENETIC VARIABILITY AND AIDS TO SELECTION USING BLOOD TYPES

by

M. Braend
Veterinary College of Norway
Oslo Dep.
Boko 8146
Oslo
Norway

Summary

The term "blood type" or "blood marker" in its broad sense includes all genetically determinad and variable characteristics of blood. There are two major categories. Differ-ences in the antigenic structures of cell membranas are characterized by the use of specific antibodies. The other category oonsists of variations in water-soluble molecules within cells and in the plasma. The latter are usually detected by various electrophoretic techniques.

A survey of blood markers in cattle, pigs, sheep, horses, water buffaloes and goats is presented. Theories and modela on the reasons for their variability and the maintenance of polymorphic systems are discussed. In the opinion of the author the neutralist view, as well as various selectionist theories, are all valid but due to evolutionary forces and environmental interaotions the mechanisms in operation change over time.

Blood markers in livestock are today utilizad for a variety of purposes. They are par­ticularly useful for the control of parentage, the characterization of bread structure and the relationship between breeds and populations. But for the improvement of production characters controlled by quantitative genes, such as milk production, they are general1y of little or no value as aids in selection. In conditions where immunological aspects are of etiological significance, the blood markers, particularly membrane antigens, may be of value for the understanding, control and eradication of diseases.

18.1 Introduction

The term "blood type" or "blood group" may be used in a narrow or a broad sense. In the narrow or classical sense the blood type of an individual is expressed by a formula of letters. These letters are designations of genetically variable characteristics of macro-molecules which are part of, or firmly bound to, the erythrocyte membrane. These character­istics or traits are oontrolled by genes which usually bear the same letter symbols as the traite themselves. We may also have the blood type formula expressing a combination of characteristics and genes. Characterization of the blood types in the erythrocyte membrane which are called antigenic determinante, blood factors or simply factors takes place through serological immunological techniques by the use of specific antibodies, hence the term immunogenetics for this branch of biology.

In the broad sense the term "blood type" includes all genetically determinad variable characteristics of blood. The white cells and the platelets also have chemical structures or macromoleeules in their cell membranes. These structures, which have been given symbols of letters or figures, may also be characterized and differentiated by the use of serological techniques.

Genetically determined variability also oceurs for molecules within cells and in the blood plasma. These may be complex molecules such as serum proteins and enzymes, but also simpler substances such as small organic molecules or minerals. The variability of these "water—Boluble" molecules within cells and in plasma may, for the complex ones, also be diagnosed by the use of serological techniques. But by far most common method for character-ization is electrophoresis.

The inheritance of blood type genes, whether they control molecules of cells or plasma, is usually of qualitative or discontinuous nature. In recent years the term "marker gene" has been commonly used for such genes. The corresponding term for the characteristics as such is "marker".

18.2 Current status of blood groups in livestock

18.2.1 Markers in the red cell membrane

Cattle. A survey is given in Table 18.1. The list is based on that compiled by Erhard (1977).The blood factors are detected by replicas of the original monospecific cattle reagents produced at the University of Wisconsin (Perguson et al», 1942) or reagents spec-ifying additional factors produced first either in U.S.A. or Europe. In addition to the 37 reagents specifying the factors of Table 18.1, of which the great majority are prepared after isoimntunizations there are an unknovm number of additional reagents in use at various laboratorios. TheBe have been given preliminary symbols. An example is F 18, for a certain Frencn reagent. The total number of cattle reagents in use is therefore probably above 100.

The J system falls in a category by itself, since the J factor is secondarily acquired by the red cell from "water-soluble" J substance in the plasma (Stormont 1949). The J substance is reported to be controlled by a series of multiple alleles (Conneally et al., 1962). Furthermore, the J factor is detected by normally oceurring antibodies which occur in some of the J-negative animals.

The first theory about the inheritance of blood factors (Perguson et al., 1942) assumed that the individual red cell membrane factors were controlled by genes, presence being dominant over absence. When the great complexity of cattle blood types was established (Stormont et al., 1950 a theory of multiple alleles was proposed for the complex systems. Accordingly, an allele might be in control of more than one blood factor. Such a combination of factors was called a "blood group", an example being BO₂Y₁A'E₃.Later the term pheno-group was introduced (Stormont 1955). The total number of multiple alleles of the B system so far reported is of the order of 1000. Auditore and Stormont (1978) also gave evidence for the single locus theory.

As more and more cattle blood group laboratorios were initiated and large numbers of cattle were typed, several cases of irregular inheritance were reported. A theory of closely linked genes making up the B system was therefore proposed (Oreen 1966; Bouw and Piorentini 1970). Additional evidence in support of the theory was provided by Ruiterkamp et al. (1977) and Grosclaude et al. (1979). Tentative linear relationships between the genetic determinante in control of the B system factors are presented in Figure 18.1. The figure also gives the relationship between determinante of factors of group of factors not yet placed on the map. Grosclaude et al. (1979) estimated the length of the DNA sequence coding for the B system to be a minimum of 0.7 centimorgan corresponding to some 100 differ-ent cistrons.

A tentativo but simpler linear map has also been proposed for the C system (Bouw et al., 1974).

Pigs. Reviews have been published by Andresen (1962, 1963) and Gahne (1977). A list of antigenic factors is given in Table 18.2. The nomenclature is different from that of cattle blood types, allowing for a much higher number of symbols within complex systems. It can further be seen that, even though there are complex systems in pigs, none of these shows a great variation as the B system of cattle.

Sheep. Reviews have beon published by Tucker (1971, 1975). In Table 18.3 the number of antigenic factors, agreed upon by sheep blood group specialists and by the International Society for Animal Blood Group Research (ISABR), are presented. It should be mentioned that a higher number of B-system factors has been reported (Rasmusen 1960) but since these were diagnoeed Tagr the use of cattle reagents the corresponding factor synibols are no longer used. There are also two additional systems which are detected by snail's and other extraots, They have been named Hel and Con (Sohmid and Uhleribruck 1972; Schmid and Cwik 1974).

Horses. The number of blood-factor reagents agreed upon by horse blood-group workers of ISABR is low (Table 18.3) compared with cattle and pigs. But the number of experimental reagents in the 1977 horse comparison test organized by the Norwegian laboratory was as high as 110, reflecting the great complexity also of horse red cell membrane antigens. For horses a system of nomenclature similar to that for pigs and sheep has been adopted.

Water buffaloes. This species has not been subjected to as much research as the species mentioned above. Two approaches have been made. Cross-reacting cattle reagents have been utilized. But isoimmune antisera provoked through experimantal blood transfusions allowed Khanna (1973), in an extensive study, to differentiate between 21 blood factors and 7 loci.

Goats. In Table 18.3 goats appear with a higher number of blood factors than sheep. This is due to the fact that there has not as yet been universal agreement on reagents. furthermore, a great number of the goat red cell factors and their genetic systems have been worked out utilizing results in comparative studies between goats and sheep (Schmid and Suzuki 1971: Schmid et al. 1975).

18.2.2 Markers in the white cell membrane

Our domestic species have as yet not been characterized to the same extent as mouse and man. But by using immune sera obtained by skin grafting, immunizations or from parous females, cattle, pigs, sheep, horses and goats have all been reported to have systems similar to the major histoeompatibility complex (MHC) in man. For references see Animal Blood Groups and Biochemical Genetics (1979, 1980).

18.2.3 Markers in the plasma

A survey of those systems which have been most extensively investigated is given in Table 18.4. In addition a number of systems have been found to vary in one or two species only.

Prealbumin. This protein which migrates ahead of albumin under certain electrophoretic conditions has been reported with two variant forms in pigs (Kristjansson 1963) and with two variable systems, each with three alleles, in sheep (Efremov et al., 1970)

In horses the Pr protein which belongs to the acidic prealbumins has been shown to be a protease inhibitor and corresponds to a₁-antitrypsin in man (Ek 1977). The equine Pr system is highly polymorphic with 12 alleles (Braend 1980) and with strong indications of additional ones. Recently Juneja et al. (1979) presented evidence that the Pr system is controlled by two linked genetic systems for which they proposed the terms Pi1 and Pi2.

Another acidic prealbumin system in horses, the Xk system occurs with 3 alleles (Braend 1970). This corresponds to a system callad postalbumin in alkaline gels. This postalbumin system is different from the postalbumin system in Table 18.4, the latter controlling the vitamin D binding protein and being closely linked to the locus controlling albumin.

Post-transferrin. Two Bystems, Ptf and Ptf2 have been described in cattle, each with two molecular patterns (Thinnes et al. 1976; Gahne et al. 1977) corresponding to two codominant alíeles.

B-globulin. Sartore et al. (1967) reported a variable system in cattle explained by two codominant alíeles. It is not known whether this system corresponds to any of the two post-transferrin systems mentioned above.

Haemopexin (Hpx). This is the haem-binding protein which is reported with 7 alleles in pige (Hesselholt 1969).

Arylesterase. Basad on activity values in pigs, Augustinsson and Olsson (1961) suggested a theory of four multiple alíeles at a single locas, each allele controlling a number of units. Gahne et al, (1972) extended the theory and suggested that the Swedish Landrace pig has at least eight multiple alleles.

Cholinesterase. Cholinesterase activity in horse serum as diagnosed by spectrophoto-metric techniques is controlled "by four codominant, autosomal alleles (Gahne et al. 1970).

Allotypes. Allotype is a designation used for variation of immunoglobulins, a-globulina, and lipoproteins when this variation is detected by serological techniques, All the six species dealt with above are reported to have different allotypes.

18.2.4 Markers within red cells

The majority of the polymorphisms of Table 18.5 are detected by electrophoretic tech­niques. Haemoglobinhas been most extensively studied, In cattle the HbA molecule occurs in all breeds studied so far, It is not known, however, whether the various HhA's, particularly of Bos indicus and Bos taurus animals, are chemically the same, Except for HbB the other Hb variants have been found only in ¿frican and Asian cattle,

Horses appear with two types of variation, Differences in amino acids at position no, 60 in the alpha chain give three phenotypes in some horse breeds, detectable by electro— phoresis. Differenoes at position no. 24 which does not lead to differences in electric cbarge can be diagnosed by chromatographic methods (for referenoes, see Braend 1973).

The majority of the polymorphic proteins in Table 18.5 are enzymes detectable by electro-phoretio techniques. Multiple molecular forms of an enzyme occurring in a single organism are often oalled isozymes or isoenzymes. Some of these are controlled by several genetic eystems. Thus there are three phosphoglucomutases, PGMj, PGM₂ and PGM-₃, In horses the PGM₁ system is the one occurring with variation, A view of enzyme polymorphism in domestic animals has been published by McDermid et al. (1975).

Glutathione (GSH), This is a tripeptide which is a widely distributed constituent of functioning biological systems (Tucker 1975). Sheep, water buffaloes and goats can eaoh be separated into two classes, one with normal values, the other being deficient (Smith and Osborn 1967: Makaveev 1978; Agar et al. 1974). The glutathione system is involved in amino acid transport across the red cell membrane (Tucker 1976). Tucker suggests two types of deficiency:

Potassium (Ke). The Ke system in sheep shows quantitative variation (Evans 1954) allowing for differentiation between two classes, high (HK) and low (LK), controlled by two alleles, Ke and Ke , the Ke^L allele being dominant (Evans et al. 1956). There is further oorrelation between the potassium and the M blood group system (Rasmusen and Hall 1966), all homozygous LK sheep being homozygous for the L factor (Mb with new nomen-clature) whereas all homozygous HK animals are homozygous for the M factor (Ma). As a consequence, the red cell antigens of the M system are involved in the mechanism of the Ma-K ionic balance within the red cells and the pumping or diffusion mechanism for trans-porting these ions across the red cell membrane (Tucker 1976).

Unspeoified red cell proteins. Two protein systems of the red cell, not characterized or known as to functions and therefore just called erythrocyte proteins, Ery-) and Ery₂ have been found to be polymorphic in cattle (Thinnes et al. 1976),

In sheep the 'X' protein system (Tucker et al, 1967) occurs with two phenotypes.

18.2 Markers within white calls.

Search for polymorphisms within white celia has so far been undertaken to a limited extent only.

Malate dehydrogenase (MOR), Variation explained by two codominant alíeles has been reporfced in eattle (Ansay et al. 1971).

Glutamic oxaloacetic transaminase (GOT). This enzyme exists in a supernatant and a mitochondrial form. Ansay and Hanset (1971) described polyraorphism of the supernatant form in cattle, explained by two codominant alleles.

In horses the GOT_m system is reportad polymorphio in Icalandic and Mongolian ponies. The variation could be explained by two codominant alleles (Putt and Fisher 1979).

a-fucosidaae (a Fuc). This monomeric enzyme showed variation in some horse breeds which could be explained by three codominant alíeles (Putt and Fisher 1979).

Mannosephosphate isomerase (MPl). This enzyme was found to be polytoorphic within all groups of horses studied (Putt and Fisher 1979). Two forms were reportad, one homozygous and one heterozygous, explained by a theory of two dominant alleles at a single locus.

Peptidase (PEP A). This enzyme occurred with two phenotypes in Mongolian ponies (Putt and Fisher 1979). These phenotypes were assumed to be one of the homozygotes and heterozygote in a system with two dominant alíeles.

Phosphoglucomutase (PGM₃). The polymorphism in goats is in agreement with two codominant alleles being in control (Pretorius et al.1976).

Unspeoified leucocyte proteins. Thinnes et al. (1976) reported two polymorphic systems, Leu₁ and Leu₂ , each with two codominant alleles.

18.3 The causes of blood type variability

The marker systems of blood can be divided into two major functional classes. One consista of those markers for which we do not know of any physiologioal functions. Markers of this type are the antigenio factors of the red oell membrana. The other class of markers comprise those which have a known physiological function. Examples are transferrin, haemo-globin and specific eazymes.

With regard to the red cell membrane markers there has been much discussion whether these have some unknown physiologioal function or whether they are without any function at all: in other words that they are physiologically neutral» In the latter case they are considered to be evolutionary relies. Also for the markers of known physiological function there are unanswered questions. Thus we do not know why extensive polymorphisms are being maintained in many of these systems and whether certain marker alleles have a selectivo advantage over other alleles within the same system.

Any genetic variability begins with a new mutation. Such a mutation may be either deleterious, neutral or adaptive. Deleterious mutations will usually be eliminated, the speed of elindnation depending on whether the mutant is dominant or recessive. But deleterious mutant genes for certain traits may be advantageous for others. A mutation of this type is the well known sickle cell gene in man, this mutant gene being advantageous in environments with malaria. Such a deleterious mutation will therefore be established and maintained in the population as long as malaria exists.

As causes and explanations of genetic variability two major views have been advocated, those of the neutralista and the selectionists respectively.

The neutralist theory. Wright (1931) in his dassical theoretical work conoluded that random drift is a significant factor in evolution. His theory attracted much attention and a number of additional studies were published; the main cpponents were Fisher and Ford and their school in England (for reference, see Kimura 1976). With the great advanoes in the field of molecular biology in the 1950's and 1960's evolution could he considered at the molecular level. Thus the rates of molecular evolution of homologous proteins over a range of different species could be calculated by coraparing amino acid differences in such proteins as haemoglobin and cytochrome. It appeared that for these proteins there is a remarkable uniformity in the mutation rate of amino acid substitution between widely different evolut-ionary linos. This was taken as support for the neutralist theory and it is claimed that random genetic drift rather than positive Darwinian selectivo forcee (Burvival of the fitt-est) prevails at the molecular level. Kimura (1968) calling the theory "neutral mutation -random drift hypothesis" claimed that the majority of mutant substitutions that can be obeerved at the molecular level are the results of random fixation of selectively neutral or nearly neutral mutations rather than seleotive substitutions of definitely advantageous mutations. Supporters of this theory (for referenoes, see Kimura, 1976) have shown that random drift can cause a neutral mutation to increase in frequenoy and eventually replace the original marker gene. It must be added that as work aocumulates the mutational rate of amino acid substitutions has been found to vary (Langley and Fitch 1974; Sonderegger and Christen 1978).

The selectionists, on the other hand, argue that the variability and the maintenance of genetic diversity is caused by selective advantage. Several mechanisms and explanatory roodels have been proposed.

Heterosis. The relatively superior reproduotive fitness of heterozygotes is called heterosis or hybrid vigour. This superiority or positivo heterosis may concern either egg-to-adult survival, longevity, fecundity or some combination of these. Various typee of model have been proposed and examples in favour of these have been provided (for refer­ence, see Berger 1975). One of the models deals with the maintaining of gene-enzyme polymorphisms (Berger 1975) and states that there is a greater catalytic efficiency of enzymee in heterozygotes, which leads to a reduction in the amount of metabolic energy required to sustain regulated levels of that enzyme's activity. The consequence is that a larger prop-ortion of the heterozygote's energy budget can be channelled into reproduotion.

In contrast to positive heterosis there may be negative heterosis or hybrid disadvantage (Manwell and Baker 1970).

Erequenoy-dependent seleotion. This theory was discussed by Clarke (1975). Clarke in an experiement with the fruit fly (Drosophila melanogaster) studied the polymorphism of the enzyme alcohol dehydrogenase. Each of the two genetic variants of this enzyme survived better when it was rare than when it was common. Rare genotypes, therefore, were more succesaful than common ones. This advantage conferred by rarity waB explained by the fact that nutriente con-sumed by common genotypes were depleted faster.

Clarke (1975) concluded that diversity exists because natural selection favours it and that the variante themselves affect the survival and the reproduotion of the individuals carrying them.

Habitat-choice models. Powell and Taylor (1979) carried out experimente on genetic variation in ecologically diverse environments. Their habitat-choice model is related to the frequency-dependent model. Also in the habitat-choice model each genotype is at an advantage when rare, because it has few con-genotypic competitors. It is at a disadvantage whon common because it then has too many competitors. Habitat-choice assumes that genotypes avoid areas of the environment in which they are least fit and concentrate in areas where their fitnesses are greatest. When a mutant arises, this new heterozygote may or may not be able to compete for some resources better than pre-existing genotypes. If an appropriate resource is avail-able the new genotype will specialize in under-utilized resources and the new allele will rise in frequency.

The habitat-choice model predicts that environmental diversity encourages genetic variat-ion and seems to support highly multi-allelic polymorphism with a minimum of genetic load. Powell and Taylor (1979) tested and proved their model using natural populations of Drosophila persimilis.

18.3.1 Possible basis for polymorphiam in domestic animals

If we now return to our domestic animals we may ask how the various models disoussed above apply to their blood markers. Shall we explain the red cell membrane factors and their genes as neutral or evolutionary relics caused by random drift or are they main-tained through Belective advantages eventually influenced by the environment such as pre-dicted by the habitat-ohoioe model?

So far we do not have enough conclusiva evidence. But there are a number of investig­ations indioating that oertain genotypes or combinations of genotypes have selectivo advan-tage over others, such as is the case of transferrins in sheep (Rasmusen and Tucker 1973). Pronounced differences in gene frequencies which occur for a large number of polymorphic systems in different environments_f even though the populations under study have not been subjected to artificial seleotion, may also be explained by some unknown selective advantage.

Which of the various theories mentioned above is to be preferred, it is too early to predict. But it seems to the author that in the literature there are more faets speaking for the theories of selective advantage. That does not mean that the neutralist theory is out of the picture. If for instance a polymorphism has been established at an early stage in evolution through selective advantage it may later be maintained through random drift only; conversely, a polymorphism maintained by random drift may be selective advant­age at a later date.

It would further be reasonable to assume that in an individual possessing a large number of polymorphisms all the various mechanisms discussed above may be in operation so that the individual may be considered to represent a complex corabination of balanced polymorphisms brought about by interactions of a variety of forces and environments.

18.4 Measures of genetic variability

Ford (1965) defined genetic polymorphism as the oceurrenoe together in the same habitat of two or more discontinuous forms or "phases" of a species in such proportions that the rarest of them cannot be maintained merely by recurrent mutations. Today it is common to call a variable genetic system polymorphic if the rarer of two alleles has a frequeney higher than 1%. Harris (1975) in his exoellent book on biochemical genetica of man calis those systems for which the rarer of two alíeles has a frequeney lower than 1% "variable systema" only. In the opinion of the author we should use the term polymorphic for any genetically determined variation independent of the rarity of variants, because such variante usually will increase over time as discussed above.

The most important element for the characterization of genetic polymorphism is technique. Sinoe today for many of the marker systems we operate at the molecular level by far the best technique is the determination of the chemical oomposition and structure, the amino acid eequenoe, of protein molecules. Since, however, such investigations are laborious and costly they have so far been undertaken only to a very limitad extent for polymorphic blood systems of domestic animals. Simpler and more crude methods are, therefore, employed for the detect-ion of blood polymorphisms, the most common ones being serological and electrophoretic techniques. This fact must be taken into account when conclusions are drawn. Thus we can­not immediately state that two molecules migrating at the same rate with the same electro­phoretic technique, are the same. We must be particularly cautious when variants ocourring .la animals of distant related populations are under consideration. An example showing the consequences of technique is the separation of the first described TfD variant in cattle into TfD₁ and TfD₂.

It also has to be remembered that variation exists in amino acid sequence which is not detec-fcable by ordinary eleotrophoresis, because mutational substitutions concern amino acids of the same electrical charge. Suoh an example is the polymorphism at position no. 24 in the horse Hb alpha chain where phenylalanine and tyrosine may occur alone or together (Kilmartin and Clegg 1967).

Another element of importance for detection of polymorphism is effort. There are many examples of proteins and enzymes being polymorphic in some populations and monomorphic in others. Utilizing improved techniques and a larger material a much higher percentage of polymorphisms will be found to occur in our domestio animals.

Polymorphism of markers and their genes can be measured in various ways, the basis for the measurements being the relative frequencies of markers and their genes within populat­ions.

The average degree of heterozygosity. This is the proportion of gene loci in a single individual at whicn are likely to occur two different alleles each specifying a different enzyme or protein. It is estimated by summing the observed values for heterozygosity at each locus and dividing by the total number of loci. In man the average degree of hetero­zygosity for enzymes is 0.067 (Harris and Hopkinson 1972). This suggests that any single human being is likely to be heterozygous for enzyme structure at about 7% of his or her loci, as measured by electrophoretic techniques. This is an under-estimate of the true average heterozygosity though, sinoe there are additional polymorphisms not detected by eleotrophoresis.

In Table 18.6 average heterozygosity is given for some species. The values for pigs are reported by Widar e_t al. (1975) whereas the values for cattle are unpublished results by Ansay (Widar et al.19757) The estimates for sheep (Baker and Manwell 1977) are pri-marily based on investigations of organ enzymes. It is of interest that the average heterozygosity for these three domestic species is of the same order as in man. The figures in Table 18.6 further show that two invertebrate species have a much higher average heterozygosity than man. The percentage of polymorphic system is correspondingly higher. In Drosophila and land snails it is of the order of 30-50%. In a survey of 24 invertebrate species the average heterozygosity was 15%, whereas in 22 vertebrate species the figure was 6% (Selander and Kaufman 1973). These results may be taken as support for the selection theories.

The degree of homozygosity. The degree of homozygosity for a locus is the sum of the squared frequencies of its individual alíeles. The average degree of homozygosity for a certain number of loci is the sum of the degrees of homozygosity divided by the number of loci. Rendel (1967) calculated the degree of homozygosity for the A,P,J,L,M,S and Z bovine red cell membrane loci and found about the same values for Icelandic and Swedish Red-and-White cattle (69.2% and 64.5%) even though these two cattle populations are rather different in their evolutionary history.

The degree of homozygosity has also been used as an estimation of the variability within complex systems. Of particular interest in this connection is the B system of cattle when this is explained by a theory of multiple alíeles. Rendel (1967) in a survey of breeds showed that the degree of homozygosity varied between 25 and 4%. The number of alleles in the same material varied between 132 and 20, the Icelandic cattle being lowest.

Blood polymorphisins as a measure of total genetic variation. When blood type genes are utilized for this purpose, they are markers in the true meaning of the word. It is a ques— tion, though, whether the blood markers can be considered as true markers if we accept the selectionist theories. Thus Rendel (1967) pointed out that the possibility of using marker genes to trace breed origin and relationships between breeds would be greatly hampered if the marker genes had pleiotropic effects on production traits, disease resistance and clim-atic tolerance. Slow but directional changes in gene frequency would then be added over hundreds of generations and similarity between breeds for marker genes would indicate a common environment rather than a common origin.

In spite of this possible effect, evidence shows that blood markers are useful for the estim­ation of total genetic variation. One of the first to discuss this was Robertson (1956) who estimated the effective number of B alleles (1/Eq²) for various breeds. Shorthorns which had gone through a bottle neck of inbreeding with an inbreeding coefficient of 25%\ had only an effective number of B alleles of 2.7. Holstein-Friesians which has not gone through a period of conservation had an effective number of alleles of 11. This is in good agreement with the blood typing results (Stormont 1958) and the fact that Shorthorns have the two common alleles BO₂Y₁A'E'₃ and b at frequencies of 40% respectively.

Rendel reported a similar example from Swedish Red-and-White (1963)* The bull Satenöas 134 greatly influenced the genetic composition of the breed, the average coefficient of relationship between a sample of bulls and 134 Satenäs amounting to 0.116. Of particular interest is the fact that this bull had the B phenogroups BO₃X₁A'E'₃ and b, these two pheno-groups probably being identical with the BO₂Y₁A'E'₃ and b in Shorthorns (Braend 1975).

Maijala and Lindstrøm (1966) introduced the so-called "similarity index" for the purpose of estimating breed similarities. They studied blood group frequencies of a number of breeds and concluded that "Information concerning blood groups of breeds seems to provide two means of estimating the degree of homozygosity in the breed. The first is the sum of squared allelic frequencies of the B system and this corresponds to the expected coefficient of in-breeding. The second is the actual homozygosity of B alleles and this corresponds to the actual inbreeding coefficient".

Braend (1979) showed that the number of variant molecular forms of haemoglobin and transferrin was greater in Nigerian zebu cattle than in European breeds. Also the number of red cell membrane reacting specificities was greater than in European breeds. These findings might be explained by greater genetic variation in Bos indicus in Nigeria than in Bos taurus of Europe.

18.5 Aids in selection

As soon as the large number of cattle blood groups and their genes were known their poss­ible use for practical purposes received attention. The matter was considered from the practical as well as the theoretical point of view.

From the very beginning blood groups have been used for solving parentage and identity problems and as a means of ensuring correct parentage on a preventive basis. Today these are the major uses of blood groups of domestic animals and it has been the experience in many countries that the blood markers are most useful and often necessary for the successful carrying out of breeding programmes and breeding schemes. It will be of even more import­ance in the future when complicated and sophisticated techniques are utilized to a far greater extent than today, through the use of deep-frozen semen, egg transplantation and computerized systems of breeding, feeding and management.

The main interest of blood groups as aids in selection, however, has been their possible use as markers for genes in control of characters of economic importance. One of the first to discuss the matter was Irwin (1956) who stated: "It would appear reasonable that such a correlation is possible but no highly probable". Since then a large number of studies on possible relationships between marker genes and production characters have been under­taken, primarily for cattle but also for other domestic animals. Significant correlations have been obtained between certain blood groups and milk yield and fat content, often quoted studies being those of Neimann-Sørensen and Robertson (1961) and Rendel (1961 )• The con­tribution to the total variation for the production traits, however, was too small to be of any practical value. Similar results were obtained for the Tf system and milk yield (Ashton 1960; Ashton et al. 1964; Jamieson and Robertson 1967; and others). Schleger et al. (1978) found a statistically significant association of heterozygosity of blood markers with calving interval, but not with milk yield and fat content. At the 1978 ISABR conference some 15 reports dealing with associations between blood markers and economic traits in cattle were reported. Correlations with production, fertility and diseases were investigated. Some associations were reported but the directions varied between materials.

On the theoretical side recent reports are those of Cunningham (1976) and Soller (1978) the latter stating (suspecting) that the a priori probability of being able to get from a marker linked effect to a known locus is small. Soller (1978), therefore, concluded that marker-linkage studies in oattle although of biological and genetic interest could probably not be justified at the present on the basis of a potential, direct and immediate contrib­ution to dairy cattle improvement.

Accordingly, for production characters controlled by quantitative genes such as milk yield, blood markers are of little or no value as aids in selection.

As regards other characters such as reproductive performance, disease resistance and climatic tolerance the possible use of blood markers has also been studied. There are three major ways in which blood markers could be of importance. They could show direct or pleiotropic effects in whioh case they would not be markers in the true meaning of the word. They could have effects through heterozygous advantage or they oould be linked to genes controlling such characters which we would like to improve. Of fundamental importance in this respect is their eventual physiological funotions as discussed above. For markers whose functions are known it is easier to understand and explain their role in fundamental functional differences between individuals.

Baker and Manwell (1977), in their studies of enzyme polymorphisms in sheep in Australia, found that NADP-dependent dehydrogenases and esterases were polymorphic whereas representat­ives of several other major classes of enzymes were not. In discussing the physiological significance they suggested that this polymorphism may be related to the tole of these enzymes in growth and detoxication, sheep having been selected by man for faster growth, of wool or of carcass, and for grazing a wide variety of plants. In agreement with this they found that heterozygotes for NADP-dependent dehydrogenases grew significantly faster (on average 10.4%) than homozygotes for these enzymes.

In pigs the marker loci PHI and H are closely linked to the halothane locus (Hal) which is involved in the control of the malignent hyperthermia syndrome (MHS) also called the pro cine stress syndrome (PSS). This locus also affects meat quality, pigs homozygous recessive at the Hal locus having inferior meat quality (PSE = pale, soft exudative). This condition and its explanatory meohanism have received much attention in recent years (for references, see Andresen 1979, 1980 and Andresen et al. 1979). The Ha antigen is strongly correlated with the PSE character in Danish pigs and selection programmes against the Ha factor have been carried out. Andresen (1980) has, however, shown that such marker genes can be of value for selection only as long as disequilibrium exists.

In conditions where immunological aspects are of etiological importance, such as disease resistance, the blood markers, particularly membrane antigens may be of possible use in selection. Thus there are many examples of cross reactions between homologous membrane anti­gens between species and between membrane antigens and receptors on microorganisms. Such cross reactions might explain resistance against infectious and parasitic diseases, which could be of value for artificial selection and lead to other specific precautions or treatment. One of the best known examples is the B 27 antigen of the human HLA complex and the strong correlation between this lymphocyte antigen and the occurrence of anchylosing spondylitis.

Low fertility is a problem in many livestock species, the atiology being only partly known. Immunological effects due to incompatibility between antigens of dam and offspring are of importance, the best known being a haemolytic disease of the newborn foal. Knowing that dams often are immunized against the lymphocytes of their foetus, as an example, it is not unreasonable to assume that such immunological reactions involving tissue antigens could interfere with normal fertility processes particularly in consecutive gestations.

The Tf locus has 'been reported to have effects on fertility in many domestic species. Whether this effect is direot, pleiotropic or due to linkage between Tf genes and genes of importance for fertility is not known. Neither is it known whether such effects of marker genes are due to heterosis.

Such a heterosis effect could be caused through the advantage of molecule variation. It may be advantageous for an individual animal to have two moleoules intead of one in a certain marker system or even three as is the case for heterozygotes for certain enzymes*

Another mechanism explaining an advantage of particular marker combination could be that combinations of molecules either within or between systems are more efficient for certain physiological functions than in other combinations. It seems that more and more evidence is pointing in this direction. Such a relationship or interaction has been reported for Hb molecules and reproductive performance and survival in sheep (Purser and Hall 1974) resulting in a state of balanced polymorphism* Similar but more oomplioated inter-relationships probably exist for Tf molecules and reproduction in sheep (Rasmusen and Tucker 1973).

Note added in proof. Reoently Stormont ("The B and C systems of cattle revisited" to be published in Frontiers in Immunology) discussed the genetic control of the complex red cell membrane systems in cattle* He defended the idea of multiple alleles based on the fact that the genes of animals and animal viruses come in pieces that are spread out along DNA* Acordingly, recombination may easily occur within genes. Stormont therefore, stated that "I have no difficulty at all in conceiving a B gene with as many as 20 or more pieces which can occur in hundreds of allelic forms".

18.6 References

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Ashton, G.C., Fallon, G.R, and Sutherland, D.N, 1964. J. agric. Sci., Cambr. 62, 27-34.

Auditore, K.J. and Stormont, C. 1978. Immunogenetics 6, 547-552.

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Baker, C.M.A. and Manwell, C. 1977. Aust. J. Biol. Sci. 30, 127-140.

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Berger, E. 1976. Amer. Hatur. 110, 823-839.

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18,7 Reviews and books

Agar, N.S., Evans, J.V. and Roberts, J. 1972. Red blood cell potassium and haemoglobin polymorphism in sheep. A reviev;. Anim. Breed. Abrst. 40, 4O7-/136.

Andresen, E. 1962. Blood groups in pigs. Ann. N.Y. Acad. Sci. 97, 205-225.

Andresen, E. 1963. A study of blood groups of the pig. 229 PP. Thesis Munksgaard, Copenhagen.

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Puschmann, H. and Sohmid, D.O. 1968. Serumgruppen bei Tieren, 272 pp. Verlag Paul Parey. Berlin-Hamburg.

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Harris, H. 1975. The principles of human biochemical genetics. 473 pp. North-Holland Publishing Company. Amsterdam-Oxford.

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Khanna, N,D. 1973. Biochemical polymorphism and blood groups in Indian buffaloes, 154 pp. Thesis. Embassy Press, Delhi-6.

Lush, I.E. 1966. The biochemical genetics of vertebrates except man. 118 pp. North-Holland Publishing Company. Amsterdam.

Manwell, C. and Baker, C.M.A. 1970. Molecular Biology and the Origin of Species: Heterosis, Protein Polymorphism and Animal Breeding, Sidgwick and Jackson. London,

McDermLd, E.M,, Agar, N.S, and Chai, C.K. 1975. Electrophoretic variation of red cell enzyme systems in farm animals. Anim* Blood Grps bioohem* Genet. 6, 127-174.

Sandberg, K. 1974. Blood typing of horses: current status and application to identification problems. Proc. 1st World Cong. Genet. appl. to Livestock. Prod. (Madr. 1974), 253-256.

Scott, A.M, 1978. Immunogenetic analysis as a means of identification in horses. Proc. 4th Int. Conf, Equine Infect. Diseases (Lyon 1976), 259-268. Veterinary Publications Inc. Princeton. New Jersey.

Stormont, C. 1962. Current status of blood groups in cattle. Ann, N,Y. Acad. Sci. 97, 251-268.

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Tucker, E.M. 1975. Genetic markers in the plasma and red blood cells, 123-153. In: M.H. Blunt (Ed) The Blood of Sheep. Springer Verlag. Berlin.

Table 18.1

Markers in the bovine red cell membrane

The number of alleles varies. In the simple systems such as L and T' there are only two alleles each controlling the presence or absence of the respective factor. In the more complex systems the number of alleles increases with the number of blood factors.

Figure 18.1 Cattle B-system maps

Table 18.2 Markers in the pig red Cell membrane

Table 18.3

Markers in the red cell membrane

Table 18.4

Number of eleotrophoretically detected variant molecules in the most common polymorphic systems in plasma

* Not confirmed

Table 18.5

Number of variant molecules of some systems within red cells

* 2 loci, each 2 alleles

Table 18.6

Average heterozygosity per locus for alleles controlling electrophoretio enzyme and protein variation

Mesure de la variabilité génétique el; aides pour la selection au moyen des groupes sanguins
Résumé

On peut donner à la définition des groupes sanguins un sens étroit ou un sens large. Au sens étroit, c'est-à-dire classique, on entend par là les structures antigénique ou macromoéEcules, appelées aussi facteurs sanguins, dans la paroi de 1éErythrocyte, qui accusent des différences d'origine génétique d'un sujet à l'autre. Au sens large, ce terme de groupe sanguin englobe toutes les molécules sanguines variables a 1'intérieur de chaque espèce, qu'elles appartiennent à des membranes cellulaires ou qu'elles se présentent sous une forme "hydrosoluble" intracellulaire ou extracellulaire.

La variabilité des groupes sanguins est fonction des techniques et des efforts mis en oeuvre pour rechercher la variation. On a recours à. deux techniques principales. Les techniques sérologiques font appel aux anticorps spécifiques. L'autre méthode repose sur le fait que les molécules protéiques ont une charge électrique nette qui permet de séparer les protéines dont la structure en acides aminés est différente en les soumettant dans des conditions appropriées à un champ électrique, méthode éppelEe Electrophorèses

On entend par groupe sanguin d'un individu une formule composée de lettres qui class© le sujet au regard des substances sanguines variables qui ont fait l'objet d'une étude selon des techniques particulières. Du fait que les substances ou macromolécules portent les mêmes symboles, généralement des lettres, que leurs gènes de contrôle, la formule du groupe sanguin désigne aussi une formule de gènes. Aujourd'hui ces macromolécules sont souvent appelées marqueurs, leurs gènes de contrôle étant appelés gènes marqueurs.

Chez les bovins, les gènes marqueurs pour les facteurs sanguins èrythrocytaires appartiennent à onze systémes génEtiques indépendants (locus). La Société internationale pour la recherche sur les groupes sanguins des animaux a adopté des symboles pour un total de 86 facteurs sanguins. Exemples: A₁, K, B', E'₁ , X₂ et U". Le système A a cinq facteurs, le système B 44_f le système C 13, le système F 5, le système M 3,le système S 7, le système Z 2, le système R' 4 et les systèmes J, L et T* un facteur chacun. Le système J diffère des autres, le facteur J étant une substance soluble acquise à titre secondaire par les Erythrocytes et qui n'est done pas au premier chef une structure dans la paroi de 1'érythrocyte. Le système J peut aussi être subdivisé. De nombreux laboratoires ont mis au point des immunsérums supplémentaires dirigés contre des facteurs sanguins qui n'ont pas encore fait l'objet d'une désignation acceptée sur le plan international.

On a étudié les antigènes lymphocytaires bovins en utilisant des immunsérums pour des épreuves de cytotoxioité. Soixante-huit sérums ont été placés dans des groupes selon leur type de réaction. Onze de ces groupes sont clairement définis: appelées antigènes lymphocytaires bovins (BoLa), ils sont designés par les chiffres 1 à 11. Les groupes supplémentaires ne sont pas aussi bien définis. Selon la théorie génétique actuelle, les antigènes dans ces groupes sont commandés par des allèles multiples en un locus unique.

On a signalé pour 25 protéines une variation des molécules protéiques, enzymes oom-priseB, déterminée par électrophorSse, les molécules ayant fait l'objet des études les plus poussées étant 1'hémoglobine et la sidérophiline. Certaines autres protéines "hydro-solubles" ont été caractérisées au moyen de techniques immunologiques. Des variantes appelées aussi allotypes éné été signalées pour les immunoglobulines, les — globulines et les lipoprotéines.

La variabilité des marqueurs sanguins de bovins et de leurs gènes est exprimée par leur fréquence relative à 1'intérieur des systèmes et leur caractère hétérozygote. Certains systèmes n'ont que deux allèles dont un peut être rare. D'autres comportent un grand nombre d'allèles multiples, par exemple le système de la sidérophiline. Les systèmes B et C de 1'érythrocyte sont très complexes. Aujourd'hui on s'accorde à penser que ces deux systèmes, où se sont produits un nombre non négligeable d'événeraents de type "crossing-over", sont commandés par une quantité relativement importante de gènes étroitement liés.

La variation combinée des groupes sanguins est d'une telle ampleur que si l'on a recours à un nombre suffisant de techniques diagnostiques, tout couple de bovins choisi au hasard -à 1'exception de certains jumeaux — accusera une différence en ce qui concerne les groupes sanguins*

Chez les pores, on connaît jusqu'à présent 15 systèmes génétiques qui oommandent les facteurs érythrocytaires. Lors des tests de comparaison auxquels a procédé en 1978 la Société internationale pour la recherche sur les groupes sanguins des animaux, on a effectué des comparaisons portant sur 75 immunsérums ayant des designations acceptées sur le plan international et 70 immunsérums expérimentaux. Les 18 laboratoires participants ont égal-ment véirifié par éiectrophorèse les marqueurs de 19 systèmes. On a signalé un certain nombre d'antigènes lymphocytaires ainsi que des allotypes différents.

Les groupes sanguins de pores ont été utilisés à diverses fins. A l'heure actuelle, on met beaucoup 1'accent sur l'association entre les marqueurs sanguins, la qualité de la viande et le syndrome de stress des porcins parce qu'il existe une liaison étroite entre les trois locus: HAL (réactivité à l'halothane), PHI (phosphohexose imérase) et système H de la membrane érythrocytaire.

Chez les ovins on a trouvé jusqu'à présent 10 systèmes de membranes érythrooytaires, décelés par les épreuves sérologiques ordinaires. Le nombre des différents allèles observés est moindre que chez les bovins et les porcins, à 1*exception du système B qui est sérolog-iquement apparenté au système B des bovins et comporte un grand nombre d'allèles. Pour les protéines du plasma, cinq systèmes décelables par électrophorèse ont été signaLés et, à 1'intérieur de 1éErythrocyte, treize systèmes de marquaurs ont été décrits. Certaines des substances solubles sont des macromolécules, mais le potassium est également un marqueur puisque la quantité accuse une variation distincte à détermination génétique avec une classe élevée et une classe faible. II existe une corrélation entre les types de potassium et le système M dela membrane éVythrocytaire. On a signalé un grand nombre d'antigènes lympho­cytaires et il existe des allotypes difféVents pour l'O^p-macroglobuline, la lipoprotéine et l'immunoglobuline.

Chez les chevaux, on a signal! 8 èystemes génétiques determinant des antigènes érythro-cytaires. La liste de nomenclature érythrocytaire agréée par la Société internationale pour la recherche sur les groupes sanguins des animaux est fondée sur 20 immunsérums specifiques. Huit de plus sont signaiés dans la littérature et les laboratoires de groupage sanguin pour les chevaux ont produit un grand nombre de réactifs expérimentaux. On utilise à des fins pratiques et scientifiques 19 systèmes basés sur des marqueurs variables diagnostiqués par èlectrophorèse.

Chez le buffle, on a signaié au total 21 facteurs sanguins érytrocytaires appartenant au moins sept systèmes génétiques. Dans le plasma et à l'intérieur des cellules, on a décrit 12 systèmes se présentant sous des formes variables.

Pour caractériser les chèvres, on a utilisé au total 32 sérums iso- et hétéroimmuns correspondant au même nombre de facteurs antigéniques appartenant à sept systèmes génétiques. En outre, on utilise des extraits de plantes et d'escargots pour diagnostiquer les systèmes dans la membrane érytrocytaire. Les systèmes de marqueurs signalés jusqu'à présent dans le plasma et dans les cellules sont au nombre de huit.

L'auteur examine un certain nombre de théories et de modèles concernant la variabilité des marqueurs de types sanguins et le maintien de systèmes polymorphes. Selon l'auteur, la thèse neutralists ainsi que diverses theories séiectionnistes sont toutes valables mais, sous l'effet des forces évolutionnistes et des interactions avec 1'environnement, les mécanismes changent avec le temps.

Les marqueurs sanguins chez le bétail sont utilisés aujourd'hui à diverses fins. lls servent particulièrement à contrôler 1'ascendance et à caractériser la structure des races et les rapports entre races et populations, Toutefois, pour améliorer les aptitudes pro-ductives dépendant de gènes quantitatifs, comme la production de lait, ils ne sont générale-ment guère ou pas utilisables aux fins de la sélection. Dans les cas où les donneSs immuno-logiques ont une signification étiologique, les marqueurs sanguins, en particulier les anti-génes de la membrane, peuvent être utiles pour comprendre, combattre et éradiquer les mala­dies.

Medidas de variabilidad genética y medios auxLliares de selección con empleo de tipos de sangre
Resumen

Los tipos sanguíneos pueden definirse en sentido estricto o lato. En sentido estricto o clásioo, por tipos de sangre se entienden aquellas estructuras antigénicas o macro-mole'culas, también denominadas factores de la sangre, en la membrana del eritrocito, que muestran variaciones controladas genéticamente entre individuos. En sentido lato, el término tipo de sangre comprende todas las moléculas variables de la sangre dentro de las especies, tanto si pertenecen a las membranas de la célula como si se encuentran en una forma "soluble en agua" dentro o fuera de las céilulas.

La variabilidad de los tipos de sangre esiá. en función de las téicnicas empleadas y de los esfuerzos hechos en busca de la variacion. Se emplean dos técnicas principales: las téicnicas serológicas utilizan anticuerpos específicos. El otro método se basa en que las moléculas de proteína tienen una carga eléctrica neta que permite la separación de pro— teínas de estructura aminoácida diferente sometiéndolas a condiciones apropiadas en un campo eléctrico, o sea la llamada electroforesis.

Por tipo de sangre determinado se entiende una fórmula de letras que clasifica al individuo con respecto a aquellas sustancias variables de la sangre que han sido sometidas a inveetigación mediante técnicas específicas. Como las sustancias o macromoléculas llevan los mismos símbolos, normalmente letras, que sus genes determinantes, la fórmula del tipo de sangre representará asimismo una fórmula de genes. Actualmente, tales macromoléculas se denominan frecuentemente marcadores y sus genes determinantes genes marcadores.

En el ganado vacuno, los genes marcadores en los factores del glóbulo rojo pertenecen a 11 sistemas genéticos independientes (loci). La Sociedad Internacional para la Investi-gación del Grupo Sanguíneo de los Animales (ISABR) ha establecido los símbolos para un total de 86 factores de la sangre. Ejemplos de estas designaciones son: A₁, K, B', E', X_1' y U". El sistema A comprende 5 factores; el sistema B, 44; el sistema C, 13; el sistema F, 5¡ el sistema M, 3; el sistema S, 7; el sistema Z, 2; el sistema R', 4; y los sistemas J, L y T' un factor cada uno. El sistema J se diferencia de los otros en que este factor es una sustanoia soluble adquirida secundariamente por los glóbulos rojos y no es por lo tanto primordialmente una estructura de la membrana del eritrocito. El sistema J puede subdividirse asimismo en otros varios. Muchos laboratorios han obtenido antisueros adicionales contra factores de la sangre que, hasta ahora, no han recibido una denominación aceptada internacionalmente.

Los antígenos linfocitos de los bovinos se han estudiado mediante el empleo de antisueros en pruebas citotóxcas. Sesenta y ocho sueros se han dividido en grupos, según sus modelos o pautas de reacción. Once de estos grupos o racimos están claramente definidos, se denom­inan antígenos de linfocitos de los bovinos (BoLa) y se signan con cifras del 1 al 11. Otros grupos no están definidos con tanta claridad. La teoría genética actual considera que los antígenos en estos grupos son regulados por alelos multiples en un solo locus.

En 25 proteínas se han senalado variaciones determinadas por electroforesis de moléoulas de proteína con enzimas. La más ampliamente estudiadas son la hemoglobina y la transferrina. Otras proteínas "hidrosolubles" han sido caracterizadas mediante el empleo de técnicas inmuno lógicas. Se nan senalado fortnas variantes, también denominadas alotipos, para inmunoglobu-linas, α -globulinas y lipoproteínas.

La variabilidad de los marcadores de la sangre en los bovinos y de sus genes, se expresa por sus frecuencias relativas dentro de los sistemas y sus heterocigosiB. Algunos sistemas sólo tienen dos alelos, uno de los cuales puede ser raro. Otros sistemas tienen buen número de alelos múltiples, como por ejemplo, el sistema de la transferrina, Los sistemas By C del eritrocito son muy complejos. Actualmente, suele creerse que estos dos sistemas en los que han tenido lugar varias veces una especie de entrecruzamientos están regulados por un número relativamente grande de genes estrechamente vinculados.

La variación combinada de tipos de sangre es de tal magnitud que, empleando un número suficiente de técnicas de diagnosis, cada dos ejemplares bovinos elegidos al azar — con excepción de ciertos gemelos - diferirán en sus tipos de sangre.

En el ganado porcino, se conocen hasta ahora 15 sistemas genéticos que regulan los factores de los glófbulos rojos. En la prueba comparativa de ISABR, realizada en 1978, se compararon 75 antisueros de designaoiones aceptadas internacionalmente con 70 experimentales. Los 18 laboratories participates ensayaron asimismo maroadores de 19 sistemas, empleando el método de la electroforesis. Se ha senalado la existencia de varios antígenos de lin-focitos diferentes, así como de alotipos variantes.

Se han utilizado con diversos fines tipos de sangre porcina. Actualmente, se da mucha importancia a la asociación entre maroadores de sangre, calidad de la carne y síndrome de tensión en el oerdo, ya que hay una estrecha vinculación entre los tres loci; HAL (re-actividad halothán), PHI (fosfohexosa imerasa) y el sistema H de la membrana del gl<5bulo rojo.

En los ovinos se conocen hasta ahora diez sistemas de la membrana del glóbulo rojo detectados en pruebas serológicas ordinarias. El número de alelos variantes observados es menor que en el ganado vacuno y en el porcino, con excepci6n del sistema B que es serolúgi-camente afín al sistema B del ganado vacuno y tiene gran número de alelos. En el caso de las proteínas plasmáticas, se han señalado cinco sistemas perceptibles por electroforesis y, dentro del glóbulo rojo, se han descrito 13 sistemas de maroadores. Algunas de las sustancias solubles son macromoléculas, pero el potasio es tamibién un marcador, ya que la cantidad indica una clara variación determinada genéticamente con una clase alta y otra baja. Existe una correlación entre los tipos de potasio y el sistema M de la membrana del glóbulo rojo. Se ha señalado gran número de antígenos de linfocitos y aparecen alto-tipos diversos para α 2-macroglobulina, lipoproteína e inmunoglobulina.

En el ganado caballar, se han señalado ocho sistemas genéticos que determinan antígenos del glóbulo rojo. La lista de la nomenclatura de glóbulos rojos aprobada por ISABR se basa en 20 antisueros espeeífioos. En la dooumentación espeoializada, se habla de ocho más, y los laboratories de tipificación de sangre del oaballo han producido gran numero de reactivot experimentales. A efeotos práctioos y científicos, se utilizan sistemas en el control de maroadores variables diagnosticados por electroforesis.

En los búfalos se ha comunicado un total de 21 factores de la membrana del glóbulo rojo pertenecientes por lo menos a siete sistemas genétioos. En plasma y en el interior de las células se han descrito 12 sistemas que se presentan en formas diferentes.

Se ha caracterizado al ganado caprino utilizando en total 32 sueros isoimnunes y hetero-inmunes correspondientes al mismo número de factores antigénicos que pertenecen a siete sistemas genéticos. Además, se están diagnosticando sistemas de la membrana del glótmlo rojo mediante el uso de extractos de plantas y caracoles. Hasta ahora se han comunicado en total ocho sistemas de maroadores en el plasma y en el interior de las céilulas.

Se examinan teorías y modelos sobre la variabilidad de maroadores del tipo da sangre y el mantenimiento de sistemas polimórficos• Según el autor, el panto de vista neutral y las varias teorías sobre la selección son todos ellos válidos, pero debido a las fuerzas de la evolución y a interacciones ambientales, los mecanismos en funcionamiento cambian en el transourso del tiempo.

Hoy en día, los maroadores de sangre en la ganado se utilizan para varios fines. Son particularmente útiles para el control de los progenitores y la caracterización de la estructura de la raza y las relaciones entre razas y poblaciones. Pero para el mejoramiento de caracteres de producción regulados por genes cuantitativos, como la producción de leohe, son por lo general de poco o ningún valor como medios auxiliares de seleccifón. En condiciones en que los aspectos inmunológicos son de importancia etiológica, los maroadores de sangre, sobre todo los antígenos de la membrana, pueden ser útiles para comprender, controlar y erradicar enfermedades.

Para preservar los recursos zoogenéticos, se debe mantener una variabilidad genética adecuadadentro de las poblaciones y entre los distintos poblaciones, porque, en primer lugar, no puede preverse fácilmente la demanda del futur y, en segundo lugar, la vulnera-bilidad de recursos genéticos deriva de la uniformidad genétioa.

Independientemente de los nuevos principios y valores que puedan adoptarse en el futuro, hay que dar gran prioridad a la resistencia a las varias enfermedades y dificultades ambientales. La productividad del animal deberá reevaluarse sobre la base de la absorción producción de energía y proteínas. Las organizaciones internacionales deben realizar las actividades relativas a vigilancia, catalogación y cotejo de la información sobre recursos zoogenéticos. Rstas instituciones deben actuar como medio de enlace con otras organizaciones para establecer un sistema adecuado que se ocupe de los recursos zoogenétioos a escala mondial.