Cattle Genetics

The Inheritance of Genetic Defects - Part 3
T. A. OLSON

Defective, often dead, calves that are the result of mutant genes are produced occasionally in all breeds of cattle. Such calves may be produced as a result of inbreeding or linebreeding which has allowed the defect to be expressed because the recessive gene responsible for the defect was homozygous in the inbred, affected animal. Genes responsible for the vast majority of all simply inherited defects in cattle are recessive. The explanation for the lack of undesirable genes with a dominant mode of inheritance is simple; those which are dominant always produce an effect on the phenotype and are immediately eliminated, thus eliminating the gene. Not all defective calves are the result of genetic conditions. Some such calves are the result of environmental conditions and others due to unknown causes.

All breeds carry genes which, when homozygous, produce genetic defects. Some of the more commonly seen genetic defects, descriptions of their effects, and the breeds in which they have been observed are listed in table 2.6. Undesirable genes are produced from normal genes through mutation. If the animal carrying the initial undesirable recessive gene or one of its descendants which also carried the gene becomes popular, the frequency of that gene can increase greatly before the gene is detected. If the gene was initially low in frequency or non-existent in the population, the gene may not be detected until linebreeding of the descendants of the original heterozygous (carrier) animal has occurred. The opportunity for widespread distribution of undesirable genes is made greater through the use of artificial insemination and multiple-ovulation/embryo transfer systems. A single sire can produce thousands of progeny through AI and thus increase the frequency of the gene in the breed considerably. Such dangers are reduced in breeds where lists of known heterozygous sires are published.

Table 2.6 A partial Listing of Defects of Cattle Controlled by Autosomal Recessive¹ Genes
Defective condition	Description²	Breeds thought to possess the gene responsible³
Arthrogryposis	Permanently contracted joints (in abnormal positions) associated with cleft palates.	Charolais
Dwarfism - compressed type	Heterozygotes demonstrate more compact thicker body type; homozygotes are crooked-legged dwarfs.	Hereford
Dwarfism - Dexter (bulldog)	Heterozygotes are short-legged and short-headed but otherwise healthy (Dexter-type). Homozygotes are "bulldog" lethals.	Dexter, Florida Cracker
Dwarfism - midget type	Heterozygotes generally indistinguishable from normal but may be slightly shorter and easier fleshing. Homozygotes are healthy and reproductive but are 50 to 60% of normal size.	Brahman
Dwarfism - snorter type	Abnormal shortened head; shortened legs as a result of disturbance of longitudinal epiphyseal growth; breathing often difficult and such animals are susceptible to bloat.	Angus, Hereford
Dwarfism - long headed type	Affected calves abnormally small but bone growth of the head not affected.	Angus, Hereford
Double muscling	Bulging muscles of the back and hind quarters. Deep creases between muscles, high-set tailhead, absence of fat. Heterozygotes may exhibit some increased muscling.	Charlois, Angus, Piedmontese, Belgian Blue
Hypotrichosis (semi-hairlessness)	Affected calves have fine, thin curly hair which is often rubbed off poll, neck, knees, and pasterns, otherwise, normal in growth and reproduction.	Polled Hereford, Hereford, Jersey
Internal hydrocephalus	Accumulation of excessive fluid within venticules of the brain. Calves usually born dead. May also be caused by environmental factors.	Hereford
Mannosidosis	Deficiency of mannosidose results in accumulation of oligosaccharides in neurons. Characterized by ataxia, incoordination, head tremor, and aggressive behavior. Onset at 6 to 12 months of age.	Angus
Osteopetrosis (marble bone disease)	Solid bones lack marrow associated with shorter lower jaw and premature birth.	Angus
Porphyria (pink tooth)	Teeth and bone store porphyrin giving them a brown color. Affected animals are sensitive to sunlight and develop sores when exposed to sunlight.	Holstein, Limousin
Syndactylism (mulefoot)	Fusion of claws on one or more foot. Affected animals also sensitive to high abient temperatures.	Holstein, Angus
¹Unless otherwise noted by descriptions of heterozygous condition. ²Adapted from Leipold and Dennis - Advances in Veterinary Science and Comparative Medicine 27:197-271 (Congenital defects affecting bovine reproduction). ³Breeds listed are those in which the undesirable gene has been reported or observed. Other breeds likely possess them as well, probably at lower frequencies.

The first genetic defects studied intensively were various types of dwarfism. Cooperation between university researchers and breeders of Hereford, Angus, and Shorthorn cattle and their respective breed associations in the study of the causes and control of dwarfism is credited by some as being responsible for "breaking the ice" that had existed between the two groups prior to that time. Today, university researchers and beef breed associations work very closely in breed improvement programs. The initial work with the pedigrees of "snorter" dwarf cattle indicated a recessive mode of inheritance for the defect. In spite of considerable effort by animal scientists, detection of heterozygotes for snorter dwarfism based on phenotype (physical measurements or x-rays) was not possible and thus it was necessary to detect carriers though progeny testing programs. A sire is a suspected carrier if his sire or maternal grandsire were known carriers of a particular recessive gene. Procedures used for testing a bull for a particular recessive gene are: (1) breed the bull to females homozygous recessive for the defective gene (if such females are viable and fertile); (2) breed the bull to known heterozygous females; and (3) use a combination of homozygous and heterozygous females. Heterozygotes may be identified on the basis of having produced affected (homozygous recessive) progeny or by having an affected parent. If a sire is being tested for the presence of recessive spotting, s, or the gene allowing normal horn growth, p⁺, homozygous recessive females are fully fertile and readily available; simply use spotted or horned cows, respectively, as tester females. The production of seven solid-colored (S⁺_) progeny sired by a Simmental bull being selected for non-spotting and from spotted cows (ss) strongly indicates that the bull in question is free of s. This statement can be made as the probability that a bull that was heterozygous for s (S⁺s) would produce seven solid-colored (S⁺_) calves from spotted cows due to chance is only .0078, less than one chance in 100. Similarly, the production of seven polled calves from horned cows and no horned calves is very strong evidence that the polled bull in question is homozygous (PP). Degrees of accuracy for various numbers of progeny produced by different types of tester females are shown in table 2.5.

When heterozygous females must be utilized due to lethality, sterility, or unavailability of homozygous females, more test matings are required. Production of 16 normal progeny from a suspect bull and known carrier cows indicates that the bull is homozygous with only a 1% chance of falsely declaring a heterozygous bull clear of the undesirable gene. As an example, an Angus bull whose sire was a carrier of osteopetrosis would have a 50% chance of being heterozygous for the gene. Such a bull could be tested by mating him to at least 16 cows which had previously given birth to calves with osteopetrosis, thus proving them to be carriers. If at least 16 calves were born and all were normal, there would be only a 1% chance that the sire was a carrier. Often, it may be difficult to locate 16 known carrier cows. In such case, those cows available could be superovulated and their embryos implanted into recipient females. It may not even be necessary to allow the resulting fetuses to go to term to determine their status. With the stage of gestation dependent on the defect in question, recipient females could be slaughtered and their fetuses recovered and evaluated to speed the process of evaluation.

In certain circumstances, it might be useful to use a combination of homozygous and heterozygous females as testers due to availability within a herd. For example, one is able to test a bull with similar accuracy with four progeny from homozygous females and seven progeny from heterozygous females as one could with seven matings to homozygous recessive matings (see table 2.5). The probability of detecting a carrier bull can be determined for any combination of homozygous and heterozygous tester females by calculating [(1-(.5)^n1*(.75)ⁿ²)], where n1 is the number of progeny from homozygous tester females and n² is the number of progeny from heterozygous tester females.

A problem with both the homozygous recessive and heterozygous female testing procedures is that they test only for the specific recessive gene carried by the tester females. Thus, it is possible (although unlikely) that a bull could be tested free of the osteopetrosis gene and then be found to carry the gene responsible for syndactylism (mulefoot) years later, after siring many heterozygous progeny. Matings of a bull to his daughters offers the opportunity to declare a bull free of all recessive genetic defects with a similar degree of accuracy as the previous tests, a probability of detection of 99% if 35 sire-daughter matings are made. The level of accuracy with fewer matings is shown in table 2.5. This procedure, of course, has certain limitations including the delay in evaluating the bull until his daughters are of breeding age and the resulting inbred progeny which may be less productive and less valuable than outcross animals even if all normal progeny are produced. Also, it should be emphasized that 35 different daughters must be utilized to test the sire. If individual daughters produce more than one progeny, more than 35 total progeny of the sire-daughter matings are required. If two progeny are produced from each daughter, a total of 19 daughters and 38 total progeny would be required to retain the same accuracy. Comparable numbers of daughters and total progeny produced would be 14 and 42 for 3 progeny per daughter and 11 and 44 for 4 progeny per daughter.

Not all genetic conditions are as simply inherited. The double-muscled condition has been described as being recessive and, indeed, seems to be inherited in this manner in some breeds. In Europe, however , double-muscled bulls are maintained in AI studs for the purpose of producing veal calves from dairy cows. Obviously, this effort would be futile if muscling were not increased in heterozygous calves. A recent Canadian study (Arthur et al., 1989) has shown that heterozygotes for double muscling had higher cutability and muscle:bone ratios than homozygous normal animals. This finding confirms the partial dominance of the gene(s). The expression of the homozygous double-muscled condition seems also to be conditioned by the genetic composition of the animal. For example, homozygous double-muscled Angus calves are usually more stress susceptible and less vigorous than normal calves, whereas in the Piedmontese breed, the modifying genes of this breed's genetic composition seem to allow for much more viable homozygotes, perhaps by delaying the onset of the extreme muscling and reducing muscling in cows relative to bulls. Belgian Blue cattle which also appear to be homozygous for double muscling have recently been imported into the United States. It is unclear whether the Belgian Blue breed possesses the modifying genes present in the Piedmontese.

Other commonly observed congenital (present at birth) defects in cattle include umbilical hernias and cryptorchidism (retained testicles). While in some studies hernias seem to be inherited as a dominant, other studies have not supported this conclusion. Perhaps it is most appropriate to conclude that there is genetic control over hernias and cryptorchidism, but that they are not simply inherited. Fortunately, umbilical hernias are fairly rare in cattle, and when they do appear, affected animals usually are not surgically corrected and then used for breeding purposes. Monorchid (unilateral cyptorchid) bulls are almost always slaughtered. Perhaps this is sufficient selection pressure against these conditions until their mode of inheritance is better understood or their incidence increases.

Ideally it would be desirable to eliminate all genes which produce genetic defects in cattle. Unfortunately, this is not feasible because, as was previously discussed, these genes are recessive in mode of inheritance and thus it is usually impossible to detect heterozygotes. The only time that an animal is proven to be a carrier (heterozygous) is by the production of affected. (homozygous recessive) progeny. Unfortunately, when an undesirable gene is at low frequency in a population, it is unlikely that two heterozygotes will be mated and even then only 25% of the progeny will be homozygous recessive. Thus, it is highly probable that most animals that are heterozygous for rare undesirable genes will never produce undesirable progeny and, therefore, never be culled. The existence of rare undesirable genes in a breed often is determined only when inbreeding is practiced. Once a genetic defect has been discovered in a breed, the question then is how to proceed. The dwarfism problem in Hereford and Angus cattle was brought under control by the elimination of entire bloodlines which carried the dwarf gene. This approach, while effective, results in the culling of homozygous normal animals as well as heterozygotes. If the bloodline in which the genetic defect occurs is superior for important economic traits, such a culling program could do considerable harm to the breed in question. If the bloodline (for example, a particular sire that is heterozygous for a genetic defect and his progeny) is sufficiently superior for traits of economic merit, a program of progeny testing could be established to identify descendants of the bull that are probably free of the genetic defect.

Because complete elimination of recessive defects in breeds of cattle is not feasible, it is necessary to develop mechanisms to prevent large increases in the frequencies of undesirable genes. This can be accomplished through prompt reporting of cases of suspected genetic defects which can allow culling or at least more restricted use of the affected animal's sire and dam once it has been established that the affected calf is indeed homozygous for an undesirable gene and that it is the progeny of the parents of record. The latter can be done through blood typing procedures (discussed later), while the former will require pedigree analysis of the affected calf and its clinical examination. Many types of congenital defects may be simply due to developmental abnormalities caused by environmental pollutants or other usually unknown factors, even if the same defect may be caused by homozygosity for a recessive gene. Arthrogryposis associated with cleft palate is one example. Due to possible environmental causes of arthrogryposis, a bull should not be culled for producing a single calf with arthrogryposis unless evaluation of the pedigree indicates that linebreeding or inbreeding was involved and/or the bull is of a breed in which the undesirable gene is commonly found.

Once a sire has been proven to carry an undesirable gene, this fact should be made known to all breeders who might consider using the bull. Dissemination of this information is best handled through breed associations. While many bulls are sent to slaughter soon after identification of their status as heterozygotes, others, if they are sufficiently genetically superior, continue to be used. Breeders who use such bulls must be particularly careful how they mate the progeny as 50% would be expected to be carriers.

Blood Typing
The primary use of blood typing in beef cattle breeding programs today is parentage determination. Calves born as a result of embryo transfer are generally required to be blood typed, along with their sire and dam, to be registered. In most breeds, bulls to be used by artificial insemination must be blood typed to allow later verification of parentage where the wrong unit of semen may have mistakenly been used. With regard to natural service sires, occasionally two bulls will breed a cow during the same estrus. When such an event happens, it is necessary to blood type both bulls, the cow, and the resulting calf to determine the likely sire of the calf. It is even possible for the calves of two cows to have been switched if cows, especially young ones, calved at the same time in close proximity. If there is reason to suspect such an event, blood typing can often resolve the question. In recent years, there also have been questions about breed purity. The possibility of Holstein and Chianina influence in some Angus and Holstein and Simmental influence in Polled Hereford has been raised in recent years. In some of these cases, blood typing can give evidence to support or refute such accusations.

Blood-Group Systems

There are over 10 different blood-group systems used in attempting to resolve these questions. Each system represents a different locus at which blood-group factors or groups of blood-group factors, called phenogroups, are inherited like alleles. The number of phenogroups present varies from two for several systems to over 600 for the B system. Blood factors tested represent antigens found on the surface of red blood cells. When red blood cells which carry a particular blood factor are injected into an animal not carrying that factor, the animal can produce antibodies specific for the blood factor (antigen) involved. When red blood cells carrying a particular blood factor are mixed with a serum containing antibodies for that factor (a reagent), the antibodies in the reagent attach themselves to the antigens on the red blood cells, resulting in hemolysis (breakage of the red blood cells). Usually, hemolysis requires the presence of complement (fresh rabbit serum) to stimulate the reaction. The B system is the most useful in parentage and other tests due to the extreme number of phenogroups (over 600) found at this locus. As many as 200 different phenogroups have been found in a given breed. Examples of B system phenogroups found within the Brahman breed are listed in table 2.7. Phenogroups, such as BI₁O₁QD'I' and PY₂A' of the Brahman breed, act as alleles in that these combinations of six and three blood factors are each inherited as a group. By this it is meant that if a bull carries BI₁O₁QD'I'(B340) and PY₂A'(B287), half of the progeny of this bull will receive B340 and half B287. All progeny of this bull must carry either B340 or B287; if potential progeny do not carry either, they are excluded as progeny of this sire. This is the principle of parentage testing using blood-grouping systems; a bull is excluded as the sire of a particular animal if the possible offspring of that sire does not carry one of the potential sire's phenogroups at all loci tested. This principle can be clarified using an example. In this hypothetical example, it is assumed that both Bull A and Bull B had bred Cow C and Calf X was the result.

Table 2.7 B System Phenogroups¹ found in the Brahman Breed
Phenogroup	Number (withing the B system)	Frequency²
BI₁O₁QD'T' BG₂I₂KQE'₃F'J'O'A" BPPB" BQTA'B'P'A" PY1₁A'Y' PY₂A' I₁J'O'P'Q'B" I₁Y₁G' BTA'B'P'A" O₁Y₂Q'	340 256 542 640 449 287 557 556 437 504	.1242 .0861 .0465 .0373 .0296 .0290 .0256 .0256 .0251 .0220
¹The 10 most common phenogroups are shown; a total of over 200 has been identified. ²Frequency as of 09/01/89 as provided by J. Caldwell, ImmGen, Inc., College Station, Texas.

In this case, Bull B is excluded as the sire of Calf X based on the B, C, and R'-S' systems. In the B system, Calf X has phenogroups B340 and B287, neither of which is possessed by Bull B, thus excluding him as a potential sire. Similarly, calf X is homozygous for C2 which excludes Bull B based on the C system as he does not carry C2 and since Cow C carries only S' at the R'-S' locus, she must have provided the S' allele of Calf X which forces the sire to have provided the R' allele, which only Bull A possesses. It should be emphasized, however, that the exclusion of Bull B does not prove that Bull A is the sire of the calf; it does show that Bull A could have been the sire and that Bull B could not have been the sire.

Blood-group system
Animal	A	B	C	F-V	S	R'- S'
Bull A	A₁D/D	B340/B287	W/C₂	F/V	H'/SH'	R'/S'
Bull B	A₁H/D	B542/B256	X₂/C₁W	F/V	U2/SH'	S'/S'
Cow C	A₁/A₁D	B340/B449	C₂/X₁	V/V	H'/SH'	S'/S'
Calf X	A₁D/D	B340/B287	C₂/C₂	V/V	H'/SH'	R'/S'

Because each breed has its own particular frequencies of phenogroups within each system, it is sometimes possible to identify the breed of an animal simply from its blood type. This is particularly true for the B system where some phenogroups are very common in one breed and nonexistent or extremely rare in another breed. For example, the most common phenogroup in the Texas Longhorn breed, BG₂ KA'O'A"B"(B506), is not found in most other breeds and should it be observed in a Hereford animal, it would strongly indicate that the Hereford with B506 contained some Longhorn breeding. In recent years, there have been some Polled Hereford cattle questioned as to being part red and white Holstein. Since the s gene of the red Holstein is recessive to S^H of the Polled Hereford, as is the p⁺ allele of the Holstein, it would not be possible to determine conclusively by visual observation whether the animal was part red and white Holstein. The presence of one of the common Holstein blood groups B3, B84, B202, etc., however, would lead one to strongly suspect that the animal was indeed part Holstein. It could not, however, be proven to be part Holstein as most of the common Holstein B system phenogroups have also been found at low frequencies in Herefords. It is because of such overlap of phenogroups from one breed to another that it may be difficult to document clearly the introduction of another breed unless the reported parents and perhaps grandparents of the animal with an unusual phenogroup combination can be examined.

In addition to red blood cell antigens, blood samples from cattle may be tested for other genetic markers by use of starch-gel electrophoresis. These markers include hemoglobin types, transferrin (-globulin) types, and carbonic anhydrases (red blood cell enzymes). These markers can be useful in parentage testing and are currently being used to test for bison markers in Beefalo cattle. Cattle have two alleles for hemoglobin type, A and B, and three associated phenotypes, A, B, and AB. The symbol bi has been used to symbolize the allele responsible for the hemoglobin type of bison. The hemoglobin produced by bi is electrophoretically distinct from that of cattle and thus animals typed as A//bi or B//bi can be said to be composed of both cattle and bison germ plasm. Bison also have been shown to have a transferrin type which is distinct from the four types in cattle and to have three electrophoretic forms of carbonic anhydrases, two of which are distinguishable from the two types in cattle. In addition to these three genetic markers, reagents are available which can differentiate between the red blood cell antigens of bison and cattle and classify animals as B, C, or BC where B indicates a reaction with bison-specific markers, C indicates a reaction with cattle specific markers, and BC indicates that the red blood reacted with both the cattle and bison specific reagents.

References

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Caldwell, J. 1986. Blood Types of Cattle and Their Application. In: D. A. Morrow (Ed.). Current Therapy in Theriogenology II. pp. 427-432. W. B. Sanders Co., Philadelphia.

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Nicholas, F. W. 1987. Veterinary Genetics. Oxford Univ. Press.

Olson, T. A. and R. L. Willham. 1982. Inheritance of Coat Coloration and Spotting Patterns of Cattle: A Review. Iowa State Univ. Agr. and Home Econ. Exp. Sta. Res. Bull. 592, Ames.

Sartore, G., C. Stormont, B. G. Morris, and A. A. Grunder. 1969. Multiple Electrophoretic Forms of Carbonic Anhydrase in Red Cells of Domestic Cattle (Bos taurus) and American Buffalo (Bison Bison). Genetics 61: 823-831.

Searle, A. G. 1968. Comparative Genetics of Coat Colour in Mammals. Logos Press Ltd. London.

Stormont, Clyde. 1962. Current Status of Blood Groups in Cattle. Ann. N.Y. Acad. Sci. 97:251-268.

Stormont, C. J., B. G. Morris, Y. Suzuki, and J. Dodd. 1986. Blood Typing Beefalo Cattle. 3rd World Congress on Genetics. Applied to Livestock Production IX:359-364.

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