Genetic Disorders

Bovine Leukocyte Adhesion Deficiency describes a hereditary fatal immunodeficiency in Holstein cattle. Affected animals suffer from impaired cellular immune defence and therefore fall ill or die from trivial infections within the first weeks of life. BLAD is caused by a single base substitution in the CD18 gene which results in a decreased formation of the beta-2 integrines of leukocytes, hindering the migration of leukocytes from the blood to the focus of an infection.
Due to its autosomal recessive inheritance, BLAD affects animals carrying two copies of the mutated gene, solely. Heterozygous carriers do not show any clinical signs but can pass on the mutation and - when mated to a BLAD-carrier – can produce affected progenies.
Genetic testing of the causative mutation in the CD18 gene enables discrimination of BLAD-carriers from non-carriers and helps preventing breeding affected offspring.

A genetic defect located in the TMEM95 locus on bovine chromosome 19 is one possible cause of reduced male fertility in cattle. It is assumed that this hereditary defect in the homozygous genotype is responsible for the majority of cases of restricted fertilization capability in Fleckvieh bulls. Bulls from other breeds are just as unaffected as Fleckvieh bulls which carry only one copy of the defect or as female animals. The BMS defect could be traced back to Fleckvieh bull Haxl (* 1966) and is spread at a high frequency in the bulls currently used for aritifical insemination.

A genetic test now facilitates the identification of carriers and fertility-impaired bulls at an early stage.

Dwarfed calves (DW) in the Fleckvieh have been known for a long time, but so far occur only very rarely. The disease is characterized by low birth weights and limited calf growth. A mutation in the GON4L gene is responsible for the disease in the homozygous genotype. It is recommended to consistently avoid risk pairings to keep the frequency of the mutation in the population low or to further reduce it.

Genetic testing allows the reliably identification of carriers and avoidance of risk pairings.

A missense mutation in the TUBD1 gene of bovine chromosome 19 is the cause of the genetic defect known as Brown Swiss haplotype 2 (BH2).
Homozygous affected animals are either stillborn or usually die within the first 50 days of life when born alive. Clinical signs in affected animals are: stillbirth, low birth weights, tapered head shape and recurring bronchopneumonia.
In 2014, it became obvious that the mutation associated with the BH2 haplotype also occurs in the Fleckvieh breed.
Nowadays, BH2 genetic testing can be performed, in order to avoid risk pairings and in order to further reduce the frequency of the mutation in the cattle population.

FH2 (Fleckvieh haplotype 2), also called Fanconi-Bickel syndrome, describes a for a long time unknown genome region that is not linked to the dwarfism syndrome, which, however, in the homozygote state leads to significant short stature of the affected animals. Birth weight and early development appear to be largely normal at first, but after the milk is discontinued, the affected calves remain significantly behind in growth and development.
A mutation in the SLC2A2 gene, which is responsible for the synthesis of a glucose transporter protein, was identified as the cause of the disease.

Based on these findings, genetic tests can now be used to implement systematic selection and mating in order to control the frequency of this mutation in the Fleckvieh population.

Fleckvieh haplotype 4 (FH4) is an autosomal recessive lethal defect located on bovine chromosome 12. A mutation within the SUGT1 gene was identified as the causative mutation for this disease.
In homozygous state, the defect usually causes embryonic death within the first few weeks of gestation or results in stillbirth of the affected calf later on. Interestingly, bulls carrying the FH4 defect in heterozygous state have normal fertilization rates, similar to those of FH4-free bulls.
The FH4 status of an animal can be determined by genotyping. By doing so, it became possible to avoid risk pairings and to further reducing the frequency of the defect gene through moderate selection.

Mating of FH5 carriers is characterized by significantly increased rates of calf mortality within the first 48 hours after birth. Affected calves suffer from congenital heart failure and severe liver damage.
Due to the economic importance and its consequences concerning animal welfare, it is necessary rapidly reducing the frequency of this defect locus in the Fleckvieh cattle population.

FH5 genetic testing is a powerful tool for the determination of the defect locus in Fleckvieh and for taking it into account in breeding practice.

Progressive ataxia in Charolais cattle describes a lethal autosomal recessive hereditary defect. A single base pair mutation in the KIF1C gene results in a loss of function of the gene and, as a result, in a loss of myelin sheath in some areas of the brain and spinal cord.
First clinical signs of this neurodegenerative disorder such as unsteady gait or crossing of stiff hind limbs usually manifest at the age of 18 to 24 months, in some cases only at the age of 2 years or older. Abrupt head movements and irregular pulsatile urination may be observed as further possible symptoms.
Since affected animals cannot be cured from this disease and as symptoms worsen over time, these animals have to be euthanized to prevent them from prolonged suffering by permanent recumbency.
Genetic testing of the KIF1C gene can be used to reliably identify heterozygous and homozygous carriers of this defect. By doing so, affected animals can be identified long before symptoms of the disease will become obvious. In addition, mating of carriers, which results in affected offspring with a probability of 25%, can be reliably avoided.

Bovine Progressive Degenerative Myeloencephalopathy (weaver disease) describes a genetic disorder of the central nervous system with apparently autosomal recessive inheritance in Brown Swiss cattle.
At an age of a few months, affected animals develop progressive signs of ataxia, paresis of the pelvic limb and deficits in proprioception.
Clinical signs of the disease deteriorate in the course of time and finally, severely affected animals become recumbent and may die from further complications. The genetic principle of this disease is now fully understood. Direct gene testing allows differentiating between homozygous healthy animals and heterozygous carriers of this disease.

Bovine Spinal dysmyelination (SDM) of Brown Swiss cattle is characterized by pathological formation of the myelin sheaths of neurons in the spinal cord. Clinical signs of this neurodegenerative disorder such as lateral recumbency with opisthotonos of varying degree and exaggeration of the spinal reflexes usually manifest immediately after birth.
Since SDM affected calves can not be cured, they are usually euthanized within the first weeks of life. The gene defect responsible for this autosomal recessive disease has recently been fully elucidated. Genetic testing of the underlying mutation allows clear distinction between homozygous healthy animals, heterozygous carriers of the disease, and homozygous affected animals.

The spinal muscular atrophy (SMA) is an autosomal recessive disease in Brown Swiss cattle. The symptoms of the disease are caused by the loss of motor neurons in the spinal cord, brain stem and motoric cortex areas. As a result of nerve cell shrinkage, affected calves display muscle weakness and atrophy of skeletal muscles associated with sternal recumbency, reduced spinal reflexes and reinforced breathing at the age of a few weeks. However, in most cases regular drinking behaviour is maintained. Secondary pneumonia is a frequently observed complication developing in the course of disease manifestation. The disease is lethal within a few weeks.
The causal mutation has been identified which enables genetic testing for this disease.

Arachnomelia in cattle is an autosomal recessive disorder of the skeletal system which is known in Simmental and Brown Swiss breed. Affected calves are born dead or non-viable deformed, in addition, there is an increased risk of injury to the dam due to forced birth assistance. After initial discovery of the cause of the disease in Braunvieh the underlying mechanism of this genetic defect has also been resolved in Simmental. In both breeds different mutations result in loss of function of an enzyme involved in bone metabolism and cause dysfunctional bone development. Direct gene testing allows differentiating between homozygous healthy animals and heterozygous carriers of this disease.

Thrombopathia (TP) in Fleckvieh cattle describes a recessive inherited dysfunction of the Thrombocytes (platelets), which in affected animals leads to an disorder of the blood coagulation. Affected animals appear to be healthy and show an undisturbed general condition. However, due to the impaired blood clotting, even minor injuries lead to massive bleeding.

By identifying the causative mutation, for some time, it has been possible to identify carriers of this disease and thereby to prevent risk mating and birth of affected calves.

DEB (Dystrophic Epidermolysis Bullosa)
DEB (Dystrophic Epidermolysis Bullosa) describes a heritable skin disease in the local cattle breeds Rotes Höhenvieh and Vorderwald cattle. The disease which is inherited in an autosomal recessive manner causes severe skin defects at the muzzle and the fetlocks. Due to an abnormal high fragility of the skin these lesions rapidly extend leading to further painful epidermal loss, ulcerations and dysungulation. There is no medical treatment for DEB in cattle and affected animals have to be euthanized to prevent them from further suffering.
A candidate causative mutation for this genetic disease has been identified and thus enables selection against the mutant allele.

ZDL (Zinc Deficiency Like Syndrome) is a hereditary disease of autosomal recessive inheritance. Its clinical appearance shows similarities to that of the feeding-related zinc deficiency syndrome.
Affected calves suffer from inflammatory lesions of face, eye region, sternum and extremities, as well as interdigital erosions and erosive / ulcerative lesions of the oral mucosa. Further clinical symptoms may be recurrent diarrhea and/or pneumonia, reduced growth rate, and poor general health. As a consequence, affected calves usually die with a few weeks up to a few months of age.

A nonsense mutation (p.W215X) in a phospholipase encoding gene (PLD4) was identified as candidate causal polymorphism. Genetic testing of this mutation allows for reliable differentiation of clinically normal carriers from ZDL-free animals.