Genotyping Technologies

RESEARCH & DEVELOPMENT

Routine Human Genotyping Technologies Have Applications for Cattle Breeders

Grant Woronuk, PhD, Research Scientist, Quantum Genetics Canada Inc.

Many parents will remember the heel prick test for their newborn child soon after delivery. This procedure is common practice in modern neonatal medical diagnostics for the detection of various genetic disorders, enabling parents to take appropriate action, if necessary. The neonatal heel prick test is primarily used to diagnose human genetic disorders, including phenylketonuria (PKU). The PKU test allows for a blood sample to be assessed for the proper functioning of the gene coding for the enzyme phenylalanine hydroxylase. Should these tests indicate improper phenylalanine hydroxylase function, caregivers can take action by adjusting the child’s diet in such a manner that ameliorates some of the more serious effects of this disorder, thereby improving the health and longevity of the child. Using the heel prick test for genetic testing of newborns for PKU and other diseases (like cystic fibrosis and hypothyroidism) is critical revealing information prior to onset of symptoms, enabling caregivers to address these special growth and development issues.

The necessity of genetics testing is not limited to infants, as diagnosing the predisposition for certain diseases is useful in adults as well. In some disorders, such as Huntington’s disease, where genotyping elucidates the malignancy in the Huntington gene, there is no cure. Huntington’s disease serves as a rare yet striking example of how fate can be completely determined by our genes, as symptoms for Huntington’s disease are almost completely masked in young people, but for those unfortunate enough to possess the malignant Huntington genotype, disease onset is an absolute certainty. Since no action can be taken with regards to mitigating the effects of Huntington’s disease, people at risk are left with the philosophical dilemma of whether or not they want to know if they possess the malignant Huntington genotype.

Many other genetic diseases, however, empower decision makers to take action to mitigate severity. For instance, genotyping of BRCA1 & BRCA2 yields information regarding possible carcinogenic mutations in these genes that increase the likelihood of breast cancer. Early BRCA1 & BRCA2 genotyping offers people who are diagnosed with carcinogenic mutations in these genes, and thus a predisposition for breast cancer, the opportunity to take proactive therapeutic avenues to reduce the likelihood of the onset of breast cancer. These examples highlight the power of genotyping technology in predicting the future, thereby arming people with accurate information such that they may take appropriate action.

How do genotyping technologies assist cattle breeders? Cattle genotyping is an extension of the same technologies used in human genotyping, as breeders take advantage of these modern technologies to not only mitigate genetic diseases in their herd, but also to optimize the production of cattle with key market characteristics. With regards to diagnosing cattle genetic disorders, one commonly used genotyping assay utilizes DNA markers to identify carriers of Curly Calf Syndrome (CCS). CCS is a disease in which calves are stillborn as a result of a form of arthrogryposis multiplex (AM), and these “curly” calves inherited two copies (one from each parent) of the lethal genotype and are homozygous for the AM gene. However, cattle may be living, symptomfree carriers of CCS if they possess only one copy of the lethal genotype of AM gene (heterozygous), while other cattle can be homozygous with two copies of the benign AM-free genotype. Cattle breeders use genotyping to determine the status of the AM genotype such that they can make informed herd management decisions, such as culling the AM-carriers or strategically breeding with AM-free homozygotes, to avoid the production and perpetuation of curly calves in their herd. Efforts to develop tests for other cattle genetic disorders, including neuropathic hydrocephalus (NH, also known as “Water Head”), contractural arachnodactyly (CA, also known as “Fawn Calf Syndrome”), mannosidosis (MA), and osteopetrosis (OS) have been successful and are now commercially available to assist cattle breeders in herd disease management.

Genotyping is not solely for purposes of diagnosing genetic diseases, however, as cattle breeders also use molecular genetics technology as another tool towards the production of cattle with enhanced market characteristics. The most well established and widely used fat-related cattle genotyping assay is the diagnosis of the leptin single nucleotide polymorphism (SNP), where a single nucleotide shift in the leptin gene significantly impacts a cattle’s predisposition for rapid fat accumulation. SNP-based genotyping is also effective for the diagnosis of another gene, IGF2, that codes for insulin-like growth factor 2 which is associated with increased rib eye area (REA) in cattle. Research conducted at the University of Saskatchewan has shown that cattle who are homozygous for one version of the IGF2 SNP have 10% more REA than cattle with other versions of IGF2 SNP. Application of genotyping and selecting bulls homozygous for key characteristics can improve a breeder’s calf crop in as little as one year.

Through the application of modern genotyping, breeders can better equip themselves with information about their herd, enabling them to make informed breeding decisions. Just as genotyping is critical for determining cattle (and human) predisposition for certain genetic disorders, modern breeders also employ genotyping technologies such that they make accurate and efficient herd management decisions when targeting key markets.