CoRSIVs, first discovered in humans, are now found in cattle

A study published in Genome Biology opens up new opportunities to improve production efficiency in the livestock industry and potentially in animal agriculture more broadly. A team of researchers at Baylor College of Medicine, Cornell University and the USDA discovered that, like humans, cattle have CoRSIV.

CoRSIVs are regions of the genome that carry chemical markers in DNA that provide information that can allow farmers to predict and select for desirable cattle traits, such as milk production, female fertility and disease resistance.

“Most people know that each person has a unique set of genes, or genome, but less well known is that the expression of those genes is regulated by a system of molecular marks in DNA—epigenetics—that tell different cells in the body which genes you have to turn on or off,” said co-corresponding author Dr. Robert A. Waterland, professor of pediatrics-nutrition at the USDA/ARS Child Nutrition Research Center at Baylor.

“We focus on DNA methylation—the addition of methyl groups, the most stable epigenetic mark. DNA methylation differences between people can influence disease risk.”

In 2019, Waterland and his colleagues discovered that the human genome contains distinct regions called CoRSIVs—correlated regions of systematic inter-individual variation.

In CoRSIV, DNA methylation levels vary between people but are consistent across different tissues within each person. This means that CoRSIV methylation can be measured in easily accessible tissues such as blood, providing information on epigenetic regulation in internal organs such as the brain, ovaries or liver.

Their previous work reported about 10,000 CoRSIVs in the human genome and proposed that studying these new regions is a powerful way to uncover the epigenetic causes of disease. Indeed, CoRSIVs have already been associated with various health outcomes, including cancer, thyroid function, cognition, type 2 diabetes, cleft palate, schizophrenia, childhood obesity, and autism spectrum disorder.

In the current study, the researchers investigated whether cattle also have CoRSIV. The team analyzed whole-genome DNA methylation sequencing data in multiple tissues of each of the two Holstein cows.

“The algorithm we developed showed that cattle do indeed have CoRSIV,” said first author Wen-Jou Chang, a bioinformatics analyst at the Waterland Laboratory. “Even more exciting, we showed that cattle CoRSIVs share key signatures with those in humans, suggesting that CoRSIVs are likely present in other mammals. The race is on to find them in other species, such as horses and pigs.”

“We validated our computational findings by laboratory analysis of liver, kidney, brain and blood tissue from 20 different Holstein calves to confirm some of the CoRSIVs Wen-Jou identified,” said Waterland, a member of the Comprehensive Center for Dan L Duncan Cancer at Baylor. . “This independent validation added great strength to the study.”

Co-corresponding author Dr. Yi Athena Ren, assistant professor in the Department of Animal Sciences at Cornell University, said: “In recent decades, cattle agriculture has focused on genetic selection to achieve substantial advances in milk production. CoRSIVs may provide an approach new to improve the selection of traits that are desirable for the cattle industry in a sustainable way that reduces cost and environmental impacts.”

“Cattle CoRSIVs, like those in humans, are established early in life and are persistent throughout the individual’s lifetime,” Waterland said.

“In newborn cattle, methylation patterns in subsets of CoRSIVs may be able to predict future performance. They may be associated with specific desirable traits, such as abundant milk production, high female fertility, resistance to diseases or even heat tolerance, helping to select individual calves with traits that will lead to increased productivity”.

The researchers showed that, as in humans, the setting of DNA methylation in CoRSIV cattle is influenced by the early embryo environment.

“This suggests that adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes from epigenetic engineering,” said Ren.

“In addition to helping select for desirable traits, CoRSIVs can help understand disease processes and individual variation among cattle. And, if, as we expect, CoRSIVs are a general feature of the mammalian genome, opportunities to such agricultural activities are not limited to livestock.