Clue to late puberty in sheep discovered by AgResearch team

AgResearch has announced that a needle-in-a-haystack search for the genetic cause of delayed puberty in a flock of Romney ewes has paid off for a team of its scientists.

Understanding what regulates the arrival of puberty is important for livestock breeding as well as human health.

Researchers in AgResearch’s Animal Reproduction team at Invermay had noticed that late puberty was a family trait in their research flock. This caused the late developers to miss out on lambing during what could be their first breeding season. They had previously demonstrated that late developers also produce fewer lambs during their lifespans.

A family tree search traced the trait back to a common grand-sire from the Davisdale line of Romneys. This line of sheep, which has become an important research tool, was established by retired AgResearch scientist Dr George Davis from the flock of his father, Stan Davis.

The researchers had the entire genome of the sire and three of his sons sequenced, and then began hunting for a gene variant that could be responsible for delayed puberty in their descendent ewes.

“We focussed our search on 60 genes known to be involved in reproductive function, as well as those involved in growth and body composition, because these are also related to puberty onset,” said co-author and Science Team Leader Dr Sara Edwards.

They then looked for the gene variants in the female descendants’ DNA and matched their occurrence with age at puberty.

“We found a strong association between age of puberty and a naturally occurring gene variant,” says lead researcher Dr Jenny Juengel.

“Those ewes who were the oldest when they reached puberty had inherited two copies of the leptin receptor gene variant. This was a new finding.”

Leptin is an important hormone for controlling fat deposition and regulating appetite.

The leptin receptor sits on the surface of cells, detecting and receiving the leptin hormone as it circulates through the body. The receptor is known to be associated with puberty onset in mice, humans and cattle.

The research has been published in the international academic journal Biology of Reproduction.

“There is more work to be done before we can be absolutely certain that the variant we found is responsible for the late puberty onset,” points out Dr Juengel. “But the current evidence is compelling.”

Searching for the responsible gene was made possible with the use of new technology that allows entire genomes to be sequenced affordably in a matter of weeks.

Much of the screening work was carried out by Research Associate Michelle French.

The next step of the project is to work with AgResearch’s Animal Genomics team to find out how common the leptin receptor variant is in the national flock. The team also aims to confirm whether the variant directly affects lambing rates throughout a ewe’s reproductive life. Breeding the trait out of flocks could significantly increase lifetime reproductive rates, and therefore farm profitability.

The research was carried out in collaboration with the Indian Council of Agriculture Research Complex for North Eastern Hill Region, and funded by the Ministry of Business, Innovation and Employment, AgResearch Core funding and an Indian Biotechnology Overseas Associateship grant.

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