Sunday, December 20, 2020

Why Clone Sheep — Don’t They All Look Alike Anyway?

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On the 20th anniversary of the birth of Dolly, the first cloned sheep, a reader asks: Don’t all sheep look alike anyway? Could anyone tell Dolly, Daisy, Diana, Debbie, and Denise apart from members of the sheep population that weren’t cloned? Wouldn’t it have made more sense, as a groundbreaking experiment, to clone members of a species where that wasn’t the case?

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JoAnna Klein, a science writer for The Times who recently wrote about Dolly and her “sisters,” considers the question.

I hear you. I thought the same thing at first, but we’re wrong. All sheep don’t look alike.

To be fair, though, some differences are easier to spot than others.

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“There are different breeds of sheep, just as there are different breeds of dogs,” said Kevin Sinclair of The University of Nottingham in Britain, who recently led a study investigating the health of Dolly the Sheep’s cloned relatives. Just as you can tell a beagle from a chocolate lab, you can tell the difference between a Finn Dorset (Dolly’s breed) and a Lleyn (the breed of other cloned sheep in the study) — as long as you get used to looking at them. “But if you took 12 beagles of the same age and litter and put them together, how easy would it be to tell them apart?” Dr. Sinclair asked. “Would it be any easier than telling apart 12 sheep of the same breed?” He doesn’t think so.




Although it was easy to identify the D-squad members among other sheep on the farm because of their breed, telling them apart from one another was a struggle for Dr. Sinclair. They even behaved similarly. With the group of clones in the Lleyn breed, however, he noticed different personalities, and there was at least one sheep that acted as a matriarch: “She’d be, ‘These are my girls, what are you doing? If you want to do anything with these other girls, come to me first.’ ”

“Let’s imagine a scenario where you are the manager of a sheep farm, and someone tells you that they have smuggled a cloned sheep into the flock, and you have to find it,” Jose Cibelli, a biotechnologist at Michigan State University who patented a method for identifying clones, wrote in an email. “You draw blood from all the animals, isolate the DNA from the nuclei of the white blood cells and then start comparing them with each other.”

With just one clone in the flock, you have no way of telling the difference. But if you have two or more clones, as with the D-squad, they will share the same nuclear DNA, meaning 20,000 to 25,000 coding genes inside their cells’ nuclei will be exactly the same. Twins also share the same nuclear DNA, though, so you’ve still got a problem. To find the clone, you have to look deeper into their mitochondria, their cells’ energy centers. Here’s why.

The process scientists used to clone the D-squad and other animals — somatic cell nuclear transfer — involves wiping out existing DNA in an egg cell and replacing it with new DNA, which isn’t always a clean sweep. Some things get left behind.

Because clones come from different eggs, an itsy-bitsy sort of essence from the original egg may remain in the DNA of the mitochondria, which is shorter and contains only 37 genes. That essence manifests as little blips of difference that could mean differences at the cellular and tissue level, as well as in behavior, personality and health: “As the animal’s age, even though they’re in a similar environment, they will respond to the environment ever so slightly differently,” Dr. Sinclair said.




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