Frameshift

“No. No, it’s one thing to let you risk being married to someone who might become very sick; it’s quite another to ask you to additionally risk financial ruin. I should have the test.”

“If you think it’s best,” said Molly. “But I’ll marry you either way.”

“Don’t say that now. Wait till we have the test results.”

“How long will that take?”

“Well, normally a lab requires you to go through months of counseling before they’ll administer the test, to make sure you really want to take it and are going to be able to deal with the results. But…”

“Yes?”

Pierre shrugged. “It’s not a hard test — no harder than any other genetic test. As I said, I could do it myself in my lab at LBL”

“I don’t want you to feel pressured into doing this.”

Pierre shrugged. “It’s not you doing the pressuring; it’s the insurance company.” He was quiet for a while. “It’s all right,” he said finally. “It’s time I found out.”

Chapter 13

“Explain what’s going on to me,” said Molly, sitting on a stool in Pierre’s lab. It was ten o’clock on a Saturday morning. “I want to understand exactly what’s happening.”

Pierre nodded. “Okay,” he said. “On Thursday, I extracted samples of my DNA from a drop of my own blood. I separated out my two copies of chromosome four, snipped off particular segments using special enzymes, and set about making radioactive images of those segments. It takes a while to develop those images, but they should be ready now, so we can actually check what my genetic code says in the specific gene associated with Huntington’s disease. That gene contains an area called IT15 — ‘interesting transcript number fifteen,’ a name given to it back when people didn’t know what it was for.”

“And if you’ve got IT15, you’ve got Huntington’s?”

“It’s not as simple as that. Everybody has IT15. Like all genes, IT15’s job is to code for the synthesis of a protein molecule. The protein IT15 makes has recently been dubbed ‘huntingtin.’ ”

“So if everyone has IT15,” said Molly, “and everybody’s body produces huntingtin, then what determines whether you have Huntington’s disease?”

“People with Huntington’s have a mutant form of IT15, which causes them to produce too much huntingtin. Huntingtin is crucial to organizing the nervous system in the first few weeks of an embryo’s development. It should cease to be produced at a certain point, but in those with Huntington’s disease it isn’t, and that causes damage to the developing brain. In both the normal and mutant versions of IT15, there’s a run of repeating nucleo-tide triplets: cytosine-adenine-guanine, or CAG, over and over again. Well, in the genetic code, each nucleotide triplet specifies the production of one specific amino acid, and amino acids are the building blocks of proteins. CAG happens to be one of the codes for making an amino acid called glutamine. In healthy individuals, IT15 contains between eleven repeats and thirty-eight repeats of this CAG triplet. But those who have Huntington’s disease have between forty-two and a hundred or so CAG repeats.”

“Okay,” said Molly, “so we look at each of your chromosome fours, find the beginning of the run of CAG triplets, then simply count the number of repeats of that triplet. Right?”

“Right.”

“You’re sure you want to go through with this?”

Pierre nodded. “I’m sure.”

“Then let’s do it.”

And they did. It was painstaking work, carefully examining the autoradiograph film. Faint lines represented each nucleotide. Pierre used a felt-tipped marker to write in the letters beneath each triplet: CAG, CAG. Molly, meanwhile, tallied the number of repeats on a sheet of paper.

Without blood samples from Elisabeth Tardivel and Henry Spade, there was no easy way to tell which of his chromosome fours had come from his father, so he had to check them both. On the first one, the string of CAG triplets ended after seventeen repeats.

Pierre breathed a sigh of relief. “One down, one to go,” he said.

He began checking the sequence on the second chromosome. No reaction when they reached the tally of eleven; that was the normal minimum. When they got to twenty-five, though, Pierre found his hand shaking.

Molly touched his arm. “Don’t worry,” she said. “You said you could have as many as thirty-eight and still be normal.”

Pierre nodded. “But what I didn’t say was that seventy percent of all normal people have twenty-four or fewer repeats.”

Molly bit her lower lip.

Pierre continued sequencing. Twenty-six, twenty-seven, twenty-eight.

His eyes were blurring.

Thirty-five. Thirty-six. Thirty-seven. Thirty-eight.

Damn. Goddamn.

Thirty-nine.

God fucking damn it.

“Still,” said Molly, trying to sound brave, “thirty-eight may be the normal limit, but you have to have at least forty-two…”

Forty.

Forty-one.

Forty-two.

“I’m sorry, honey,” said Molly. “I’m so sorry.”

Pierre put down his marker. His whole body was shaking.

“God, I am so sorry,” said Molly.

A fifty-fifty shot.

A flip of a coin.

Heads or tails.

Call it!

Pierre said nothing. His heart was pounding.