Booster Shots

Oddities, musings and news from the health world

Category: genetics

Genes alone don't foretell Alzheimer's disease risk

May 11, 2010 |  1:00 pm

Alzheimers Researchers looking for genes that contribute to late-onset Alzheimer's disease have found little to help them predict who is at higher risk of developing the condition.

The study, released Tuesday in the Journal of the American Medical Assn., was a genome-wide association study of 35,000 people. The researchers identified several genes linked to the disease but found that knowledge of these genes and their location on chromosomes did not improve their ability to predict who would develop Alzheimer's disease. The knowledge of genes related to the disease could, however, help with research into what causes it, the researchers concluded.

Identifying a number of genes involved in a disease that only have a small effect may not be very helpful, said Nancy L. Pedersen, of the Karolinska Institute in Sweden, in a commentary accompanying the study. She notes that Alzheimer's disease is highly hereditary but that only one known gene -- the APOE gene -- significantly increases the risk. The disease likely is the result of a number of genes, their combinations and, possibly, a combination of those genes and the environment.

The study, Pedersen writes, "is a fresh reminder that family history is very important, even for late-onset disease that was once thought to be sporadic." One's age, sex, family history and APOE status remain the most important factors for predicting risk of the disease.

-- Shari Roan

Photo: Steve Osman  /  Los Angeles Times

Kissin' cousins meant health problems for Charles Darwin's children, researchers say

May 5, 2010 |  7:00 am

For a guy who spent so much of his career studying natural selection, it is perhaps surprising that Charles Darwin married his first cousin, Emma Wedgwood.

Darwin He knew from his own experiments with plants that inbreeding led to less vigorous offspring. What’s more, marriages of cousins were frowned upon in England and elsewhere in Europe due to their “supposed injurious consequences,” Darwin wrote in an 1870 letter to his neighbor. But, he added, “this belief rests on no direct evidence.”

It was a question Darwin was anxious to answer. Three of his 10 children – Anne Elizabeth, Mary Eleanor and Charles Waring – died during childhood. Six of the surviving seven went on to have long-term marriages, but three of those marriages bore no children, suggesting that his children suffered from infertility.

Scholars have documented Darwin’s worries that his own consanguineous marriage contributed to the poor health of his offspring, but he wasn’t able to resolve the question. Nearly 130 years after his death, a group of American and Spanish experts in evolution and genetics have done it for him.

Their conclusion? Darwin’s close genetic ties to his wife probably did play a role in the poor health of his children.

Not only were Darwin and his wife first cousins, but his mother’s parents were third cousins. The researchers calculated that for 6.3% of their genetic sequences, Darwin's children inherited the same DNA from their mother and father. That certainly increased their risk of developing health problems that only occur when the faulty genes are inherited from both parents. It probably explains the high rate of infertility among his adult children, the researchers write.

In addition, scientists discovered last year that inbreeding can make children more susceptible to infectious diseases. Anne Elizabeth died from childhood tuberculosis, and Charles Waring died of scarlet fever. The cause of death of Mary Eleanor, who lived only 23 days, is unknown.

“Charles Darwin’s fears of consanguinity appear to have been justified,” the researchers concluded. But they also noted that three of Darwin’s sons – George, Francis and Horace – became fellows of the Royal Society and were knighted. George went on to advocate against consanguineous marriages.

The report appears in the May issue of the journal BioScience.

-- Karen Kaplan

Photo: Charles Darwin suspected his children paid the price for his marriage to first-cousin Emma. Credit: Henry Chu/Los Angeles Times

Events help launch muscular dystrophy clinic

May 3, 2010 |  7:38 am
Dylan Boys in the Los Angeles area with the genetic disorder muscular dystrophy will soon have a clinic to attend that does not require long-distance travel. The UCLA Muscular Dystrophy Clinic is slated to open later this year. The efforts to open the clinic, which began when two UCLA scientists learned their youngest son had the disease, are described in Monday's L.A. Times story, "A personal fight against a lethal childhood illness."
But several families have come together to make the clinic possible. Seven year ago, Paul and Debra Miller founded CureDuchenne, a national nonprofit advocacy group based in Newport Beach. The organization has focused much-needed attention on the plight of local MD families. CureDuchenne was aided by Chris and Amy Martin, a Los Angeles couple who have organized yearly fundraisers that have raised $200,000 for the clinic. The third-annual "Dealing for Duchenne Los Angeles Celebrity Poker Tournament" will be held June 12 at the Petersen Automotive Museum. Proceeds will benefit the clinic.
The efforts come at an opportune time, said Dr. Eric Hoffman, a leading researcher on the disorder at Children's National Medical Center in Washington.
"It's the best place the field has been in since I've been involved," he said. "There's a lot of progress in clinical trials."
-- Shari Roan
Photo: Photo of Stan Nelson and Carrie Miceli, both UCLA scientists, with their children, Calvin Miceli-Nelson, 16, and Dylan Miceli-Nelson, 9, at their Los Angeles home. Credit: Allen J. Schaben / Los Angeles Times

Environmental factors likely play a role in multiple sclerosis

April 28, 2010 | 10:40 am

Speculation about the cause of multiple sclerosis includes genes and environmental factors. A study published Thursday supplies strong evidence that environmental factors play a critical role.

MS Multiple sclerosis is a disease in which the immune system goes awry and attacks healthy tissue in the body. Researchers at UC San Francisco conducted the most advanced gene analysis ever on identical twins in which one twin has MS and the other does not. The analysis did not yield evidence for genetic differences that could explain why one sibling had the disease and the other did not. Nor did researchers find any differences in the epigenome -- mechanisms that change the way genes are expressed apart from changes in DNA -- to explain the disease in one twin.

Exactly what environmental factors contribute to causing MS is still unknown, however. The leading theory is that a virus triggers the immune system reaction that leads to the disease. Smoking and vitamin D deficiency have also been suggested as possible environmental contributors. But, "the results put us a step closer to teasing out the relative contributions of genetic and environmental factors on multiple sclerosis," the lead author of the study, Sergio Baranzini, said in a news release.

The findings do not mean genes don't play a role in the disease. When one identical twin has MS, there is 30% increased risk that the identical sibling will develop it. That compares with an increased risk of only 5% for a nonidentical twin.

The study is in the current issue of the journal Nature.

-- Shari Roan

Photo: A doctor uses a fluorescent microscope to view a brain section of a patient with MS. Credit: Julia Malakie / Associated Press

Assessing the first 10 years of the human genome era

April 1, 2010 | 11:40 am

This year marks the 10th anniversary of one of the greatest achievements in science: the sequencing of the human genome. On June 25, 2000, two teams – one funded by the U.S. government, the other headed by an independent maverick – jointly announced that they had completed a first draft of all the As, Cs, Gs and Ts in human DNA.

Collinsventer It would still take another year of analysis to estimate that the 3.1 billion letters contain instructions for making 30,000 to 35,000 genes (those figures were later reduced by 10,000) and two additional years for the “complete” genome to be finished. But with the first draft in hand, then-President Clinton proclaimed that humankind was "on the verge of gaining immense, new power to heal.”

As Dr. Francis Collins, the leader of the government-funded team, says in an opinion piece published in Thursday’s special edition of the journal Nature, “Wisely, the president did not attach timetables to his bold predictions.” Andm indeed, that vision is still a long way off.

Collins himself made a PowerPoint presentation with his own predictions for the first decade of post-genome medicine. A scrupulous keeper of all his PowerPoint files, he was able to dig it up and share with the world his predictions for 2010:

All of these have turned out to be true (though he failed to include a prediction that he would become director of the National Institutes of Health). But looking at the big picture, Collins writes, “it is fair to say that the Human Genome Project has not yet directly affected the health care of most individuals.”

That will change soon, writes J. Craig Venter, who spearheaded the rival genome sequencing project.

Venter’s company, Celera, spurred the private sector to develop faster and cheaper sequencing machines. As he writes in Nature, the sequencer he used in his NIH lab in 1987 could decode 4,800 base pairs per day. Today, a company called Life Technologies in Carlsbad sells a machine that can produce 100 billion base pairs per day.

With all that sequencing power available, Venter writes that the new goal is not to produce a personal genome for everyone, it’s to have multiple genomes per person. For instance, sequencing of sperm and egg cells could make for healthier babies, and the sequencing of cancer cells will help to target treatments. Even the millions of bacteria that live on and in our bodies should be sequenced, he writes: “The genome revolution is only just beginning.”

-- Karen Kaplan

Photo: Craig Venter and Francis Collins announced the completion of a “working draft” of a human genome at the White House on June 26, 2000. Both assessed the effect of the Human Genome Project 10 years later. Credit: Joyce Naltchayan / AFP/Getty Images

Gene patents are the talk of the town following surprise court ruling

March 31, 2010 |  8:28 pm

Lawyers have been trying to digest this week's surprising court ruling that invalidated seven patents for the breast cancer genes BRCA1 and BRCA2.

Myriad Genetics Inc. had held an exclusive license for these patents and consequently controlled the market for DNA tests designed to gauge women’s risk for developing breast and ovarian cancer. Many scientists also said the company forced them to halt research projects involving the two genes.

U.S. District Judge Robert Sweet ruled that Myriad “discovered” the DNA sequences that make up the two genes, but it did not “invent” them. Therefore, the genes cannot be patented.

“It’s certainly a bombshell,” Robert Cook-Deegan, an expert on gene patents at Duke University, said in an interview. “The blogosphere is pretty shocked at this outcome.”

Companies have won patents on thousands of genes, and the idea that they could be worthless has whipped biotech firms into a frenzy, said Lisa Haile, an attorney with the DLA Piper in San Diego who co-chairs the firm’s global life sciences practice. Haile said she has advised her clients that the ruling is sure to be appealed.

“It’s definitely not the last word,” she said in an interview. “I see this going up to the Supreme Court.”

Why? It’s not just gene patents that are at issue, Haile said. If DNA can’t be patented because it is created by nature, what about patents for proteins, enzymes, bacteria and other biological entities that companies have turned into medicines and other useful products? “That’s where I think this could get blown out of proportion,” she said.

Sandra Park, an attorney for the American Civil Liberties Union, one of the plaintiffs in the lawsuit, said it’s not just anti-business liberals who oppose the idea of gene patents.

“This is not a partisan issue,” she said in an interview. “A lot of very conservative religious folks have come out against gene patents because they believe God has given us these genes, and they should not be parsed out for patents.”

Park noted that an advisory committee in the Department of Health and Human Services approved a report in February about gene patents and their impact on diagnostic tests for patients. The report suggests that Congress pass legislation that would prevent monopolies on diagnostic genetic tests and allow scientists to conduct research on any gene regardless of its patent status, Park said.

Had such a law been in place already, she said, “our clients – who are labs and researchers and patients – would not have been motivated, most likely, to bring this lawsuit.”

You can read the full decision here. It includes a very readable primer on genetics and DNA.

-- Karen Kaplan

Breast cancer genes can't be patented, federal court rules

March 29, 2010 |  4:28 pm

Until today, women who wanted to know whether they had inherited a version of the BRCA1 and BRCA2 genes that increased their risk of breast or ovarian cancer could find out only by sending their DNA to Myriad Genetics Inc.The Salt Lake City company patented the two genes in the 1990s and invented a test to identify some of the telltale mutations.

You might be asking yourself how a company could get a patent on a gene, which isn’t a man-made invention. You wouldn’t be alone. Several medical groups have wondered that too. So have the American Civil Liberties Union and the Public Patent Foundation. Last year, they challenged those patents in a federal district court in New York.

On Monday afternoon, they won. U.S. District Judge Robert Sweet ruled that the U.S. Patent and Trademark Office never should have granted the patents in the first place because the genes are “a law of nature.”

The Patent and Trademark Office has granted patents for roughly 20% of human genes. The office’s rationale was that the patents can be earned by isolating and purifying genes from their “natural state.”

In oral arguments last month, Myriad’s attorney said that companies wouldn’t have any incentive to develop genetic tests if they weren’t allowed to patent genes and warned that a ruling against Myriad could “undermine the entire biotechnology sector,” according to this report from GenomeWeb. The company has not yet commented on the ruling.

The ACLU and other groups argued that women – and the whole of science – have already suffered as a result of the way Myriad treats its BRCA patents. On its website devoted to the case, the ACLU says that individual patients are harmed because Myriad’s monopoly on genetic testing for BRCA1 and BRCA2 keeps prices high and prevents them from getting a second opinion from another company. Scientists are also harmed because the company restricts their ability to conduct research on the genes, according to the ACLU.

Myriad hasn't said whether it would appeal the decision.

You can read the original lawsuit here.

-- Karen Kaplan

What can SNPs tell us about breast cancer risk? Not much, researchers say

March 17, 2010 |  4:29 pm

There are certainly many genetic mutations that increase a woman’s risk of developing breast cancer. The most famous examples are variations in the genes BRCA1 and BRCA2 (whose names are short for BReast CAncer).

More common are the single-letter DNA changes called single nucleotide polymorphisms– or SNPs for short. Researchers have identified many SNPs that appear to be associated with breast cancer because they are more common in women who have the disease.

But can those SNPs be used to predict an individual woman’s risk of developing breast cancer? That was the question that a large group of researchers from the National Cancer Institute, the American Cancer Society and a host of other esteemed institutions set out to answer.

The group tested 10 SNPs that have “established associations with breast cancer,” they write in Thursday’s issue of the New England Journal of Medicine. Using data on 5,590 women with breast cancer and 5,998 healthy controls, they found that those SNPs alone did just as good a job of predicting a woman’s breast cancer risk as the government’s Breast Cancer Risk Assessment Tool, which relies on family health history, age at the time of first menstrual period and other personal information. Combining the SNPs and the traditional risk model boosted their predictive accuracy only slightly, the researchers found.

They also looked at how the addition of the SNP data changed the risk prediction for the women in the study. In 26% of cases, it moved women into a higher risk category, and in 28% of cases it moved women to a lower risk category. In the remaining 46% of cases, there was no change.

All in all, the researchers said the use of SNPs to predict breast cancer risk still isn’t ready for prime time. “Our results indicate that the recent identification of common genetic variants does not herald the arrival of personalized prevention of breast cancer in most women,” they wrote.

Perhaps researchers are getting a little more realistic about the predictive value of SNPs. A study published last month in the Journal of the American Medical Assn. found that nearly 100 SNPs linked to heart disease did almost nothing to predict the risk of heart attacks, strokes, coronary artery disease or cardiovascular death.

However, in an editorial accompanying the study, a pair of European scientists who focus on breast cancer genetics said the problem isn’t that the SNPs don’t work – it’s that we haven’t identified enough of them.

The 10 SNPs examined in the study “are no more than the tip of the iceberg,” they wrote. “A more pressing question is why … only a dozen risk alleles have been identified.”

-- Karen Kaplan

A new genetic test for autism is a big improvement but still has a long way to go

March 14, 2010 |  9:02 pm

Autism For a reality check on how much scientists know about the genetics of autism, consider a study being published in Monday’s edition of the journal Pediatrics.

The study reports that a kind of genetic testing method known as a chromosomal microarray analysis – CMA for short – is about three times better at finding genetic variants related to autism-spectrum disorders than the two kinds of tests currently used.

Researchers from Children’s Hospital Boston and their colleagues ran the tests on DNA samples from 933 patients age 13 months to 22 years. All were diagnosed with autism-spectrum disorders. Here’s how the tests stacked up:

  • A karyotyping test, which analyzes the size, shape and number of chromosomes, found “abnormal results” in 2.23% of patients.
  • A test for Fragile X syndrome, a genetic condition known to cause autistic behavior, found abnormal results in 0.46% of patients.
  • The CMA test, which looked for telltale duplications and deletions of DNA, found abnormal results in 7.3% of patients.

Clearly, the CMA test was most effective, and the study’s authors say the test should be offered to patients as a first-line test.

“CMA clearly detects more abnormalities than other genetic tests that have been the standard of care for many years,” said study coauthor Dr. David Miller, of the hospital’s Division of Genetics and its Department of Laboratory Medicine, in a statement. “We’re hoping this evidence will convince insurance companies to cover this testing universally.”

However, for the overwhelming majority of patients who take it, the test won’t turn up anything suspicious. That’s not necessarily surprising, considering that only about 15% of autism cases have a known genetic cause. But it certainly underscores the limitation of all of these types of tests, said Andy Shih, vice president for scientific affairs for Autism Speaks, which funds research on the disease.

“The utility of this test in actual clinical settings is not clear,” Shih said. “Until we know more about the association between some of these variants and actual autism risk, it’s difficult to see how this could benefit the family now.”

-- Karen Kaplan

Photo: Genetic testing still has a long way to go to benefit families of patients with autism. Credit: Richard Hartog / Los Angeles Times

One more genome decoded, this one for Oscar week: Glenn Close's

March 11, 2010 |  9:16 am

A San Diego company said Thursday that it had decoded the complete genome of actress Glenn Close, whom the company called "the first named woman to have her entire genome sequenced." Illumina Inc. said the process of producing a personal genome now costs $48,000 and takes eight weeks to complete.


Close, currently featured on the FX show "Damages" and star of the classic thriller "Fatal Attraction," has been active in promoting mental health issues and attempting to remove the stigma from such diseases. She is a founder of the nonprofit BringChange2Mind, which promotes those efforts.

"There is bipolar disorder and schizophrenia in my family, illnesses that, like other medical conditions, are thought to have a genetic underpinning," Close said in a statement. "My hope is that researchers will unravel the genetic aspects of mental illnesses to bring greater awareness about the diseases, de-stigmatize them and pave the way for more effective treatments."

-- Thomas H. Maugh II

Photo: Glenn Close. Credit: Jason Kempin / Getty Images


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