2012年9月27日木曜日

出生前診断ビジネス

出生前診断ビジネスがあるようだ。
 妊娠中に母親の血液中に含まれる胎児のDNAを調べ、父親を特定する親子
鑑定の出生前診断ビジネスが、日本でも始まった。母親と、父親と考えら
れる男性の血液を調べれば、父親かどうか、10日間で99%以上の確率で分か
るという。

親子鑑定は、子供が生まれてから、専門の施設で、有料で鑑定してもらう
とのこと。
親子鑑定も出生前診断ビジネスとなり、生まれる前から鑑定できるようだ。

Seatle test
・父親の唾液か血液と母親の血液で、胎児の遺伝子の変異を予測可能。
・遺伝的父親を明確。
・ダウン症検出率90%、偽陽性率2-5%。(Sequnom資金提供)

Stanford test
・母体の血液より、胎児の遺伝子の変異を予測可能。

危険度が少ない出生前診断は、エコー検査と思っていたら、血液検査で
診断できるようになった。
ゲノム配列の解析が進むことで、子供を作る前に、親による遺伝子の変異
を検査する可能性や社会的に個人の遺伝子情報を検査する可能性もある。
米国では、法律で規制されたようだが、日本では、個人保護法で、外部に
提供しないだけで、収集することに規制はないようだから、色々な面で
差別を受ける可能性がある。
出生前診断も遺伝子検査ビジネスの分野として成立しそう。

遺伝子検査ビジネス
出生前診断 MaterniT21(+) test


---出生前、血液で父子判定 精度99%、1年で150件---
2012年9月24日03時00分
http://www.asahi.com/national/intro/TKY201209230406.html?id1=2&id2=cabcajce

 妊娠中に母親の血液中に含まれる胎児のDNAを調べ、父親を特定する親子鑑定の出生前診断ビジネスが、日本でも始まった。母親と、父親と考えられる男性の血液を調べれば、父親かどうか、10日間で99%以上の確率で分かるという。


---両親の血液などで胎児の遺伝子異常予測 米チームが成功---
2012年9月4日10時43分
http://www.asahi.com/science/update/0904/TKY201209040130.html

 両親の血液などから採取したDNAで生まれる前の胎児のゲノムを予測することに、米ワシントン大のチームが成功し、米医学誌サイエンス・トランスレーショナル・メディシン(電子版)に掲載された。研究が実用化されれば、母体に負担をかける検査をせずに、遺伝子の異常で起きる様々な病気の出生前診断ができるようになるという。
 研究チームは、妊娠18週の母親の血液と、胎児の父親の唾液(だえき)からDNAを採取し分析。98%を超える精度で、母親と父親から胎児に受け継がれた遺伝子変異を予測した。
 さらに、妊娠中の母親の血漿(けっしょう)中にわずかに存在する胎児のDNAの一部を解析し、新たに起こった遺伝子変異も予測。生まれてから検査して見つかった44カ所の変異のうち、39カ所が胎児のうちに予測できた。


---New Tests Could Divine a Baby's Genome Before Birth---
Wednesday, August 29, 2012
http://www.technologyreview.com/news/428791/new-tests-could-divine-a-babys-genome-before/

The blood tests may herald a new wave of noninvasive prenatal screening.

Expectant mothers are used to fuzzy images on ultrasound monitors and blood tests to screen for potential health problems in their unborn babies. But what if one of those blood tests came back with a readout of the baby's entire genome? What if a simple test gave parents every nuance of a baby's genetic makeup before birth?

Recent studies show that it's possible to decode an entire fetal genome from a sample of the mother's blood (see "Using Parents' Blood to Decode the Genome of a Fetus"). In the future, doctors may be able to divine a wealth of information about genetic diseases or other characteristics of a fetus from the pregnant mother's blood. Such tests will raise ethical questions about how to act on such information. But they could also lead to research on treating diseases before birth, and leave parents and their doctors better prepared to care for babies after birth.

It's been about 15 years since Dennis Lo, a chemical pathologist at the Chinese University of Hong Kong, first discovered that fragments of DNA from a fetus could be found in a pregnant woman's blood. The work was a breakthrough, since obtaining fetal DNA from the amniotic fluid, placenta, or directly from the  fetus's blood requires an invasive procedure and carries a risk of miscarriage. A noninvasive test would make genetic testing safer and much more widely accessible.

Since then, several labs have worked to analyze this fetal DNA and exploit it for noninvasive prenatal tests. The field has progressed rapidly in the past couple of years as genetic sequencing technologies have become vastly cheaper and faster, and methods to analyze genetic data have improved (see "Analyzing the Unborn Genome").

One of the first tests to be developed is for RhD factor, a type of blood protein that can lead to fetal disease or death if the mother is RhD negative and her fetus is RhD positive. Sequenom, a San Diego, California-based company that licensed  Lo's research, began offering a noninvasive RhD test in 2010 (prior tests required invasive procedures such as amniocentesis or chorionic villus sampling, which carry a small risk of miscarriage).  Several companies have also offered tests for sex determination and paternity.

But what has gained more attention in the United States is a recent wave of tests that detect Down syndrome, which is caused by an extra copy of chromosome 21. Because women in the United States are routinely offered testing for Down syndrome, the market for such a test is large.

The test for Down syndrome could, in particular, have an enormous beneficial impact. Typically, a pregnant woman receives an initial screening test for substances in her blood associated with Down syndrome. Jacob Canick, a professor of pathology and laboratory medicine at Brown University, explains that the tests will detect 90 percent of Down syndrome cases, but have a false positive rate of 2 to 5 percent. That may sound small, but given that Down syndrome affects only one in 500 pregnancies, the number of women with a false positive is much higher than those who are truly carrying an affected fetus. The only definitive diagnosis is through amniocentesis or chorionic villus sampling. "That means that 19 out of 20 women that undergo an invasive procedure will find out that they don't have the genetic abnormality," Canick says.

With those low odds, many women choose not to undergo an invasive procedure at all. But new noninvasive tests could make screening much more widespread. "It looks, from our data and other data, that these tests are very, very good," says Canick, who led a trial, funded by Sequenom, on one these tests. They are still not definitive, but could ensure that far fewer women unnecessarily undergo invasive tests.

A number of startups have begun offering fetal tests for Down syndrome and other health problems caused by extra copies or missing chromosomes. Diana Bianchi, executive director of the Mother Infant Research Institute at Tufts Medical Center, who is on the advisory board of a startup called Verinata Health that is developing such fetal tests, says it's been surprising how quickly the tests have made their way into the clinic.

That speed has some people concerned. "There's not a minimum standard of accuracy that's required before they go to market," says Mildred Cho, a bioethicist at Stanford University. She says that the tests are being adopted even as their accuracy is being evaluated in clinical studies. Whereas most prenatal genetic tests have been developed through academic laboratories, this technology was quickly commercialized and disseminated through companies. Sequenom has claimed  broad intellectual property rights and has sued other companies for patent infringement. Cho worries that such a monopoly, if upheld, will prevent other companies from improving the technology.

Meanwhile, recent studies suggest that noninvasive testing could expand in the coming years beyond simply counting chromosomes to hunting for smaller genetic aberrations, including mutations in single genes. A study published this June by a group at the University of Washington in Seattle decoded a fetus's genome using a blood sample from the mother and saliva sample from the father. Meanwhile, Stanford University researchers have accomplished a similar feat using only a blood sample from the mother.

That means parents could soon receive a comprehensive test that could screen for all kinds of genetic abnormalities and characteristics. "When you open it up to whole-genome analysis, that brings up the possibility of testing for traits that are not diseases," says Cho, and for complex diseases that are not as genetically determined as Down syndrome. "People may be making decisions about terminating a pregnancy based on these very tiny risk factors," she says. "They may misunderstand that the tests are not predictive."

But more knowledge could also help women and doctors anticipate a risky birth, or better prepare for treatable health problems that are not currently diagnosed until birth. Bianchi hopes that the ability to uncover disease in fetuses will also spur a new interest in treating disease before birth. "Things that are treatable are really going to change the landscape," she says. "That's where it's going to be transformative."

Fetal medicine, she says, has been confined largely to surgeries for anatomical abnormalities that are visible with ultrasound. But many diseases may be treatable medically-even genetically determined ones. Bianchi's lab is studying fetal Down syndrome to see if it's possible to alleviate some of the effects of the disease while the baby is still in the womb. "If we can improve the biochemical environment at a time when the brain is developing," she says, "perhaps we can improve learning and memory."


--- A genetic blueprint of your unborn baby---
08 September 2012 by Harriet A. Washington
http://www.newscientist.com/article/mg21528814.200-a-genetic-blueprint-of-your-unborn-baby.html

Sequencing the whole genome of a fetus could provide a medical early warning on a previously unknown scale - but it also brings dilemmas, says Harriet A. Washington

BOY or girl? This you can easily discover, but wouldn't you like to know more? If you could peer into your baby's medical future, what traits would you most want assurance about?

Most parents wouldn't hesitate: a healthy child. Soon science will be able to help them with that more quickly, completely - and safely - than ever before.

In June, a team at the University of Washington in Seattle announced a new technique that enables the construction of a comprehensive genome sequence - a genetic "blueprint", as they described it - of the developing fetus from as early as the first trimester (Science Translational Medicine, vol 4, p 137ra76). The test could be available in clinics in as little as five years.

Then, in July, a team at Stanford University in California announced a slightly different technique for obtaining the same information (Nature, vol 487, p 320).

Both techniques rely on the fact that fetal DNA circulates in the mother's bloodstream and can be isolated and sequenced. The Seattle test needs only a sample of saliva or blood from the father and blood from the mother. After determining the parents' genomes, it is possible to discern which DNA comes from the fetus. The Stanford test requires only maternal blood.

Both tests are non-invasive, thus avoiding the 2 per cent risk of miscarriage posed by today's most common antenatal genetic tests, amniocentesis and chorionic villus sampling. These require a needle to be inserted into the amniotic sac so that the fetal DNA can be tested for Down's syndrome and other genetic disorders.

The existing antenatal tests can also spot other chromosomal abnormalities, including cystic fibrosis, trisomy 13, and Turner, Klinefelter and fragile-X syndromes. In contrast, the genetic blueprint can finger thousands of potentially problematic genes. It is "like going from being able to see that two books are stuck together to being able to notice one word misspelled on a page", says Jacob Kitzman, a member of the University of Washington team.

The benefit is a medical early warning on a previously unknown scale. Children with the genetic disorder phenylketonuria, for example, are usually diagnosed after birth and must be put on a strict, lifelong diet. Knowing the child's status beforehand would be helpful.

Given this and other potential benefits, should we not hasten to make blueprint screening mandatory, as many newborn tests are today? Not until we know more, and maybe not even then.

Today, only around 5 per cent of women who have prenatal tests receive bad news. Full genome screens will detect many more problems - and will introduce much more uncertainty because whole-genome mapping predicts the mere possibility of disease. Not all genetic anomalies are expressed as pathology.

The test will also produce false positives that frighten parents into thinking their child will have a disability when in fact he or she will be healthy.

For that matter, what is "healthy" anyway? When is a genetic anomaly a disease? Males with the chromosome disorder XYY were once thought to have a high risk of violent behaviour, and many XYY fetuses were aborted. But research has shown that XYY males are essentially normal.

The price of genetic knowledge can be high because of the anxiety caused by the knowledge of a propensity for a disease that has no known treatment or cure, or that may never appear.

Before using such a test parents must ask themselves "what can we do with the information?" If abortion is not an option, perhaps because the fetus is past the maximum gestation period or because of moral beliefs, the information can be useless - or worse than useless, thanks to the needless anxiety. Moreover, the dearth of treatment options for some disorders makes the information medically useless, but potentially risky if insurers use it to hike rates or deny cover.

If abortion is an option, new problems emerge: which disorders justify abortion? For some conditions the choice is perhaps clearer. For example, children with the infantile form of Tay-Sachs or Canavan disease go into an immediate, inexorable decline. There is no cure or effective treatment and most children with the disease die in childhood.

But what of genes that entail a higher risk of Alzheimer's, typical prostate cancers or Huntington's? These diseases emerge only after decades of productive life, and may not emerge at all.

Changing perceptions of disorders over time must also be taken into consideration. For example, we have seen a cultural sea change in the perception of Down's syndrome. Fifty years ago, parents were often advised to institutionalise affected children. Today people with the condition mostly live in mainstream society and have found wide acceptance.

There are other ethically and legally sensitive issues. Who has a right to a child's genetic information? If the screen reveals an unmanageable condition such as Huntington's that will not manifest until the child is old enough to make his or her own decisions, should the parents decide whether to share the information with other family members who may share the risk? Should there be regulations that compel a physician or the parents to alert siblings and others who may be at high risk of harbouring the gene?

The Seattle test can also reveal unexpected paternity. Should doctors have to disclose this, or should parents be able to opt out of being informed?

Whole-genome fetal sequencing is still years away from being used in the real world. It's a good job, as we have a lot to sort out before then.


---Using Parents' Blood to Decode the Genome of a Fetus
Wednesday, June 6, 2012
http://www.technologyreview.com/news/428101/using-parents-blood-to-decode-the-genome-of-a/

The advance could lead to noninvasive ways to test for diseases in the womb.

For the first time, scientists have deciphered the genome of a fetus using only DNA from the unborn child's parents. The advance represents a significant step forward in the effort to create noninvasive genetic tests that could assess a wide array of genetic diseases.

A small percentage of the DNA in a pregnant woman's blood comes from her fetus, a fact that scientists have begun exploiting to create prenatal genetic tests that don't require invasive sampling of fluid from the uterus. So far, tests have been limited to specific measures such as the genetic aberration that leads to Down syndrome; but the ability to sequence the entire fetal genome suggests that parents could someday get a much broader picture of their baby's disease risk before birth.

In a previous paper, a team led by Dennis Lo, director of the Li Ka Shing Institute of Health Sciences in Hong Kong, demonstrated a strategy for deducing the genetic code of a fetus by sampling its mother's blood.

Lo's team found that enough fetal DNA is present in a mother's blood to capture its entire genome; they showed how information about the maternal haplotype-blocks of genetic variants that are usually inherited together-could be used to reconstruct the fetal genome together with the sequences of both parents. But at the time, the ability to reconstruct haplotypes across the entire genome was limited, and the researchers still had to rely on an invasive procedure to obtain some fetal DNA for their analysis.

In this latest study, published today in Science Translational Medicine, a team led by Jay Shendure (a TR35 winner in 2006) at the University of Washington in Seattle took the approach further. The researchers first sequenced the parental genomes using blood from the mother and saliva from the father. This enabled them to find the possible genetic variants the parents could have passed on to the fetus.

Researchers then analyzed the mother's plasma to reconstruct the fetal genome. The presence of DNA sequences from the father could be used to determine which of his variants he had passed to the fetus. Determining which variants the mother passed on to the fetus is trickier, says first author Jacob Kitzman, because most of the DNA available in the plasma is hers.

The team applied a statistical technique it had previously developed to deduce the mother's haplotype arrangement that she had inherited from her own parents, which "goes a long way to predicting the arrangement passed on to the fetus," Kitzman says. The researchers used this information to create a statistical model of which variants were inherited from each parent, which they did with 98 percent accuracy (evaluated against a DNA sample from the baby collected after birth).

Lo says that because of their more complete sequencing, the University of Washington researchers "were able to deduce the fetal genomic map with much higher resolution than we have." Another advance is an analytical method that predicted 39 of 44 mutations in the fetus that were not inherited from either parent. Such "de novo" mutations are thought to play a role in diseases with complex genetic origins. But Lo points out that the analysis identified a great deal more false-positive mutations, so more work is necessary to refine the technique.

Lo and others have already developed noninvasive tests for Down syndrome using the fetal DNA present in a mother's blood. Kitzman says there are around 3,500 known disorders involving small changes in a single gene, and a more comprehensive sequencing of the genome "would, in theory, allow you to scan for all these genes in a comprehensive way."

But an even more difficult task will be interpreting the results, since the relationship between genetics and disease is not always clear, and knowing such information will undoubtedly pose ethical challenges.

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