December 01, 2008
DNA Chip Detects More Fetal Genetic Defects
Baylor researchers used DNA chips to test 270 genetic conditions in developing fetuses.
Many pregnant women have their unborn children screened for genetic abnormalities, such as Down syndrome. But standard tests cannot identify all problems, and many extremely serious conditions go undetected until birth. In a new study, researchers from the Baylor College of Medicine in Houston used DNA chips to test unborn babies for more than 270 genetic syndromes. They found that this procedure provided a more detailed and accurate view of the fetus's genetic profile than the approach commonly used today.
The study was done on 300 women, mostly at older ages. The cost at this time is $1600 but the researchers expect the price to drop. I also expect we will see more powerful DNA chips that can test tens of thousands and even hundreds of thousands of genetic differences.
What will people do with this information? More selective abortion. See my post Eugenics Cuts Down's Syndrome In Half In Denmark.
But selective abortion allows a woman only a binary decision: abort or not. It is also a tough decision. Some see it as killing a human life. Some others are uncertain and at least uneasy about it. Though still others do not see it as an act with moral significance or see a net moral benefit from it.
Granted, some women will use genetic testing information to decide on a medical intervention to fix a fetal problem. But the ability to do that sort of intervention will come many years after the ability to do very detailed genetic testing. So cheap powerful fetal genetic testing is going to be used mostly to decide whether to abort.
That binary decision of whether to abort will eventually be supplanted by the decision of which embryo to choose from among embryos created by in vitro fertilization (IVF). The increasing power of gene chips and what they can tell us will reach a threshold where IVF babies become superior in average looks, healthiness, intelligence and other characteristics as compared to babies born from naturally started pregnancies. IVF with in vitro maturation plus genetic testing will become the preferred way to start pregnancies, especially among the most educated and affluent.
The Brave New World is starting to come into view around the bend.
Whether you agree with it or not, destroying unwanted blastocyts is certainly preferable to destroying unwanted fetuses. Some remaining hurdle to getting to the Gatacca era still remain:
What is the defect rate caused by IVF techniques? Forgive my ignorance since my formal instruction in biology ended in 7th grade (I've focused my life around physical sciences rather than life sciences.) Since you have to sample a cell or two out of the blastocyst, you might damage it a bit. You could cause all sorts of potential epigenic problems. I'm sure it worlds well most of the time but is there a large-scale longitudinal follow up of IVF children that have been DNA sampled.
Can the DNA amplification techniques only work if they have one or two cells. Otherwise you'd need a whole developing fetus so you could get a decent DNA sample size.
While major genetic diseases can be detected by simple SNPs, aren't most of the more interesting differences between people copy number variants? Isn't that harder to measure with a small sample?
Have we even really found many IQ genes or beauty genes so far?
Jerry, Yes, copy number variations are harder to measure than SNPs. But I expect tech for both to continue to advance rapidly. I do not expect a big obstacle to this sort of measurement.
Also, first genetically measure the parents in detail and discover their SNPs and copy variations. Then detect which chromosome from got donated to each embryo from each parent. That can be done with SNPs. That'll tell you most of what you need to know aside from detecting new mutations.
IQ and beauty genes: Not many. But that'll change greatly in the next 5 years. We still aren't seeing the effect of recent price declines in DNA sequencing. The resulting knowledge is going to come blasting out in the next 5 years.
Damage from taking out a cell to test: By letting the embryo divide more times I think the potential negative effect is reduced.
DNA amplification: probably not necessary if nanopore sequencing is used.
Randall: "Also, first genetically measure the parents in detail and discover their SNPs and copy variations. Then detect which chromosome from got donated to each embryo from each parent. That can be done with SNPs. That'll tell you most of what you need to know aside from detecting new mutations."
Interesting idea...two possible difficulties.
First, meiosis recombination crossover events are frequent. There are an average of 20 crossover events per chromosome pair during sperm gamete production and approximately 10 crossover events per chromosome pair during egg gamete production. So it might be hard to accurately reconstruct the embryo genome from the parental genomes and a limited number of markers from the embryo genome.
Second, some types of new deletion/duplication events are common. I.e., neither parent had the variant but the embryo has it. DNA strands that contain multiple copies of the same sequence are prone to deletion/duplication events during recombination. Up to 5% of mental retardation cases may be due to new deletion/duplication mutations.
I've wondered how frequent the crossovers are. Do you have a source for these frequencies?
As for their ramifications: Granted, tying a chromosome to a parent doesn't mean we know the full story. But this approach will let us know more sooner. Using this incomplete info will allow prospective parents to make far better decisions than they can today. The average baby's quality of genetic endowment will rise as more deleterious genetic variants will be avoided.
"I've wondered how frequent the crossovers are. Do you have a source for these frequencies?"
Randall, sometime in the last year I read an article that discussed an allele that appeared to affect the human crossover rate. In that article they gave the average male/female crossover frequencies I stated. I was unable to find the reference using Google. Most papers I did find discussed the recombination rate in terms of the probability of a recombination event per kilobase and focused on the fine structure of recombination hotspots in the human genome.
Here is an abstract from 2003:
"Meiotic recombination is essential for the segregation of chromosomes and the formation of normal haploid gametes, yet we know very little about the meiotic process in humans. We present the first (to our knowledge) recombination maps for every autosome in the human male obtained by new immunofluorescence techniques followed by centromere-specific multicolor fluorescence in situ hybridization in human spermatocytes. The mean frequency of autosomal recombination foci was 49.8±4.3, corresponding to a genetic length of 2,490 cM. All autosomal bivalents had at least one recombination focus. In contrast, the XY bivalent had a recombination focus in 73% of nuclei, suggesting that a relatively large proportion of spermatocytes may be at risk for nondisjunction of the XY bivalent or elimination by meiotic arrest. There was a very strong correlation between mean length of the synaptonemal complex (SC) and the number of recombination foci per SC. Each bivalent presented a distinct distribution of recombination foci, but in general, foci were near the distal parts of the chromosome, with repression of foci near the centromere. The position of recombination foci demonstrated positive interference, but, in rare instances, foci were very close to one another."