The Economist has a new article called The looming crisis in human genetics relating to the complexity of finding genetic variants linked to common diseases. They are basically saying that genetic studies have so far failed to determine the causes of most diseases.
It is obvious that Mendelian genetics based on family studies should work better to determine some health risk. Knowing what the parents have, it is easy to estimate the risk for the children, because they may have inherited exactly the same noxious mutations. But that's beside the point. DNA studies attempt to discover underlying genetic mechanism that cause diseases. You cannot create efficient drugs without knowing exactly what's wrong in the body.
It's obvious that if one's parents died of Cystic Fibrosis one's chances have having it too are 50%. If 3 of your grandparents had Alzheimer's, your chance of developing it are very high. That's Mendelian genetics.
If family studies are always more accurate than comparison between strangers or across ethnic groups, it is not in itself a reason to shun personal genomics. First of all, not everybody knows his or her family's medical history. I am not just talking about adopted people or children who do not know their real biological father. What if a parent or grand-parent died fairly young in an accident ? That erases the potential information about old-age diseases like cancer or cardiovascular diseases.
If you are young and your parents are middle-aged and healthy, you are not going to wait that they die before having clues about your future health risk and the life-style changes you should undergo to prevent developing the same diseases. Even when you know everything about your family, you could always have inherited a series of minor mutations that are completely benign in isolation but have devastating effects when all combined together. This is the kind of information that Mendelian genetics cannot tell.
Another purpose of understanding the genetics of a disease, besides developing efficient medicine) is to be able to screen for it so as to prevent/eliminate it in future generations. This has already proved a successful method among Jewish couples. Ashkenazi Jews in particular have more genetic diseases than average due to the limited gene pool from which they evolved (a few founders) and the constant intermarriages within the community. Genetic screening has permitted to a young couple dating to know if they both carried the mutation for a genetic disease (e.g. Tay-Sachs). If they both did, they were advised to seek another partner to marry and have children with, or to resort to in vitro fertilisation, then selecting an embryo that lacks the disease mutations before implanting it.
This method of genetic selection can work for every disease that has a strong genetic component and does not involved too many genes.
This is indeed the reason of the apparent failure to identify the heritability in genes. If they know the answer to the problem why the alarming title for the article ? Just a way of making people read ?
The graph on the number of scientific publications on genome-wide association studies is enlightening with regards to the boom in genetics technologies in the last few years. In 2003 there were only 50 such publications. There are now 750. The soar is even more impressive for other species.
I don't see how this is a problem. Understanding evolution and human history are always good things. Understanding more deeply the racial, ethnic and individual differences is not likely lead to racial problems because interpersonal differences within a same ethnicity can be bigger than across ethnicities. If anything genetics will prove the best argument against racism. Just Y-DNA studies, which have no (known) connection to health, character, intelligence or any other trait, have already shattered a lot of racist arguments and misconceptions. For example, Europeans have a considerable amount of fairly recent Middle Eastern and African ancestors. Germanic people aren't a "pure" race, but recent admixture of many different ethnic groups (which also includes Mongoloid and Near Eastern genes).
As for the mis-attributed paternity, scientific studies won't tell us that. People will only know if they and their father take a DNA test and compare their genes. Paternity tests have existed for decades, in fact at least since the 1930's (through serological testing), and with a good level of accuracy since the 1970's (with HLA tests). Some people want to know, others don't. That's a personal choice. It has nothing to do with scientific research.
These ideological reactions will have no ground. Only people who do not understand anything about genetics (and therefore about themselves, about life, about the world) could be outraged by or deny the facts.
Economist said:Certainly, GWAS papers have reported a couple of hundred genetic variants that show statistically significant associations with a few traits. But the genes typically do not replicate across studies. Even when they do replicate, they never explain more than a tiny fraction of any interesting trait. In fact, classical Mendelian genetics based on family studies has identified far more disease-risk genes with larger effects than GWAS research has so far.
It is obvious that Mendelian genetics based on family studies should work better to determine some health risk. Knowing what the parents have, it is easy to estimate the risk for the children, because they may have inherited exactly the same noxious mutations. But that's beside the point. DNA studies attempt to discover underlying genetic mechanism that cause diseases. You cannot create efficient drugs without knowing exactly what's wrong in the body.
It's obvious that if one's parents died of Cystic Fibrosis one's chances have having it too are 50%. If 3 of your grandparents had Alzheimer's, your chance of developing it are very high. That's Mendelian genetics.
If family studies are always more accurate than comparison between strangers or across ethnic groups, it is not in itself a reason to shun personal genomics. First of all, not everybody knows his or her family's medical history. I am not just talking about adopted people or children who do not know their real biological father. What if a parent or grand-parent died fairly young in an accident ? That erases the potential information about old-age diseases like cancer or cardiovascular diseases.
If you are young and your parents are middle-aged and healthy, you are not going to wait that they die before having clues about your future health risk and the life-style changes you should undergo to prevent developing the same diseases. Even when you know everything about your family, you could always have inherited a series of minor mutations that are completely benign in isolation but have devastating effects when all combined together. This is the kind of information that Mendelian genetics cannot tell.
Another purpose of understanding the genetics of a disease, besides developing efficient medicine) is to be able to screen for it so as to prevent/eliminate it in future generations. This has already proved a successful method among Jewish couples. Ashkenazi Jews in particular have more genetic diseases than average due to the limited gene pool from which they evolved (a few founders) and the constant intermarriages within the community. Genetic screening has permitted to a young couple dating to know if they both carried the mutation for a genetic disease (e.g. Tay-Sachs). If they both did, they were advised to seek another partner to marry and have children with, or to resort to in vitro fertilisation, then selecting an embryo that lacks the disease mutations before implanting it.
This method of genetic selection can work for every disease that has a strong genetic component and does not involved too many genes.
Economist said:Why the failure? The missing heritability may reflect limitations of DNA-chip design: GWAS methods so far focus on relatively common genetic variants in regions of DNA that code for proteins. They under-sample rare variants and DNA regions translated into non-coding RNA, which seems to orchestrate most organic development in vertebrates. Or it may be that thousands of small mutations disrupt body and brain in different ways in different populations. At worst, each human trait may depend on hundreds of thousands of genetic variants that add up through gene-expression patterns of mind-numbing complexity.
...
Full sequencing means analysing all 3 billion base pairs of an individual’s DNA rather than just a sample of 1m genetic variants as the DNA chips do. When sequencing costs drop within a few years below $1,000 per genome, researchers in Europe, China and India will start huge projects with vast sample sizes, sophisticated bioinformatics, diverse trait measures and detailed family structures. (American bioscience will prove too politically squeamish to fund such studies.) The missing heritability problem will surely be solved sooner or later.
This is indeed the reason of the apparent failure to identify the heritability in genes. If they know the answer to the problem why the alarming title for the article ? Just a way of making people read ?
The graph on the number of scientific publications on genome-wide association studies is enlightening with regards to the boom in genetics technologies in the last few years. In 2003 there were only 50 such publications. There are now 750. The soar is even more impressive for other species.
The trouble is, the resequencing data will reveal much more about human evolutionary history and ethnic differences than they will about disease genes. Once enough DNA is analysed around the world, science will have a panoramic view of human genetic variation across races, ethnicities and regions. We will start reconstructing a detailed family tree that links all living humans, discovering many surprises about mis-attributed paternity and covert mating between classes, castes, regions and ethnicities.
I don't see how this is a problem. Understanding evolution and human history are always good things. Understanding more deeply the racial, ethnic and individual differences is not likely lead to racial problems because interpersonal differences within a same ethnicity can be bigger than across ethnicities. If anything genetics will prove the best argument against racism. Just Y-DNA studies, which have no (known) connection to health, character, intelligence or any other trait, have already shattered a lot of racist arguments and misconceptions. For example, Europeans have a considerable amount of fairly recent Middle Eastern and African ancestors. Germanic people aren't a "pure" race, but recent admixture of many different ethnic groups (which also includes Mongoloid and Near Eastern genes).
As for the mis-attributed paternity, scientific studies won't tell us that. People will only know if they and their father take a DNA test and compare their genes. Paternity tests have existed for decades, in fact at least since the 1930's (through serological testing), and with a good level of accuracy since the 1970's (with HLA tests). Some people want to know, others don't. That's a personal choice. It has nothing to do with scientific research.
Economist said:If the shift from GWAS to sequencing studies finds evidence of such politically awkward and morally perplexing facts, we can expect the usual range of ideological reactions, including nationalistic retro-racism from conservatives and outraged denial from blank-slate liberals. The few who really understand the genetics will gain a more enlightened, live-and-let-live recognition of the biodiversity within our extraordinary species—including a clearer view of likely comparative advantages between the world’s different economies.
These ideological reactions will have no ground. Only people who do not understand anything about genetics (and therefore about themselves, about life, about the world) could be outraged by or deny the facts.
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