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Rare family diseases tend to be genetic diseases with a relatively simple genetic cause that can be found by comparing family members. This article is about tr

by shubb 8y ago

Rare family diseases tend to be genetic diseases with a relatively simple genetic cause that can be found by comparing family members. This article is about treating rare diseases, but there is a simpler way - having identified the genes for the disease, we could screen for them, and then advise people carrying them to reproduce only via selective IVF. That way, the next generation of that family can be free of carriers, eliminating the disease in the long term even if a treatment isn't found. (This is not an either or with finding a treatment) The above approach is much cheaper, effective, but raises important moral questions we need to think hard about. At what point does a disease become bad enough that it needs to be excluded like this? Slippery slope, etc.

brfox 8y ago
See here: http://www.counsyl.com/ http://www.counsyl.com/ But, about 30 genomic mutations are spontaneous every generation. I have one that causes brittle bone disease. So, just knowing the parents' genomic profile and screening out with IVF will not be sufficient. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322360/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322360/
dbbolton 8y ago
Perspective from a US physician: Pre-implantation genetic diagnosis (or PGD, what you described as 'selective IVF') is not cheap. It costs upwards of US$100,000 and no commercial or government insurance will cover it. Genetic screening is also not cheap. An exome (essentially looks at all ~22,000 known exons, or the genes that directly contribute to protein formation) costs US$6,000 - $8,000 and most insurances will fight tooth and nail not to have to cover it even when it is ordered by a geneticist. You might think "but there are much cheaper genetic tests besides an exome" which is true, but remember we are talking about rare diseases. Exome testing is still imperfect but it is essentially the only realistic option if your goal is to rule out as many known genetic diseases as possible, or if you know there is a high pretest probability of a genetic disease but less exhaustive testing was negative or inconclusive. Actually, current PGD doesn't use exome testing but much more selective testing often based on the parents. One technique is FISH which can essentially only tell you if there are any "large" genetic abnormalities, like (micro-) duplications or deletions, which are large relative to, say, a point mutation. As an example, FISH testing would not reveal cystic fibrosis. The other is PCR, which is currently the technological limit for PGD testing because of the small number of cells and minimal amount of genetic material available for testing. There are several PCR assays available for specific conditions in the setting of PGD, which is where the parents fit in. We will probably see more and more assays becoming available, but it is unlikely that anything resembling an exome will be feasible for PGD in the foreseeable future. Disclaimer: I am not a geneticist or reproductive specialist. If you can find sources by physicians in these fields, I would defer to them.
the_grue 8y ago
Matt Might makes the argument that there are a lot more rare diseases than many people realize. About every instance of cancer is effectively a rare disease (even though we agree to classify them according to a taxonomy), because each is caused by some kind of unique gene mutation which requires a specialized treatment, just like genetic disorders. Furthermore, once a cancer is in the body, it can keep mutating, and one can have several (or many) slightly different kinds of cancer at the same time, which is one of the primary reasons it is so hard to treat them. So by creating tools to treat rare diseases we are getting closer to curing any and every kind of cancer. And you can't prevent cancer by screening, we all become susceptible at later stages of our lives.

by shubb 8y ago

brfox 8y ago

See here: http://www.counsyl.com/ http://www.counsyl.com/ But, about 30 genomic mutations are spontaneous every generation. I have one that causes brittle bone disease. So, just knowing the parents' genomic profile and screening out with IVF will not be sufficient. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322360/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322360/

dbbolton 8y ago

Perspective from a US physician: Pre-implantation genetic diagnosis (or PGD, what you described as 'selective IVF') is not cheap. It costs upwards of US$100,000 and no commercial or government insurance will cover it. Genetic screening is also not cheap. An exome (essentially looks at all ~22,000 known exons, or the genes that directly contribute to protein formation) costs US$6,000 - $8,000 and most insurances will fight tooth and nail not to have to cover it even when it is ordered by a geneticist. You might think "but there are much cheaper genetic tests besides an exome" which is true, but remember we are talking about rare diseases. Exome testing is still imperfect but it is essentially the only realistic option if your goal is to rule out as many known genetic diseases as possible, or if you know there is a high pretest probability of a genetic disease but less exhaustive testing was negative or inconclusive. Actually, current PGD doesn't use exome testing but much more selective testing often based on the parents. One technique is FISH which can essentially only tell you if there are any "large" genetic abnormalities, like (micro-) duplications or deletions, which are large relative to, say, a point mutation. As an example, FISH testing would not reveal cystic fibrosis. The other is PCR, which is currently the technological limit for PGD testing because of the small number of cells and minimal amount of genetic material available for testing. There are several PCR assays available for specific conditions in the setting of PGD, which is where the parents fit in. We will probably see more and more assays becoming available, but it is unlikely that anything resembling an exome will be feasible for PGD in the foreseeable future. Disclaimer: I am not a geneticist or reproductive specialist. If you can find sources by physicians in these fields, I would defer to them.

the_grue 8y ago

Matt Might makes the argument that there are a lot more rare diseases than many people realize. About every instance of cancer is effectively a rare disease (even though we agree to classify them according to a taxonomy), because each is caused by some kind of unique gene mutation which requires a specialized treatment, just like genetic disorders. Furthermore, once a cancer is in the body, it can keep mutating, and one can have several (or many) slightly different kinds of cancer at the same time, which is one of the primary reasons it is so hard to treat them. So by creating tools to treat rare diseases we are getting closer to curing any and every kind of cancer. And you can't prevent cancer by screening, we all become susceptible at later stages of our lives.