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Parents and Science
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Petrichor
Maria S
doofus_maximus
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Page 1 of 1
Parents and Science
on a dogged pursuit to diagnose a child's genetic disorder. Cutting edge molecular medicine pushes the boundaries and reveals a novel mutation in a child in less than 4 years. It would have never been possible 10 years ago. Future is already here.
Hunting down my son's killer
[article index] [email me] [@mattmight] [ mattmight] [rss]
I found my son's killer.
It took three years.
But we did it.
I should clarify one point: my son is very much alive.
Yet, my wife Cristina and I have been found responsible for his death.
My son Bertrand has a new genetic disorder.
Patient 0.
To find it, a team of scientists at Duke University used whole-exome sequencing (a protein-focused variant of whole-genome sequencing) on me, my wife and my son.
We discovered that my son inherited two different (thus-far-unique) mutations in the same gene--the NGLY1 gene--which encodes the enzyme N-glycanase 1. Consequently, he cannot make this enzyme.
My son is the only human being known to lack this enzyme.
Below, I'm documenting our journey to the unlikeliest of diagnoses.
This is a story about the kind of hope that only science can provide.
[An open access article in The Journal of Medical Genetics contains the detailed results from ground-breaking experiment that diagnosed him.]
Normal
Aside from severe jaundice, Bertrand was normal at birth.
For two months, he developed normally.
At three months, his development had slowed, but it was "within normal variations."
By six months, he had little to no motor control.
He seemed, as we described it, "jiggly."
Something was wrong.
"Brain damage"
Bertrand was eight months old when he met with his developmental pediatrician for the first time--just after our move to Utah.
I was at my first faculty retreat on the day of his exam, and after it let out, I found a flood of voicemail and text messages from my wife.
My heart jumped.
The pediatrician thought Bertrand had brain damage, so she scheduled an MRI for the following week.
No brain damage
The MRI showed an apparently healthy, normal brain.
So, his case was escalated to a pediatric neurologist.
The neurologist confirmed that he had a movement disorder, but his presentation was "puzzling": he had neither characteristic chorea nor ataxia.
The neurologist ordered a round of bloodwork.
This was the first of dozens of blood draws to come.
(We now send Bertrand's "favorite" phlebotomists holiday cards.)
The first death sentence
The lab results reported only one anomaly: extremely elevated alpha-fetoprotein (AFP) relative to what it should have been for his age.
Only a handful of known disorders cause elevated alpha-fetoprotein.
Only one of them sits at the intersection of movement disorder and elevated AFP: ataxia telangiectasia (A-T).
A-T is a degenerative, fatal, incurable, untreatable disorder.
My wife and I were heartbroken.
Are you related?
Because A-T is an autosomal recessive genetic disorder, this would be the first of many times that my wife and I were asked:
Are you two sure you're not related?
I'm of Ohio farmland and northern European desent. My wife is multigenerational Puerto Rican.
We can trace our family trees backward for centuries.
No.
We are not related.
Genetics for programmers
[Note: My formal education in biology is two months in high school. Please email me corrections if I made any mistakes.]
To understand why every doctor kept asking us whether we were related and how unlikely Bertrand's final diagnosis is, you need to understand how genes and mutations work.
DNA
Your genome contains the information necessary to build and operate you.
Your genome is transcribed in DNA--a molecular encoding of a language with just four letters: A, C, T and G.
(A, C, T and G stand for adenine, cytosine, thymine and guanine.)
A, C, T and G are to life what 0 and 1 are to computers.
What's important in life, as in computing, is how these sequences encode information or computation.
In computing, a sequence like 00000100 might mean "add in place", so that 000001000 0001 0010 could mean "add the number in register 1 to the number in register 2".
Codons and the standard genetic code
In computing, most computers run on the x86 instruction set.
Remarkably, in life, there is also a dominant instruction set--the standard genetic code, as described in the DNA codon table.
The genetic code is an instruction set for making proteins by chaining together individual amino acids.
The genetic code is made up of instructions called codons.
Each codon is a three-letter sequence in DNA that encodes either an amino acid to insert or the command "stop construction of this protein."
For example, the codon TTG means "insert a Leucine."
With four letters in the alphabet, there are 43 = 64 possible codons, but there are only 25 genetic instructions, since some codons encode the same amino acid and several encode "stop."
Genes
In the human genome, a gene is a functional unit--kind of like the code for a procedure in a program. Each one is composed of exons (codon sequences that are involved in expressing the protein) and introns (ignored sequences that have about the same effect as code comments).
The exons describe a sequence of amino acids to fold into a protein.
When a gene is compiled into a protein--usually as an enzyme--that enzyme acts like a function inside the cell: enzymes enable the reaction of input molecules into output molecules.
....continued in the link the posted above.
Hunting down my son's killer
[article index] [email me] [@mattmight] [ mattmight] [rss]
I found my son's killer.
It took three years.
But we did it.
I should clarify one point: my son is very much alive.
Yet, my wife Cristina and I have been found responsible for his death.
My son Bertrand has a new genetic disorder.
Patient 0.
To find it, a team of scientists at Duke University used whole-exome sequencing (a protein-focused variant of whole-genome sequencing) on me, my wife and my son.
We discovered that my son inherited two different (thus-far-unique) mutations in the same gene--the NGLY1 gene--which encodes the enzyme N-glycanase 1. Consequently, he cannot make this enzyme.
My son is the only human being known to lack this enzyme.
Below, I'm documenting our journey to the unlikeliest of diagnoses.
This is a story about the kind of hope that only science can provide.
[An open access article in The Journal of Medical Genetics contains the detailed results from ground-breaking experiment that diagnosed him.]
Normal
Aside from severe jaundice, Bertrand was normal at birth.
For two months, he developed normally.
At three months, his development had slowed, but it was "within normal variations."
By six months, he had little to no motor control.
He seemed, as we described it, "jiggly."
Something was wrong.
"Brain damage"
Bertrand was eight months old when he met with his developmental pediatrician for the first time--just after our move to Utah.
I was at my first faculty retreat on the day of his exam, and after it let out, I found a flood of voicemail and text messages from my wife.
My heart jumped.
The pediatrician thought Bertrand had brain damage, so she scheduled an MRI for the following week.
No brain damage
The MRI showed an apparently healthy, normal brain.
So, his case was escalated to a pediatric neurologist.
The neurologist confirmed that he had a movement disorder, but his presentation was "puzzling": he had neither characteristic chorea nor ataxia.
The neurologist ordered a round of bloodwork.
This was the first of dozens of blood draws to come.
(We now send Bertrand's "favorite" phlebotomists holiday cards.)
The first death sentence
The lab results reported only one anomaly: extremely elevated alpha-fetoprotein (AFP) relative to what it should have been for his age.
Only a handful of known disorders cause elevated alpha-fetoprotein.
Only one of them sits at the intersection of movement disorder and elevated AFP: ataxia telangiectasia (A-T).
A-T is a degenerative, fatal, incurable, untreatable disorder.
My wife and I were heartbroken.
Are you related?
Because A-T is an autosomal recessive genetic disorder, this would be the first of many times that my wife and I were asked:
Are you two sure you're not related?
I'm of Ohio farmland and northern European desent. My wife is multigenerational Puerto Rican.
We can trace our family trees backward for centuries.
No.
We are not related.
Genetics for programmers
[Note: My formal education in biology is two months in high school. Please email me corrections if I made any mistakes.]
To understand why every doctor kept asking us whether we were related and how unlikely Bertrand's final diagnosis is, you need to understand how genes and mutations work.
DNA
Your genome contains the information necessary to build and operate you.
Your genome is transcribed in DNA--a molecular encoding of a language with just four letters: A, C, T and G.
(A, C, T and G stand for adenine, cytosine, thymine and guanine.)
A, C, T and G are to life what 0 and 1 are to computers.
What's important in life, as in computing, is how these sequences encode information or computation.
In computing, a sequence like 00000100 might mean "add in place", so that 000001000 0001 0010 could mean "add the number in register 1 to the number in register 2".
Codons and the standard genetic code
In computing, most computers run on the x86 instruction set.
Remarkably, in life, there is also a dominant instruction set--the standard genetic code, as described in the DNA codon table.
The genetic code is an instruction set for making proteins by chaining together individual amino acids.
The genetic code is made up of instructions called codons.
Each codon is a three-letter sequence in DNA that encodes either an amino acid to insert or the command "stop construction of this protein."
For example, the codon TTG means "insert a Leucine."
With four letters in the alphabet, there are 43 = 64 possible codons, but there are only 25 genetic instructions, since some codons encode the same amino acid and several encode "stop."
Genes
In the human genome, a gene is a functional unit--kind of like the code for a procedure in a program. Each one is composed of exons (codon sequences that are involved in expressing the protein) and introns (ignored sequences that have about the same effect as code comments).
The exons describe a sequence of amino acids to fold into a protein.
When a gene is compiled into a protein--usually as an enzyme--that enzyme acts like a function inside the cell: enzymes enable the reaction of input molecules into output molecules.
....continued in the link the posted above.
doofus_maximus- Posts : 1903
Join date : 2011-04-29
Re: Parents and Science
aiyoo.. what happened to Maria's reply.
I was rejoicing at the fact that I got a reply and now I am down in the dumps.
I was rejoicing at the fact that I got a reply and now I am down in the dumps.
doofus_maximus- Posts : 1903
Join date : 2011-04-29
Re: Parents and Science
Maria says sorry! But, Maria is happy to see that DM missed her reply!
So you saw the flash response:) I was trying to edit the response and repost, but, had to leave- so just deleted the post!
Ok..
It seems like an easy read even for lay people.
Besides the complex science of coding, chimeras etc..the agony of the parents in dealing with the A-T diagnosis of the child, is palpable and wrenching.
And I'm sure the decision to have another child/children with the possibility of a genetic disorder is enormously difficult. It's a leap of faith indeed.
Hope these parents keep pushing to find answers- which will enormously help others.
So you saw the flash response:) I was trying to edit the response and repost, but, had to leave- so just deleted the post!
Ok..
It seems like an easy read even for lay people.
Besides the complex science of coding, chimeras etc..the agony of the parents in dealing with the A-T diagnosis of the child, is palpable and wrenching.
And I'm sure the decision to have another child/children with the possibility of a genetic disorder is enormously difficult. It's a leap of faith indeed.
Hope these parents keep pushing to find answers- which will enormously help others.
Maria S- Posts : 2879
Join date : 2011-12-31
Re: Parents and Science
Maria S wrote:Maria says sorry! But, Maria is happy to see that DM missed her reply!
So you saw the flash response:) I was trying to edit the response and repost, but, had to leave- so just deleted the post!
Ok..
It seems like an easy read even for lay people.
Besides the complex science of coding, chimeras etc..the agony of the parents in dealing with the A-T diagnosis of the child, is palpable and wrenching.
And I'm sure the decision to have another child/children with the possibility of a genetic disorder is enormously difficult. It's a leap of faith indeed.
Hope these parents keep pushing to find answers- which will enormously help others.
This forum has become so boring with no posts other than language
posts getting replies. I try to post something sciency and all I get is
silence. Like you said, it wasn't difficult to understand either.
Anyways, I will keep posting what interests me.
Maria S wrote:Hope these parents keep pushing to find answers- which will enormously help others
They already did. It is N-Glycanase deficiency. Now it morphs into quest for a cure.
doofus_maximus- Posts : 1903
Join date : 2011-04-29
Re: Parents and Science
I do look for you posts when I come here DM..will def. respond if I am interested in the topic!
Maria S- Posts : 2879
Join date : 2011-12-31
Re: Parents and Science
How much future does cellular/molecular biology have? What kind of future does a student majoring in cellular biology in undergrad have? What are his prospects (apart from getting into a med school)? Any idea?
Guest- Guest
Re: Parents and Science
Kinnera,
As you know, careers in the Medical Field are constantly expanding, merging, are interchangeable, depending on demands.
Undergrads majoring in Cellular Biology can find jobs as Research Assistants and Associates. They can also work in Clinical Settings as Medical Assistants (esp. in labs), and nowadays they can be cross trained to do Admin work- assist with electronic records, billing etc. The pay may be in the 30-50k range at entry level, and if they go to grad.school, get a Ph.D, have more opportunities.. they can be Genetic Counselors, Teaching and Research Faculty in Univs etc with a nice increase in pay scales.
As you know, careers in the Medical Field are constantly expanding, merging, are interchangeable, depending on demands.
Undergrads majoring in Cellular Biology can find jobs as Research Assistants and Associates. They can also work in Clinical Settings as Medical Assistants (esp. in labs), and nowadays they can be cross trained to do Admin work- assist with electronic records, billing etc. The pay may be in the 30-50k range at entry level, and if they go to grad.school, get a Ph.D, have more opportunities.. they can be Genetic Counselors, Teaching and Research Faculty in Univs etc with a nice increase in pay scales.
Maria S- Posts : 2879
Join date : 2011-12-31
Re: Parents and Science
Maria S wrote:Kinnera,
As you know, careers in the Medical Field are constantly expanding, merging, are interchangeable, depending on demands.
Undergrads majoring in Cellular Biology can find jobs as Research Assistants and Associates. They can also work in Clinical Settings as Medical Assistants (esp. in labs), and nowadays they can be cross trained to do Admin work- assist with electronic records, billing etc. The pay may be in the 30-50k range at entry level, and if they go to grad.school, get a Ph.D, have more opportunities.. they can be Genetic Counselors, Teaching and Research Faculty in Univs etc with a nice increase in pay scales.
Thanks Maria. Doesn't seem too exciting though. Grrr!
Guest- Guest
Re: Parents and Science
Maria and Kinnera, Undergraduate Biology majors can get jobs in biotech/pharma industry. Starting salaries will be around 50K , but with experience one can quickly rise up and make a lot of money in these industries.
Masters will yield a 70-80K starting salary in these industries.
Phd will get next to nothing in these industries
Masters will yield a 70-80K starting salary in these industries.
Phd will get next to nothing in these industries
doofus_maximus- Posts : 1903
Join date : 2011-04-29
Re: Parents and Science
Please recommend an industry that will have the following cashflows:
First year after graduation: $90K
Starter condo (studio/1 br): Negative ($30K)
Second year : $100K
Third year: $105K
Post Graduation - 18 months: Negative ($130K)
Fourth year: $130K with stock options
Seventh year: $160K with in-the-money options worth $300K
Wedding: Negative ($50K)
Family home (2br): Negative ($100K)
Ninth year: $170K with vested options
Twelfth year: $240K with 1 mil. in liquid assets
First year after graduation: $90K
Starter condo (studio/1 br): Negative ($30K)
Second year : $100K
Third year: $105K
Post Graduation - 18 months: Negative ($130K)
Fourth year: $130K with stock options
Seventh year: $160K with in-the-money options worth $300K
Wedding: Negative ($50K)
Family home (2br): Negative ($100K)
Ninth year: $170K with vested options
Twelfth year: $240K with 1 mil. in liquid assets
Petrichor- Posts : 1725
Join date : 2012-04-10
Re: Parents and Science
atcg wrote:Please recommend an industry that will have the following cashflows:
First year after graduation: $90K
Starter condo (studio/1 br): Negative ($30K)
Second year : $100K
Third year: $105K
Post Graduation - 18 months: Negative ($130K)
Fourth year: $130K with stock options
Seventh year: $160K with in-the-money options worth $300K
Wedding: Negative ($50K)
Family home (2br): Negative ($100K)
Ninth year: $170K with vested options
Twelfth year: $240K with 1 mil. in liquid assets
Will he/she be still working while doing PG? Shouldn't the salary shoot up quite a bit after the completion of Post Graduation? 90k as starting salary soon after undergraduation is a li'l too high. If there's any such dream job, pls let me know. I'll push my sonny jr into it
Guest- Guest
Re: Parents and Science
Great article. May I know how you found this blog?
Kumarg- Posts : 205
Join date : 2012-05-08
Re: Parents and Science
>>Will he/she be still working while doing PG?
I am imagining No.
The only industries that I know where this kind of cashflows is possible, is Technology, Finance or Management Consulting. Also, it takes a lot of out-of-the-box skills such as arcane programming, domain experience during internships, tutelage under a generous Master craftsman, and luck.
I am imagining No.
The only industries that I know where this kind of cashflows is possible, is Technology, Finance or Management Consulting. Also, it takes a lot of out-of-the-box skills such as arcane programming, domain experience during internships, tutelage under a generous Master craftsman, and luck.
Petrichor- Posts : 1725
Join date : 2012-04-10
Re: Parents and Science
The positive cash flows mentioned here are possible to achieve. The problem is with the property-related negative cash flows. I can't imagine any place where you can get a condo for $30k and a 2 br home for $100k. Are you thinking of those as annual rent numbers? Then it makes sense.atcg wrote:Please recommend an industry that will have the following cashflows:
First year after graduation: $90K
Starter condo (studio/1 br): Negative ($30K)
Second year : $100K
Third year: $105K
Post Graduation - 18 months: Negative ($130K)
Fourth year: $130K with stock options
Seventh year: $160K with in-the-money options worth $300K
Wedding: Negative ($50K)
Family home (2br): Negative ($100K)
Ninth year: $170K with vested options
Twelfth year: $240K with 1 mil. in liquid assets
Idéfix- Posts : 8808
Join date : 2012-04-26
Location : Berkeley, CA
Re: Parents and Science
Maria S wrote:
Hope these parents keep pushing to find answers- which will enormously help others.
Wow if you read the article carefully, you would know that they already did- they found the culprit, thats what the article is about. I wish though he had published this as a news article in a scientific journal instead of a blog so that it got more attention from scientists.
Kumarg- Posts : 205
Join date : 2012-05-08
Re: Parents and Science
money is not everything in life, you know. if you don't believe me, then start an experiment and give me 1 million dollars, tax free. I will either prove you wrong, you win. Or I will be happy, which was our initial goal anyway.
Guest- Guest
Re: Parents and Science
panini press wrote: The problem is with the property-related negative cash flows. I can't imagine any place where you can get a condo for $30k and a 2 br home for $100k. Are you thinking of those as annual rent numbers? Then it makes sense.
Those are downpayments for realestate, possibly augmented with other loans.
Petrichor- Posts : 1725
Join date : 2012-04-10
Re: Parents and Science
atcg wrote:Please recommend an industry that will have the following cashflows:
First year after graduation: $90K
Starter condo (studio/1 br): Negative ($30K)
Second year : $100K
Third year: $105K
Post Graduation - 18 months: Negative ($130K)
Fourth year: $130K with stock options
Seventh year: $160K with in-the-money options worth $300K
Wedding: Negative ($50K)
Family home (2br): Negative ($100K)
Ninth year: $170K with vested options
Twelfth year: $240K with 1 mil. in liquid assets
wall street job. or narcotics dealer.
MaxEntropy_Man- Posts : 14702
Join date : 2011-04-28
Re: Parents and Science
doofus_maximus wrote:on a dogged pursuit to diagnose a child's genetic disorder. Cutting edge molecular medicine pushes the boundaries and reveals a novel mutation in a child in less than 4 years. It would have never been possible 10 years ago. Future is already here.
Read the article...very interesting and inspiring parental commitment.
Especially appreciated the
- borderline cynicism and realism
- obsessive focus on what works and willingness to be objective in the face of emotional distress
- the cast of professionals that were selfish in the pursuit of an intellectually challenging and rare problem while delivering care
It is very lonely at 7 standard deviations out but reaching out to us mortals on the fat peak of the bell curve shows the author's humanity.
Petrichor- Posts : 1725
Join date : 2012-04-10
Re: Parents and Science
Thanks for the article.
I found it intriguing that they decided to go ahead with another child despite a 1 in 4 chance of things going wrong all over again.
I found it intriguing that they decided to go ahead with another child despite a 1 in 4 chance of things going wrong all over again.
Guest- Guest
Re: Parents and Science
blabberwock wrote:Thanks for the article.
I found it intriguing that they decided to go ahead with another child despite a 1 in 4 chance of things going wrong all over again.
1 in 4 is very high a risk. I would say anything above 1 in 1000 is very high when it comes to kids.
artood2- Posts : 1321
Join date : 2011-04-30
Re: Parents and Science
artood2 wrote:blabberwock wrote:Thanks for the article.
I found it intriguing that they decided to go ahead with another child despite a 1 in 4 chance of things going wrong all over again.
1 in 4 is very high a risk. I would say anything above 1 in 1000 is very high when it comes to kids.
I call it irresponsible.
Guest- Guest
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