mellowtigger

On April 25th, 57 years ago, Watson and Crick published their article in Nature magazine about the structure of DNA.  To celebrate the 50th anniversary (7 years ago), the US Congress established April 25th as "DNA Day".

Since my last gattaca post, the company that did my own dna testing has further specified my maternal haplogroup.  I am now officially a member of the U5b2c segment of humanity.  Here's an image showing the geographic distribution of the encompassing U5 group.
About 44-55 thousand years ago, a woman was born within the R haplogroup. This woman had a mutation in her mitochondrial dna that allows us to distinguish her from other humans of the time.  Her descendants became the U haplogroup, and U5 may be the oldest sub-group in the European region.  This wikipedia chart shows how the main maternal group names are related.

Human mitochondrial DNA (mtDNA) haplogroups

Mitochondrial Eve (L)

L0

L1

L2

L3

L4

L5

L6

M

N

CZ

D

E

G

Q

A

S

R

I

W

X

Y

C

Z

B

F

R0

pre-JT

P

U

HV

JT

K

H

V

J

T

Former Clusters IWX

Semi-related, there is recent news that Homo sapiens may have interbred with other species of hominids.  And you probably thought that family trees these days were complicated because of all the trans-continental adoptions, illegitimate births, and serial marriages!

Testing such as I had done at 23andme.com is not quite as useful as researchers (and afficionados like me) had once hoped.  They're finding that creatures are much more complex than just the programming in their dna.  Part of the problem is that genetics includes lots and lots of evolutionary baggage.  Study of the machinery that decides which parts gets used (instead of locked into "cold storage" indefinitely) is now called the science of epigenetics.  It's a second layer of inherited information.

Genetics covers the 4 main bases of dna, the chemicals that encode every protein that the body CAN produce.  Epigenetics covers additional chemical markers that are latched onto dna, "methylated" bases, that determine which of these possible proteins that a body actually WILL produce.

"One key epigenetic player is DNA methylation, which targets sites where cytosine precedes guanine in the DNA code. An enzyme called DNA methyltransferase affixes a methyl group to cytosine, creating a different but stable nucleotide called 5-methylcytosine. This modification in the promoter region of a gene results in gene silencing."
- http://www.physorg.com/news159111225.html

Quoting David Goldstein of Duke University, "With only a few exceptions, what the genomics companies are doing right now is recreational genomics... the information has little or in many cases no clinical relevance.”
- http://blogs.wsj.com/health/2009/04/16/genetic-testing-provides-few-easy-answers/

So I added $400 to my Visa bill (in addition to about $1500 recently for car repairs *SIGH*) for entertainment.  I knew it was such when I did it, but I succumbed to curiosity.  That happens sometimes.  :)  I don't mind going into debt for that kind of entertainment.  I learn a lot from the process eventually.  I just need to get back onto this project, after other recent distractions are finally over.

I know nothing about my family heritage other than "Irish".  Someone once mentioned: Tennessee, 1800s, Irish.  Someone else would mention Irish marrying other Irish, and later more Irish marrying into the family, and later some more Irish.  Mind you, I never once heard a name associated with any of these cases.  There was only the word Irish.  That, plus we'd always been poor and there was alcoholism in the family too.  Not that racist stereotypes are to always be believed, of course.  *big shrug*  I'm just saying that the little bit I'd heard seemed to fit with the reality of American history, where the Irish lived and worked on plantations with the slaves... in Tennessee... in the mid-1800s, I think.

Well, the haplogroup testing seems to confirm it.
http://en.wikipedia.org/wiki/Human_mitochondrial_DNA_haplogroup
http://en.wikipedia.org/wiki/Human_Y-chromosome_DNA_haplogroup



The maternal haplogroup U5b2 (left photo) is generally northern European, but it is also commonly found throughout Europe.  The paternal haplogroup R1b1c7 (right photo) is much more specific though.  The text at 23andme even says, "R1b1c7 reaches its peak in Ireland".

So, yes, I am Irish.

The group called "Autism Speaks" has a really bad reputation amongst the autistic rabble rousers (otherwise known as self-advocates), about the same reputation as "Cure Autism Now" does.  The usual complaint is that they want to eliminate autism, and they have no autistic people on their board or in their programs.  The rallying cry is, "Autism Speaks does not speak for me!"

Well, I ran into another problem with the group.  They solicit genetic information from autistic people (and their neurotypical families), but they don't seem to offer their results to the autistic population either.  They host the project called "Autism Genetic Resource Exchange" (AGRE), but I can't tell what's being offered in exchange for our dna data.  I wanted to use their database to check for SNP addresses that I can then compare to my results from 23andme.com.  They publish no such information that I can find.
http://www.autismspeaks.org/science/programs/agre/index.php

They do have a webpage form where I can apply for access to AGRE data.
http://www.agre.org/application/app.cfm?do=app

For "Project Abstract", I submitted:
For "Intended Use of database", I submitted:
Afterwards, I found that they have a 10-page contract that I have to print, sign, and mail off to them.  The application does say, "AGRE shall notify Principal Investigator in writing when action has been taken on said Application."  Guess I'll force them to answer my request by printing it out and mailing it off.

Their website does have a link for downloading data.  It leads to a site called ISAAC.  It says that ISAAC is founded and funded by "Cure Autism Now".  Remember them from the introductory paragraph?  *sigh*
https://www.autismtools.org/

All I want is a SNP list to add to my own compilation.  Criminy. 

Saturday morning, I mailed off a tube of my spit.  It will take about 8 weeks to get back my results.  When the results are posted online, I will be able to view a vast number of specific points of my DNA to see how they compare against known differences in the human genome.  I'll be using the tag "gattaca" here on LiveJournal to follow my results of this personal journey.  I suspect that I will be learning a great deal about the human genome starting about 8 weeks from now.  *laugh*

"Gattaca", for those who don't know, was a great movie about the dangers of predicting human life outcomes based on the results of genetic testing.  The name of the movie is built using the same letters as the 4 chemical parts used to build a dna molecule: guanine, adenine, thymine, cytosine.

I first learned about 23andme.com a few months ago.  (Hello, lordalfredhenry .)  I did not feel any overwhelming urge to run my own DNA through their system, but I confess that pure unadulterated curiosity finally got the better of me.  I added $400 to my credit card debt, and now here I am waiting for results.  I've already created my community profile there, although I think you have to have paid your money and claimed your special test kit code in order to participate.
https://www.23andme.com/user/?community_profile=92caa46f527ff773

Using their sample result data set as an example, I will get about 633,000 data points from my DNA.  These data points are called SNPs ("snips"), Single Nucleotide Polymorphisms.  These are places in the long strand of DNA code that a single difference is found.  So instead of getting my complete genetic code back, I'll be getting the "deltas", the differences.  They are using as a reference template, the published "human genome, build 36".
http://www.ncbi.nlm.nih.gov/projects/mapview/map_search.cgi?taxid=9606&build=36

8 weeks until I see results.   That's 56 days.  Or 1,344 hours.  Or even 80,640 minutes.

*twiddle*

Remember the tv show Hercules that presented tales of the adventures of Hercules and Iolaus? Well, they had more interesting adventures than even that good series was capable of showing. According to Plutarch, the fidelity of Iolaus to Hercules (but not vice versa) was so famed that male couples would use him as an example and profess their fidelity to each other at the tomb of Iolaus.

"And as to the loves of Hercules, it is difficult to record them because of their number; but those who think that Iolaus was one of them do to this day worship and honor him, and make their loved ones swear fidelity at his tomb."
- Plutarch, "Eroticus", par. 17

"It is a tradition likewise that Iolaus, who assisted Hercules in his labors and fought at his side, was beloved of him; and Aristotle observes that even in his time lovers plighted their faith at Iolaus' tomb."
- Plutarch, "Life of Pelopidas", Clough translation

Sexual fidelity, however, is such a rare thing. Not just among humans but also other animals. Rare, though, is not the same thing as absent. According to a PubMed article:

"The Wandering Albatross provides a striking exception to partner infidelity. This albatross is one of the most remarkable animals in the world (Figure 13). These enormous birds, with a wingspan that measures 11 feet, the longest of any bird (one wing is as long as your outstretched arms), mate for life, which is often 6 decades or longer."

I had originally thought that maybe "til death do us part" would have made a lot more sense for humans back when we only lived to our 30s, but this albatross proves that it is natural (for them) even across long lifetimes. A few days ago, news broke about a study that found what seems to be an infidelity gene that was linked statistically to the strength of the bond that a male (human) feels to his partner. Men without the gene had higher fidelity and higher relationship satisfaction (as reported by their partner).  Men with one copy of the gene had lower scores on those attributes.  Men with two copies of the gene had even lower scores.  The researchers looked at this gene after it was previously found to play a role in the fidelity of male voles (a small rodent).

When talking about the feature in humans, it's much too easy to get caught up in political maneuvering instead of rational inquiry.  Since that article, though, I've been pondering what sexual reproductive strategy would be "best" for a species (any species) given a few starting conditions:

1. males and females have comparable abilities (no significant disparity in survival skills individually)
2. long lifespan (>60 years)
3. long child development (>15 years)
4. one adult is designated primary caregiver for each child born
5. permanent sexual fertility (not annual/seasonal like many animals) across lifespan
6. pathogens that can kill "quickly" (<2 years)

Given those simplistic terms, what reproductive strategy yields the highest number of healthy children?

I find that #3 takes precedence.  Since child rearing takes so very long, it requires more resources than can reasonably be expected from only one adult.  (Let's call that Corollary 3a.)  I see some kind of fidelity involved in arranging for these long relationships.  Why?  If sexual attraction is responsible for creating children, then anyone who creates a child will want to ensure that another adult can be relied upon to continue providing resources.  If sexual attraction produced one child, then it can produce another with a different sexual partner, leading to loss of resources to the first child's primary caregiver.

At first, I kept thinking that some form of group fidelity would be an excellent arrangement.  If the group remains small, then problems introduced by #6 can still be minimized.  Even if one particular partner dies, then the cost of child rearing can still be shared amongst the other available (and committed) adults.  Sounds great.  But then I realized the complication that appears across generations.  The group must continually bring in new members to avoid inbreeding.  In return, it must continuously shed old members to other groups.  So the pathogen issue comes up again.  Unless (cruelty alert) newcomers are quarantined for the 2 years during which pathogens can make their presence apparent.

So I was back to shrinking the group down to only a couple.  Pathogen involvement is limited (with fidelity).  Except, of course, when one partner dies and the remaining partner looks for a new caregiver to share in child rearing.  But at least risk affects only one adult and their children rather than an entire group.

Promiscuity is excellent at avoiding the inbreeding problem (thereby introducing necessary genetic variety) but loses its luster when faced with the pathogen problem.  The only way I can get it to "work" is if transmission of genetic material (mating) happens only once and then the receiving partner maintains the genetic material to use slowly across time.  Some animals can do that for short periods of time.  In this scenario, pathogen exposure (sexually transmitted, anyway) happens only once.  If the receiving partner survives, then they can continuously produce offspring from that one encounter.  No additional risk necessary.  Then finding someone to share resources during child development would likely occur in groups only with other surviving child-producers (since they have proven themselves free of deadly pathogen).  It could be the females (like mammals) or the males (like the seahorse), whichever protects the fetus during development.

So that's the best that I can come up with, examining things without involving religious tradition or political propaganda.  My 6 starting rules seem to yield 3 possible outcomes that are very good for the stated goal of producing lots of healthy children.

1. binary couples with fidelity
2. group structure with fidelity and newcomer sequestration
3. random promiscuity during sole lifetime encounter, followed by parent-group association

Did I miss something?

New research from the Children's Hospital of Boston finds several new genes implicated in some forms of autism. They ran a study involving 104 Middle Eastern families (88 of which had cousin marriages, increasing the likelihood of transmission for rare mutations), looking for recessive genes that could be linked to autism diagnoses. They found that 6% of the families had DNA deletions (5 were identified) linked to autism. One of those genes was also found mutated in European and American children (especially those with autism and seizures).

In most of these "deletions", however, it wasn't the gene itself that was missing but instead it was nearby "switches" adjacent to it, suggesting the possibility that someday science could find a way to reactivate the dormant genes. The report notes:

It is the refinement of these synaptic connections that is the basis of learning and memory, suggesting that autism at its heart may represent molecular defects of learning. ... The findings also support the use of behavioral therapies in autism, which expose children to a rich environment and highly repetitive activities that may help turn on the genes and strengthen synaptic connections, Morrow adds.

I'm still not real keen on the idea that one person could decide for someone else whether to "change" them in such a way or not, but I still think it's fine for any person to make the decision only for their own self.  Anyone who suffers deserves relief.  It does make me ponder, though, what "normal" could even be in such a world.  Suppose I want to reactivate some long-buried gene that would give me a fur coat like a dog or a tail like a monkey or gills in my neck like a fish?

If it's not a matter of adding new protein encoding but merely reactivating what codes are already in my body, then it still counts as "my natural self", doesn't it?

This kind of stuff strikes me as odd in the same way as gender reassignment surgery on infants.  You don't like the body/mind that chance gave you, so you exchange that person for a different one.  Seems really dangerous to do that sort of thing to another person, but acceptable if they choose to do it for themselves.

Everything that your cells are capable of producing is recorded in your genetics, the arrangement of base pairs in the spiral-staircase-shaped molecule of your DNA. The sequence of those base pairs are step-by-step recipes for producing the molecules that your body needs to exist.   The DNA, however, is a junked up basement chock full of recipes. It includes some remnants of our entire evolutionary development for the last billion years or so. What makes the recipes useful and active, however, is another chemical signal that piggybacks onto the DNA molecule.

DNA doesn't exist by itself, you see.  It comes packaged with other chemicals that scientists are discovering will code for other useful information. The parts of your DNA library that are actually produced are marked differently by chemicals called methyl groups. These extra markers identify sections of DNA as being "heavy use" (easily pulled out for use by your cells) or "light use" (requiring more time and effort to unlock and use). So, for instance (and oversimplified), the cells in your heart are actively using only the muscle recipes while the cells in your brain are actively using only the neuron recipes. All of your cells have the same DNA, but they have different methylation patterns so they behave differently. Exposure to stressors can even activate some old sections of DNA, and leave them active for future use. Post-it notes for DNA... provided by methylation patterns attached to the DNA.

The DNA and these other markers is altogether called chromatin. Scientists have discovered that it's not just DNA information that is passed down along generations. The whole chromatin passes information from parent to child. So the environment and lifestyle of the parent shapes both the genetics (DNA) and the epigenetics (methylation) of the child.

Which brings me to today's news...

A team of McGill University scientists has discovered important differences between the brains of suicide victims and so-called normal brains. Although the genetic sequence was identical in the suicide and non-suicide brains, there were differences in their epigenetic marking – a chemical coating influenced by environmental factors.

It appears that humans abused as children can undergo epigenetic change. Their brains are functionally different. Moreover, since we keep finding evidence that epigenetic changes can be inherited, it could very well be true that the trauma will remain with the family line for generations after the initial incident. Mother Nature, she tries to keep future generations prepared for the hardships of previous generations. A different way of arguing "original sin", perhaps.

It is my personal theory that autism represents an epigenetic response to the current chemical environment (altered by modern human society). I claim that autistics are humans with an awakened genetic machinery from our recent (in evolutionary terms) past. There's still a lot of research to be done, but so far I think the results are already very promising.

My favorite epigenetic database is in New Zealand, the catalog of imprinted genes and related effects. I like their database because it's easy to search across species and for particular effects. Go ahead, search for autism. They have several curiosities identified already.
http://igc.otago.ac.nz/Search.html

PubMed talks about a new database under development called MethDB. I don't like its search features as well, but I suppose that can improve in the future. For general information, there's Epigenetics Station.  (*sing* Conjunction junction, what's your function?)

So there you have it, gentle students. A short introduction to the new science of epigenetics.  It's going to change a lot of our thinking about product safety.  What medicines or manufacturing chemicals have tested safe against genetics but may still alter our epigenetics?  Nobody knows.... yet.

Two important genetic discoveries announced today.

1) It's happened before with TRIM5 gene

Monkeys have, more than once, evolved a genetic defense to lentiviruses (which includes HIV). "An intriguing possibility is that the newly formed genes prevented infection by prehistoric viruses related to modern AIDS viruses. If so, this could mean that AIDS-like epidemics are not unique to our time, but in fact may have plagued our primate ancestors long before the modern AIDS epidemic. " Which, if their idea is correct, means that we can definitively beat this epidemic this time, since it's been done multiple times before by nature.

2) It's happening now with TRIM22 gene

Researchers find a gene that can prevent a cell from assembling more copies of HIV.  "This means that TRIM22 is an essential part of our body's ability to fight off HIV. The results are very exciting because they show that our bodies have a gene that is capable of stopping the spread of HIV."

Good to hear.  :)

Here's a report that may be of interest to the "locals".  A Minnesota fossil has helped to pin down the date, 96 million years ago, when insects started playing a role in plant pollination. Apparently air pollinators make their little pollen grains solitary so that they're easy to suspend in a small breeze and get carried to another plant. Insect pollinators, though, improve their chances by clumping together pollen grains (from 5 to 100 of them) for easy-carry packages that insects can haul around.  Researchers found this earliest evidence of clumping in Minnesota rock.

"The researchers sampled pollen from three sites in Minnesota’s Dakota Formation, which represents a time period when a shallow seaway covered North America’s interior."

Of special interest to me, however, is this news that autistic folk seem to be mutating at a faster rate than the general population. That fits into my own pet theory that Mother Nature is experimenting with creating a new kind of human.

"While most chromosomal abnormalities were inherited, the researchers found that seven percent of children with autism carry structural changes in the genome that are not found in their parents. The rate of such de novo changes in the general population is typically less than one percent, Scherer said."

Our understanding of genetic changes in humans is already improving at an impressive rate. That rate is likely to increase soon though, now that 1000 people will be fully mapped.  Called plainly "The 1000 Genome Project", it will make the results freely available through public databases, so scientists around the globe can readily access their results.