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NYT: Human Genome Works Best Divided Up Into Segregated Neighborhoods

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From the often heterodox Science section of the New York Times:

A Family’s Shared Defect Sheds Light on the Human Genome


The mutations affect a newly discovered design feature of the DNA molecule called topologically associating domains, or TADs. It turns out that the vast informational expanse of the genome is divvied up into a series of manageable, parochial and law-abiding neighborhoods with strict nucleic partitions between them — each one a TAD.

Breach a TAD barrier, and you end up with the molecular equivalent of that famous final scene in Mel Brooks’s comedy, “Blazing Saddles,” when the cowboy actors from one movie set burst through a wall and onto the rehearsal stage of a campy Fred Astaire-style musical. Soon fists, top hats and cream pies are flying.

Dom DeLuise’s line about the chorus boys saying “Yessssssssssss” is like “steam escaping” is part of Mel Brooks’ long-running noticing that male homosexuals often have a hissy “s” lisssssp sound, the opposite of the very hetero Daffy Duck’s lithp sound.

Daffy’s accent was based on producer Leon Schlesinger, who used to offer the animators helpful advice such as, “Put in lotth of joketh, boyth, joketh are funny!”

When they debuted Daffy’s new voice for Schlesinger, they were worried that he’d get mad at them for mocking his speech impediment. But instead he enthused, “Jethuth Critht, thatth a funny acthent! Where’d you get that acthent?” (Or at least that’s Chuck Jones version. Mel Blanc’s version is somewhat different. Over many years of repeating these kind of Hollywood anecdotes, I’ve found, much to my surprise, that the world’s best joke tellers tended to improve their stories in the retelling.)

But with Singin’ in the Rain back in the news (here’s Mark Steyn on the death of Debbie Reynolds), I’m starting to think that there is a lot of Gene Kelly in Daffy Duck.

When I was a teenager in the 1970s, Gene Kelly was on TV all the time. If the weather was bad in Beverly Hills, the local TV news truck would drive over to Gene Kelly’s house and he’d come out on the lawn and give his comments on the weather. One thing I noticed was that Kelly had a huge ego: amour propre. He was like a really successful Daffy Duck. Dignity, always dignity:

Daffy was like Gene Kelly if you didn’t like him because he was so cocky and could torment him by keeping him from getting the career breaks he deserved.

Anyway, back to DNA science:

… For much of the past 50 years, genetic research has focused on DNA as a kind of computer code, a sequence of genetic “letters” that inscribe instructions for piecing together amino acids into proteins, which in turn do the work of keeping us alive.

… “We realized that in order to understand how genetic information is controlled, we had to figure out how DNA was folded in space,” said Bing Ren of the University of California, San Diego.

… Through chromosome conformation studies and related research, scientists have discovered the genome is organized into about 2,000 jurisdictions, and they are beginning to understand how these TADs operate.

As with city neighborhoods, TADs come in a range of sizes, from tiny walkable zones a few dozen DNA subunits long to TADs that sprawl over tens of thousands of bases and you’re better off taking the subway. TAD borders serve as folding instructions for DNA. “They’re like the dotted lines on a paper model kit,” Dr. Dekker said.

TAD boundaries also dictate the rules of genetic engagement. …

Because TADs can be quite large, the way the Upper West Side of Manhattan comprises an area of about 250 square blocks, a genetic enhancer located at the equivalent of, say, Lincoln Center on West 65th Street, can amplify the activity of a gene positioned at the Cathedral of St. John the Divine, 45 blocks north.

But under normal circumstances, one thing an Upper West Side enhancer will not do is reach across town to twiddle genes residing on the Upper East Side.

“Genes and regulatory elements are like people,” Dr. Dekker said. “They care about and communicate with those in their own domain, and they ignore everything else.”

Scientists have learned that disruptions of the genome’s boundaries may cause syndactyly and other diseases, including some pediatric brain disorders that affect the brain’s white matter. …

The best evidence for the importance of TADs is to see what happens when they break down. Researchers have lately linked a number of disorders to a loss of boundaries between genomic domains, including cancers of the colon, esophagus, brain and blood.

In such cases, scientists have failed to find mutations in any of the protein-coding sequences commonly associated with the malignancies, but instead identified DNA damage that appeared to shuffle around or eliminate TAD boundaries. As a result, enhancers from neighboring estates suddenly had access to genes they were not meant to activate.

Reporting in the journal Science, Dr. Young and his colleagues described a case of leukemia in which a binding site for insulator proteins had been altered not far from a gene called TAL1, which if improperly activated is known to cause leukemia. In this instance, disruption of the nearby binding site, Dr. Young said, “broke up the neighborhood and allowed an outside enhancer to push TAL1 to the point of tumorigenesis,” the production of tumors.

Now that researchers know what to look for, he said, TAD disruptions may prove to be a common cause of cancer.

So, integration is kind of like cancer is what you’re saying, Natalie?

This Trump Era could be interesting if it encourages greater freedom of speech from fed-up old-timers like Angier.

Make Journalism Great Again.


37 Comments to "NYT: Human Genome Works Best Divided Up Into Segregated Neighborhoods"

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  1. My experience is that Natalie Angier is the most unreliable of the NYT science writers, more than willing to reconstruct evidence to suit a political angle. Her “Woman: an Intimate Geography” was one of the worst, tendentious and poorly argued books I was assigned in college. (Another feminism-does-biology book I read in the same class, Sarah Hrdy’s “Mother Nature,” is excellent, though Hrdy is a real biologist who as I recall thanks Robert Trivers of Unz fame in the acknowledgments.)

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  2. Over many years of repeating these kind of Hollywood anecdotes, I’ve found, much to my surprise, that the world’s best joke tellers tended to improve their stories in the retelling.

    Storytelling is closely related to life itself. Cf. “You can’t enter the same river twice.”

    So – how come you were surprised?

    (Being astonished means, being able to philosophize – Ernst Bloch)

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  3. “Genes and regulatory elements are like people,” Dr. Dekker said. “They care about and communicate with those in their own domain, and they ignore everything else.”

    Sort of like the echo chamber bubble the liberals were living in before Trump was elected.

  4. He uses the word “faggot” there, right?

    Look at how fascistic SJWs have become in just the last five years.

    A few days ago an Indonesian Muslim girl mentioned on facebook that she felt intimidated hitch hiking while wearing a hijab because of the Muslim men who excoriate her for it.

    She mentioned one recent example in particular that Just happened.

    There were plenty of encouraging responses along the lines of “do what you like and don’t care”.

    In tandem with the rest of the trite pats on the back one commenter said, “just live your life, i hate guys like that, what a fag”.

    This of course received the reply – quote -

    “Why do you think it’s okay to use a homophobic slur?”

    I good naturedly and rationally defended the guy for utilizing the English language.

    This got me a suspension from Facebook and a threat of losing complete access to my Facebook account.

    Talk about “controlling the conversation”.

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  5. Bugs: “Duck season.” Daffy: “Wabbit season.” Elmer…..Blam! And Daffy’s bill spins around his head and down to his feet like an over sized collar. Still love those cartoons. Elmer and Daffy both had speech impediments, as did Donald Duck, not very PC.

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  6. The Lefty media knowingly misinterpreted last year’s polls which showed Hillary 12% ahead of Trump in the dog days of August, when Hillary was having so many Parkinson’s seizures she was kept out of public view. Now, every day and in every way, we are told by the same media that Obama’s “Approval Rating” is at 58% and rising.

    A goodly part of that 58% are people who are absolutely beside themselves with joy at the prospect that Barack Hussein Obama will not be POTUS after high noon on January 2o, 2017. They are just afraid to say so because, you know, RACISM!

    With Trump in office, Blacks might even be encouraged to kill each other at a slightly lower rate.

  7. It seems our host was shocked, shocked to find the world’s best joke tellers tend to improve their stories in the retelling.

  8. A shame that the author missed the obvious analogy to the concept of a class in computer programming.

  9. What is the preferred SJW word to use in that situation? How do they want us to describe a guy who is being a total fag, without using the word fag?

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  10. The NYTimes science section was more heterodox (allowing occasional glimpses of the mountain of accumulating evidence supporting HBD) back when Nicholas Wade was in charge. He has since retired, under a cloud of political incorrectness, and the thought police are now more vigilant in their patrols.

  11. OT: Ax-wielding tranny in Australian 7-Eleven attacks man and white woman with dreads (!)

    The whole attack is shown in the video. The first victim apparently hasn’t watched enough John Waters films to know that you never turn your back on a tranny holding an ax.

  12. Gene Kelly was surprisingly unlikable for a musical/comedy star. He always seemed to be arrogant and forcing himself to be “charming”. And what I’ve read, he terrorized his co-workers and directors by being a real taskmaster.

    He burnt his bridges with MGM by being a complete dick toward the execs after An American in Paris, including blackmailing them into allowing his communist then wife Betsy Blair to act in Marty. MGM paid him back by refusing to help him get the lead role in “Pal Joey”

    I don’t know how trustworthy wikipedia is, but it states he left the Catholic Church after the church sided with Franco in the Spanish civil war. He was then “agnostic” for the rest of his life.
    It reminds me of Howard Dean leaving his Protestant church over a bike path.

  13. ‘… This Trump Era could be interesting if it encourages greater freedom of speech from fed-up old-timers like Angier…’

    There’s a flaw in depending on old-timers that and Steve don’t get.

    Eventually old-timers become no-timers.

  14. “manageable, parochial and law-abiding neighborhoods with strict nucleic partitions between them”

    It does sound like a Trump Effect, I agree. Here’s another one:

    Deutsche Bank: “Good fences make good neighbors”

    Trump’s plans could double US GDP growth by 2018, Deutsche Bank says

    The analysis also takes a more optimistic view of Trump’s expected “America first” agenda when compared with other Wall Street views that have cited the danger of a potentially isolationist U.S. that starts trade wars with global competitors … “This approach should produce a new order that will ultimately be more stable in the sense that ‘good fences make good neighbors,’” Folkers-Landau said.

    Hat Tip: Conservative Treehouse:

  15. The Schlesinger stories are great but here’s the real Schlesinger on screen and there’s no lithp that I can discern:

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  16. The Schlesinger stories are great but here’s the real Schlesinger on screen and there’s no lithp that I can discern:

    Well, that was for public consumption. Perhaps he put a little extra care into how he pronounced his words?

  17. OT: Hilarious, Sailerbait story out of SoCal.

    Charges were dropped against Michelle Susan Hadley, 30, of Ontario, who was “the innocent victim of a diabolical scheme” that also included phony death threats, Orange County District Attorney Tony Rackauckas announced.

    Prosecutors instead have charged Angela Marie Diaz, 31, with kidnapping, false imprisonment and perjury. Diaz, who is originally from Arizona and had moved back there, was arrested in Phoenix on Friday and is awaiting extradition.

    The man who links the two women is Ian Diaz, an agent with the U.S. Marshals Service, who dated Hadley in Anaheim, Calif., from 2013 to 2015 before marrying Diaz, according to court records. Prosecutors said they have no evidence he was involved.

    The bizarre events began in June, when Diaz reported to Anaheim police that men had been arriving at her home to engage in a “rape fantasy” encounter, prosecutors said.

    Prosecutors said men were intercepted by police and told them they thought they were going to engage in a consensual act.

    The officials said Diaz also called 911 and falsely reported that a man attempted to rape her in her garage, and she appeared with her shirt ripped and her neck red.

    At the same time, Diaz told police Hadley had been threatening to have her raped, and had also sent threats that included graphic photos saying she would kill her and her unborn child. Diaz had faked the pregnancy, prosecutors allege.

    The false evidence led authorities to arrest Hadley, who then faced 10 felony charges and the possibility of life in prison, according to The Los Angeles Times.

    But the case fell apart as authorities learned all the threats and solicitations had allegedly come from Diaz herself. Diaz used her phone, the condo she shared with her husband, and her father’s home in Arizona to make the calls and emails, prosecutors said.

    Hadley was released in October and was officially exonerated Monday.

    “This has been a huge nightmare for me — probably the most traumatic experience of my life,” Hadley said on the courthouse steps Monday, the newspaper reported.

    “I’m glad it’s finally over, and I can move on.”

    Diaz is also accused of faking cervical cancer, forging doctor’s notes, and posing as an attorney, prosecutors said.

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  18. onto the rehearsal stage of a campy Fred Astaire-style musical.

    Either this writer is a moron or deliberately lying about the scene.

    The musical is clearly reminiscent of a campy Busby Berkeley-style musical, not Fred Astaire. Astaire’s musicals were always stylish and delicate (hence why gays love them) but very, very straight. No one ever made up gay rumors about Fred Astaire, mainly because Astaire was so famously ugly that gay men simply weren’t all that interested in him in that way, no matter how well he danced.

    Berkeley’s style, however, was camp all the way, (though he was apparently straight as an arrow):

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  19. It looks like that short has a fair bit of ADR going on; difficult to tell if any one’s voice is actually theirs. The guard’s voice, for example, is clearly dubbed in.

  20. Just judging by the pictures, never mind the Munchausen syndrome, that US marshal has terrible taste in women.

  21. “When they debuted Daffy’s new voice for Schlesinger, they were worried that he’d get mad at them for mocking his speech impediment. But instead he enthused, ‘Jethuth Critht, thatth a funny acthent! Where’d you get that acthent?’”

    I had a friend with a very unusual accent, and after a while I developed a dead-on imitation of it that cracked all our friends up. After continual begging, I finally did it in front of him. He said, “Jeeth, when you thay it like that, it maketh me thound like fleeking leetahd.”

  22. Mel Blanc had only ONE vocal tonality, but spread that out with dozens of speech impediments for his characterizations.

  23. So, integration is kind of like cancer is what you’re saying, Natalie?

    She’s also saying that Michael Phelps would’ve been unbeatable for at least five Olympics if he had full syndactyly flippers.

  24. “Bing Ren of the University of California, San Diego”: any relation to Bing Crosby?

  25. SAVAGE ATTACK German cops hunt gang of migrants ‘who lured an off duty nurse into a children’s park, beat her unconscious and raped her’
    Detectives said the attackers pounced on the 28-year-old nurse who had just left her shift at a clinic in Hamburg

  26. Another triumph for Mad Merkel.

  27. I did not understand the significance of this story about the human genome. In fact I understand most stories about the human genome less and less. When human genome was sequenced in circa 2003 there was a high expectation for breakthroughs and understanding. 15 years later it does not feel like the promises were fulfilled. Yes, we learned that humans have 50% less genes than expected. But we still do not know how these genes work. And even bigger mystery is what is the so-called junk DNA. What does it do?

    How many viable variants (alleles) are there for a given gene? If there are approximately 20,000 protein coding genes are there some among them that are the same for all human beings? How many genes one must change to transform a pure blood Nigerian into a Swede? It seems that nobody publishes results that would answer similar questions. I suspect that they are not even sure how to delineate genes in the sequences of A,T,C and G pairs. They do not know where one gene begins and when it ends in the sequence. It seems they do not really know what are the exact rules of heredity. Not all chunks are equally likely to be swapped in the crossover phase?

  28. Mel Blanc wouldn’t even have a job today. Making fun of speech impediments is simply not who we are this current year.

  29. Over many years of repeating these kind of Hollywood anecdotes, I’ve found, much to my surprise, that the world’s best joke tellers tended to improve their stories in the retelling.

    On the other hand, the Tin Pan Alley anecdote I recounted here never seems to change except for one irrelevant detail– the identity of the onlooker who asked Harry Woods’s companion the question. It can be a woman, a cop, or the bartender. Everything else is the same.

    Would that add to or detract from the story’s authenticity?

  30. There is no word. They don’t call it crimestop for nuthin.

  31. Movie musicals are an inherently campy medium.

    (Not that there’s anything wrong with that).

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  32. Blazing Saddles on TV is down to about an hour now. I have a kind of reverse dementia in which I laugh at things that are no longer there; my memory is more complete than reality.

    First they got rid of all the profanity. Then they got rid of the word “n*****”. Then they got rid of “faggot”. I’ve seen a version on TV where the scene with the Indian chief (Mel Brooks cleverly disguised) sees the black family crossing the west and says “Schwarzes! They’re darker than us! Whuff” is removed. (Lily von Shtup is apparently considered too obscure for the Gentiles, and remains.) They’ve ditched Hedley Lamar fondling a statue, they’ve ditched Governor LePtomaine being told to “think of your secretary” while sticking a pen back in its desk holder.

    Civilizational decline.

  33. Hmmm… Reminds me of this:

    No camp there.

  34. It’s one of my pet movie peeves, but I hate how we’ve all forgotten that musicals were very popular among straight men until the 1960s/early 1970s. Yes, other dancing/singing was a bit off putting for a lot of breeder men initially, but the musicals would make up for it by having stories that appealed to straight gentile men (war stories, boy-gets-girl stories, adventure stories) and making the songs jumpy and making the male dancing macho (Gene Kelly, Fred Astaire, a lot of West Side Story).

    The the gay revolution happened and gays (and ((certain other folk))) ) whole hog took over and made every musical “cynical” or “subversive” with hard to sing music or just about how minorities need to overthrow whitey and how whitey’s ideas are so bad and wrong. Heck, the most watchable musical for straight men in 15 years has been Wicked, and that’s about the gay-claimed movie (Wizard of Oz), an attack on white blond leadership, and an undercurrent of lesbianism—-and those are severely underplayed for the most part in favor of singable songs.

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  35. Musicals have always been campy, Jewy and gay.

    That’s sort of how things are when it comes to genres popularized by (((Rodgers))) and (((Hammerstein))) on (((Broadway))), (((New York City))).

    Here’s the first line of the Wikipedia page on the one you picked as the archetypal goyishe, heterosexual musical:

    West Side Story is a musical with a book by (((▵Arthur Laurents▵))), music by (((▵Leonard Bernstein▵))), lyrics by (((▵Stephen Sondheim▵))) and conception and choreography by (((▵Jerome Robbins▵))).

    With movie musicals we of course change venue to (((Hollywood))), where (((Mervyn LeRoy))) of Metro-(((Goldwyn)))-(((Mayer))) would produce The Wizard of Oz, music by (((Harold Arlen))) and lyrics by (((Yip Harburg))).

    That in turn set the country revolving towards the gay revolution, as the confirmed bachelors of the nation got to talking with the other men who bought tickets to see it over and over.

    They liked it so much because it was super-campy. You could almost define “campy” as “similar to a movie musical.” But, to be more precise, camp is when completely ridiculous things happen with no acknowledgment of how ridiculous they are.

    Working as they do from the premise that the characters frequently pause the narrative for choreographed song and dance numbers, musicals are inherently campy. Movie musicals even more so, since film is usually a more “realistic” medium than theater.

    (Incidentally, West Side Story is even campier than Wizard).

    As for how the Friends of Dorothy relate to trends towards cynical subversion, if you’re thinking of Rent, that was written by the straight (((Jonathan Larson))). Wicked was (((Stephen Schwartz))) and (((Winnie Holzman))), also straight. “Cynical”/“subversive” is a feminist/lesbian thing and to a lesser extent a Jew thing, not a gay thing.

    What camp definitely isn’t is anything that’s “cynical” or a downer, unless it’s poorly-executed to the point of being comical—when the director aims for “cynical” but lands at “completely exploitative trash,” you get high camp (Valley of the Dolls, Mommie Dearest).*

    *Those two movies are but one of the many examples of how gay men tend to like stuff that feminists/lesbians hate and vice-versa. Gays like dancy disco and pop, feminists and lesbians like talky folk and alternative…

    A Facebook search for “my friends who like Rent” shows 6 straight girls and 1 lesbian, whereas “my friends who like RuPaul’s Drag Race” results in 6 gay and 1 straight guy. “My friends who like The Wizard of Oz” are 6 straight females, 5 gay and 2 straight males. “My friends who like Wicked” — 2 straight girls, both Jewish.

    And, the trend in musicals is if anything away from gays and Jews. The top three names in today’s musical theater—Andrew Lloyd Webber, (((Julie Taymor))), Lin-Manuel Miranda—are all straight. Only Taymor is Jewish, and only Miranda’s body of work could be considered in any way “cynical” or “subversive,” even by 1939 standards.

    Hamilton aside, most of the stuff on Broadway now is licensed properties, “jukebox musicals,” long-runners, and revivals, which might mostly not be worth seeing but also don’t tend to have particularly high subversion quotients.

    From my vantage point at least, a lot of recent original shows and revivals get away with a lot more non-PC jokes and themes than they could in a movie or TV show. (Chicago, The Producers, Avenue Q, Spamalot, The Book of Mormon).

    Also, again, nothing wrong with campy. 1. Campy is fun, and 2. it doesn’t matter which other people do or don’t like something, only what you think of it.

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