New Clues to Sex Anomalies in How Y Chromosomes Are Copied

From the New York Times Science Section

http://www.nytimes.com/2009/09/15/science/15chrom.html?ref=science

9/15/2009

The first words ever spoken, so fable holds, were a palindrome and an introduction: “Madam, I’m Adam.”

A few years ago palindromes — phrases that read the same backward as forward — turned out to be an essential protective feature of Adam’s Y, the male-determining chromosome that all living men have inherited from a single individual who lived some 60,000 years ago. Each man carries a Y from his father and an X chromosome from his mother. Women have two X chromosomes, one from each parent.

The new twist in the story is the discovery that the palindrome system has a simple weakness, one that explains a wide range of sex anomalies from feminization to sex reversal similar to Turner’s syndrome, the condition of women who carry only one X chromosome.

The palindromes were discovered in 2003 when the Y chromosome’s sequence of bases, represented by the familiar letters G, C, T and A, was first worked out by David C. Page of the Whitehead Institute in Cambridge, Mass., and colleagues at the DNA sequencing center at Washington University School of Medicine in St. Louis.

They came as a total surprise but one that immediately explained a serious evolutionary puzzle, that of how the genes on the Y chromosome are protected from crippling mutations.

Unlike the other chromosomes, which can repair one another because they come in pairs, one from each parent, the Y has no evident backup system. Nature has prevented it from recombining with its partner, the X, except at its very tips, lest its male-determining gene should sneak into the X and cause genetic chaos.

Discovery of the palindromes explained how the Y chromosome has managed over evolutionary time to discard bad genes: it recombines with itself. Its essential genes are embedded in a series of eight giant palindromes, some up to three million DNA units in length. Each palindrome readily folds like a hairpin, bringing its two arms together. The cell’s DNA control machinery detects any difference between the two arms and can convert a mutation back to the correct sequence, saving the Y’s genes from mutational decay.

After Dr. Page discovered the palindromes, he wondered whether the system had weaknesses that might explain the male sex chromosome anomalies that are a major object of his studies. In the current issue of Cell, with Julian Lange and others, he describes what they call the “Achilles’ heel” of the Y chromosome and the wide variety of sexual disorders that it leads to.

The danger of the palindrome protection system occurs when a cell has duplicated all its chromosomes prior to cell division, and each pair is held together at a site called the centromere. Soon, the centromere will split, with each half and its chromosome tugged to opposite sides of the dividing cell.

Before the split, however, a serious error can occur. Palindromes on one Y chromosome can occasionally reach over and form a fatal attraction with the counterpart palindrome on its neighbor. The two Y’s fuse at the point of joining, and everything from the juncture to the end of the chromosome is lost

The double-Y’s so generated come in a range of lengths, depending on which of the palindromes makes the unintended liaison. Like other chromosomes, the Y has a left arm and a right arm with the centromere in between. The male-determining gene lies close to the end of the left arm. If the palindromes at the very end of the right arm make the join, a very long double-Y results in which the two centromeres are widely separated. But if the joining palindromes are just to the right of the centromere, a short double-Y is formed in which the two centromeres lie close together.

Dr. Page detected among his patients both short and long double-Y’s and those of all lengths in between. He and his colleagues then noticed a surprising difference in the patients’ sexual appearance that depended on the length between the centromeres of their double-Y’s.

The patients in whom the distance between the Y’s two centromeres is short are males. But the greater the distance between the centromeres, the more likely the patients are to be anatomically feminized. A few of the patients were so feminized that they had the symptoms of Turner’s syndrome, a condition in which women are born with a single X chromosome.

The explanation for this spectrum of results, in Dr. Page’s view, lies in how the double-Y’s are treated in dividing cells and in the consequences for determining the sex of the fetus.

When the centromeres are close together, they are seen as one and dragged to one side of the dividing cell. As long as the Y’s male-determining gene is active in the cells of the fetal sex tissue, or gonad, the gonads will turn into testes whose hormones will masculinize the rest of the body.

But when the centromeres lie far apart, chromosomal chaos results. During cell division, both centromeres are recognized by the cell division machinery, and in the tug of war the double-Y chromosome may sometimes survive and sometimes be broken and lost to the cell.

Such individuals can carry a mixture of cells, some of which carry a double-Y and some of which carry no Y chromosome. In the fetal gonads, that mixture of cells produces people of intermediate sex. In many of these cases the patients had been raised as female but had testicular tissue on one side of the body and ovarian tissue on the other.

In the extreme version of this process, the distribution of cells may be such that none of the fetal gonad cells possess a Y chromosome, even though other cells in the body may do so. Dr. Page and his colleagues found five of the feminized patients had symptoms typical of Turner’s syndrome. The patients had been brought to Dr. Page’s attention because their blood cells contained Y chromosomes. Evidently by the luck of the draw, the blood cell lineage had retained Y chromosomes but the all important fetal gonad cells had been denied them.

In 75 percent of women with Turner’s syndrome, the single X comes from the mother. “Since they are females, everyone imagines it’s Dad’s X that is missing,” Dr. Page said. “But it could easily be Dad’s Y.”

That the degree of feminization parallels the distance between the two centromeres of the double Y chromosome is “a fantastic experiment of nature,” Dr. Page said. Despite having studied the Y chromosome for nearly 30 years, he has learned that it is always full of surprises.

“I continue to see the Y as an infinitely rich national park where we go to see unusual things, and we are never disappointed,” he said.

Dr. Cynthia Morton, editor of the American Journal of Human Genetics, said the new explanation of Turner’s syndrome was plausible. “It’s another beautiful David Page contribution to the science of genetics,” Dr. Morton said.

Having Extraordinary Gifts

Perhaps I was too harsh calling Cassandra and others on classism for not realizing that often, but not always it is money and access to SRS that makes the difference.  I actually think there is something else that often makes the difference in those of us who overcome our situations and those who do not.

I was born poor.  My father was an iron worker, who I rarely saw during the first 10 years of my life.  My mother was at times on welfare and at other times worked for minimum wages.  But she read and imparted a love of books and knowledge to me.  She liked movies and taught me how films could broaden my range of understanding.

I was seriously oppressed by the abuse I endured in school and only sporadically studied yet I had an IQ that was way up there and an ability to make high enough grades to pass with minimal effort.  Instead I put my real efforts into self education of subjects not touched upon in school.

For me that meant philosophy, history and literature.

I was given a left world view by my mother and having a father with a union card.

As a working class kid with mediocre grades I wasn’t expected to go to college, but I won a scholarship to any New York State College I could get into.  I wasn’t planning on going and hadn’t applied yet they found a school to take me.  I deliberately failed out.

When I left home I didn’t wind up in the Tenderloin trap even though that would have been the logical place for a transkid like me to end up.  I saw what was going on there as sort of deadend and a trap, a ghetto that could contain our lives.

Instead I wound up in Berkeley across the Bay.  Close enough to SF to access the doctors and clinics but far enough away to not get caught up in the drag queen/transie tizzy.

I was gifted with an ordinary girl prettiness and enough charm that people bent over backwards wanting to help me.  As a friend reminds me we were the divas, back in the day.

At one point a bunch of us from the office (NTCU), the divas and scholars had a dinner at one sister’s house.  Over wine and much pot we got into a discussion about how easy it was for some of us and how hard it was for others.

The dumb luck of being born looking more like a girl than a boy played a big role in the days before widely available FFS, as did being smaller and having a naturally feminine build.  Being one of those that the doctors said were definitely “born that way”.  You see even in those days we had the stupid and ungainly and those of us who knew them could tell they often wanted SRS as badly as any of us even though it would not do much to change their lives the way it would change ours.

Some of us amassed our money through hard work and borrowing, others by the dumb luck of having someone pay the tab.

But one thing the divas had in common was that they tended to be smarter, quicker witted and prettier with reasonable organizational skills.  They succeeded because of the combination of these factors.  You see the same in some of the kids today.  Ariablue and Anonymous-T-Girl have that same sort of quickness and the intelligence that lets them succeed when others fail.

What really often makes “classic transsexual” different from “classic transgenders” is the ability to focus on attaining goals.  If we get knocked down we get up again and we don’t get side tracked.  Transgender politics are often an energy side track as are addictions, self -pity and the blaming of others. Not to mention the tendency for people with histories of childhood abuse to wind up in self destructive life patterns that include self-defeating behaviors and substance abuse.

Now this accounts for people who are probably really transsexual settling for living transgender lives.

Humanity doesn’t fit in rigid ideological boxes because individuality promotes a personal anarchy that defies such neat and simple boxes.  People fall into ruts, some societally manufactured and some the result of their own actions.

Perhaps those who would have SRS were the situation different are not transgender but are actually the perpetual pre-op that so many of them claim to be.  As an old hippie woman filled with questionable wisdom I am faced with the rhetorical question of: “Who am I to judge?”

On the other hand we do have the true transgenders or if you will the classic transgenders including the often self invented and reinvented Lowman/Prince, whose worst sin of all was his/her (depending on time frame) being taken as the authoritative expert.  There are people who do want to live as the gender not commonly associated with their present genitalia and to not get SRS.

As an old hippie, the adage of “Do as you must, just so long as you don’t feel the need to crap in the space where I live.” applies.  It isn’t any skin off my ass.  Hell I’ll even work to pass laws to guarantee your civil rights and protections just so long as you don’t try to define me.

After all queens have a long history as part of the hip and alternative bohemian culture.  If I’m going to throw rocks at people I’d rather throw them at misogynistic right wing supporters of religious fascist persuasions who oppress women, LGBT/T folks, people of color, the poor and working classes and do so indiscriminately.

They are my enemy not some other poor oppressed person muddling their way through a life made more difficult by laws and customs that also oppress me as a working class woman holding alternative social views.

I’ve been offering an alternative to wasting our energies fighting each other.  It isn’t coming from anything I am reading from either transgender activists or the classic transsexual/HBS faction.  Rather it is grounded in the idea of unifying to fight a common shared oppression that makes life harder for everyone who has to negotiate their paths through these various forms of oppressions.

When I look back at where I came from and what I lived through I can see that I succeeded due to being extraordinarily gifted, both physically and mentally.  Also I was extremely lucky and escaped situations that prove lethal to many.  Including not dying when I over dosed a couple of times and talking my way out of getting murdered a couple of times.

Luck too is a random extraordinary gift.

In Uganda, Rioters Strip Women Wearing Trousers

From Women’s E-News

http://www.womensenews.org/article.cfm/dyn/aid/4140

09/15/09
By Rebecca Harshbarger
WeNews correspondent

Rioters attacked and stripped about 20 Ugandan women who were wearing trousers last week during deadly riots in Kampala. The humiliations were part of a major confrontation between a traditional kingdom and President Yoweri Museveni’s government.

KAMPALA, Uganda (WOMENSENEWS)–Male rioters in a suburb here on September 11 attacked about 20 women wearing trousers.

The men, in Rubaga, a Kampala suburb, began detaining women during their protests, police spokeswoman Judith Nabakooba said at a press conference that took place that same day.

Women wearing skirts were allowed to pass, Nabakooba said, but those wearing trousers were forcibly undressed and left to walk home in their underwear.

The abuse occurred amid violence in the Ugandan capital, which officials say has claimed 14 lives and injured about 70.

Women’s rights advocate Jackie Asiimwe denounced the rioters for using the clash to abuse women and commit criminal acts in New Vision, a Kampala-based newspaper. “It is an invasion of women’s privacy,” the newspaper quoted Asiimwe as saying.

Trousers a Western Thing

“Traditionally, trousers are not acceptable and are a Western thing,” Rizzan Nassuna, a writer and human rights advocate in Kampala told Women’s eNews. “In (the kingdom of) Buganda, you are supposed to wear long skirts. This is coming out of a local belief that women are not supposed to wear trousers, but this has never been formalized or really come out in the open. They violated their dignity as women, making them walk naked, because they are wearing trousers.”

In neighboring Sudan, journalist Lubna Ahmed al-Hussein was recently arrested for wearing trousers in Khartoum before being released on September 8.

Nassuna, however, said she doubted any direct connection between the two incidents. Instead, she viewed the attack on women wearing pants as a byproduct of a larger effort by protesters to assert the customs of their Buganda kingdom, a pre-colonial cultural and political structure that, with 5.5 million members in a country of 30.9 million, is the largest of Uganda’s traditional communities.

The riots were sparked on September 10 when the Ugandan government blocked an advance team for the Kabaka, the king of the Buganda kingdom, from entering Kayunga, a district in central Uganda.

The inspector general of police, Major General Kale Kayihura, said in a press conference on September 12 that the clashes spread from the city center to more than 11 suburbs of Kampala, a city of about 1.6 million people. He said that so far 14 people have died in the disturbances and more than 70 have been injured.

Kayihura said that the police had arrested 550 people since Thursday and charged 83. “Investigations are still on,” he said at the press conference.

Some Unnecessary Force Used

He said some police officers had used unnecessary force after they were instructed by their commanders and the Ugandan president to kill looters on sight. “I know that some police officers mistreated civilians during the riots,” said Kayihura. “This should stop immediately.”

Two minority ethnic groups in Kayunga, the Banyala and Baluuli, have been demanding this month to secede from the kingdom to establish cultural autonomy.

On September 9, President Yoweri Museveni, citing fears that the king’s visit might trigger violence in the district, said that the Kabaka could not visit Kayunga unless leaders from the minority groups, Buganda representatives and government officials met beforehand.

In the ensuing violent backlash to that decision, a mob burned two people to death in the suburb of Ndeeba on September 10. One woman was almost lynched by a mob in Namirembe, a neighborhood in Kampala, after youth declared her not to be a Muganda, or a member of the Baganda people. She was saved by police.

Justine Busulwa, an accountant who works in Kampala, gave Women’s eNews an account of barely surviving the riots.

She said in an interview that when news of the riots first broke last week her boss initially locked the office to protect the workers. She eventually left her office late and had a motorbike driver take her home to avoid using public transport. On her way home, she passed through Wandegaya, a Kampala neighborhood, and saw riots erupting.

A Ugandan soldier stopped her, but rather than protecting her, she said he asked her to lie down on the ground and began taunting her for not being a Muganda, or member of the kingdom, even though she belongs to that ethnic group.

Mob Begins Harassment

After begging for the release of her driver and herself, the soldier let her go. But then Busulwa said she was stopped by a mob that had formed in another section of the city, which began harassing her. She said she only got away by giving the rioters money.

“I was almost killed,” Busulwa said. “My son came home at midnight when the riots almost reached his university, too afraid to stay in his hostel.”

She waited until Sunday before entering town again.

The government called on the police, military and the Presidential Guard, raising hope that the violence would be curbed. But gunfire began in Kampala early on Friday, September 11. Public transport was paralyzed and rioters began humiliating women and attacking Indian merchants. Many Indian business owners closed their stores on that day to prevent attacks, and some Indian families took refuge at police stations.

Although the riots subsided somewhat on Saturday, gunshots were still audible throughout the city.

The crisis could be one of the biggest tests of Museveni’s career.

The president, an ethnic Ankole from southwestern Uganda, took power in 1986 and is up for re-election in 2011.

Although praised initially for his regime’s efforts to both empower women and reinstate the cultural kingdoms, his government has clashed with Buganda officials in recent years over land issues in Kampala, positioned at the heart of the traditional kingdom.

Museveni said he has tried to communicate with the Kabaka for the past two years, but the cultural leader refused to take his phone calls.

“Whenever any controversy came up, I would telephone His Highness, the Kabaka, but he would not answer my telephone as usual,” said Museveni, who took a hard line against rioters harassing and humiliating civilians, in a press statement. “The ring leaders are being hunted down and some have been arrested. Looters will be shot on sight, as will those who attack other civilians.”

Rebecca Harshbarger is a journalist based in Kampala, Uganda. You can visit her Web site at http://www.ugandabeat.wordpress.co

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NOW Supports Legislation to Repeal the Defense of Marriage Act

Statement of NOW Executive Vice President Bonnie Grabenhofer

September 15, 2009

The National Organization for Women is proud to stand with Rep. Jerry Nadler (D-N.Y.) in support of legislation to repeal the Defense of Marriage Act (DOMA) — a discriminatory law that is deceptive and harmful. Under DOMA, same-sex couples who legally wed are still denied federal marriage benefits, and other states may refuse to recognize their unions. NOW thanks Rep. Tammy Baldwin (D-Wis.) and Rep. Jared Polis (D-Colo.) for cosponsoring this important legislation.

Loving couples and their families deserve the same recognition and legal protection as their neighbors. NOW applauds Massachusetts, Connecticut, Iowa, Vermont and Maine for legalizing same-sex marriages.

Last month, the Obama Administration strongly denounced and defended DOMA, placing itself in a neutral position and forcing Congress to take up the fight.

Rep. Nadler is doing what the Obama administration has failed to do: take a hard line on DOMA and say discrimination and bigotry do not belong in the law. The right to marry has been recognized by the Supreme Court as a fundamental right under the U.S. Constitution. DOMA singles out a group of people and categorizes them as second-class citizens. NOW urges Congress to support this bill and remove one more barrier to fulfilling the promise of equality and justice for all.

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