Featured Research

from universities, journals, and other organizations

'Achilles' Heel' In Y Chromosome Linked To Sex Disorders

Date:
September 7, 2009
Source:
Whitehead Institute for Biomedical Research
Summary:
The unique mechanism behind the evolutionary survival of the human Y chromosome may also be responsible for a range of sex disorders, from failed sperm production to sex reversal to Turner Syndrome.

A tug of war between nascent daughter cells can snap isodicentric in two, leading to its loss during development of the fetus.
Credit: Tom DiCesare/Whitehead

The unique mechanism behind the evolutionary survival of the human Y chromosome may also be responsible for a range of sex disorders, from failed sperm production to sex reversal to Turner Syndrome.

Roughly six years ago, David Page's lab at Whitehead Institute for Biomedical Research reported the discovery of eight large areas of mirror-imaged genetic sequences, or palindromes, along the Y chromosome. Because the Y chromosome essentially has no partner with which to swap genes, a process that between ordinary chromosome pairs leads to genetic diversity and the exchange of good genes for damaged ones, it relies on its own palindromes to swap genes with itself. The Y, as it turns out, folds itself in the middle of palindromic regions, thereby pairing identical sequences to allow for potentially beneficial genetic exchange.

At the time, the finding provided explanation for why, despite much-heralded reports to the contrary, the Y chromosome is not doomed to extinction. Now, the Page lab has discovered that the Y's process of self-preservation can randomly go awry, with considerable clinical consequence.

"This is the sequel to the Y chromosome palindrome story," says Page, Whitehead Institute Director and a Howard Hughes Medical Institute investigator.

The latest chapter of the story, whose conclusion is published in the September 4 issue of Cell, began with the intriguing hypothesis that perhaps the Y's process of self-recombination can inadvertently turn the entire chromosome into a palindrome—literally, a mirror-image of itself. The result would be a so-called isodicentric Y chromosome (idicY), an abnormal structure with, as the name implies, two centromeres.

"We began to think seriously about the centromeres and the activity around them. Two centromeres render the chromosome susceptible to damage," says Julian Lange, first author of the Cell paper and a former graduate student in the Page lab. Because of the Y chromosome's well known roles in sex determination and male fertility, Lange began to speculate about the potential clinical impact of the transmission of an idicY during fertilization.

"Because the Y chromosome is not essential to an individual's survival, these isodicentric Ys can persist," says Lange, who, after completing this research at Whitehead, became a postdoctoral fellow at Memorial Sloan-Kettering Cancer Center. "They can be found in the population."

And Lange found them, in the DNA samples of 51 patients screened from a field of nearly 2400 individuals who had come under study over the course of many years because of failed sperm production, structurally abnormal Y chromosomes, or sex reversal. Through sophisticated genetic analysis, it became clear that idicYs were responsible for spermatogenic failure in many of the male patients.

However, 18 of the 51 patients were anatomically female—despite having two copies of the male-determining SRY gene on their idicY chromosomes. Lange and Page began to hypothesize that the feminization they had identified was related to the instability of the idicYs themselves. Suspecting that the level of instability of an idicY increases with the size of the chromosome, they looked for a connection and found something somewhat paradoxical: the larger the Y chromosome, the greater the likelihood of sex reversal.

"We had predicted this correlation, which relates to the overall distance between the centromeres," says Page. "But when we confirmed it with the patient data, we were blown away."

Page believes that this new model for the formation of idicY chromosomes, coupled with the size-instability correlation, suggests a causal link to Turner syndrome, a chromosomal abnormality in girls or women, characterized by the lack of one sex chromosome. Turner syndrome affects an estimated 1 in 2500 females. Page won't yet speculate as to what percentage of Turner syndrome could be caused by this palindrome-to-palindrome recombination, but he does think it's significant.

David Page's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Matt Fearer. Note: Materials may be edited for content and length.


Journal Reference:

  1. Julian Lange, Helen Skaletsky, Saskia K.M. van Daalen, Stephanie L. Embry, Cindy M. Korver, Laura G. Brown, Robert D. Oates, Sherman Silber, Sjoerd Repping, David C. Page. Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes. Cell, 2009; DOI: 10.1016/j.cell.2009.07.042

Cite This Page:

Whitehead Institute for Biomedical Research. "'Achilles' Heel' In Y Chromosome Linked To Sex Disorders." ScienceDaily. ScienceDaily, 7 September 2009. <www.sciencedaily.com/releases/2009/09/090903163715.htm>.
Whitehead Institute for Biomedical Research. (2009, September 7). 'Achilles' Heel' In Y Chromosome Linked To Sex Disorders. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2009/09/090903163715.htm
Whitehead Institute for Biomedical Research. "'Achilles' Heel' In Y Chromosome Linked To Sex Disorders." ScienceDaily. www.sciencedaily.com/releases/2009/09/090903163715.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins