Featured Research

from universities, journals, and other organizations

Study reveals rate at which key genetic deletions contribute to male infertility

Date:
October 25, 2012
Source:
Whitehead Institute for Biomedical Research
Summary:
A large-scale analysis of Y chromosomes from more than 20,000 men finds that two spontaneously recurring deletions along a complex region of the Y chromosome are responsible for approximately 8 percent of cases of failed sperm production, according to researchers.

Egg fertilization illustration.
Credit: © Kheng Guan Toh / Fotolia

A large-scale analysis of Y chromosomes from more than 20,000 men finds that two spontaneously recurring deletions along a complex region of the Y chromosome are responsible for approximately 8% of cases of failed sperm production.

Related Articles


Although previous research had identified deletions in the region of the Y known as AZFc (for azoospermia factor c) as causing severe spermatogenic failure (SSF), this latest analysis, conducted by Whitehead Institute Director David Page and colleagues, is the first to determine how prevalent these deletions are in the general population.

According to the study, published in the November issue of the American Journal of Human Genetics, the deletion known as b2/b4 is found in one of every 2,300 men, increases the risk of SSF 145 times, and is responsible for roughly 6% of cases.

"This deletion almost always results in spermatogenic failure, so it would be extremely rare for it to be transmitted from father to son without medically assisted reproduction," says Page. "Because of this, we can conclude that its prevalence in the population essentially reflects the rate at which this deletion arises spontaneously in men."

"Medically relevant population genetics studies are well established for most of the human genome, but this is the first study of this kind for the Y chromosome," says Steven Rozen, an associate professor at Duke-NUS Graduate Medical School Singapore and first author of the study.

Page notes that this study would not have been possible without the unique sequencing method he developed with collaborators at Washington University in St. Louis to help navigate the structural complexities of the Y chromosome. As Page reported years ago, the Y comprises several regions of large palindromes -- areas of mirror-imaged genetic sequences. Such regions render conventional sequencing approaches incapable of detecting extremely subtle genetic differences found hidden among the "mirrors." In response, Page and colleagues developed an approach known as SHIMS (single-haplotype iterative mapping and sequencing) to establish a definitive reference DNA sequence of the Y chromosome.

Such structural complexity is not exclusive to the Y chromosome, however. Smaller "halls of mirrors" can be found scattered throughout the human genome, and these areas are likely to be as unstable and prone to mutation as those on the Y chromosome. While the effects of the known deletions of the AZFc region appear to be limited to sperm production, substantially more harmful health effects are apt to arise from mutations elsewhere. Given the inherent challenges of obtaining accurate and complete DNA sequences of mirrored regions, Page believes that the current reference sequence of the human genome is missing potentially meaningful detail -- and that the time has come to apply SHIMS broadly.

"The key to SHIMS starts with the realization that there are areas of the human genome that are almost perfectly mirrored repeated sequences that are greater than 99% identical," says Page, who is also an investigator of the Howard Hughes Medical Institute. "When you assemble a sequence from multiple unrelated chromosomes, as was done with the human genome, you cannot make sense of minute but critical differences."

"The human genome reference is a consensus sequence, which is a politically wonderful outcome," he adds. "But in mirrored regions, consensus doesn't really represent anything. A complete and accurate assembly of the human genome will answer questions we do not even know to ask."

This work was supported by the National Institutes of Health, the Howard Hughes Medical Institute, and the Singapore Ministry of Health and Agency for Science, Technology, and Research.

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 professor of biology at Massachusetts Institute of Technology and an investigator of the Howard Hughes Medical Institute.


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. Steven G. Rozen, Janet D. Marszalek, Kathryn Irenze, Helen Skaletsky, Laura G. Brown, Robert D. Oates, Sherman J. Silber, Kristin Ardlie, David C. Page. AZFc Deletions and Spermatogenic Failure: A Population-Based Survey of 20,000 Y Chromosomes. The American Journal of Human Genetics, 2012; DOI: 10.1016/j.ajhg.2012.09.003

Cite This Page:

Whitehead Institute for Biomedical Research. "Study reveals rate at which key genetic deletions contribute to male infertility." ScienceDaily. ScienceDaily, 25 October 2012. <www.sciencedaily.com/releases/2012/10/121025121839.htm>.
Whitehead Institute for Biomedical Research. (2012, October 25). Study reveals rate at which key genetic deletions contribute to male infertility. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2012/10/121025121839.htm
Whitehead Institute for Biomedical Research. "Study reveals rate at which key genetic deletions contribute to male infertility." ScienceDaily. www.sciencedaily.com/releases/2012/10/121025121839.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) — According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) — A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) 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