Genetic study – Genetic Science Services http://geneticscienceservices.com/ Thu, 19 May 2022 19:17:38 +0000 en-US hourly 1 https://wordpress.org/?v=5.9.3 https://geneticscienceservices.com/wp-content/uploads/2021/10/icon-7.png Genetic study – Genetic Science Services http://geneticscienceservices.com/ 32 32 Genetic Study Confirms Sarin Gas Caused Gulf War Illness – ARAB TIMES https://geneticscienceservices.com/genetic-study-confirms-sarin-gas-caused-gulf-war-illness-arab-times/ Thu, 19 May 2022 19:17:38 +0000 https://geneticscienceservices.com/genetic-study-confirms-sarin-gas-caused-gulf-war-illness-arab-times/ WhatsApp Facebook Twitter E-mail Messenger This post has been read 18152 times! UT Southwestern Medical Center releases study results DALLAS, May 19: For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Arab Gulf War. Now researchers led by Robert […]]]>





This post has been read 18152 times!

UT Southwestern Medical Center releases study results

DALLAS, May 19: For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Arab Gulf War. Now researchers led by Robert Haley, MD, professor of internal medicine and director of the division of epidemiology at the University of Texas Southwestern Medical Center (UT Southwestern), have solved the mystery, showing through a detailed genetic study that the nerve gas sarin was largely responsible for the syndrome.

A Marine Cobra gunship flies over a column of Allied tanks during the Battle of Khafji on January 31, 1991 in Saudi Arabia on the border between Saudi Arabia and Kuwait. (AP)

The findings were published May 11, 2022 in Environmental Health Perspectives, a peer-reviewed journal supported by the National Institute of Environmental Health Sciences, with an accompanying editorial on the article by leading environmental epidemiologists. . Dr. Haley’s research group not only identified that veterans exposed to sarin were more likely to develop GWI, but also discovered that the risk was modulated by a gene that normally allows some people’s bodies to break down sarin better. nerve gas. Gulf War soldiers with a weak variant of the gene who were exposed to sarin were more likely to develop symptoms of GWI than other exposed veterans who had the strong form of the gene. “Quite simply, our findings prove that Gulf War sickness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities,” said Dr Haley, a medical epidemiologist who has been investigating GWI for 28 years.

“There are still over 100,000 Gulf War veterans not getting help for this disease and we hope these findings will accelerate the search for better treatment.” In the years immediately following the Gulf War, more than a quarter of American and coalition veterans who served in the war began to report a series of chronic symptoms, including fatigue, fever, night sweats, memory and concentration problems, difficulty finding words, diarrhea. , sexual dysfunction and chronic body pain. Since then, university researchers and those from the Army and Department of Veterans Affairs have studied a list of possible causes of GWI, ranging from stress, vaccinations and oil well burning to exposure to pesticides, nerve gas, anti-nerve gas drugs, and depleted uranium.

Identified
Over the years, these studies have identified statistical associations with several of them, but no cause has been widely accepted. More recently, Dr. Haley and a colleague reported on a large study testing veterans’ urine for depleted uranium that would still be present if it had caused GWI and found none. “As early as 1995, when we first defined Gulf War Illness, the evidence pointed to exposure to nerve agents, but it took many years to build a compelling case,” said Dr. Haley, incumbent. from the U.S. Armed Forces Veterans Distinguished Chair in Medical Research, honoring Robert Haley, MD, and U.S. veterans of the Gulf War. Sarin is a poisonous synthetic nerve agent, first developed as a pesticide, which has been used in chemical warfare; its production was banned in 1997. When people are exposed to the liquid or gaseous form, sarin enters the body through the skin or breath and attacks the nervous system. High-level sarin often results in death, but studies of survivors have found that exposure to lower-level sarin can lead to long-term impairment of brain function.

The US military has confirmed that chemical agents, including sarin, were detected in Iraq during the Gulf War. In particular, satellite imagery documented a large cloud of debris rising from an Iraqi chemical weapons storage site bombed by US and coalition aircraft and transiting over US ground troop positions where it set off thousands of nerve gas alarms and was found to contain sarin. Previous studies have found an association between Gulf War veterans who reported exposure to sarin and symptoms of GWI. However, critics have raised questions of recall bias, including whether veterans with GWI are simply more likely to recall and report exposure due to their assumption that it might be related to their disease. “What makes this new study a game-changer is that it links GWI to a very strong gene-environment interaction that cannot be explained by environmental exposure recall errors or other biases. in the data,” Dr. Haley said.

Deployed
In the new paper, Dr. Haley and colleagues studied 508 deployed veterans with GWI and 508 deployed veterans who developed no symptoms of GWI, all randomly selected from more than 8,000 representative Gulf War veterans who responded to the US military health survey. They not only measured sarin exposure – asking if the veterans had heard any chemical nerve gas alarms sounding while deployed – but also took blood and DNA samples from each veteran. The researchers tested the samples for variants of a gene called PON1. There are two versions of PON1: the Q variant generates a blood enzyme that effectively breaks down sarin while the R variant helps the body break down other chemicals but is not effective at destroying sarin.

Everyone carries two copies of PON1, giving them either a QQ, RR, or QR genotype. For Gulf War veterans with the QQ genotype, hearing nerve agent alarms — an indicator of chemical exposure — increased their odds of developing GWI by 3.75 times. For those with the QR genotype, alarms increased their risk of GWI by 4.43 times. And for those with two copies of the R gene, ineffective at breaking down sarin, the risk of GWI was increased 8.91 times. Soldiers with both the RR genotype and low sarin exposure were more than seven times more likely to develop GWI due to the interaction per se, beyond the increased risk of both risk factors acting alone. For genetic epidemiologists, this number leads to a high degree of confidence that sarin is a causative agent of GWI. “Your risk gradually increases depending on your genotype, because these genes determine how well your body inactivates sarin,” Dr. Haley said. “That doesn’t mean you can’t get Gulf War disease if you have the QQ genotype, because even the highest genetic protection can be overridden by higher intensity exposure.” This kind of strong gene-environment interaction is considered a gold standard for showing that a disease like GWI was caused by a particular environmental toxic exposure, he added. The research does not rule out that other chemical exposures may be responsible for a small number of Gulf War illness cases. However, Dr. Haley and his team performed additional genetic analyzes on the new data, testing for other factors that might be linked, and found no other contributing causes.

“There is no other risk factor that comes close to having this level of causal evidence for Gulf War illness,” Dr. Haley said. The team is continuing to research the impact of GWI on the body, particularly on the immune system, whether any of its effects are reversible, and whether there are biomarkers to detect previous exposure to sarin or GWI. . By UT Southwestern Medical Center

References: “Assessment of a gene-environment interaction of PON1 and low-level nerve agent exposure with Gulf War disease: a prevalence case-control study drawn from the national population sample of the ‘United States Military Health Survey’ by Robert W. Haley, Gerald Kramer, Junhui Xiao, Jill A. Dever, and John F. Teiber, May 11, 2022, Environmental Health Perspectives. “Guest Perspective: Causal Implications of Environmental Genetic Studies Applied to Gulf War Diseases” Marc G. Weisskopf and Kimberly A. Sullivan, May 11, 2022, Environmental Health Perspectives. Other UTSW researchers who contributed to this study include John Teiber, Gerald Kramer and Junhui Xiao. The US military health survey was a collaborative effort of UTSW and a large survey research team from RTI International, including Jill Dever, who also contributed to this article. The study was funded by the US Departments of Defense and Veterans Affairs. The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Departments of Defense or Veterans Affairs.





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Genetic study on oats will help unlock their health benefits • Earth.com https://geneticscienceservices.com/genetic-study-on-oats-will-help-unlock-their-health-benefits-earth-com/ Thu, 19 May 2022 15:14:36 +0000 https://geneticscienceservices.com/genetic-study-on-oats-will-help-unlock-their-health-benefits-earth-com/ An international team of scientists recently decoded the oat genome, and the results will help experts determine which health benefits are associated with which genes. Oats have complicated genetics, with six sets of chromosomes and over 80,000 genes. By comparison, humans have two sets of chromosomes and about 20,000 genes. This explains why it took […]]]>

An international team of scientists recently decoded the oat genome, and the results will help experts determine which health benefits are associated with which genes. Oats have complicated genetics, with six sets of chromosomes and over 80,000 genes. By comparison, humans have two sets of chromosomes and about 20,000 genes.

This explains why it took Manuel Spannagl, a scientist at the Helmholtz Munich Environmental Health Center, six years to sequence and analyze the oat genome.

Why decode the genome? The researchers wanted to know why fewer people are allergic to oats compared to foods like wheat and rye. They found that oats have less protein that correlates with gluten, which means fewer people will be allergic to them.

“This allowed us to confirm at the genomic level that oats in their pure form are suitable for a gluten-free diet,” said study co-author Nadia Kamal.

Scientists have also discovered the gene that produces beta-glucans, a type of dietary fiber. Compared to other cereals, oats have a much higher level of beta-glucans. These fibers are beneficial for people with type 2 diabetes and have also been shown to lower cholesterol.

Oats are also good for the environment and can grow in less than ideal soil and generally require less land than wheat. Compared to other cereals, growing oats generally requires less chemical use for insecticides, fungicides and fertilizers.

Plus, now that we know more about their genetics, researchers think we can grow oats even more sustainably.

“We have created the potential for targeted breeding, since we are now able to tell which oat varieties are compatible with each other,” said Nick Sirijovski of Lund University and ScanOats. “At this point, we can combine traits for an even more favorable health profile, higher yields, better pest and drought resistance, and most importantly, in preparation for climate change.”

The study is published in the journal Nature.

By Erin Moody , Terre.com Personal editor

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Sarin Nerve Gas Caused Gulf War Sickness, New Genetic Study Shows https://geneticscienceservices.com/sarin-nerve-gas-caused-gulf-war-sickness-new-genetic-study-shows/ Wed, 18 May 2022 22:36:42 +0000 https://geneticscienceservices.com/sarin-nerve-gas-caused-gulf-war-sickness-new-genetic-study-shows/ More than 30 years after Gulf War veterans began to suffer from mysterious medical conditions, researchers say they have proven that exposure to sarin nerve gas caused the disease. According to Department of Defense. Upon returning home, veterans complained of a wide range of chronic symptoms, such as fatigue, joint and muscle pain, rashes, headaches, […]]]>

More than 30 years after Gulf War veterans began to suffer from mysterious medical conditions, researchers say they have proven that exposure to sarin nerve gas caused the disease.

According to Department of Defense. Upon returning home, veterans complained of a wide range of chronic symptoms, such as fatigue, joint and muscle pain, rashes, headaches, mood swings and respiratory. Doctors and federal agencies struggled to identify an exact cause and for years attributed the symptoms to stress or other psychological disorders.

But one study published on May 11 in the journal Environmental Health Perspectives used genetic research to point to one chemical agent in particular: sarin gas.

“Quite simply, our findings prove that Gulf War sickness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities,” said Dr Robert Haley. , a medical epidemiologist at the University of Texas Southwestern Medical Center. a Press release about the study.

Dr Robert Haley pictured while examining brain scans of Gulf War veterans. Photo courtesy of the University of Texas Southwestern Medical Center.

Haley studied Gulf War illness for 28 years and said that while the evidence still pointed to exposure to nerve agents as the cause, it was difficult to “construct a compelling case.”

Sarin is a toxic nerve agent that was first developed as a pesticide in 1938 by scientists in Nazi Germany. But it wasn’t used as a weapon until 1988when Iraqi dictator Saddam Hussein launched chemical attacks against thousands of Kurdish civilians.

Sarin attacks the neurotransmitters responsible for stimulating the muscles, which in the worst case can cause breathing to stop. It was banned in 1997, but there are allegations that Syrian President Bashar al-Assad used sarin against coalition forces and civilians on several occasions around 2013.

the Department of Veterans Affairs acknowledged that more than 100,000 veterans may have been exposed to low levels of sarin and cyclosarin after coalition troops destroyed an ammunition storage depot in Khamisiyah, Iraq, housing chemical weapons. A previous study by Haley and other researchers claimed that winds may have blown the sarin gas plume more than 300 miles toward Saudi Arabia, affecting even more soldiers and often setting off nerve gas alarms.

82nd Airborne Division
Soldiers from the 82nd Airborne Division wait for the signal to board a UH-60A Black Hawk helicopter during Operation Desert Shield. US Army photo courtesy of the US National Archives.

The results

Haley and her team now believe the key to knowing whether someone got sick after exposure to sarin was a gene known as PON1, which helps the body break down pesticides.

According to Haley, there are two versions of the PON1 gene: the Q variant, which breaks down sarin efficiently; and the R variant, which breaks down other chemicals but not sarin. People have two copies of the gene in their DNA, giving three possible combinations: QQ, QR or RR.

The researchers randomly selected 1,116 Gulf War veterans for the study, half of whom had symptoms of GWI and half of whom did not. They took blood and DNA samples from each veteran and asked if the veterans had heard any chemical nerve gas alarms sounding during their deployments.

The study found that those with the weakest form of the PON1 gene were significantly more likely to have Gulf War Illness.

the gulf war
An ordnance specialist carries a 105mm armor sabot round, for use in an M1 Abrams tank, during Operation Desert Shield. Photo by the US Department of Defense.

The researchers said their study did not rule out the possibility that other chemical exposures may have caused a small number of GWI cases, but the study adds to existing confidence that sarin is a causative agent.

A “forgotten generation”

For decades, Gulf War illness has been misunderstood or even ignored by medical professionals and federal authorities, leading to intense frustration among veterans.

“The early Gulf War veterans are like a forgotten generation,” said Kaitlin Chacon, an Air Force veteran and research coordinator at a Stanford neuroscience lab. Coffee or Die Magazine. “They are sandwiched between Vietnam veterans and also OIF veterans, who have been very intense and combative campaigns […] and they have not been informed of the toxic substances to which they have been exposed for a very long time.

A 1997 Congressional investigation found that the DOD and VA were uninterested in finding a cause for GWI, did not listen to the concerns of ill veterans, and consistently attributed symptoms to post-traumatic stress or other psychological conditions. The House Committee on Government Reform and Oversight called the federal government “satisfied to assume that the Gulf War produced no delayed casualties and determined to shift the burden of proof onto sick veterans.” .

“Unfortunately, when it comes to diagnosis, treatment and research for Gulf War veterans, we find that the federal government too often has a tin ear, a cold heart and a closed mind,” the report said. .

gulf war disease
Three Marines watch as a CH-53E Super Stallion helicopter lands during Operation Desert Shield November 22, 1990. U.S. Marine Corps photo courtesy of U.S. National Archives.

But the problem persisted, and in 2013 former VA epidemiologist Steven Coughlin testified before Congress that the VA had hidden or manipulated research findings that would have validated Gulf War Illness as a neurological condition.

While the DOD finally acknowledged that people with chronic, undiagnosed illnesses were likely exposed to multiple chemical agents overseas, affected veterans struggled for years to get VA benefits.

The VA previously estimated that 44% of veterans who served in the Persian Gulf War had medical conditions commonly referred to as Gulf War sickness, and that those deployed to Southwest Asia in the years that followed could suffer from similar problems, according to the Office of Government Accountability.

However, the GAO found that the VA rejected about 83% of the 102,000 Gulf War illness claims it received between 2010 and 2015. The approval rate for GWI was about three times lower than that of all other medical issues, the GAO wrote in its 2017 report.

Office of Government Accountability
Screenshot via Government Accountability Office.

“Gulf War illness is not always well understood by VA personnel,” the GAO researchers wrote in the report, and suggested that medical examiners could benefit from training on the disease.

Haley’s latest study was funded by the DOD and VA. He said he hoped the results would speed up the search for a better treatment.

But Chacon, who is currently conducting a study on the use of neurostimulation to relieve pain associated with GWI, warned that veterans should not expect immediate real-life impacts after new findings are published. . She pointed out that the process of doing studies, replicating research, and getting to the stage where doctors can act on the results is extremely slow. But the research can be extremely meaningful for veterans who have suffered for years from an unexplained illness.

“I see my patients burst into tears when they are finally confirmed to have a legitimate illness due to their stay in the Gulf region,” she said. “It’s very cathartic.”

Read more : VA adds 9 rare respiratory cancers to list of burn pit diseases

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After 30 years, genetic study confirms that sarin nerve gas is the cause of Gulf War sickness https://geneticscienceservices.com/after-30-years-genetic-study-confirms-that-sarin-nerve-gas-is-the-cause-of-gulf-war-sickness/ Sun, 15 May 2022 07:00:00 +0000 https://geneticscienceservices.com/after-30-years-genetic-study-confirms-that-sarin-nerve-gas-is-the-cause-of-gulf-war-sickness/ Troops who had genes that help metabolize the nerve gas sarin were less likely to develop symptoms. For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers led by Robert Haley, MD, professor of internal […]]]>

Troops who had genes that help metabolize the nerve gas sarin were less likely to develop symptoms.

For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers led by Robert Haley, MD, professor of internal medicine and director of the division of epidemiology at the University of Texas Southwestern Medical Center (UT Southwestern), have solved the mystery, showing through a detailed genetic study that the nerve gas sarin was largely responsible for the syndrome.

The results were published on May 11, 2022 in Environmental Health Perspectivesa peer-reviewed journal supported by the National Institute of Environmental Health Sciences, with an accompanying editorial on the article by leading environmental epidemiologists.

Dr. Haley’s research group not only identified that veterans exposed to sarin were more likely to develop GWI, but also discovered that the risk was modulated by a gene that normally allows some people’s bodies to break down sarin better. nerve gas. Gulf War soldiers with a weak variant of the gene who were exposed to sarin were more likely to develop symptoms of GWI than other exposed veterans who had the strong form of the gene.

Robert Haley, Kay Bailey Hutchison and Ross Perot

Robert Haley, MD (left) visits two longtime supporters of GWI research, former Senator Kay Bailey Hutchison and the late Ross Perot, at a campus event in 2006. Credit: UT Southwestern Medical Center

“Quite simply, our findings prove that Gulf War sickness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities,” said Dr Haley, a medical epidemiologist who has been investigating GWI for 28 years. “There are still over 100,000 Gulf War veterans not getting help for this disease and we hope these findings will accelerate the search for better treatment.”

In the years immediately following the Gulf War, more than a quarter of American and coalition veterans who served in the war began to report a series of chronic symptoms, including fatigue, fever, night sweats, memory and concentration problems, difficulty finding words, diarrhea. , sexual dysfunction and chronic body pain. Since then, university researchers and those from the Army and the Department of Veterans Affairs have studied a list of possible causes of GWI, ranging from stress, vaccinations and burning oil wells to exposure to pesticides, nerve gas, anti-nerve gas drugs, and depleted uranium.

Over the years, these studies have identified statistical associations with several of them, but no cause has been widely accepted. More recently, Dr. Haley and a colleague reported on a large study testing veterans’ urine for depleted uranium that would still be present if it had caused GWI and found none.

“As early as 1995, when we first defined Gulf War Illness, the evidence pointed to exposure to nerve agents, but it took many years to build a compelling case,” said Dr. Haley, incumbent. from the U.S. Armed Forces Veterans Distinguished Chair in Medical Research, honoring Robert Haley, MD, and U.S. veterans of the Gulf War.

Sarin is a poisonous man-made nerve agent, first developed as a pesticide, which has been used in chemical warfare; its production was banned in 1997. When people are exposed to the liquid or gaseous form, sarin enters the body through the skin or breath and attacks the nervous system. High-level sarin often results in death, but studies of survivors have found that exposure to lower-level sarin can lead to long-term impairment of brain function. The US military has confirmed that chemical agents, including sarin, were detected in Iraq during the Gulf War. In particular, satellite imagery documented a large cloud of debris rising from an Iraqi chemical weapons storage site bombed by US and coalition aircraft and transiting over US ground troop positions where it set off thousands of nerve gas alarms and was found to contain sarin.

Previous studies have found an association between Gulf War veterans who reported being exposed to sarin and symptoms of GWI. However, critics have raised questions of recall bias, including whether veterans with GWI are simply more likely to recall and report exposure due to their assumption that it might be related to their disease. “What makes this new study a game-changer is that it links GWI to a very strong gene-environment interaction that cannot be explained by environmental exposure recall errors or other biases. in the data,” Dr. Haley said.

Robert Haley

Robert Haley, MD, reviewing the brain scans of Gulf War veterans here, has studied the disease for 27 years. Credit: UT Southwestern Medical Center

In the new paper, Dr. Haley and colleagues studied 508 deployed veterans with GWI and 508 deployed veterans who developed no symptoms of GWI, all randomly selected from more than 8,000 representative Gulf War veterans who responded to the US military health survey. They not only measured exposure to sarin – asking if the veterans had heard any chemical nerve gas alarms sounding during their deployment – but also drew blood and DNA samples of each veteran.

The researchers tested the samples for variants of a gene called PON1. There are two versions of PON1: the Q variant generates a blood enzyme that effectively breaks down sarin while the R variant helps the body break down other chemicals but is not effective in destroying sarin. Each carries two copies of PON1giving them either a QQ, RR or QR genotype.

For Gulf War veterans with the QQ genotype, hearing nerve agent alarms — an indicator of chemical exposure — increased their odds of developing GWI by 3.75 times. For those with the QR genotype, the alarms increased their chances of GWI by 4.43 times. And for those with two copies of the R gene, ineffective at breaking down sarin, the risk of GWI was increased 8.91 times. Soldiers with both the RR genotype and low sarin exposure were over seven times more likely to develop GWI due to the interaction per se, beyond the increased risk of both risk factors acting alone. For genetic epidemiologists, this number leads to a high degree of confidence that sarin is a causative agent of GWI.

“Your risk gradually increases depending on your genotype, because these genes determine how well your body inactivates sarin,” Dr. Haley said. “That doesn’t mean you can’t get Gulf War disease if you have the QQ genotype, because even the highest genetic protection can be overridden by higher intensity exposure.”

This kind of strong gene-environment interaction is considered a gold standard for showing that a disease like GWI was caused by a particular environmental toxic exposure, he added. The research does not rule out that other chemical exposures may be responsible for a small number of Gulf War illness cases. However, Dr. Haley and his team performed additional genetic analyzes on the new data, testing for other factors that might be linked, and found no other contributing causes.

“There is no other risk factor that comes close to having this level of causal evidence for Gulf War illness,” Dr. Haley said.

The team is continuing to research the impact of GWI on the body, particularly on the immune system, whether any of its effects are reversible, and whether there are biomarkers to detect previous exposure to sarin or GWI. .

References:

“Assessment of a gene-environment interaction of PON1 and Low-Level Nerve Agent Exposure with Gulf War Illness: A Prevalence Case-Control Study from the United States Military Health Survey National Population Sample” by Robert W. Haley, Gerald Kramer, Junhui Xiao, Jill A. Dever, and John F. Teiber, May 11, 2022, Environmental Health Perspectives.
DOI: 10.1289/EHP9009

“Guest Perspective: Causal Implications of Environmental Genetic Studies Applied to Gulf War Illness” Marc G. Weisskopf and Kimberly A. Sullivan, May 11, 2022, Environmental Health Perspectives.
DOI: 10.1289/EHP11057

Other UTSW researchers who contributed to this study include John Teiber, Gerald Kramer and Junhui Xiao. The US military health survey was a collaborative effort of UTSW and a large survey research team from RTI International, including Jill Dever, who also contributed to this article. The study was funded by the US Departments of Defense and Veterans Affairs. The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Departments of Defense or Veterans Affairs.

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Genetic Study Confirms Sarin Nerve Gas Caused Gulf War Illness https://geneticscienceservices.com/genetic-study-confirms-sarin-nerve-gas-caused-gulf-war-illness/ Thu, 12 May 2022 14:45:49 +0000 https://geneticscienceservices.com/genetic-study-confirms-sarin-nerve-gas-caused-gulf-war-illness/ For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers led by Robert Haley, MD, professor of internal medicine and chair of the division of epidemiology at UT Southwestern, have solved the mystery, showing through […]]]>

For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers led by Robert Haley, MD, professor of internal medicine and chair of the division of epidemiology at UT Southwestern, have solved the mystery, showing through detailed genetic study that nerve gas sarin was largely responsible for the syndrome. The findings were published in Environmental Health Perspectivesa peer-reviewed journal supported by the National Institute of Environmental Health Sciences, with an accompanying editorial on the article by leading environmental epidemiologists.

Dr. Haley’s research group not only found that veterans exposed to sarin were more likely to develop GWI, but also found that the risk was modulated by a gene that normally allows some people’s bodies to break down sarin better. nerve gas. Gulf War veterans with a weak variant of the gene who were exposed to sarin were more likely to develop symptoms of GWI than other exposed veterans who had the strong form of the gene.

“Quite simply, our findings prove that Gulf War sickness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities,” said Dr Haley, a medical epidemiologist who has been investigating GWI for 28 years. “There are still over 100,000 Gulf War veterans not getting help for this disease and we hope these findings will accelerate the search for better treatment.”

In the years immediately following the Gulf War, more than a quarter of American and coalition veterans who served in the war began to report a series of chronic symptoms, including fatigue, fever, night sweats, memory and concentration problems, difficulty finding words, diarrhea. , sexual dysfunction and chronic body pain. Since then, university researchers and those from the Army and Department of Veterans Affairs have studied a list of possible causes of GWI, ranging from stress, vaccinations and oil well burning to exposure to pesticides, nerve gas, anti-nerve gas drugs, and depleted uranium.

Over the years, these studies have identified statistical associations with several of them, but no cause has been widely accepted. More recently, Dr. Haley and a colleague reported on a large study testing veterans’ urine for depleted uranium that would still be present if it had caused GWI and found none.

“As early as 1995, when we first defined Gulf War sickness, the evidence pointed to exposure to nerve agents, but it took many years to build a compelling case,” said Dr Haley, who holds the Distinguished Veterans of the United States Armed Forces award. Medical Research Chair, honoring Robert Haley, MD, and American veterans of the Gulf War.

Sarin is a toxic man-made nerve agent, first developed as a pesticide, which has been used in chemical warfare; its production was banned in 1997. When people are exposed to the liquid or gaseous form, sarin enters the body through the skin or breath and attacks the nervous system. High-level sarin often results in death, but studies of survivors have found that exposure to lower-level sarin can lead to long-term impairment of brain function. The US military has confirmed that chemical agents, including sarin, were detected in Iraq during the Gulf War. In particular, satellite imagery documented a large cloud of debris rising from an Iraqi chemical weapons storage site bombed by US and coalition aircraft and transiting over US ground troop positions where it set off thousands of nerve gas alarms and was found to contain sarin.

Previous studies have found an association between Gulf War veterans who reported exposure to sarin and symptoms of GWI. However, critics have raised questions of recall bias, including whether veterans with GWI are simply more likely to recall and report exposure due to their assumption that it might be related to their disease. “What makes this new study a game-changer is that it links GWI to a very strong gene-environment interaction that cannot be explained by environmental exposure recall errors or other biases. in the data,” Dr. Haley said.

In the new paper, Dr. Haley and colleagues studied 508 deployed veterans with GWI and 508 deployed veterans who developed no symptoms of GWI, all randomly selected from more than 8,000 representative Gulf War veterans who responded to the US military health survey. They not only measured sarin exposure – asking if the veterans had heard any chemical nerve gas alarms sounding while deployed – but also took blood and DNA samples from each veteran.

The researchers tested the samples for variants of a gene called PON1. There are two versions of PON1: the Q variant generates a blood enzyme that effectively breaks down sarin while the R variant helps the body break down other chemicals but is not effective in destroying sarin. Each carries two copies of PON1giving them either a QQ, RR or QR genotype.

For Gulf War veterans with the QQ genotype, hearing nerve agent alarms — an indicator of chemical exposure — increased their odds of developing GWI by 3.75 times. For those with the QR genotype, the alarms increased their chances of GWI by 4.43 times. And for those with two copies of the R gene, ineffective at breaking down sarin, the risk of GWI was increased 8.91 times. Soldiers with both the RR genotype and low sarin exposure were more than seven times more likely to develop GWI due to the interaction per se, beyond the increased risk of both risk factors acting alone. For genetic epidemiologists, this number leads to a high degree of confidence that sarin is a causative agent of GWI.

“Your risk gradually increases depending on your genotype, because these genes determine how well your body inactivates sarin,” Dr. Haley said. “That doesn’t mean you can’t get Gulf War disease if you have the QQ genotype, because even the highest genetic protection can be overridden by higher intensity exposure.”

This kind of strong gene-environment interaction is considered a gold standard for showing that a disease like GWI was caused by a particular environmental toxic exposure, he added. The research does not rule out that other chemical exposures may be responsible for a small number of Gulf War illness cases. However, Dr. Haley and his team performed additional genetic analyzes on the new data, testing for other factors that might be linked, and found no other contributing causes.

“There are no other risk factors that come close to this level of causal evidence for Gulf War illness,” Dr. Haley said.

The team is continuing to research the impact of GWI on the body, particularly on the immune system, whether any of its effects are reversible, and whether there are biomarkers to detect previous exposure to sarin or GWI. .

Other UTSW researchers who contributed to this study include John Teiber, Gerald Kramer and Junhui Xiao. The US military health survey was a collaborative effort of UTSW and a large survey research team from RTI International, including Jill Dever, who also contributed to this article. The study was funded by the US Departments of Defense and Veterans Affairs. The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Departments of Defense or Veterans Affairs.

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UTSW Genetic Study Confirms Sarin Nerve Gas Causes Gulf War Illness https://geneticscienceservices.com/utsw-genetic-study-confirms-sarin-nerve-gas-causes-gulf-war-illness/ Thu, 12 May 2022 04:05:00 +0000 https://geneticscienceservices.com/utsw-genetic-study-confirms-sarin-nerve-gas-causes-gulf-war-illness/ Newswise – For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers led by Robert Haley, MD, professor of internal medicine and director of UT Southwestern’s division of epidemiology, have solved the mystery, showing through […]]]>

Newswise – For three decades, scientists have debated the underlying cause of Gulf War Illness (GWI), a set of unexplained and chronic symptoms affecting veterans of the Persian Gulf War. Now researchers led by Robert Haley, MD, professor of internal medicine and director of UT Southwestern’s division of epidemiology, have solved the mystery, showing through detailed genetic study that the nerve gas sarin was largely responsible for the syndrome. The findings were published in Environmental Health Perspectivesa peer-reviewed journal supported by the National Institute of Environmental Health Sciences, with an accompanying editorial on the article by leading environmental epidemiologists.

Dr. Haley’s research group not only found that veterans exposed to sarin were more likely to develop GWI, but also found that the risk was modulated by a gene that normally allows some people’s bodies to break down sarin better. nerve gas. Gulf War veterans with a weak variant of the gene who were exposed to sarin were more likely to develop symptoms of GWI than other exposed veterans who had the strong form of the gene.

“Quite simply, our findings prove that Gulf War sickness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities,” said Dr Haley, a medical epidemiologist who has been investigating GWI for 28 years. “There are still over 100,000 Gulf War veterans not getting help for this disease and we hope these findings will accelerate the search for better treatment.”

In the years immediately following the Gulf War, more than a quarter of American and coalition veterans who served in the war began to report a series of chronic symptoms, including fatigue, fever, night sweats, memory and concentration problems, difficulty finding words, diarrhea. , sexual dysfunction and chronic body pain. Since then, university researchers and those from the Army and Department of Veterans Affairs have studied a list of possible causes of GWI, ranging from stress, vaccinations and oil well burning to exposure to pesticides, nerve gas, anti-nerve gas drugs, and depleted uranium.

Over the years, these studies have identified statistical associations with several of them, but no cause has been widely accepted. More recently, Dr. Haley and a colleague reported on a large study testing veterans’ urine for depleted uranium that would still be present if it had caused GWI and found none.

“As early as 1995, when we first defined Gulf War Illness, the evidence pointed to exposure to nerve agents, but it took many years to build a compelling case,” said Dr. Haley, incumbent. from the U.S. Armed Forces Veterans Distinguished Chair in Medical Research, honoring Robert Haley, MD, and American veterans of the Gulf War.

Sarin is a poisonous synthetic nerve agent, first developed as a pesticide, which has been used in chemical warfare; its production was banned in 1997. When people are exposed to the liquid or gaseous form, sarin enters the body through the skin or breath and attacks the nervous system. High-level sarin often results in death, but studies of survivors have found that exposure to lower-level sarin can lead to long-term impairment of brain function. The US military has confirmed that chemical agents, including sarin, were detected in Iraq during the Gulf War. In particular, satellite imagery documented a large cloud of debris rising from an Iraqi chemical weapons storage site bombed by US and coalition aircraft and transiting over US ground troop positions where it set off thousands of nerve gas alarms and was found to contain sarin.

Previous studies have found an association between Gulf War veterans who reported exposure to sarin and symptoms of GWI. However, critics have raised questions of recall bias, including whether veterans with GWI are simply more likely to recall and report exposure due to their assumption that it might be related to their disease. “What makes this new study a game-changer is that it links GWI to a very strong gene-environment interaction that cannot be explained by environmental exposure recall errors or other biases. in the data,” Dr. Haley said.

In the new paper, Dr. Haley and colleagues studied 508 deployed veterans with GWI and 508 deployed veterans who developed no symptoms of GWI, all randomly selected from more than 8,000 representative Gulf War veterans who responded to the US military health survey. They not only measured sarin exposure – asking if the veterans had heard any chemical nerve gas alarms sounding while deployed – but also took blood and DNA samples from each veteran.

The researchers tested the samples for variants of a gene called PON1. There are two versions of PON1: the Q variant generates a blood enzyme that effectively breaks down sarin while the R variant helps the body break down other chemicals but is not effective in destroying sarin. Each carries two copies of PON1giving them either a QQ, RR or QR genotype.

For Gulf War veterans with the QQ genotype, hearing nerve agent alarms — an indicator of chemical exposure — increased their odds of developing GWI by 3.75 times. For those with the QR genotype, the alarms increased their chances of GWI by 4.43 times. And for those with two copies of the R gene, ineffective at breaking down sarin, the risk of GWI was increased 8.91 times. Soldiers with both the RR genotype and low sarin exposure were more than seven times more likely to develop GWI due to the interaction per se, beyond the increased risk of both risk factors acting alone. For genetic epidemiologists, this number leads to a high degree of confidence that sarin is a causative agent of GWI.

“Your risk gradually increases depending on your genotype, because these genes determine how well your body inactivates sarin,” Dr. Haley said. “That doesn’t mean you can’t get Gulf War disease if you have the QQ genotype, because even the highest genetic protection can be overridden by higher intensity exposure.”

This kind of strong gene-environment interaction is considered a gold standard for showing that a disease like GWI was caused by a particular environmental toxic exposure, he added. The research does not rule out that other chemical exposures may be responsible for a small number of Gulf War illness cases. However, Dr. Haley and his team performed additional genetic analyzes on the new data, testing for other factors that might be linked, and found no other contributing causes.

“There is no other risk factor that comes close to having this level of causal evidence for Gulf War illness,” Dr. Haley said.

The team is continuing to research the impact of GWI on the body, particularly on the immune system, whether any of its effects are reversible, and whether there are biomarkers to detect previous exposure to sarin or GWI. .

Other UTSW researchers who contributed to this study include John Teiber, Gerald Kramer and Junhui Xiao. The US military health survey was a collaborative effort of UTSW and a large survey research team from RTI International, including Jill Dever, who also contributed to this article. The study was funded by the US Departments of Defense and Veterans Affairs. The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Departments of Defense or Veterans Affairs.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 researchers from the Howard Hughes Medical Institute. Full-time faculty of more than 2,900 are responsible for groundbreaking medical advances and committed to rapidly translating scientific research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits annually.

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ISLAND RESEARCH TEAM SUPPORTS MAJOR GENETIC STUDY ON SEVERE COVID-19 – Island Echo https://geneticscienceservices.com/island-research-team-supports-major-genetic-study-on-severe-covid-19-island-echo/ Tue, 10 May 2022 05:58:49 +0000 https://geneticscienceservices.com/island-research-team-supports-major-genetic-study-on-severe-covid-19-island-echo/ The Isle of Wight NHS Trust research team has supported the world’s largest study into the genetics of critical COVID-19. The study involving more than 57,000 people worldwide has revealed new details about some of the biological mechanisms behind the severe form of the disease. Researchers from the GenOMICC (Genetics of Mortality in Critical Care) […]]]>

The Isle of Wight NHS Trust research team has supported the world’s largest study into the genetics of critical COVID-19.

The study involving more than 57,000 people worldwide has revealed new details about some of the biological mechanisms behind the severe form of the disease.

Researchers from the GenOMICC (Genetics of Mortality in Critical Care) consortium – a global collaboration to study genetics in critical illness – led by the University of Edinburgh in partnership with Genomics England, made the discoveries by sequencing the genomes of 7 491 patients from 224 intensive care units in the UK.

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Professor Kenneth Baillie, Consultant in Critical Care Medicine at the University of Edinburgh, said:

“Our latest findings point to specific molecular targets in critical Covid-19. These findings explain why some people develop life-threatening COVID-19, while others have no symptoms. But more importantly, it gives us a deeper understanding of the disease process and is a big step forward in the search for more effective treatments.

“It is now true to say that we understand the mechanisms of Covid better than the other syndromes that we treat in intensive care in normal times – sepsis, influenza, and other forms of serious illness. Covid-19 shows us the way to solve these problems in the future.

Support for the NHS is evident, with large signs erected

Dr Gabor Debreceni, anesthesia and critical care consultant at the Isle of Wight NHS Trust, said:

“The GenOMICC study compares the genomes of critically ill patients with population controls to find the underlying mechanisms of disease.

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“Our intensive care unit began enrolling patients in this study from May 2020 and the last patient was recruited in September 2021. A total of 59 of our patients participated, which is an incredible achievement from the small Research Team.

“Members of the St. Mary’s Hospital team, including Dr. Alexander Moss, Dr. Azra Khatun, Dr. Luke Sylvester, Dr. Henry Barrington-White and Nurse Consultant Vikki Crickmore, have been instrumental in obtaining consent and enrolling patients in this project.

“In addition, research nurses Joy Wilkins and Alison Brown, with the support of research officer Sarah Knight, tirelessly collected the blood samples and worked on the forms, which is the most laborious part of the study.

“Everyone involved has gone the extra mile to support this study despite the challenges encountered at the height of the pandemic and as a result many drug developments have been initiated which will hopefully contribute to the successful treatment of COVID-19 in the future.”

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The DNA of participating island patients was compared to 48,400 others who had not had COVID-19, participants in Genomics England’s 100,000 Genomes Project and 1,630 others who had experienced mild COVID .

Determining the entire genome sequence for all study participants allowed the team to create an accurate map and identify genetic variation related to COVID-19 severity. The team found key differences in 16 genes in intensive care patients compared to DNA from other groups.

These findings will now serve as a roadmap for future efforts, opening new areas of research focused on potential new therapies and diagnostics with pinpoint accuracy.

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The most comprehensive genetic study gives hope to endangered vaquitas https://geneticscienceservices.com/the-most-comprehensive-genetic-study-gives-hope-to-endangered-vaquitas/ Fri, 06 May 2022 08:55:00 +0000 https://geneticscienceservices.com/the-most-comprehensive-genetic-study-gives-hope-to-endangered-vaquitas/ The world’s rarest marine mammals may not be doomed, as the most comprehensive genetic evaluation to date of the vaquita offers a glimmer of hope that this tiny tropical porpoise native to Mexico’s Gulf of California could avoid doom. extinction despite its population dwindling to about 10. Researchers said on Thursday that genomic data from […]]]>

The world’s rarest marine mammals may not be doomed, as the most comprehensive genetic evaluation to date of the vaquita offers a glimmer of hope that this tiny tropical porpoise native to Mexico’s Gulf of California could avoid doom. extinction despite its population dwindling to about 10.

Researchers said on Thursday that genomic data from 20 vaquitas showed that while the species has low genetic diversity – differences in DNA between different individuals – the number of potentially harmful mutations that could endanger its survival by inbreeding was quite low.

The vaquita, first described by scientists in 1958 and now considered critically endangered, is the smallest cetacean, the group including whales, dolphins and porpoises, growing to around 1.5 meters (5 feet) long and 54 kilograms (120 pounds). Its torpedo-shaped body is gray above and white below with a dark ring around the eyes.

Computer simulations carried out by the researchers to predict the risk of extinction have shown that vaquitas, whose population has fallen by more than 99% since the beginning of the 20th century due to human activities, have a strong chance of rebounding if the fishing gillnets are completely eliminated from their habitat. Gillnets, large curtains of nets that hang in the water, are used to catch fish and shrimp, but have killed many vaquitas who become entangled and drowned.

“Our key findings are that the vaquita is not genetically driven to extinction, as some have begun to assume,” said co-lead author Christopher Kyriazis, a UCLA doctoral student in ecology and evolutionary biology. of the study published in the journal Science. “These findings are important because they give hope for a species that is on the brink of extinction, a species that many are now abandoning.”

A particular threat is the gillnet poaching of an endangered fish called the totoaba. Totoaba swim bladders, believed to improve fertility, are prized in China.

“Dried totoaba swim bladders are traded on the black market in China for traditional medicinal purposes and cost more than cocaine,” said study co-author Phillip Morin, a research geneticist at the Southwest Fisheries Science Center. from the United States National Oceanic and Atmospheric Administration. .

Vaquitas, which are still actively breeding despite their small numbers, inhabit the northern Gulf of California, also called the Sea of ​​Cortez, between mainland Mexico and the Baja Peninsula.

“Gillnet fishing in vaquita habitat has been banned, but the ban has not been enforced and vaquitas continue to perish in the nets,” said study co-lead author Jacqueline Robinson, a postdoctoral researcher at the University of California, San Francisco’s Institute for Human Genetics.

The first population estimate, made in 1997, found that there were about 570 vaquitas. The population has since declined by up to about 50% per year.

The researchers assessed the genetic health of the species, which diverged evolutionarily from its closest relatives around 2.5 million years ago, by examining samples of 20 individuals obtained between 1985 and 2017, mostly archived from of deceased vaquitas. A concern with such a small population is that unavoidable mating between closely related individuals could increase deleterious mutations detrimental to the survival of the species.

Genomic data indicated that the vaquita population was already relatively small – about 5,000 individuals – for hundreds of thousands of years before the crash caused by human activities, making low genetic diversity a natural feature of the species. .

It also showed that there was relatively little inbreeding among vaquitas and very few harmful recessive mutations that could lead to birth defects upon inbreeding that could jeopardize species survival – fewer than 11 other cetacean species assessed. , including the blue whale.

A species of cetacean already seems to have been driven to extinction by humans in recent decades: the baiji, or Chinese river dolphin.

“Due to its shy nature, very little is known about the vaquita,” Robinson said. “The species is at risk of extinction before we even fully know what we are losing, and there is no way to replace it once it is gone.”

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Genetic study challenges dog breed stereotypes https://geneticscienceservices.com/genetic-study-challenges-dog-breed-stereotypes/ Thu, 28 Apr 2022 18:01:13 +0000 https://geneticscienceservices.com/genetic-study-challenges-dog-breed-stereotypes/ The American Kennel Club website outlines the ideal shape and temperament of 204 dog breeds, from the Affenpinscher (“loyal, curious, and notoriously fun”) to the Yorkshire Terrier (“feisty, courageous, and sometimes bossy”). The idea that certain breeds reliably exhibit distinct behaviors is embedded in dog shows, obedience training, and canine DNA testing, not to mention […]]]>

The American Kennel Club website outlines the ideal shape and temperament of 204 dog breeds, from the Affenpinscher (“loyal, curious, and notoriously fun”) to the Yorkshire Terrier (“feisty, courageous, and sometimes bossy”). The idea that certain breeds reliably exhibit distinct behaviors is embedded in dog shows, obedience training, and canine DNA testing, not to mention laws targeting breeds known to be prone to aggression.

Yet a detailed new study of dog behavior and genetics suggests that breed is actually of little value in anticipating an individual animal’s behavior or behavior.

After collecting extensive data from the owners of more than 18,000 dogs and sequencing the DNA of more than 2,100 of these pets, the researchers found surprisingly few links between breed and most behavioral traits.

Yes, owners of Labrador Retrievers and Golden Retrievers were slightly more likely to rate their puppies in the top 25% for “human sociability” than the owner of a randomly selected dog. And yes, dogs of hunting breeds were more likely to score higher in terms of “submissiveness,” or the ease with which they respond to human commands. But such associations were neither strong nor consistent.

Indeed, breed explained no more than 9% of behavioral variation in the dogs in the study, said study co-author Elinor Karlsson, a geneticist at the University’s Chan Medical School. from Massachusetts. A dog’s age and sex were often much better predictors of its behavior, and for some traits, including aggression, breed made no difference.

The results were published Thursday in the journal Science.

Each of the nearly 1 billion dogs currently prancing around the planet belongs to the same species – Canis familiaris. They separated from wolves around 10,000 years ago, which wasn’t long enough for them to accumulate that much genetic diversity. (Mammalian species typically evolve over hundreds of thousands of years.)

The concept of the modern dog breed was invented only about 160 years ago, in what the authors call “a blink of an eye in evolutionary history.” Only a few genetic differences are responsible for the striking variations we see in the shape and appearance of dogs.

Physical traits are strongly inherited; behavioral traits, less. These are governed by a complex mix of genetic and environmental factors in which race plays only a small, often insignificant role.

“A dog’s appearance won’t really tell you what a dog looks like,” said Marjie Alonso, executive director of the International Assn. of Animal Behavior Consultants and co-author of the study.

The team created an open database, Darwin’s Ark, to collect information about individual dogs. Owners were asked to answer over 100 questions about their dog’s appearance, behaviors and personality.

Jack, who is a one-quarter American pit bull terrier, was included in the dog breed and behavior study.

(Jane O’Donnell)

The result was a dataset that well reflected the companion dog population in the United States. Nearly half (49.2%) of participants described their dogs as purebred, with the proportion of breeds represented roughly matching dog ownership in the United States.

Purebred dog owners tend to describe their pets’ behavior in ways that fit breed stereotypes, the authors wrote. This raised the possibility that owners’ ratings were influenced – consciously or not – by the reputation of their dog’s breed.

Fortunately, the other dogs in the study were pooches whose ambiguous ancestry left their owners relatively free of any preconceptions about their past or behavior. They served as a sort of control group.

Researchers found that golden retriever owners tended to say their pets weren’t afraid of strangers, a description that fits the breed’s outgoing reputation. However, pooch owners with golden retriever ancestry were no more likely to describe their pets as unafraid of strangers than pooch owners without golden retriever DNA.

Similarly, Labrador Retriever owners tended to say their pets were social with humans, consistent with the stereotype that the breed is friendly and outgoing. But pooch owners with a Labrador retriever in their bloodlines were no more likely to call their dogs social around humans than pooch owners without that heritage.

If breed were a strong predictor of behavior, it stands to reason that the traits of those breeds would have manifested to some degree among pooches with those breeds’ DNA.

Even among purebred dogs, genetics was a much more reliable predictor of a dog’s appearance than its behavior.

“Physical traits are super hereditary,” Karlsson said. Yet when it comes to behavior, “race is a very poor predictor. It is not an accurate way to predict the behavior of any particular dog.

But there were patterns in certain traits like submissiveness and a dog’s propensity to grab and bite toys, she added.

Border collies, for example, tend to fetch more than the average dog. Choosing a border collie as a pet can increase your chances of getting a compliant animal, but it doesn’t guarantee that the specific dog you bring home will be naturally inclined to follow your commands.

Ellie, an avid hiker and rescue dog, stands on a steep rock near a shore.

Ellie, an avid hiker and rescue dog, was one of the pooches included in the study of dog breeds and behavior.

(@wanderswild / Instagram)

In the millennia before the Victorian obsession with dog herding began, humans distinguished dogs mainly by the tasks they did best. Some puppies were good at herding, others at hunting or guarding. A now-extinct type known as a “tournebroche”, or kitchen dog, was bred to run on a kind of dog-sized hamster wheel that turned roasting spits above the flames, said Katherine Grier, a retired University of Delaware history professor and author of the book “Pets in America: A History.”

In “The Invention of the Modern Dog: Breed and Blood in Victorian Britain”, authors Michael Worboys, Julie-Marie Strange and Neil Pemberton compared the difference between dogs before and after breeding in the colors of a rainbow. sky compared to a paint book. fries. Initially, there were a few large types of dogs with a lot of overlap between them. Breeding has taken this barking rainbow and broken it down into isolated, clearly defined units.

The American Kennel Club maintains the largest registry of purebred dogs in the United States, along with detailed descriptions for each breed standard, including personality traits. (The chow chow is “dignified, brilliant, earnest”; the Chihuahua is “charming, graceful, sassy.”)

The club said it believed the data from the study was strong, but disagreed with the authors’ conclusions.

“Racial behavior was not created with the formation of races 100 years ago. It was created based on selected working behaviors over centuries – and before the separation of individual races,” said chief veterinarian, Dr. Jerry Klein, in a statement, “Therefore, attempting to separate individual breeds based on behavior would not be successful without separating them into selected ancestral populations of sheepdogs, gundogs, etc. .”

Historians of dog breeding counter that breeders’ preference for specific physical traits over the years has often come at the expense of original behaviors. Dog breed is largely defined by an animal’s appearance, and “when you breed for looks, you can lose behaviors,” Grier said.

When it comes to canine behavior, genes “have an effect, but it’s less than the effect that genes have on physical traits,” said Danika Bannasch, an animal genetics specialist at UC Davis who has no not participated in the study. “This is the largest-scale study of genes and behavior of its kind and is sure to make a lot of people stop and think about dogs a little differently.”

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Largest genetic study to date uncovers DNA profiles that lead to cancer https://geneticscienceservices.com/largest-genetic-study-to-date-uncovers-dna-profiles-that-lead-to-cancer/ Tue, 26 Apr 2022 07:00:33 +0000 https://geneticscienceservices.com/largest-genetic-study-to-date-uncovers-dna-profiles-that-lead-to-cancer/ Cancers are like malevolent snowflakes. Each harbors a unique set of mutations in their genes, gradually turning them to the dark side. Eventually, without regard for their neighbors, the mutated cells destroy tissues, organs and life. But their set of genetic mutations – a signature – may also be their downfall. Like fingerprints or DNA […]]]>

Cancers are like malevolent snowflakes. Each harbors a unique set of mutations in their genes, gradually turning them to the dark side. Eventually, without regard for their neighbors, the mutated cells destroy tissues, organs and life.

But their set of genetic mutations – a signature – may also be their downfall. Like fingerprints or DNA left at a crime scene, we can use these signatures to hunt down cancer cells, nailing the culprits with drugs while leaving innocent, healthy cells alone.

The key is a database documenting these signatures. Fingerprints are useless if there is nothing to compare them to. Researching family trees would not be possible without open source genealogy sites. Similarly, to hunt biological terrorists like cancer, we need a whole registry of genetic mutation culprits as a benchmark.

We just received it. In a massive study covering more than 12,000 tumours, a team from the UK mapped the genetic changes that lead normal cells to develop into cancer cells. A treasure trove, the dataset captured unique genetic “fingerprints” of common types of cancer, but also of rare individual mutations that reflect a person’s history.

The study and its resulting catalog is the largest of its kind. By comparing the new mutation atlas to previous studies, the team found 58 new ones, which informed them of potential genetic changes and lifestyle factors that lead to cancer. They then developed an algorithm to match mutational signatures from the database to new tissue samples, creating a comprehensive crime scene investigation system for cancer screening.

“The reason it’s important to identify mutational signatures is that they’re like fingerprints at a crime scene – they help identify the culprits of cancer,” said the study’s lead author, Dr Serena Nik-Zainal from the University of Cambridge. “Certain mutational signatures have clinical or therapeutic implications – they may highlight abnormalities that can be targeted by specific drugs or may indicate a potential ‘Achilles heel’ in individual cancers.”

Turning

We have about 30 billion cells in our body. With age, the genome of each cell slowly changes its DNA letters.

“Right now, every cell in my body is accumulating mutations, so if they live long enough, it will be inevitable that they will eventually develop into a tumor,” Nik-Zainal said. “Having said that, let’s remember that a human being is made up of 30 billion cells, all accumulating mutations, and only one of them will trigger cancer throughout my life. This is amazing.”

So why do some normal cells deteriorate?

We have known for decades that DNA copy changes can activate oncogenic or pro-cancer genes, while blocking genes that normally protect against this process. Cancer cells also divide more often than normal cells. These discoveries have led to powerful treatments, including chemotherapy and immunotherapies.

But these ideas are relatively crude, like painting the genomic landscape of cancer with a broad brushstroke; little individuality seeps through. And with cancer, the uniqueness of the host and the pattern of genetic mutations are important.

Enter mutational signatures.

Here, the focus is on the changes in the precise DNA lettering when a cell becomes cancerous. Different types of cancer have distinct mutations while sharing some commonalities. These signatures capture both the habits of the host – for example, if they smoke – and the cancer itself, such as its inability to repair damaged DNA.

In other words, a mutational signature captures a specific pattern of DNA letter changes and repairs into a highly personalized fingerprint of a person’s cancer. As with actual fingerprints, there are similarities between different people and cancers. The study followed a clever route: First, they looked for common signatures in cancers from different organs and people. They then cross-examined the signatures between the organs, ultimately identifying 120 key mutational signatures common to all cancers in the study.

The process is like taking photos of different faces, but eventually mixing them together to find commonalities in features, while highlighting the differences.

The team lucked out with a huge asset: Genomics England’s 100,000 Genomes Project, which sequenced the entire genome of tens of thousands of people. It “has a greater number of whole-genome sequences than previous major cancer sequencing projects combined,” said Dr Dávid Szüts from the Center for Natural Science Research in Budapest, who was not involved in the study. . “Because the mechanism behind many signatures is still unknown, the study … also provides fertile ground for further investigation.”

A rainbow of mutations

In total, the team looked for single or double DNA letter changes in 12,222 cancer samples. The resulting dataset was a beast to kill. To fish out mutational signatures, they developed a computational method that analyzes common mutations from rarer ones. To verify integrity, the team validated their findings by comparing their data from two open-source databases, each containing around 3,000 cancer samples.

[We looked at] “Thousands and thousands of mutations, and that gives us a lot of power to be able to look at patterns across patient samples,” Nik-Zainal said.

For each organ, the team found only 5 to 10 common signatures, suggesting a common thread in cancers that could be co-opted for better treatment. By matching signatures between organs, they found 58 new fingerprints, which were compared to a previous global attempt to document cancer mutations. Some were common to all patients; others more unique, teasing the “snowflake” character of Cancers.

With additional detective work, they searched for potential causes of the mutation signatures. Some culprits were already well known: nip-tucks that compromise DNA’s ability to repair itself after a break.

Others revealed more enigmatic damage. A signature for brain tumors, for example, was strikingly similar to samples blasted with UV light. Platinum exposure was correlated with several types of cancers, including ovarian, stomach, and breast cancers. Another signature, dubbed SBS4 (yes, they don’t have the catchiest names) is strongly associated with tobacco use, but with a surprising correspondence to breast and colon cancer – potentially, a target for the development of drugs to kill several birds with one stone.

Similar to colors, mutational signatures can be combined into a spectrum, a rainbow of different mutation profiles. If that sounds complex, it’s because cancer is extremely complex. Different signatures can help us deconstruct a complex and cancerous genetic recipe so that we can understand it and thus know how to control it.

After that ?

Fingerprinting cancer genomes isn’t exactly eye-catching, but the database could power the next generation of cancer treatments.

The amount of information is staggering – even the authors admitted to abandoning further analyses. Instead, they developed and published an algorithm that fits the new genetic cancer data to the dataset. Dubbed FitMS, or Signature Fit Multi-Step, the software takes the same approach as the study: first fitting signatures to common signatures, then expanding the scope to identify other rare signatures.

The tool is available free of charge so doctors can match a new tissue sample to the database. This “signature fitting” process can, in theory, diagnose and tailor the patient’s cancer treatment to their particular set of mutations.

“This study shows how powerful whole genome sequencing tests can be in giving clues about how the cancer may have developed, how it behaved, and which treatment options would work best,” said Michelle Mitchell of Cancer Research UK.

Image Credit: Zita / Shutterstock.com

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