PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases

PNRI's landmark study reveals DNA rearrangement's role in genetic disorders, paving way for new treatments

Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases
2024-06-21
(Press-News.org)

Seattle, WA — June 21, 2024 — Researchers at the Pacific Northwest Research Institute (PNRI) and collaborating institutions have made a groundbreaking discovery that could significantly advance our understanding of genomic disorders. Their latest study, funded by the National Institutes of Health[1] and published in the journal Cell Genomics, reveals how specific DNA rearrangements called inverted triplications contribute to the development of various genetic diseases.

Understanding the Study

Genomic disorders occur when there are changes or mutations in DNA that disrupt normal biological functions. These can lead to a range of health issues, including developmental delays and neurological problems. One type of complex DNA mutation involves a structure known as a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP). This study delves into how these complex rearrangements form and their impact on human health.

Key Findings

The research team, led by PNRI Assistant Investigator Cláudia Carvalho, Ph.D., collaborated with her lab colleagues, study lead author Christopher Grochowski, Ph.D.,  from the James R. Lupski Lab at Baylor College of Medicine, and other scientists to analyze the DNA of 24 individuals with inverted triplications. 

They discovered that these rearrangements are caused by segments of DNA switching templates during the repair process. Normally, DNA repair mechanisms use the undamaged complementary strand as a template to accurately repair the damaged DNA. However, sometimes during repair, the repair machinery may inadvertently switch to a different but similar sequence elsewhere in the genome. 

These switches occur within pairs of inverted repeats—sections of DNA that are mirror images of each other. Inverted repeats can confuse the repair machinery, leading to the use of the wrong template, which can disrupt normal gene function and contribute to genetic disorders.

Structural Diversity: The study found that these inverted triplications generate a surprising variety of structural variations in the genome, which can lead to different health outcomes. Gene Dosage Impact: These rearrangements can alter the number of copies of certain genes, known as gene dosage. The correct number of gene copies is crucial for normal human development and function. Changes in gene dosage can cause diseases like MECP2 duplication syndrome, a rare neurodevelopmental disorder. Mapping Breakpoints: By using advanced DNA sequencing techniques, the researchers identified the precise locations where these DNA segments switch templates leading to an altered number of genes including MECP2.

Dr. Carvalho and Baylor scientists first observed this pathogenic genomic structure in 2011 while studying MECP2duplication syndrome. Only recently, with the advent of long-read sequencing technology, has it become possible to investigate in detail how it forms in the genome.

Implications for Rare Disease Research and Treatment

"This study sheds light on the intricate mechanisms driving genetic rearrangements and their profound impact on rare diseases," said Dr. Cláudia Carvalho, PNRI’s lead scientist on the study. "By unraveling these complex DNA structures, we open new avenues for understanding the genetic causes of rare diseases and developing targeted treatments to improve patient outcomes."

These findings are being applied in a follow-up study led by Baylor's Davut Pehlivan, M.D., investigating how complex genomic structures influence the clinical features of MECP2 duplication syndrome and their impact on targeted therapeutic approaches.

###

About PNRI:
Pacific Northwest Research Institute (PNRI) is a nonprofit biomedical research institute, where scientists are using innovative approaches in genetics and genomics to tackle some of the most difficult problems in science and medicine. The institute was founded 67 years ago in Seattle, Washington, as a place where scientists were free to pursue discoveries that promised the highest chance of improving human health. The goal was at the beginning, and remains today, to conduct foundational science leading to impactful medical innovations. To learn more, visit pnri.org.

Media contact:
Louise Maxwell
lmaxwell@pnri.org
206-568-1479

 

[1] Research reported in this press release was supported in part by National Institute of General Medical Sciences of the National Institutes of Health under award number R01132589.

 

END


[Attachments] See images for this press release:
Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases 2 Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases 3

ELSE PRESS RELEASES FROM THIS DATE:

Empowering older adults: Wearable tech made easier with personalized support

2024-06-21
(Toronto, June 20, 2024) A new review in the Journal of Medical Internet Research, published by JMIR Publications, found that community-dwelling older adults are more likely to continue using wearable monitoring devices (WMDs), like trackers, pedometers, and smartwatches, if they receive support from health care professionals or peers. The research team from The Hong Kong Polytechnic University, led by Dr. Arkers Kwan Ching Wong, reviewed data from 3 randomized controlled trials involving over 150 older adults. The evaluation showed that the interventions that focused on increasing awareness of being monitored and used collaborative goal-setting and feedback tools, such as the SystemCHANGE ...

Pennington Biomedical researchers partner on award-winning Long Covid study

Pennington Biomedical researchers partner on award-winning Long Covid study
2024-06-21
Dr. John Kirwan, Executive Director of Pennington Biomedical Research Center, is serving as a co-principal investigator on the Pathobiology in RECOVER of Metabolic and Immune Systems, or PROMIS, study. The study has been awarded more than $802,000 by the National Institutes of Health to identify potential causes of Long COVID. “The PROMIS study will help us better understand what is driving Long COVID,” Dr. Kirwan said. “In the early days of the pandemic, Pennington Biomedical directed its resources to address the urgent health needs of our population. Now with estimates that more than 25 percent of people in the U.S. who had COVID have experienced ...

Cooling ‘blood oranges’ could make them even healthier – a bonus for consumers

Cooling ‘blood oranges’ could make them even healthier – a bonus for consumers
2024-06-21
An orange teeming with antioxidants and other health benefits may be a shot in the arm for consumers and citrus growers, if the fruit is stored at cool temperatures, a new University of Florida study shows.   But it’s too soon to know if the so-called “blood oranges” are a viable crop for the Florida citrus industry, says Ali Sarkhosh, a UF/IFAS associate professor of horticultural sciences. Sarkhosh’s post-doctoral associate Fariborz Habibi explains further. “Although blood oranges typically command higher prices than other common varieties, such as navel or ...

Body image and overall health found important to the sexual health of older gay men, according to new studies

2024-06-21
According to a National Poll on Healthy Aging, 93% of people in the U.S. between 50-80 years old report experiencing at least one form of ageism from other people. Internalized ageism is when a person believes ageist ideas about themselves, such as thinking they had a “senior moment” or thinking they are too old to learn new technology. Internalizing ageist stereotypes can impact older people’s mental and physical health, including sexual health. Various aspects of older adults’ sexual ...

Lab-grown muscles reveal mysteries of rare muscle diseases

Lab-grown muscles reveal mysteries of rare muscle diseases
2024-06-21
DURHAM, N.C. – Biomedical engineers at Duke University have developed a new technique to better understand and test treatments for a group of extremely rare muscle disorders called dysferlinopathy or limb girdle muscular dystrophies 2B (LGMD2B). The approach grows complex, functional 3D muscle tissue from stem cells in the laboratory, creating a platform that replicates patient symptoms and treatment responses. In its debut study, researchers reveal some of the biological mechanisms underlying the characteristic loss of mobility caused by LGMD2B. They also demonstrate that a combination of existing treatments may be able to alleviate some ...

Primary hepatic angiosarcoma: Treatment options for a rare tumor

Primary hepatic angiosarcoma: Treatment options for a rare tumor
2024-06-21
“[...] PHA is a rare yet aggressive mesenchymal tumor of the liver, which requires a multi-disciplinary approach to achieve the best patient outcomes.” BUFFALO, NY- June 21, 2024 – A new editorial paper was published in Oncoscience (Volume 11) on May 20, 2024, entitled, “Primary hepatic angiosarcoma: Treatment options for a rare tumor.” In this new editorial, researchers Gregory L. Guzik and Ankit Mangla from University Hospitals Cleveland Medical Center, University Hospitals Seidman Cancer ...

Research finds causal evidence tying cerebral small-vessel disease to Alzheimer’s, dementia

2024-06-21
SAN ANTONIO, June 21, 2024 – Research led by in part by The University of Texas Health Science Center at San Antonio (UT Health San Antonio) finds that the most common cerebral small-vessel disease feature seen in brain magnetic resonance imaging is a primary vascular factor associated with dementia risk. Results of the major international study emphasize the significance of that feature, known as white matter hyperintensity (WMH) burden, in preventive strategies for dementia. “Our findings provide converging evidence that WMH is a major vascular factor ...

Navigating the Pyrocene: Recent Cell Press papers on managing fire risk

2024-06-21
As wildfires become more intense and the fire season grows longer across parts of the world, humans will need to adapt. In this collection of papers from Cell Press journals One Earth and Cell Reports Sustainability, an intersection of fire management researchers comment on what needs to change to ensure we can collaborate across stakeholders in a more fire-resistant future. The papers are publishing in advance of a Cell Press 50th Anniversary sustainabiltiy forum on the topic of “Navigating the Pyrocene: Managing fire risk in a warming world.” The virtual event, free to register, takes place Thursday, July 11, 2024 at 11:00 am ET. This ...

Restoring the Great Salt Lake would have environmental justice as well as ecological benefits

Restoring the Great Salt Lake would have environmental justice as well as ecological benefits
2024-06-21
Inland seas around the world are drying up due to increasing human water use and accelerating climate change, and their desiccation is releasing harmful dust that pollutes the surrounding areas during acute dust storms. Using the Great Salt Lake in Utah as a case study, researchers show that dust exposure was highest among Pacific Islanders and Hispanic people and lower in white people compared to all other racial/ethnic groups, and higher for individuals without a high school diploma. Restoring the lake ...

Cannabis, tobacco use, and COVID-19 outcomes

2024-06-21
About The Study: The findings of this cohort study suggest that cannabis use may be an independent risk factor for COVID-19–related complications, even after considering cigarette smoking, vaccination status, comorbidities, and other risk factors.  Corresponding Author: To contact the corresponding author, Li-Shiun Chen, M.D., M.P.H., Sc.D., email li-shiun@wustl.edu. To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ (doi:10.1001/jamanetworkopen.2024.17977) Editor’s ...

LAST 30 PRESS RELEASES:

Samuel Pepys’ fashion prints reveal his guilty pleasure: Fancy French clothes

New genetic test will eliminate a form of inherited blindness in dogs

Cancer risk: Most Australian welders exposed to high levels of dangerous fumes

Two-in-one mapping of temperature and flow around microscale convective flows

Texas A&M engineers explore intelligence augmentation to improve safety

ORNL economist honored at international hydropower conference

UCLA selected by Centers for Medicare & Medicaid Services to test Medicare dementia care model

Fish adjust reproduction in response to predators

DDX41 and its unique contribution to myeloid leukemogenesis

Digital games on vaping devices could lure more youth to nicotine addiction

Cracking the code of hydrogen embrittlement

Long-term results from Testicular Cancer treatment are positive, study shows

EPA awards UMass Amherst nearly $6.4 million to help shrink the steel industry’s carbon footprint

Valentina Greco takes on new position as President of the ISSCR

Komen supports UVA Engineering researchers targeting ‘triple negative' breast cancer

Panel issues first guidelines to prevent anal cancer in people with HIV

Estimating rainfall intensity using surveillance audio and deep-learning

Targeting factors for chemoprevention and cancer interception to tackle mesothelioma

New snake discovery rewrites history, points to North America’s role in snake evolution

Large and unequal life expectancy declines in India during COVID-19

A study of 156,000 UK residents found that urban residents score the lowest in social and economic satisfaction and well-being

Global study by Hawaiʻi Institute of Marine Biology demonstrates benefit of marine protected areas to recreational fisheries

Researchers clarify how soft materials fail under stress

Revolutionizing the abilities of adaptive radar with AI

Plastic waste can now be converted to electronic devices

Health equity scholar Darrell Hudson named Health Behavior and Health Education chair at the University of Michigan School of Public Health

Research will establish best ‘managed retreat’ practices for communities faced with climate change disaster

Marshall University awarded grant to further fentanyl addiction research

Wash U researchers shine light on amyloid architecture

New dawn for space storm alerts could help shield Earth's tech

[Press-News.org] Pacific Northwest Research Institute uncovers hidden DNA mechanisms of rare genetic diseases
PNRI's landmark study reveals DNA rearrangement's role in genetic disorders, paving way for new treatments