Tag Archives: mutations

Comprehensive DNA Mapping for Enhanced Detection of Cancer-Causing Mutations – Sciworthy

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When researchers examine intricate human diseases like cancer, a crucial step involves comparing the DNA sequence of a affected individual to a template of genetic information from a healthy individual known as the reference genome. This process helps identify changes in the DNA, referred to as variations. Researchers strive to label the disease accurately to uncover its causes and how it responds to various treatments.

Since the year 2000, the prevailing human reference genome has been incomplete due to technological limitations in accessing challenging genomic regions. Consequently, some changes detected by scientists were false positives, complicating the identification of variants responsible for tumor growth.

In 2022, the Society of Scientists heralded the advent of the first truly complete human genome, employing a new methodology that is less fragmented than prior techniques. Since then, numerous researchers have begun to explore the benefits of utilizing this new genome in lieu of older reference genomes for studying complex genetic diseases like cancer.

Recent hypotheses from researchers in Canada and the United States suggest that the complete human genome can more accurately detect substantial mutations, or structural variants, providing superior cancer detection compared to standard reference genomes. If our genome were a textbook, these mutations would manifest as missing, added, or reversed paragraphs or pages. Studies have shown that structural mutations can lead to cancer by amplifying cancer-promoting genes, causing abnormal gene fusions, and disabling genes that naturally suppress cancer growth.

The researchers validated their hypothesis using established cancer cell lines in combination with a cancer-free control known as COLO829. This cell line serves as a benchmark for analyzing structural mutation data. The research team scrutinized four independent cell line samples sequenced by different laboratories and analyzed three tumor samples from patients with blood cancer, brain cancer, and ovarian cancer to assess their findings in a real-world clinical context. Additionally, they compared the cancer’s DNA sequence to both reference genomes and employed four distinct computational tools to identify structural variations.

The new complete human reference genome contains approximately 200 million additional base pairs of DNA sequence, addressing gaps and completing regions missing from the standard reference genome. Upon manual inspection of the COLO829 sample results, researchers noted a significant reduction in incorrectly identified structural variants—down from 225 to only 83 when utilizing the complete reference genome. This indicates a marked enhancement in our capability to detect structural variations.

While the new human reference genome has improved the accuracy of DNA change identification, it lacks the extensive medical annotations present in older reference genomes used to associate DNA changes with diseases. To bridge this gap, the researchers employed a tool called Levio SAM2 to match and lift over results between the new and old genomes. This strategy allows researchers to leverage the enhanced accuracy of new genomes while retaining the detailed medical knowledge linked to older genomes, effectively yielding the best of both worlds.

The integrated approach was applied to three patient samples, revealing that fewer cancer-specific mutation candidates necessitated manual clinical review compared to analyses based solely on standard reference genomes. The fewer candidates streamline the challenging process of pinpointing cancer-causing mutations amidst a myriad of false alarms. One notable mutation, spanning 609,000 base pairs and affecting a gene previously associated with several cancers, was detected in a patient’s sample. This variant exhibited a weak signal in the older reference genome but strong evidence in the new reference genome.

In conclusion, the researchers assert that their method optimizes the detection of structural mutations in cancer by minimizing false positives, aiding physicians in prioritizing clinically significant mutations. They emphasized that reducing false positives is vital for analyzing patient samples, as filtering out errant mutations to isolate genuine cancer drivers requires both time and expertise. Although their lifting strategy extended analysis time by approximately 50% compared to using only the older reference genome, researchers deemed this trade-off acceptable due to the substantial accuracy improvements observed.


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Study: Neanderthal-Inherited Genetic Mutations Decrease Major Muscle Enzyme Activity

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An AMPD1 variant from Neanderthals reduces enzyme activity by 25% in lab-produced proteins and up to 80% in muscles of genetically modified mice. This variant is present in all sequenced Neanderthals but absent in other species. It entered the modern human gene pool through interbreeding approximately 50,000 years ago, leading to its presence in up to 8% of today’s Europeans.

Maccak et al. Research indicates that genetic variants inherited from Neanderthals impair essential enzyme functions in muscle performance. Image credit: Holger Neumann/Neanderthal Museum.

The enzyme AMPD1 is crucial for muscle energy production and overall muscle function.

A decrease in its activity due to genetic mutations is the leading cause of metabolic myopathy in Europeans, with a prevalence of 9-14%.

In a recent study led by Dr. Dominik Macak from the Max Planck Institute for Evolutionary Anthropology, researchers compared ancient Neanderthal DNA with modern human genomes.

They discovered that all Neanderthals have specific AMPD1 variants absent in other species.

Enzymes produced in the lab with this variant exhibited a 25% decrease in AMPD1 activity.

In genetically modified mice, this reduction in muscle tissue activity reached 80%, negatively affecting enzyme performance.

Moreover, the study shows that modern humans acquired this variant from Neanderthals who lived in Europe and Western Asia before interacting with modern humans around 50,000 years ago.

Currently, approximately 1-2% of non-African individuals carry Neanderthal DNA.

The Neanderthal AMPD1 variant is found in 2-8% of Europeans today, indicating general acceptance in the gene pool.

“Interestingly, most individuals with these variants do not face serious health concerns,” noted Dr. McCuck.

“However, enzymes seem to significantly influence athletic performance.”

Analysis of over 1,000 elite athletes across diverse sports showed that those with non-functional AMPD1 are less likely to reach the highest athletic levels.

“Having defective AMPD1 enzymes decreases the chances of achieving elite athletic ability by half,” Dr. McCuck said.

While AMPD1 activity appears to have moderate significance in contemporary Western societies, it becomes crucial under extreme physical conditions, such as those faced by athletes.

Researchers highlight the need for studying genetic variation within physiological and evolutionary contexts to grasp biological implications.

“Cultural and technological advancements in both modern humans and Neanderthals may have lessened the necessity for extreme muscle performance,” explains Dr. Hugo Zeberg, a researcher at the Max Planck Institute for Evolutionary Anthropology and Karolinska Institute.

“Understanding how current gene variants influence human physiology can yield valuable insights into health, performance, and genetic diversity.”

Survey results were published in the journal Natural Communication on July 10, 2025.

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D. McCuck et al. 2025. Muscle AMPD1 exhibited reduced deaminase activity in Neanderthals compared to modern humans. Nat Commun 16, 6371; doi:10.1038/s41467-025-61605-4

Source: www.sci.news

Human eggs accumulate fewer mutations than previously believed.

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Like all cells, human eggs are subject to mutations

CC Studio/Science Photo Library

Research indicates that human eggs may be shielded from certain types of mutations associated with aging. In a recent study, scientists discovered that as women age, there are no signs of accumulating mutations in the mitochondrial DNA of their egg cells.

“When we consider age-related mutations, we typically think about older individuals having more mutations compared to younger ones,” notes Kateryna Makova from Pennsylvania State University. “However, this assumption doesn’t always hold true.”

Mitochondria, which provide the primary energy source for the body’s cells, are inherited solely from the mother. While mitochondrial DNA mutations are generally benign, they can sometimes result in complications that impact muscles and neurons, particularly due to their high energy demands. “Oocytes” [egg cells] serve as this biological reservoir,” explains Ruth Lehmann from Massachusetts Institute of Technology, who was not part of this study.

Prior research has shown that older mothers tend to pass down more chromosomal mutations, leading to the general assumption that a similar pattern exists with mitochondrial DNA mutations. To investigate this, Makova and her team utilized DNA sequencing to identify new mutations across 80 eggs sourced from 22 women aged 20 to 42 years.

The findings revealed that mitochondrial mutations in female eggs do not actually escalate with advancing age, unlike those found in salivary and blood cells. “It seems we have evolved a mechanism that mitigates the accumulation of mutations, allowing for their replication later in life,” remarks Makova.

Previous research has indicated that mitochondrial DNA mutations in macaque eggs showed an increase while their reproductive capacity remained stable until the animal reached about nine years of age. “It would be worthwhile to also study younger women. This could apply to humans as well,” comments team member Barbara Arbetuber from Penn State University.

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Source: www.newscientist.com

Shared DNA Mutations Impacting the Genome in Cancer Cells

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The human genome consists of approximately 3 billion DNA base pairs. If these base pairs were letters grouped together on a single line, they would fill more than 6,000 novels, too large to fit in a cell. Instead, some proteins organize and reform DNA into a more functional 3D structure called DNA. chromatin. These proteins regulate how different parts of the genome interact, controlling which genes are activated and which remain silent within each cell. One such protein is CCCTC binding factor or CTCF.

For CTCF to work, it must first bind to a specific spot on the DNA called CTCF. binding site. Scientists report that these CTCF binding sites behave differently in each scenario. Some lose their binding ability due to chemical interactions within the DNA, while others remain stable. Scientists call something stable Persistent CTCF binding site.

Scientists have previously reported that mutations in CTCF binding sites are common in cancer cells and disrupt the normal 3D structure of the genome. However, it was unclear whether these mutations were concentrated at persistence sites or what role they played. Australian researchers sought to understand mutations in persistent CTCF binding sites and how they affect different cancers.

To address these questions, the research team developed a computational tool based on machine learning models. CTCF-INSITE. Their tool uses genetic data and the interactions of organic compounds such as methyl in the genome to predict which CTCF binding sites are likely to persist even as CTCF protein levels decline. Researchers will use this tool to determine which persistent CTCF binding sites across the genome may be particularly vulnerable to mutations and whether these mutations are associated with cancer growth. I mapped it.

Using data from several human cell culture samples, including prostate cancer cells, breast cancer cells, and lung cancer cells, researchers developed a tool that allows them to distinguish between stable and unstable CTCF binding sites. trained. They exploited characteristics such as protein binding strength, the relative location of binding sites within the genome, and how distant regions of DNA interact to produce proteins.

The researchers then looked at mutation data from 12 types of cancer. International Cancer Genome Consortium. To avoid imbalance, we filtered out data entries with too few or too many mutations. Next, we applied CTCF-INSITE. A tool to test whether persistent CTCF binding sites are more likely to mutate in cancer cells than other CTCF binding sites.

They found significantly more mutations in persistent CTCF binding sites in all cancer types examined. This means that there were more mutations at these sites than would be expected by random chance. The researchers noted that the mutations were specific to the CTCF binding site, rather than in parts of the DNA close to it. They also reported that these mutations were more prominent in breast and prostate cancer cells than in other types of cancer.

The researchers also sought to understand whether these mutations alter the 3D structure of the genome. Using experimental techniques such as fluorescence imaging, they examined some of these cancer-specific mutations and found that many of them alter the genome structure and reduce the strength and effectiveness of CTCF binding. It turned out that. They explained that this reduction could affect gene expression in a way that promotes cancer growth.

The researchers emphasized that their findings were not limited to one or two types of cancer, as similar results were found for stomach, lung, prostate, breast and skin cancers. Although the exact mutation patterns vary between cancers, persistent CTCF binding sites were reported to have consistently higher mutations overall.

The researchers concluded that their findings may help other cancer researchers understand similarities in the onset and progression of multiple cancer types. They also proposed that their machine learning tools could provide future researchers with CTCF binding site candidates relevant to experiments investigating undocumented causes of cancer.


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Source: sciworthy.com

Kuhl: Genetic Mutations Could Provide Protection Against Brain Diseases Linked to Cannibalism

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Cerebellum of a person suffering from kuru disease

Liberski PP (2013)

Genetic research in a very remote community in Papua New Guinea has revealed new insights into a brain disease that is spread when people eat dead relatives and has killed thousands of people over two decades.

Dotted with mountains, gorges, and fast-flowing rivers, Papua New Guinea’s Eastern Highlands province is extremely isolated from the rest of the world, and it wasn’t until the beginning of the 20th century that outsiders realized that about 1 million people lived there.

Some tribes known as the Fore practiced a form of cannibalism called “funeral feasts,” in which they consumed the bodies of their deceased relatives as part of their funeral rites. This could mean they ingested an abnormally folded protein called a prion, which can cause a fatal neurodegenerative condition called kuru associated with Creutzfeldt-Jakob disease (CJD). However, the local people believed that the Kuru phenomenon was caused by witchcraft. At least 2,700 Kuru deaths have been recorded in the eastern highlands.

Simon Mead Researchers at University College London examined the genomes of 943 people representing 68 villages and 21 language groups in the region. Although this region of Papua New Guinea covers just over 11,000 square kilometers, smaller than Jamaica, researchers say the different groups are as genetically different as the peoples of Finland and Spain, some 3,000 kilometers apart.

The study found that not everyone who attended the funeral died from the disease. Mead and his colleagues say it appears communities were beginning to develop a resistance to kuru, which led to tremors, loss of coordination, and, ultimately, death.

The study found that some of the elderly women who survived the feast had mutations in the gene encoding the prion protein, which likely conferred resistance to kuru disease.

By the 1950s, funeral feasts had become illegal, and the kuru epidemic began to subside, but visitors say that the number of women in some villages had dwindled because so many women had died from kuru. It pointed out. Mead said women and children are most susceptible to the disease, likely because they ate the brains of deceased relatives.

However, genetic evidence shows that despite fears of the disease, there was a large influx of women into Fora tribal areas, particularly in areas where the highest levels of kuru were present.

“We believe it is likely that the sexual prejudice caused by Kuru caused single men in Kuru-affected communities to look further afield for wives than usual because they were unable to find potential wives locally. “We will,” Meade said.

He said the team wants to understand what factors confer resistance to prion diseases such as CJD, which caused a severe epidemic in the UK in the 1990s.

“[Our work sets] “This is a site to detect genetic factors that may have helped the Fore people resist kuru,” Mead said. “Such resistance genes may suggest therapeutic targets.”

Ira Debson Researchers from the Garvan Institute of Medical Research in Sydney, Australia, say the study provides new insight into the “rich and unique cultural, linguistic and genomic diversity” of the Eastern Highlands region.

“This is a demonstration of how genomics can be used to look almost back in time, reading the genetic signature of past epidemics and understanding how they have shaped today’s populations. It helps.”

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Source: www.newscientist.com

Kuhl: Genetic mutations could provide protection against brain diseases linked to cannibalism

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Cerebellum of a person suffering from kuru disease

Liberski PP (2013)

Genetic research in a very remote community in Papua New Guinea has revealed new insights into a brain disease that is spread when people eat dead relatives and has killed thousands of people over two decades.

Dotted with mountains, gorges, and fast-flowing rivers, Papua New Guinea’s Eastern Highlands province is extremely isolated from the rest of the world, and it wasn’t until the beginning of the 20th century that outsiders realized that about 1 million people lived there.

Some tribes known as the Fore practiced a form of cannibalism called “funeral feasts,” in which they consumed the bodies of their deceased relatives as part of their funeral rites.

This could mean they ingested an abnormally folded protein called a prion, which can cause a fatal neurodegenerative condition called kuru associated with Creutzfeldt-Jakob disease (CJD). there was. However, local people believed that the Kuru phenomenon was caused by witchcraft. At least 2,700 Kuru deaths have been recorded in the eastern highlands.

simon mead Researchers at University College London examined the genomes of 943 people representing 68 villages and 21 language groups in the region. Although this region of Papua New Guinea covers just over 11,000 square kilometers, smaller than Jamaica, researchers say the different groups are as genetically different as the peoples of Finland and Spain, some 3,000 kilometers apart. ing.

The study found that not everyone who attended the funeral died from the disease. Meade and his colleagues say it appears that communities were beginning to develop a resistance to kuru, which led to tremors, loss of coordination and, ultimately, death.

The study found that some of the elderly women who survived the feast had mutations in the gene encoding the prion protein, which likely conferred resistance to kuru disease.

By the 1950s, funeral feasts had become illegal and the kuru epidemic began to subside, but visitors say that the number of women in some villages had dwindled because so many women died from kuru. It pointed out. Mead said women and children are most susceptible to the disease, likely because they ate the brains of deceased relatives.

However, genetic evidence shows that despite fears of the disease, there was a large influx of women into Fora tribal areas, particularly in areas where the highest levels of kuru were present.

“We believe it is likely that the sexual prejudice caused by Kuru caused single men in Kuru-affected communities to look further afield for wives than usual because they were unable to find potential wives locally. “We will,” Meade said.

He said the team wants to understand what factors confer resistance to prion diseases such as CJD, which caused a severe epidemic in the UK in the 1990s.

“[Our work sets] “This is a site to detect genetic factors that may have helped the Fore people resist kuru,” Mead said. “Such resistance genes may suggest therapeutic targets.”

Ira Debson Researchers from the Garvan Institute of Medical Research in Sydney, Australia, say the study provides new insight into the “rich and unique cultural, linguistic and genomic diversity” of the Eastern Highlands region.

“This is a demonstration of how genomics can be used to almost look back in time, reading the genetic signature of past epidemics and understanding how they have shaped today’s populations. It helps.”

topic:

Source: www.newscientist.com

Rare genetic mutations may enhance treatment efficacy for migraine headaches

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Migraines can cause debilitation

Nikki Lloyd/Getty Images

An analysis of the genomes of 1.3 million people has revealed dozens of variations associated with migraine, which could lead to more effective treatments for migraines.

Up to 20% of adults worldwide are thought to experience migraines. Migraines are recurring headaches that are often difficult to treat and can interfere with daily life. Some people have sensory symptoms, such as flashing lights or tingling in the body, before the headache begins, but others do not. It is not known why these two types of migraine, known as migraine with aura and migraine without aura, exist.

“While it is well known that migraines run in families, it has not been easy to identify a clear genetic basis for each subtype,” he says. Debbie Hay at the University of Otago in New Zealand.

now, Kari Stephenson Researchers from the Icelandic biopharmaceutical company deCODE Genetics have identified a genetic variation that appears to influence whether people develop migraines.

Researchers analyzed the DNA of 1.3 million people in Iceland, Denmark, the UK, the US and Norway, and found that around 80,000 of them had experienced migraines.

They discovered 44 genetic mutations associated with the condition, 12 of which had never been reported before. Among these, the research team PRRT2 Genes that help control signaling between neurons are correlated with a greater risk of migraine with aura and epilepsy.

the other A rare mutant that suppresses the function of a gene SCN11A and KCNK5which play a role in transporting sodium and potassium between cells, respectively, and appear to prevent both types of migraines.

The discovery could lead to new treatments that target the causes of migraines, such as drugs that can inhibit the production of a protein encoded by migraines. SCN11A and KCNK5 gene.

“Findings like this should bring great hope to people who suffer from migraine,” Stefansson said. “Current treatments cannot completely eliminate the tendency to develop migraines, so there is a lot of room for better treatments.”

“While great advances have been made in migraine treatment recently, there is still much work to be done in understanding the mechanisms of migraine and how to tailor treatment to each patient,” Hay says.

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Source: www.newscientist.com