Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: genetics – Page 8

Analysis of genomic heterogeneity and the mutational landscape in cutaneous squamous cell carcinoma through multi-patient-targeted single-cell DNA sequencing

Cutaneous squamous cell carcinoma (CSCC) is a prevalent skin cancer with aggressive progression that poses significant challenges, especially in metastatic cases. Single-cell DNA sequencing (scDNA-seq) has become an advanced technology for elucidating tumor heterogeneity and clonal evolution. However, comprehensive scDNA-seq studies and tailored mutation panels for CSCC are lacking.

We analyzed the genomic landscape of Chinese CSCC patients via a Multi-Patient-Targeted (MPT) scDNA-seq approach. This method combined bulk exome sequencing with Tapestri scDNA-seq. Mutations identified through bulk sequencing were used to design a targeted panel for scDNA-seq. Comparative analysis was conducted to explore the associations between specific gene mutations and clinical characteristics such as tumor stage and patient sex. Clonal evolution analysis was performed to understand the evolutionary trajectories of the tumors.

Bulk sequencing revealed a diverse spectrum of somatic mutations in CSCC tumors, with missense mutations being predominant. The top tumor mutations, such as those in NOTCH1, TP53, NOTCH2, TTN, MUC16, RYR2, PRUNE2, DMD, HRAS, and CDKN2A, presented similar frequencies to those reported in studies in Korean and Caucasian populations. However, the mutation frequencies of HRAS, TTN, MUC16 and MUC4 were significantly different from the Korean and Caucasian populations. Comparative analysis revealed associations between specific gene mutations and clinical characteristics such as tumor stage and patient sex. Clonal evolution analysis via scDNA-seq revealed distinct evolutionary trajectories and their potential correlation with tumor development and patient prognosis. Furthermore, scDNA-seq identified two low-frequency mutation clones, NLRP5 and HMMR, which play important roles in the clonal evolution of CSCC.

“A Google for DNA”: Scientists Launch Groundbreaking Search Engine for Genetic Code

A new tool developed at ETH Zurich, MetaGraph, allows scientists to search through vast public DNA and RNA databases in seconds — like a “Google for DNA.” DNA sequencing has transformed biomedical research, making it possible to identify rare hereditary disorders in patients and pinpoint specific

P53 in the DNA-Damage-Repair Process

The cells in the human body are continuously challenged by a variety of genotoxic attacks. Erroneous repair of the DNA can lead to mutations and chromosomal aberrations that can alter the functions of tumor suppressor genes or oncogenes, thus causing cancer development. As a central tumor suppressor, p53 guards the genome by orchestrating a variety of DNA-damage-response (DDR) mechanisms. Already early in metazoan evolution, p53 started controlling the apoptotic demise of genomically compromised cells. p53 plays a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability. In addition, p53 took on diverse roles to also directly impact the activity of various DNA-repair systems. It thus appears as if p53 is multitasking in providing protection from cancer development by maintaining genome stability.

What’s The Biochemistry Of Fitness In 80yr Olds?

Join us on Patreon! https://www.patreon.com/MichaelLustgartenPhD

Discount Links/Affiliates:
Blood testing (where I get the majority of my labs): https://www.ultalabtests.com/partners/michaellustgarten.

At-Home Metabolomics: https://www.iollo.com?ref=michael-lustgarten.
Use Code: CONQUERAGING At Checkout.

Clearly Filtered Water Filter: https://get.aspr.app/SHoPY

Epigenetic, Telomere Testing: https://trudiagnostic.com/?irclickid=U-s3Ii2r7xyIU-LSYLyQdQ6…M0&irgwc=1
Use Code: CONQUERAGING

NAD+ Quantification: https://www.jinfiniti.com/intracellular-nad-test/

Continue reading “What’s The Biochemistry Of Fitness In 80yr Olds?” | >

Fundamental engineering principles can help identify disease biomarkers more quickly

People often compare the genome to a computer’s program, with the cell using its genetic code to process environmental inputs and produce appropriate responses.

But the machine metaphor can be extended even further to any , and applying established concepts of engineering to biology could revolutionize how scientists make their observations within biology, according to research from University of Michigan.

In a paper published in Proceedings of the National Academy of Sciences, Indika Rajapakse, Ph.D., Joshua Pickard, Ph.D. (now an Eric and Wendy Schmidt Postdoctoral Fellow at the Broad Institute), and their team propose that fundamental principles of and observability can be applied to study that change over time.

DNA repair mechanisms help explain why naked mole-rats live a long life

Naked mole-rats are one of nature’s most extraordinary creatures. These burrowing rodents can live for up to 37 years, around ten times longer than relatives of a similar size. But what is the secret to their extreme longevity? How are they able to delay the decay and decline that befalls other rodents? The answer, at least in part, is due to a switch in a common protein that boosts DNA repair, according to new research published in the journal Science.

One of the main causes of aging in all animals, including humans, is the accumulation of damaged DNA, our genetic instruction manual. When this damage is not fixed, it leads to , damaged proteins and eventually a breakdown in the body’s functions.

To understand how the naked mole-rat is so resistant to DNA damage, a study led by researchers at Tongji University in China focused on a common protein called cGAS (cyclic GMP-AMP synthase). In most mammals, cGAS interferes with DNA repair, but the researchers suspected it may have evolved a different function in the long-living rats.

New tool offers single-cell study of specific genetic variants

Scientists have long suspected connections between heredity and disease, dating back to Hippocrates, who observed certain diseases “ran in families.” However, through the years, scientists have kept getting better at finding ways to also understand the source of those genetic links in the human genome.

EMBL scientists and collaborators have now developed a tool that goes beyond current single-cell technology by capturing genomic variations and RNA together in the same cell, increasing precision and scalability compared to previous technologies. Able to determine variations in non-coding regions of the genome, this tool transforms how scientists can study the parts of DNA where variations linked to disease are most likely to occur. This single-cell tool, with its high precision and throughput, represents an important advance in drawing correlations between genetic variants and disease.

“This has been a long-standing problem, as current single-cell methods to study DNA and RNA in the same cell have had limited throughput, lacked sensitivity, and are complicated,” said Dominik Lindenhofer, the lead author on a new paper about SDR-Seq published in Nature Methods and a postdoctoral fellow in EMBL’s Steinmetz Group.

Genetically engineered pig-to-human liver xenotransplantation

The advent of genetically edited porcine-to-human xenotransplantation has predominantly focused on cardiac and renal applications, with no reported cases of porcine-to-human liver xenotransplantation. This study presents the world’s first successful genetically modified pig auxiliary liver xenotransplantation in a living human, achieving an unprecedented survival of 171 days, and provides valuable insights into the critical factors influencing the procedure’s success.

/* */