Genetics

Clinical Utility of GBinsight Comprehensive Genetic Testing Showcased at the 2020 National Lipid Association’s Scientific Sessions – PR Web

"GBinsight reflects the biological complexity of humans and, through comprehensive genetic testing and analysis, facilitates precise diagnosis and targeted treatment and prevention," said Dr. Mendel Roth, Senior Scientist at GBinsight.

SAN DIEGO (PRWEB) December 17, 2020

Genetics was a major theme of the National Lipid Associations (NLA) Scientific Sessions, December 2020. Genetic testing for lipid disorders, polygenic risk scores for atherosclerotic cardiovascular disease (ASCVD) and the implications of genetics on clinical care, medical ethics and identifying individuals at high risk and preventive strategies were among the headlining topics. The clinical utility of GBinsight comprehensive genetic testing and analysis was highlighted by several leading physicians and scientists throughout the sessions.

Dr. Christie M. Ballantyne, Professor of Medicine and Genetics at Baylor College of Medicine, started off his presentation reflecting on the current state of clinical cardiovascular genetics, noting how wonderful it is to see where we are now and what the impact of genetics will be on how we practice preventive cardiology. Dr. Ballantyne then reinforced the statements of a previous presenter and another client of GBinsight, Dr. Zahid Ahmed, Assistant Professor of Medicine at the University of Texas, Southwestern, highlighting the clinical benefits of genetic testing for dyslipidemias and ASCVD patients including how definitive diagnoses increase the likelihood of payer coverage and provide more accurate risk stratification, enhance cascade screening that may prompt initiation of therapies at an earlier age, and allow for more precise medication regimens.

Drs. Christie Ballantyne and Zahid Ahmed, both GBinsight collaborators, emphasized that there is a 50% chance of passing on heterozygous familial hypercholesterolemia (FH) to ones children. Genetic testing is the preferred method for screening young family members of adults with FH. The earlier a person is diagnosed, the sooner he or she can begin lifestyle and drug therapies that reduce risk of ASCVD.

The clinical applications of GBinsight were demonstrated by several presentations and posters from Baylor College of Medicine, UT Southwestern, and the University of Pennsylvania. Case studies of patients referred for severe hypertriglyceridemia, pancreatitis, and type 2 diabetes were showcased. GBinsight's Comprehensive Dyslipidemia Panel identified pathogenic genetic variants causal for familial partial lipodystrophy (FPLD) in these patients and allowed physicians to identify precise diagnoses and offer precise therapies. GBinsight analyzes the multitude of pathways that cause severe hypertriglyceridemia beyond LPL deficiency.

GBinsight recognizes the biological complexity and heterogeneity of humans and, through comprehensive genetic analysis, facilitates precise diagnosis. GBinsight comprehensively analyzes the genetics of the multitude of pathways that can cause dyslipidemia and ASCVD in a single assay, said Dr. Mendel Roth, Senior Scientist at GBinsight.

GBinsight differentiates itself from other genetic testing services in several important ways: 1) Since ASCVD risk is ultimately determined by additive risk factors, GBinsight analyzes broad risk categories within a single comprehensive assay. This includes hypercholesterolemia, hypertriglyceridemia, reverse cholesterol transport defects, high Lp(a), homocysteinemia, familial obesity and familial diabetes. The analysis includes copy number variations that are a common cause of dyslipidemias. 2) Analyzes both rare, large-effect sized, monogenic variants largely in coding and splicing regions of genes as well as common, small-to-moderate-effect sized variants that contribute to polygenic risk in a single assay. 3) This assay includes full coverage of the APOE gene that is an underappreciated genetic cause of dyslipidemias and ASCVD. The APOE gene presents a technical challenge in getting quality sequencing results. 4) Analyzes both single nucleotide polymorphisms (SNP) known to increase and decrease Lp(a) levels as well as directly quantifies the variable Kringle-IV region. 5) Analyzes pharmacogenomics including the multiple genetic causes of statin intolerance.

GBinsight is the only next-generation sequencing (NGS) test that can directly quantify the variable region within the LPA gene which is the single greatest cause of high Lp(a), said Dr. Roth. GBinsight employs a machine-learning algorithm that assesses the comprehensive genetic basis of high Lp(a).

GBinsights scientific team has collaborated with key clinical opinion leaders to explore and validate the clinical utility of comprehensive genetic analysis for dyslipidemia and ASCVD. For example, using monogenic and polygenic analysis, up to 80% of patients referred to GBinsight for FH and other dyslipidemias was correctly identified. Of those with high Lp(a), validation results showed an overall accuracy of 84% with a sensitivity of 82% and specificity of 87%. Including the direct quantitation of the variable polymorphism increased the accuracy call by 23 percentage points. These results were formulated in partnerships with Drs. Christie M. Ballantyne, Michael Davidson at University of Chicago, Patrick Moriarty at University of Kansas, and Sotirios Tsimikas of University of California, San Diego and presented at the NLA Scientific Sessions.

GBinsight NGS services are performed at a CLIA-certified and medically licensed genetic testing laboratory using Illuminas HiSeq platform.

GBinsights Test Catalog includes the following:

Because genetic risk for most common metabolic diseases can be mitigated by dietary and lifestyle factors, in addition to GBinsight comprehensive genetic analysis, GB HealthWatch also developed the HealthWatch 360 mobile app for delivering dietary and lifestyle interventions to the general population. The app works in conjunction with the HealthWatch 360 Research Portal, which allows researchers to manage and analyze the diet, exercise and health data collected with the mobile app. Integration of GBinsight genetics panels with the research portal advantageously enables researchers to study gene-gene and gene-lifestyle interactions in observational and interventional cohort trials. With this system, prevention and medical intervention strategies, and especially dietary interventions, for complex diseases can be experimented with, validated and refined. Given the epidemic of diet-induced chronic diseases in the United States and worldwide, it is imperative that we focus our efforts on precision nutrition as a key preventive strategy for improving the health of our future.

GBinsight was developed by GB HealthWatch in partnership with the Otogenetics Corporation, a CLIA-certified and licensed medically licensed genetic testing company.

About GB HealthWatchGB HealthWatch is a nutritional genomics company. We develop state-of-the-art technologies to facilitate research on the molecular mechanisms, clinical efficacy and cost-effectiveness of translating genetic insights into personalized prevention and treatment strategies for complex diseases. GB HealthWatch offers the following tools:

About Otogenetics CorporationOtogenetics Corporation is a CLIA-certified and licensed medical genetic testing company specializing in next generation sequencing services. Otogenetics offers high quality services for genome, exome, and RNA-seq for government and academic institutions, biotechnology and pharmaceutical companies, as well as medical doctors and clinics. Additional services and products provided by Otogenetics Corporation can be found at: http://www.otogenetics.com

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Clinical Utility of GBinsight Comprehensive Genetic Testing Showcased at the 2020 National Lipid Association's Scientific Sessions - PR Web

Genetics

CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes – Science Magazine

CiBER-seq dissects genetic networks

Cells integrate environmental signals and internal states to dynamically control gene expression. Muller et al. developed a technique to dissect this cellular logic by linking targeted, genome-wide genetic perturbations with a deep-sequencing readout that quantitatively measured the expression phenotype induced by each perturbation. The method, dubbed CiBER-seq, was able to recapitulate known regulatory pathways linking protein synthesis with nutrient availability in budding yeast cells. Unexpectedly, the authors found that the cellular logic also appears to consider protein production machinery in this decision. By uncovering additional facets of this deeply conserved pathway, the findings demonstrate the utility of comprehensive and quantitative CiBER-seq profiling in mapping the gene networks underlying cellular decisions.

Science, this issue p. eabb9662

Systematically profiling the effects of genetic perturbations is a powerful approach that has revealed the molecular basis for a wide range of biological phenomena. The simple, programmable DNA recognition of CRISPR-Cas9 enables genome-wide genetic analysis in human cells and many other systems. Cas9 is guided by a short RNA to a complementary sequence in the genome, where it can introduce mutations or alter gene expression. Pooled libraries of guide RNAs (gRNAs) that individually target each gene in the genome allow us to introduce genetic perturbations systematically into a population of cells. A key challenge is measuring the phenotypic effects caused by individual guides in these pooled libraries and linking these phenotypes back to the associated gRNA, thereby finding the gene that is responsible.

Molecular phenotypes such as gene expression changes provide a clear and sensitive measure for many cellular processes. We sought a general approach to profile how the expression of a particular gene of interest changed when other genes were perturbed. We began with a library of gRNAs, each disrupting one gene, and linked these guides with an expression reporter containing a guide-specific nucleotide barcode. gRNAs that alter reporter expression will change the abundance of the expressed RNA barcode specifically associated with that guide. Deep sequencing of these expressed barcodes quantifies each of these guide-specific reporter expression effects individually within a pooled, complex population. We have implemented this strategy by combining CRISPR interference (CRISPRi) with barcoded expression reporter sequencing (CiBER-seq).

We used CiBER-seq to profile the responses of several yeast promoters tied to a range of biological functions. Each promoter yielded a distinct pattern of responses that could be understood in terms of its known function and regulation. For example, we rediscover the control of MET6 expression by regulatory ubiquitylation and connect the bud scar protein Cwp1 to other genes required for budding and cytokinesis. Our analysis of the HIS4 promoter, a well-characterized target of the integrated stress response, yielded a range of genetic perturbations that activate this pathway by causing the accumulation of uncharged transfer RNAs (tRNAs). We also uncovered a notable role for tRNA depletion in this response, as impaired tRNA biogenesis activated HIS4 expression through a distinct pathway. In order to understand this regulation, we carried out genetic interaction analysis and looked for quantitative deviations in CiBER-seq profiles caused by the introduction of a second genetic perturbation. We also developed an indirect CiBER-seq approach to measure translational and posttranslational regulation, which both play roles in the signaling pathways upstream of HIS4.

CiBER-seq produces comprehensive phenotypic profiles that offer insights into gene function and regulation. These high-throughput and quantitative phenotypic measurements are also well suited for the systematic measurement of genetic interactions, which contain rich information about the operation of biological processes. This approach can be applied to study a wide range of transcriptional, translational, and posttranslational regulatory responses, and it has the potential to shed light on many areas of biology.

CRISPR-Cas9 gRNA cassettes are linked with transcriptional reporters containing specific barcodes. The RNA-to-DNA ratio for each barcode, measured by deep sequencing, reveals the reporter expression phenotype induced by each gRNA.

To realize the promise of CRISPR-Cas9based genetics, approaches are needed to quantify a specific, molecular phenotype across genome-wide libraries of genetic perturbations. We addressed this challenge by profiling transcriptional, translational, and posttranslational reporters using CRISPR interference (CRISPRi) with barcoded expression reporter sequencing (CiBER-seq). Our barcoding approach allowed us to connect an entire library of guides to their individual phenotypic consequences using pooled sequencing. CiBER-seq profiling fully recapitulated the integrated stress response (ISR) pathway in yeast. Genetic perturbations causing uncharged transfer RNA (tRNA) accumulation activated ISR reporter transcription. Notably, tRNA insufficiency also activated the reporter, independent of the uncharged tRNA sensor. By uncovering alternate triggers for ISR activation, we illustrate how precise, comprehensive CiBER-seq profiling provides a powerful and broadly applicable tool for dissecting genetic networks.

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CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes - Science Magazine

Genetics

Oklahoma researchers looking for additional patients across the US with rare genetic mutation – KFOR Oklahoma City

OKLAHOMA CITY (KFOR) Behind one Oklahoma 8-year-olds infectious smile is a fighter.

Im smaller than most people, said Madison Cain.

Madison was born smaller than most babies, too, at 5 lbs. 9 oz.

She was teeny tiny, she calls herself a little itty-bitty baby,said Madisons mom, Melissa Cain.

For Madisons first year, Melissa says there werent many issues.

Around 15 months or so she quit growing in length, she quit gaining weight, and so that began our journey to figure out what was going on, said Melissa.

The Tulsa residents had no idea what this journey would entail.

By age two, Madison was diagnosed with hip dysplasia and cataracts.

She got those initial diagnoses treated, but still wasnt growing.

Then we really started thinking this isnt all adding up she doesnt grow, she has the hip thing, she has cataracts, there has to be something, said Melissa.

The family started genetic testing, while Madisons symptoms persisted.

Still low energy not growing well, said Melissa. She couldnt keep up with her peers, you know running and things werent the same we were doing all kinds of things and just not a lot of answers.

The Cains spent hours researching, and even more time at the doctors office, but it was years of dead ends.

No energy, sleeping 16 hours a day barely making it through school, not gaining any weight, said Melissa.She was 5 and weighed about 25-28 pounds, but she is the most easy going, not stressed out, tough child.

Madisons strength paid off.

A break-through finally coming in 2019.

The genetics doctor called and said here this is what it is, theres one published paper, with a patient with this. Its not her, so well just put it in a database and see if anything ever hits, said Melissa.

But as a nurse practitioner herself, Melissa sat down and read the article.

She realized it was written by doctors, just down the turnpike, at the Oklahoma Medical Research Foundation.

This is a new disease and were the first ones that discovered it, said Dr. Lijun Xia,Member and Chair, Cardiovascular Biology Research Program at OMRF.

Madison has rare gene mutation to the MBTPS1 gene.

Madison, inherited a wrong copy from her mother and the father so, therefore even though she has two copies of the gene both are wrong both have mutation, said Dr. Xia.

The mutation, resulted in a condition called Spondyloepiphyseal Dysplasia, Kondo-Fu type, or SEDKF for short.

The condition named after two of Oklahomas scientists.

The disorder hinders Madisons bone growth and development.

This is a very rare genetic disease,said Dr. Xia.

There are only two known cases in the state, Madisons and another girl named Sydney in Yukon, who was the first diagnosed.

Since publishing the article, OMRF now knows of about eight cases worldwide.

We have one contact us from Germany, one from Brazil, and theres also one from San Francisco, said Dr. Xia.

Doctors think that could be because many patients are misdiagnosed.

The mutation can also affect every patient differently.

However, theres hope on the horizon.

Researchers have come up with a possible treatment but need 50 patients for a clinical trial.

Now theyre searching for cases across the country.

Of course, I wish that we had the answer plus enough patients to do a trial and see if the treatment would work and Im hopeful that we can get there before her bones stop growing, said Cain.

The protein used for treatment has already been approved by the FDA to treat a different disease.

Researchers have tested the treatment on mice successfully.

For Madison, this treatment could mean everything.

It could change our life and change her life for the rest of her life, said Cain. We never thought weve get a Madison, but theres no one like Madison.

For more information visit the OMRF website.

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Oklahoma researchers looking for additional patients across the US with rare genetic mutation - KFOR Oklahoma City

Genetics

Genetic interaction mapping informs integrative structure determination of protein complexes – Science Magazine

From phenotype to structure

Much insight has come from structures of macromolecular complexes determined by methods such as crystallography or cryoelectron microscopy. However, looking at transient complexes remains challenging, as does determining structures in the context of the cellular environment. Braberg et al. used an integrative approach in which they mapped the phenotypic profiles of a comprehensive set of mutants in a protein complex in the context of gene deletions or environmental perturbations (see the Perspective by Wang). By associating the similarity between phenotypic profiles with the distance between residues, they determined structures for the yeast histone H3-H4 complex, subunits Rpb1-Rpb2 of yeast RNA polymerase II, and subunits RpoB-RpoC of bacterial RNA polymerase. Comparison with known structures shows that the accuracy is comparable to structures determined based on chemical cross-links.

Science, this issue p. eaaz4910; see also p. 1269

Determining the structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo quantitative measurements of genetic interactions. Genetic interactions report on how the effect of one mutation is altered by the presence of a second mutation and have proven effective for identifying groups of genes or residues that function in the same pathway. The point mutant epistatic miniarray profile (pE-MAP) platform allows for rapid measurement of genetic interactions between sets of point mutations and deletion libraries. A pE-MAP is made up of phenotypic profiles, each of which contains all genetic interactions between a single point mutant and the entire deletion library.

We observe a statistical association between the distance spanned by two mutated residues in a protein complex and the similarity of their phenotypic profiles (phenotypic similarity) in a pE-MAP. This observation is in agreement with the expectation that mutations within the same functional region (e.g., active, allosteric, and binding sites) are likely to share more similar phenotypes than those that are distant in space. Here, we explore how to use these associations for determining in vivo structures of protein complexes using integrative modeling.

We generated a large pE-MAP by crossing 350 mutations in yeast histones H3 and H4 against 1370 gene deletions (or hypomorphic alleles of essential genes). The phenotypic similarities were then used to generate spatial restraints for integrative modeling of the H3-H4 complex structure. The resulting ensemble of H3-H4 configurations is accurate and precise, as evidenced by its close similarity to the crystal structure. This finding indicates the utility of the pE-MAP data for integrative structure determination. Furthermore, we show that the pE-MAP provides a wealth of biological insight into the function of the nucleosome and can connect individual histone residues and regions to associated complexes and processes. For example, we observe very high phenotypic similarities between modifiable histone residues and their cognate enzymes, such as H3K4 and COMPASS, or H3K36 and members of the Set2 pathway. Furthermore, the pE-MAP reveals several residues involved in DNA repair and others that function in cryptic transcription.

We demonstrate that the approach is transferable to other complexes and other types of phenotypic profiles by determining the structures of two complexes of known structure: (i) subunits Rpb1 and Rpb2 of yeast RNA polymerase II, using a pE-MAP of 53 point mutants crossed against 1200 deletions and hypomorphic alleles; and (ii) subunits RpoB and RpoC of bacterial RNA polymerase, using a chemical genetics map of 44 point mutants subjected to 83 environmental stresses. The accuracy and precision of the models are comparable to those based on chemical cross-linking, which is commonly used to determine protein complex structures. Moreover, the accuracy and precision improve when using pE-MAP and cross-linking data together, indicating complementarity between these methods and demonstrating a premise of integrative structure determination.

We show that the architectures of protein complexes can be determined using quantitative genetic interaction maps. Because pE-MAPs contain purely phenotypic measurements, collected in living cells, they generate spatial restraints that are orthogonal to other commonly used data for integrative modeling. The pE-MAP data may also enable the characterization of complexes that are difficult to isolate and purify, or those that are only transiently stable. Recent advances in CRISPR-Cas9 genome editing provide a means for extending our platform to human cells, allowing for identification and characterization of functionally relevant structural changes that take place in disease alleles. Expanding this analysis to look at structural changes in host-pathogen complexes and how they affect infection will also be feasible by introducing specific mutations into the pathogenic genome and studying the phenotypic consequences using genetic interaction profiling of relevant host genes.

pE-MAPs are generated by measuring the growth of yeast colonies (left) and visualized as a heatmap (background). We present an application of pE-MAPs to determine protein complex structures, using integrative modeling, and apply it to histones H3 and H4 (right) and other complexes. H3 (purple) and H4 (teal) are highlighted in the context of the nucleosome [gray, modified Protein Data Bank (PDB) 1ID3].

Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on ~500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations.

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Genetic interaction mapping informs integrative structure determination of protein complexes - Science Magazine

Genetics

All of Us Returns First Genetic Results To Participants – Bio-IT World

By Bio-IT World Staff

December 10, 2020 | The All of Us Research Program has begun to return genetic results to participants who have donated biosamples for research, NIH announced. The program prioritizes information return to its research volunteers. Initially, participants can choose to receive information about their genetic ancestry and traits, with health-related results available at a later date.

The All of Us Research Program is working to build a diverse community of 1 million or more participant partners across the U.S. to help researchers learn more about how genetics, environment and lifestyle factors affect health outcomes. So far, more than 270,000 people have contributed biosamples and more than 80% come from communities that are historically underrepresented in biomedical research. These include racial and ethnic minorities, sexual and gender minorities, and other groups.

Participants can also share data via surveys and their electronic health records. Data are stripped of personal identifiers and made available for research through the All of Us Research Hub.

As part of its core values, the program is committed to ensuring that participants have access to their own information, and many participants have expressed a strong desire to understand what their DNA can tell them.

Were changing the paradigm for research, said Josh Denny, M.D., All of Uss chief executive officer, in the announcement. Participants are our most important partners in this effort, and we know many of them are eager to get their genetic results and learn about the science theyre making possible. Were working to provide that valuable information in a responsible way.

The program's in-depth genetic analyses include both whole genome sequencing and genotyping. To return genetic information, the program has developed a robust informed consent process, giving participants information and choice about whether or not to receive results and which results they want to get back. The program also provides access to genetic counselors to help answer questions from participants and their health care providers.

All of Us teamed up with a network of awardees across the country to support this work, including the health technology company Color (Color received an initial $4.6 million in funding in August 2019) and a set of leading genome centers: Baylor College of Medicine, the Broad Institute and the Northwest Genomics Center at the University of Washington, with their partners.

With the All of Us Research Program, were beginning to return results for a genomics program that is of unprecedented scale, said Alicia Zhou, Ph.D., chief science officer at Color. For a long time, the research community has recruited participants into large-population genomics studies without returning any results back to them. With All of Us, weve provided the tools to do just thatin a convenient and accessible way. We now have a real opportunity to return value to participants.

All of Us is taking a phased approach to the return of genetic results and will offer additional results over time. In about a year, the program plans to begin offering participants the option to receive information about how their DNA may affect their bodys response to certain types of medicines (pharmacogenetics), and about genetic variants associated with the increased risk of certain diseases, based on guidelines of the American College of Medical Genetic and Genomics. Participants will receive information back as their DNA samples are processed, so not everyone will receive information immediately.

We need programs like All of Us to build diverse datasets so that research findings ultimately benefit everyone, said Brad Ozenberger, Ph.D., All of Uss genomics director. Too many groups have been left out of research in the past, so much of what we know about genomics is based mainly on people of European ancestry. And often, genomic data are explored without critical context like environment, economics and other social determinants of health. Were trying to help change that, enabling the entire research community to help fill in these knowledge gaps.

All of Us plans to begin making genetic data available to researchers in about a year, with strict privacy and security safeguards in place to protect participants information. The program seeks to engage researchers from diverse backgrounds to undertake a wide range of studies and learn more about how to tailor care to peoples different needs.

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All of Us Returns First Genetic Results To Participants - Bio-IT World

Genetics

Unique genetic factors and ancestry, along with lifestyle, influence skin cancer risk – Kaiser Permanente Division of Research

Investigators find clues in large database of Kaiser Permanente members

By Jan Greene

People can look to the Northern European side of their genetic heritage for increased risk of nonmelanoma skin cancer, according to the first large analysis of genetic risk factors for cutaneous squamous cell carcinoma in diverse populations with European ancestry. The study was published Dec. 14 in the journal Communications Biology.

Hlne Choquet, PhD, staff scientist, Division of Research

The authors examined people of varying race and ethnicity who participated in the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). They focused on the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, a subgroup of more than 100,000 Kaiser Permanente Northern California members who volunteered their genetic and medical information for research.

We knew that people of European ancestry with lighter skin have a higher risk of cutaneous squamous cell carcinoma, said lead author Hlne Choquet, PhD, a staff scientist with the Kaiser Permanente Division of Research (DOR). We wanted to find out the risk both within and between European ancestry populations and other populations, and whether there are genetic factors involved, and it appears that there are.

Cutaneous squamous cell carcinoma is a common cancer and its incidence is increasing not only in non-Hispanic white people but also in Latinos and Asians. While it is not usually life-threatening, if allowed to grow it can become disfiguring, spread, and even become deadly.

Latinos are complex to study because they may have ancestry deriving from multiple continents; a 2015 study of the GERA cohort by the same research group found most of those who described themselves as Latinos have European genetic ancestry along with Native American ancestry, and some have evidence of African ancestry as well.

Scatter plot shows cutaneous squamous cell carcinoma prevalence by genetic ancestry in GERA cohort; axes reflect first 2 principal components of ancestry.

In this study, the researchers examined records of 11,396 people with cutaneous squamous cell carcinoma and 86,186 control subjects in the GERA cohort and found widely varying risk by race or ethnicity group: 14% for non-Hispanic white people, compared with 3.5% for Latinos, 0.8% for East Asians, and 0.4% for African Americans.

The analysis went on to consider genetically predicted skin pigmentation, genetic risk factors for cutaneous squamous cell carcinoma, and a clinical marker for chronic sun exposure (actinic keratoses). This found that skin pigmentation accounts for a large amount of the difference within and between white people and Latinos, but not all of it. Sun exposure is also a major contributing factor.

For Latinos, the percentage of Northern European ancestry at one particular location in the genome (the SLC24A5 locus) was strongly correlated with cutaneous squamous cell carcinoma risk. The researchers also found that this risk could differ among Latinos, depending on which version of a genetic variant they inherited at the SLC24A5 locus, which is known to influence skin pigmentation.

These findings suggest skin pigmentation alone may not be the primary determinant of cutaneous squamous cell carcinoma in Latinos, but rather the specific genetic factors underlying that pigmentation, said co-author Neil Risch, PhD, an adjunct investigator with DOR and the founding director of the Institute for Human Genetics at the University of California, San Francisco.

This is a striking example of a health disparity due largely to genetics, Risch said. The GERA cohort had limited numbers of East Asian and African American patients with cutaneous squamous cell carcinoma so we could not do a deep genetic analysis in this study but future research should explore these populations to better understand the role of their genetics and environmental exposures. For example, East Asians, who also have fair skin, appear to be strongly protected from the same skin cancer.

Lifestyle factors such as sun exposure, use of sunscreen, and smoking also affect skin cancer risk, as does immunosuppression and use of certain medications.

For clinicians, the research is a reminder that our patients of Latino ethnicity, particularly those with a lighter skin phenotype, are at risk for skin cancer, and would benefit from increased awareness, education, and skin cancer screening initiatives, said senior author Maryam Asgari, MD, MPH, an adjunct investigator with DOR, associate dermatologist at Massachusetts General Hospital, and professor of dermatology and population medicine at Harvard Medical School.

The study was funded by various grants from the National Institutes of Health.

Co-authors also included co-lead author Eric Jorgensen, PhD, a former DOR research scientist; Jie Yin and Catherine Schaefer, PhD, of DOR; and Thomas J. Hoffmann, PhD, Yambazi Banda, PhD, and Mark N. Kvale, PhD, of the UCSF Institute for Human Genetics.

Originally posted here:
Unique genetic factors and ancestry, along with lifestyle, influence skin cancer risk - Kaiser Permanente Division of Research

Genetics

VIU Researchers Examining Genetics of Canada Lynx | News | Vancouver Island University | Canada – Vancouver Island University News

The lynx-hare predator-prey cycle that has existed for thousands of years in North America is increasingly under threat from climate change.

The lynx are specialist predators that rely almost exclusively on snowshoe hare for food. This has led to a tight link between the populations of the two species; as the snowshoe hare populations rise and fall over a roughly 10-year cycle, lynx populations follow suit, says Dr. Jamie Gorrell, a VIU Biology Professor. When hare abundance is at its peak, lynx have plenty of food and have high survival rates, causing population booms that match, but lag slightly behind, those of the hare.

As snowshoe hare populations begin to decline, some lynx change their behaviour and begin to travel long distances, sometimes more than 1,000 kilometres, in search of food.

To understand how this cycle, which helps maintain the biodiversity of more than a dozen species in the boreal forest, could be impacted by climate change Gorrell and Dr. Evan Hersh, a VIU post-doctoral fellow, are studying the genetics of Canada lynx.

The genetic information will help researchers and conservationists understand lynx movements and connectivity among populations to identify potential habitat corridors that are essential to ensuring lynx populations remain genetically diverse.

Genetically mixed lynx populations will in turn help lessen the impact climate change may have on the stability of the lynx-hare cycle, a process vital to the functioning of boreal and sub-boreal ecosystems, says Gorrell.

Hersh is using genomic analyses and bioinformatics to analyze DNA samples that were collected with the help of Yukon residents, fur trappers and the Yukon Community Ecological Monitoring Program. The samples were collected at multiple phases during a 10-year cycle in hare abundance.

Hersh recently finished his PhD in plant ecology and evolution at the University of British Columbia and has extensive experience in genomic techniques. He says biologists now also need to be computer programmers to be able to crunch the huge amounts of data being generated in the genomic era.

Hersh will be comparing the genetic differences between Canada lynx from different areas. He said with newer techniques, instead of comparing a few hundred genetic markers, researchers can now compare tens of thousands of genetic markers.

Were hoping this thousandfold increase in the amount of data will give us the ability to figure out what is going on with their population structure. To date, no one has really applied these cutting-edge genomic techniques that produce huge amounts of data to analyze the population structure of Canada lynx within a conservation and management context, says Hersh.

The lynx needs these huge chunks of boreal forest that are continuous, not broken into little patches. If something happens in the southern portion of the boreal region, due to human use or climate change, and the area starts getting fragmented, then lynx movement can potentially be impacted, says Hersh.

They could have trouble passing over certain regions where there isnt enough boreal forest for them to travel through, which could have cascading effects on hare populations and potentially disrupt the cycle.

Hersh said if lynx and hare populations no longer follow predictable cycles, this can have tremendous impacts on the biodiversity of Boreal forests. It is estimated that the abundances of over 25 vertebrates are also regulated by this cycle. While the exact consequences of a disruption are difficult to predict, it could alter the natural patterns of genetic variation in all species that fluctuate with the cycle, which could ultimately reduce their ability to respond to future changes in their habitat and climate.

The concern is if climate change reduces the continuity of the forest and lynx cant move as far anymore, then this could disrupt that 10-year cycle.

This relationship between predator and prey could start to fall apart, so thats a potential consequence of climate change that we might not expect to happen. No one knows whats going to happen to the lynx and hare populations, says Gorrell. Most predator-prey relationships are generally stable over time and the abundance of predators and prey will stay relatively constant, but the lynx and hare have these huge peaks and crashes that happen like clockwork and its amazing how that cyclical relationship has maintained over time.

Gorrell and Hersh will be completing their research over the next two years thanks to an Accelerate Fellowship grant for $90,000 awarded jointly from Mitacs and Bill Harrower, principal biologist at High-Country Wildlife.

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MEDIA CONTACT:

Rachel Stern, Communications Officer, Vancouver Island University

C: 250.618.0373 lE: Rachel.Stern@viu.ca | T: @VIUNews

List of Project Supports/Partners

Research will be completed thanks to a grant from Mitacs and Bill Harrower, principal biologist at High-Country Wildlife.

This project is also being supported by:

The Community Ecological Monitoring project includes collaboration among researchers from:

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VIU Researchers Examining Genetics of Canada Lynx | News | Vancouver Island University | Canada - Vancouver Island University News

Cell Biology

Professor in Molecular Cell Biology job with DURHAM UNIVERSITY | 238578 – Times Higher Education (THE)

The Department of Biosciences at Durham University seeks to appoint a talented individual to the role of Professor in Molecular Cell Biology. We welcome applications from those with research and teaching interests that are consistent with research priorities in the Department and whose research is complementary to other staff in the animal cells & systems, bio-molecular interactions, or plant molecular sciences groups

The Department of Biosciences is consistently ranked in the top 5 UK Biological Sciences Departments in the Complete University Guide and was ranked 8th for Research Impact in REF2014.

We aim to appoint outstanding new academic staff to strengthen research in cross-disciplinary approaches to fundamental biological questions, potentially with impact on the bioeconomy, and to provide students with an outstanding educational and training experience. Research is focused around four key themes - animal cells & systems; biomolecular interactions; ecology, evolution & environment; and molecular plant sciences. We welcome applicants with interests in relevant areas of molecular cell biology.This post offers an exciting opportunity to make a major contribution to the development of internationally excellent research and teaching while allowing you unrivalled opportunities to progress and embed your career in an exciting and progressive institution. For more information, please visit our Department pages at https://www.dur.ac.uk/biosciences/.

We offer degree programmes in BSc Biological Sciences and a 4-year MBiol, while also contributing to Natural Sciences. Our research and teaching is supported by outstanding research infrastructure in advanced bioimaging (including super-resolution, confocal and electron microscopy), genomics, proteomics, metabolomics, high-performance computing and field research. We promote research at the interface with other disciplines.

The Department of Biosciences is particularly interested in receiving applications from women and candidates from ethnic minority backgrounds. The University is home to several networks that support researchers (e.g., women@DU, DU BAME, WHEN, and a vibrant departmental community of recent hires) https://www.dur.ac.uk/biosciences/ecrs/.

Durham University offers a generous scheme for maternity leave as well as a nursery run by the University. As an employer committed to promoting the very best talent, we also encourage applications from researchers who may have taken career breaks for family or other reasons, or who may need to consider flexible working. For more information, please visit our Department pages at http://www.dur.ac.uk/biosciences.

As one of the UK's leading universities, Durham is an incredible place to define your career while enjoying a high quality work/life balance. We are home to some of the most talented scholars and researchers from around the world who are tackling global issues and making a difference to people's lives.

The University sits in a beautiful historic city where it shares ownership of a UNESCO World Heritage Site with Durham Cathedral. A collegiate University, Durham recruits outstanding students from across the world and offers an unmatched wider student experience.

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Professor in Molecular Cell Biology job with DURHAM UNIVERSITY | 238578 - Times Higher Education (THE)

Cell Biology

Stanford Scientists Use Marlborough Company’s CODEX System in Study of Muscle Strength and Aging Published in Science – framinghamsource.com

The following is a press release from Akoya Biosciences, Inc. submitted to SOURCE through its business wire service.

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MARLBOROUGH Akoya Biosciences, Inc., The Spatial Biology Company announced that CODEX was used for spatial phenotyping to identify the source of a protein that can reverse age-related muscle atrophy.

This study represents the first demonstration of the CODEX system in imaging muscle tissues.

The paper, titled Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength was publishedonlineinScienceon December 10from the laboratory of Helen Blau, PhD, Professor and Director of the Baxter Laboratory for Stem Cell Biology at Stanford Universitys School of Medicine.

Muscle loss due to aging, called sarcopenia, is estimated to cost the US healthcare system billions of dollars each year, and results in a reduced quality of life for patients. Dr. Blau and her team are experts in investigating mechanisms of muscle structure and function related to aging and muscle disorders.

In this study of muscle fibers in mouse models and human tissue, the authors discovered an elevated level of a protein called 15-PGDH associated with old muscles. By blocking the activity of 15-PGDH in old mice, physical strength and muscle mass were restored in the animals. The opposite happened when the researchers increased the expression of 15-PGDH in young mice, causing their muscles to atrophy and weaken, as if having an aging effect. This is the first time that the protein has been associated with aging.

A CODEX assay was used to discover and understand the source of 15-PGDH, which acts as a regulator of muscle function. CODEXs multiplexing capabilities allowed researchers to look across numerous cell types and determine where the protein was localized in the tissue and which cells were expressing it. If standard methods had been used, the study would not have had the rich data of spatial phenotyping that made a difference in the results.

We adopted CODEX for this study because the platforms multiplexing capabilities simplified our search for different cell types in a tissue sample, what proteins they express and where theyre localized, said Helen Blau, PhD, Professor of Microbiology and Immunology at Stanford University. This is how we were able to identify the cells that express 15-PGDH. Were hopeful that new ways to improve health and peoples quality of life can be uncovered with the findings from this study.

Were excited that CODEX has once again supported a novel discovery and provides researchers the ability to image protein expression and cell phenotypes within their spatial context. Studying proteinsin situbrings us as close as possible to a clinical phenotype, said Brian McKelligon, CEO of Akoya. As Akoya continues to work with an ever-increasing number of researchers across the biological spectrum, we are eager to see more of these high-impact studies that help define the future of human health.

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Akoya Biosciences offers the most comprehensive, end-to-end solutions for high-parameter tissue analysis from discovery through clinical and translational research, enabling the development of more precise therapies for immuno-oncology and other drug development applications. The company has two industry-leading platforms that empower investigators and researchers to gain a deeper understanding of complex diseases such as cancer, and other immune system or neurological disorders. The CODEXsystem is the only benchtop platform that can efficiently quantify more than 40 biomarkers and is ideally suited for biomarker discovery. The Phenoptics platform is the only end-to-end multiplexed immunofluorescence solution with the robustness and high throughput necessary for translational research and clinical trials. The company has its HQ in Marlborough.

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Stanford Scientists Use Marlborough Company's CODEX System in Study of Muscle Strength and Aging Published in Science - framinghamsource.com

Cell Biology

Global Artificial Photosynthesis Market Report 2020: Department of Genetics, Cell Biology, and Development, University of Minnesota, Department of…

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Vendor LandscapeDepartment of Genetics, Cell Biology, and Development, University of MinnesotaDepartment of Chemistry, University of Illinois Urbana-ChampaignDepartment of Chemistry, University of CambridgeDepartment of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial Department of Biochemistry and Synthetic Metabolism, Max Planck Institute for Terrestrial MicrobiologyUniversity of Bordeaux, CNRS, Centre de Recherche Paul PascalInstitut Universitaire de FranceResearch Center for Solar Energy Chemistry, and Division of Chemical Engineering, Graduate School of Engineering Science, Osaka UniversityEnergy Materials Laboratory, Korea Institute of Energy ResearchJoint Center for Artificial Photosynthesis, Lawrence Berkeley National LaboratoryTechnical Chemistry, Department of Chemistry, Chemical-Biological Centre, Ume UniversityCatalysis Division, National Chemical Laboratory

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