Category Archives: Genetics

Jul 01, 2021 5:30 PM

Author: Doug Dollemore

During his 17-year career with the New York Yankees, Lou Gehrig was famed for his prowess as a hitter and for his durability on the baseball field, which earned him his nickname "The Iron Horse. Then, mysteriously, in 1938, his iron body began to figuratively rust. He couldnt run, hit, or field his position as well as he once did. When doctors finally diagnosed his condition, the news was devastating.

Gehrig had amyotrophic lateral sclerosis (ALS), a rare progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. People who have ALS gradually lose their ability to control muscle movement. Eventually, the condition, now often referred to as Lou Gehrigs disease, leads to total paralysis and death. Then, as now, there is no cure.

In the 80 years since Gehrigs death at age 37, scientists have sought to unravel what causes the disease and develop better treatments for it.

In the latest advance, University of Utah Health researchers have detected a set of genetic mutations that appear to increase a persons risk of developing ALS. They say the discovery of mutations in TP73, a gene that has never been associated with ALS before, could help scientists develop new therapies to slow or even stop the progression of the disease.

Its really a novel discovery that suggests a very different pathway for the onset of at least some cases of ALS that hasnt been explored before, says Lynn Jorde, Ph.D., chair of the Department of Human Genetics at U of U Health and the senior author of the study. From a scientific standpoint, its going to provide us with a more complete picture of what is going wrong in ALS and expand our understanding of what can be done to mitigate its devastating consequences.

The study appears in Neurology, the medical journal of the American Academy of Neurology.

"From a scientific standpoint, its going to provide us with a more complete picture of what is going wrong in ALS and expand our understanding of what can be done to mitigate its devastating consequences."

About 85% of ALS cases are sporadic, meaning that no one in a patients family has a history of the disease. However, researchers suspect that up to 61% of sporadic ALS cases are influenced by genetic factors. But detecting those factors has been challenging.

In the past, it has been difficult to determine ALS-causing genes because only recently has sequencing technology advanced enough to feasibly sequence many patients, says Kristi L. Russell, a graduate research assistant at U of U Health and lead author of the study. Additionally, many mutations in a single patient could be considered deleterious, so one must test the candidate mutations in animal models or cell culture, an incredibly time-consuming process.

For this study, Jorde, Russell, and colleagues analyzed blood samples provided by 87 people with sporadic ALS who were being treated at U of U Health. Using a technique called exome sequencing, which zeroes in on the protein-coding regions within genes, they found five people who had rare, deleterious mutations in the TP73 gene, which plays a key role in apoptosis or programmed cell death. Then, the researchers studied data from 2,900 other sporadic ALS patients from the Utah Heritage 1K Project and the ALSdb cohort. Within these groups, they identified 24 different, rare protein-coding variants in TP73.

When the researchers did a similar analysis among 324 people who did not have ALS, the patient mutations in TP73 were not present.

In subsequent laboratory studies, knocking out or disabling TP73 in zebrafish impaired the development of nerve cells in a way that mimicked what appears to occur in ALS. Like in ALS, the zebrafish had fewer motor neurons and shorter axons, nerve fibers that transmit electrical impulses from neurons to muscle cells. This shortening could impede the axons ability to transmit impulses. Shorter axons transmit these impulses far less efficiently.

During their experiments, the researchers also found evidence that mutant TP73, which normally inhibits apoptosis in motor neurons, doesnt work properly. As a result, they suspect that apoptosis is more likely to occur.

It seems that mutant TP73 disrupts apoptosis, which leads to more neuronal death, Russell says. Many biological pathways have been implicated in ALS progression, but our study highlights the underappreciated role of apoptosis in ALS pathology. Apoptosis could potentially become a new focus or target for treatment drug screens.

More here:
Newly Discovered Genetic Mutations May Increase Risk for Lou Gehrig's Disease - University of Utah Health Sciences

With so many great cannabis brands releasing exciting new products in new markets, it can be hard to keep track of every release. So we're rounding up a few significant releases. This week, we look at releases by Insane, Kal, and more.

Insane just came out with a new strain available at all Dr. Greenthumb dispensaries in California. Stuffed French Toast is a cross between Paris OG and Faceoff OG, and appeals to the wake 'n' bake crowd with a flavor profile of cinnamon, pine, and orange, tasting just like the breakfast staple it was named after.

Available: California

California-based topicals brand Papa & Barkley just announced infused THC capsules to its lineup. The two-ingredient, whole-plant THC Releaf Capsules are made from coconut and cannabis oils and contain 25 to 50 milligrams of THC.

Available: California

Compound Genetics started dropping three strains at the June 26 grand opening of the Cookies Santa Ana location. These strains include Apples and Bananas, Gummiez, dropping on July 1, and Pav, which was made in collaboration with rapper Quavo.

Available: California

Kal will be dropping new flavors on July 2 in its seltzer line in time for summer. Each 12-ounce can of Kal contains 15 milligrams of hemp-derived CBD and 2 grams of sugar. The new flavors include black cherry, ruby red grapefruit, ginger lemonade, and blood orange mango.

Available: Nationwide

High Tales, a video series produced by Monogram, the cannabis line from Jay-Z, just dropped its latest episode featuring rapper Curren$y. The episode shows Curren$y's very own grilled-cheese recipe, along with weed-related stories he's experienced throughout his life and career.

Available: Nationwide

Featured image by Gina Coleman/Weedmaps

Hannah is a Seattle-based writer and editor. Shes worked in the cannabis industry for three years and continues to learn and explore.

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4 new weed products to try from Compound Genetics, Papa & Barkley, and more - Weedmaps News

Introduction

Fragile X syndrome (FXS), OMIM # 300624, is a X-linked inherited genetic disease classified as a triplet repeat condition. FXS is the most common cause of inherited intellectual disability and autism in the world. It has a prevalence of 1 in 5000 men and 1 in 8000 women. Affected individuals are characterized by intellectual disability, autism, language deficit, typical facies, and macroorchidism.1,2

Alterations in the FMR1 gene with locus Xq27.3 are causative of Fragile X Syndrome and other disorders. This gene harbors a CGG repeat within the 5 untranslated region and, depending on the number of repetitions, 4 types of alleles are defined with different clinical manifestations:3 Normal alleles, which have up to 44 CGG repeats; grey zone or intermediate alleles that contain between 45 and 54 repeats; premutation (PM) alleles with between 55 and 200 repeats; and full mutation (FM) alleles, with more than 200 repeats. In most cases, this is due to an expansion of the CGG triplet from one generation to the next.4

The Fragile Mental Retardation Protein (FMRP) is coded by the FMR1 gene. The absence of FMRP expression is usually secondary to the methylation of the FMR1 gene that occurs when more than 200 CGG repeats are present in the 5UTR region; this can also be explained by a point mutation in the coding region for FMR1 or a deletion that includes this gene, but these changes have only been reported in a few cases. The absence of FMRP is related to the classic FXS phenotype.5,6

FMRP expression is slightly lower in the carriers of a PM allele. Lower levels of FMRP are found particularly in the upper premutation (PM) range however, they typically do not present the classic FXS syndrome phenotype.7 Furthermore, they have elevated FMR1 mRNA levels between 2 to 8 times normal levels, which also leads to RNA toxicity. These elevated levels of mRNA are a risk for a number of medical conditions that are not explained by decreased FMRP.2,4,8

FMRP has roles in chromatin dynamics, RNA binding, mRNA transport, and mRNA translation9,10 and for certain subgroups of cerebral transcripts.11

This protein is involved in the regulation of RNA stability, subcellular transport and translation of neural mRNAs that codify proteins involved in synapsis development, neural plasticity and brain development.8

In addition, FMRP interacts with at least 180 proteins expressed in the brain and connective tissue. This interactome comprises known FMRP-binding proteins, including the ribosomal proteins FXR1P, NUFIP2, Caprin-1, and other novel FMRP-interacting candidate proteins located in different subcellular compartments, including CARF, LARP1, LEO1, NOG2, G3BP1, NONO, NPM1, SKIP, SND1, SQSTM1 and TRIM28. This interactome suggests that, besides its known functions, FMRP is involved in transcription, RNA metabolism, ribonucleoprotein stress granule formation, translation, DNA damage response, chromatin dynamics, cell cycle regulation, ribosome biogenesis, miRNA biogenesis and mitochondrial organization.9

Several studies have shown that in the absence of FMRP, a wide range of neural mRNAs are affected, boosting neural protein synthesis, which results in dendritic spine dysmorphogenesis and glutamate/GABA imbalance, which in turn produce variations in neural excitation/inhibition, phenomena that are present in FXS. Dendritic spine dysmorphogenesis plays a role in the intellectual deficits and behavioral problems, due to the weak synaptic connections found in this syndrome.12,13

Fragile X syndrome (FXS) has incomplete penetrance and variable expressivity and biological sex is a decisive factor of the phenotype. Full mutation of the FMR1 gene has a 100% penetrance of intellectual disability in males and 60% in females. Other characteristics associated with FXS Appear with varying frequencies in affected individuals. Autism spectrum disorder (ASD) symptoms appear during early childhood in 50% to 60% of males and 20% of females with FXS.1417

Physical features include elongated face, large and prominent ears (7578% of affected males), mandibular prognathism (80% of adult men), hyperlaxity and macroorchidism (95% of adult men). Other characteristics also vary in their frequency of presentation: seizures (23%), strabismus (8%), and cardiac abnormalities such as abnormal aortic root dimensions (18%) and mitral valve prolapse (55%). In general, the female phenotype is less severe and less specific.4,18

The variation in the phenotype of monogenic diseases is common,19,20 it is explained by a combination of genetic, environmental, and lifestyle factors,21 and FXS is not an exception.

Here, we present a review of the knowledge about the molecular factors involved in the variable expressivity of FXS.

The presence of a full mutation in FMR1 is associated with the hypermethylation of a CpG island located in the promoter of the FMR1 gene. Methylation of DNA regions (mDNA) is one of the main epigenetic modifications related to transcription regulation.22 A CpG island is located proximal to the CGG repeat tract, which is expanded in FXS. Hypermethylation of the CpG island generates transcriptional silencing of the FMR1 gene.23 As a consequence, the Fragile Mental Retardation Protein (FMRP), codified by the FMR1 gene, is not produced24 and in turn, the absence or low expression of FMRP causes FXS.

CGG tract repetition expansion in the untranslated region (UTR) of exon 1 in the FMR1 gene generates instability of that region during the replication process, inducing size mosaicism, which is defined as the presence of premutation and mutation alleles in several cells.25

In males with FXS caused by full mutation, the detection of FMR1 mRNA levels in peripheral blood lymphocytes is common. This phenomenon is due to both size mosaicism and mDNA in the CpG island and nearby regions that vary between cells and tissues.26 Furthermore, longitudinal studies in women with FXS have shown that levels of mRNA transcribed from FMR1 decrease significantly with age.23 Complicating even more the behavior of mDNA and FXS, it has been found that in premutation alleles, a considerable number of cells have mDNA.27 The variation between methylation states of the CpG island and nearby regions among different cells and tissue of the same person is known as methylation mosaicism.28 It is estimated that around 50% of people with FXS have this type of mosaicism.29 In cells where mutated alleles are not methylated, they are transcriptionally active and can be expressed.30 However, in these cells there is no FMRP synthesis since mRNA with CGG expansion greater than 200 repeats is not translated efficiently in ribosomes.31,32

The absence or low levels of FMRP is a decisive factor for FXS development, as several studies have aimed to discover the relationship between protein levels and phenotypic characteristics of the patients. Since the late 1990s, correlations between FMRP levels and the neurological phenotype of FXS have been established.29,33,34 The first studies about this topic established the standard levels of FMRP in peripheral blood leucocytes through immunoblotting. When comparing protein levels with the allele type and the presence of size mosaicism, it was demonstrated that people with the lowest FMRP levels were males with FM. Males with size mosaicism and females with FM had slightly higher levels of FMRP than males with FM.33,35,36 Via multiple regression models, it was found that FMRP levels were significantly correlated with the intelligence quotient (IQ) of the patients in the study.33 However, studies did not identify the same relation between FMRP levels and behavioral symptoms.34,37 More recent evidence supports a partial overlap between the pathogenic mechanisms that lead to FXS and ASD.38 Lower FMRP levels have been documented in samples of individuals with FXS and ASD compared to patients with FXS only.29,34 The relation between FMRP levels and IQ in males and females with different expansions in CGG repeats was studied recently.39 This last study has two important advantages compared with previous studies: firstly, the use of fluorescence resonance energy transfer (FRET), which has a higher sensibility when measuring protein levels, and also FMRP levels were measured in dermal fibroblasts. Unlike leucocytes, fibroblasts derive from the ectoderm, the same germ layer from which nervous system cells originate. Researchers found a strong and positive relation between FMRP levels and cognitive skills in patients with levels below 30% of the standard levels in controls. Interestingly, above this level, there was a higher dependence between low FMRP levels and low IQ.39

In parallel with the aforementioned studies, researchers reported the incidence of size and methylation mosaicism in cognitive impairment severity.4042 The classic definition of premutation alleles behavior as non-methylated alleles, and mutated alleles as methylated or partially methylated ones in order to categorize premutation carriers and patients with FXS has been extended progressively to include a detailed classification that takes into account the existence of size and methylation mosaicisms.

Regarding size mosaicisms, different combinations have been described, including patients with some FM cells and other cells with PM. Indeed, patients with FM, PM, grey zone alleles and even alleles with normal size have been reported.40 The presence of size mosaicisms with PM and FM alleles is related with a less severe phenotype and a higher risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS).43

When exploring the possible relation between size mosaicisms and the intellectual functioning of patients with FXS disregarding sex, it was found that patients with FM/PM had better intellectual functioning and less maladaptive behavior, compared with FM-affected individuals.42 Interestingly, the same study found that ASD features and maladaptive behaviors were similar between FM-only and PM/FM mosaics within each sex, after controlling for overall intellectual functioning. A limitation of this study is that they used venous blood and real time PCR and Southern blot analysis to quantify the level of methylation.

Recently, methylation mosaicism has been taken into account as an important variable in phenotype traits. The most frequent mosaicism found in males is the presence of FM-methylated alleles and non-methylated FM and PM alleles (combination of size and methylation mosaicism).25,44 However, in patients with FM and not PM mosaicisms, methylated alleles do not express mRNA, while non-methylated alleles do. An aspect that highlights the importance of detecting the presence of this kind of mosaicism is the influence on phenotype severity. Additionally, according to some case reports, the presence of synthesized mRNA from PM and FM alleles increases the odds of developing the FXTAS phenotype.45,46 The final consequence of methylation mosaicism is the cells reduced ability to express FMR1 mRNA, measure mRNA and determine if there is a relation with phenotypic traits. When analyzing mRNA levels between males and females, it was found that females had higher levels. Also, in females, higher levels of FMR1 mRNA were related positively with age but not with intellectual functioning and autistic features. Males with FM that express FMR1 mRNA had significantly higher ADOS calibrated severity scores, when compared with males with fully methylated FM. Interestingly, no differences were found regarding intellectual functioning.41 Likewise, when contrasting FMR1 mRNA levels and scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-CfX) it was found that in males with FM, higher values of FMR1 mRNA were related with elevated irritability and lower health-related quality of life scores.47 This association was not found in males with PM/FM, suggesting that for improved genotype/phenotype associations, it is essential to take into consideration not only sex but also size and methylation mosaicism.

Recent investigations explored simultaneously how FMR1 mRNA levels of FMRP are related to phenotypic alterations in males with PM and FM.48 In a study composed of 14 cases of patients with PM or PM and FM mosaicism and mental illnesses such as bipolar disorder, schizophrenia and psychosis, among others, low levels of FMRP and increased FMR1 mRNA were evident in these patients. This combination of characteristics in patients with FM, decreased FMRP, PM and increased FMR1 mRNA represents a dual mechanism of clinical significance that may generate characteristics of both FXS and FXTAS.48 In a clinic-based ascertained group of patients with FXS of both gender, a significant difference was found between FXS with ASD and low levels of FMRP when comparing concentrations of the protein in patients with FXS without ASD.29 They found that the mean full scale IQ and adaptive skills composite scores were significantly lower in males than in females (p = 0.016 and p = 0.001, respectively, MannWhitney). Additionally, all individuals with moderate or severe ID were males. Not surprisingly, ASD was present more frequently in males with FXS (46% vs 20% females). This association was not found in males with PM/FM, suggesting that for improved genotype/phenotype associations is essential to take into consideration not only sex but size and methylation mosaicism.29

There is a small proportion of FXS patients without expansions in the CGG-repeat tract. In this group, the condition is caused by missense or nonsense mutations,5,16 or deletions in FMR1.1,6 Patients with these mutations have similar physical, cognitive and behavioral characteristics to FXS patients. With the increasing availability of diagnostic methods based on next-generation sequencing and comparative genomic hybridization, a higher rate of diagnosis of mutations causing FMR1 function loss is expected. This will allow a clear delimitation of the phenotype caused by the loss of the protein in the absence of CGG tract expansions.

For many monogenic diseases it is known that, besides the allelic variance, the effect of modifier genes has an important role in incomplete penetrance and variable expressivity. The identification of modifier genes that affect the phenotype in monogenic diseases has many challenges that complicate their description. A genetic variant can modify the effect in the phenotype of another variant in many ways, including epistasis and genetic interactions.49,50

In studies using FXS murine models, important new evidence was acquired in order to establish the importance of potential modifier genes and their impact on FXS phenotype development. The knockout mouse model for FXS was generated in the last decade of the XX century. Fmr1 KO mice had learning deficits, abnormal synaptic connections, seizures, hyperactivity and macroorchidism.51,52 When describing the mouse phenotype in detail, it was evident that abnormal phenotypic characteristics depend, at least in some proportion, on their genetic background.53

During the identification of modifier genes in the FXS phenotype, a large proportion of the research has aimed towards the susceptibility to developing certain clinical behavioral characteristics, such as aggression, ASD and seizures.34,5459 All of the studies use a similar methodological design: they arrange groups of people with or without a specific phenotypic trait and establish the frequency of specific variants in modifier gene candidates.

The possibility that Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene may modulate the epilepsy phenotype in FXS patients has also been investigated. The replacement of a methionine for a valine in the 66th position of the BDNF protein interferes with normal intracellular traffic and BDNF dependent secretory activity in cortical neurons.60 This polymorphism has been related to cerebral anatomy alterations61 and neuropsychiatric disorders.62,63 In a sample of 27 males with FXS from Finland, it was found that all the patients with epilepsy (15%) had the Met66 allele, whereas the prevalence of this allele is 20% in the normal population. Research suggests that the Met66 allele in BDNF interacting with FM in FMR1 may partially explain the higher incidence of seizures in patients with FXS.56 In a more recent study with a higher number of males with FXS (77 patients), the results were not replicated and there was no association between seizures and Val66Met polymorphism.58 These results show the importance of validating studies about modifier genes in different populations.

In research about genes that affect mood and aggression, such as the serotonin transporter (5-HTTLPR), the monoamine oxidase A (MAOA-VNTR) and COMT, conflicting results were found. All of those genes are involved in regulatory pathways for different neurotransmitters, and their variants have been associated with the development of behavioral phenotypes in different contexts other than FXS. In one group of 50 males with FXS, the relationship of 5-HTTLPR and MAOA-VNTR polymorphisms with the frequency/severity of aggressive/destructive, self-injurious and stereotypic behaviors was studied. It was found that the high-transcribing long (L/L) genotype in 5-HTTLPR was related with a higher frequency of aggressive/destructive and stereotypic behavior, while patients with the short (S/S) genotype had less aggression. The MAOA-VNTR genotype had no effect on behavior.55 On the other hand, in a study of 64 males with FXS where the COMT gene was also included, the results of the previous study were not replicated. There was no association between behavioral characteristics and either 5-HTTL PR (serotonin) or MAOA genotypes. Nevertheless, the A/A genotype in COMT that modifies dopamine levels was associated with greater interest and pleasure in the environment, and with less risk of property destruction, stereotyped behavior and compulsive behavior.54 The authors of the study suggest that the non-reproducibility of the results regarding MAOA-VNTR can be explained by differences in the prevalence of aggressive and stereotyped behavior among the studied populations or by differences in the measurements used to characterize each behavior.

The importance of identifying potential modifier genes was explored in a clinical trial. The researchers investigated the relation between polymorphisms in several genes and the response of sertraline in 51 children. They found that BDNF, MAOA, 5-HTTLPR, Cytochrome P450 2C19 and 2D6 polymorphisms had significant correlations with treatment response.64

Currently the knowledge about molecular causes of the variable phenotype in patients with FXS include characteristics associated with the FMR1 gene itself and to secondary, modifying gene effects.

Regarding FMR1, when the diagnosis is established, the type of mutation causing FXS is identified: CGG repeat tract expansion vs pathological variant causing loss of function in FMR1.

When the CGG is identified, is it expected that about half of the patients have size or methylation mosaicism or both.29 The presence of any of those mosaicisms determines the expression or not of FMR1 mRNA and FMRP. The quantity of FMRP is directly related with IQ.34,37,39 While the presence of size mosaicism is related with better intellectual functioning and less maladaptive behavior,29,42 elevated concentrations of FMR1 mRNA in patients with FM have been associated with a higher risk of developing FXTAS45,46,48 and with the severity of behavioral symptoms.47

The search for modifier genes affecting the phenotype has been carried out using the candidate genes strategy. Because high impact clinical manifestations in FXS are related with neurologic phenotypes, the studied candidate genes are involved in CNS development and the appearance of seizures (BNDF)56,6062 and associated with mood and aggression (5-HTTLPR, MAOA-VNTR y COMT).54,55 Recent research has been done with small groups of patients and there are no conclusive results about the importance of these variants in modifier genes.

Scientific and clinical evidence about molecular causes of variable expressivity in FXS is growing quickly. It is evident that aspects of the mutation type in FMR1 and the behavior of the CGG repeat tract are relevant in the presentation of the condition. Research about modifier genes is still emerging. There are important limitations such as sample size and comparability of different studies, mainly due to smaller groups of selected patients and the use of different tools for measuring the phenotypes.

Independent cohorts of patients with FXS across different continents have shown evidence that mosaicism, FMR1 mRNA or FMRP quantification are associated with the severity of the phenotype. However, this information cannot currently be used effectively in the integral management of patients. When intervention strategies become available in order to prevent the development of FXTAS, or when certain molecules can regulate levels of FMRP expression to measure FMR1 mRNA and FMRP, they could be crucial for selecting patients and identifying the best therapeutic intervention.

In clinical trials there is an important window of opportunity. Identifying mosaicism, measuring transcription/translation activity of FMR1 and stratifying patients by modifier genotypes29,65 will permit the identification of subgroups of patients with greater potential to respond to specific treatments.

The authors report no conflicts of interest in this work.

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56. Louhivuori V, Arvio M, Soronen P, Oksanen V, Paunio T, Castrn ML. The Val66Met polymorphism in the BDNF gene is associated with epilepsy in fragile X syndrome. Epilepsy Res. 2009;85(1):114117. doi:10.1016/j.eplepsyres.2009.01.005

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58. Tondo M, Poo P, Naud M, et al. Predisposition to epilepsy in fragile X syndrome: does the Val66Met polymorphism in the BDNF gene play a role? Epilepsy Behav. 2011;22(3):581583. doi:10.1016/j.yebeh.2011.08.003

59. Wassink TH, Hazlett HC, Davis LK, Reiss AL, Piven J. Testing for association of the monoamine oxidase a promoter polymorphism with brain structure volumes in both autism and the fragile X syndrome. J Neurodev Disord. 2014;6(1). doi:10.1186/1866-1955-6-6

60. Chen ZY, Patel PD, Sant G, et al. Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004;24(18):44014411. doi:10.1523/JNEUROSCI.0348-04.2004

61. Szeszko PR, Lipsky R, Mentschel C, et al. Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry. 2005;10(7):631636. doi:10.1038/sj.mp.4001656

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63. Gratacs M, Gonzlez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry. 2007;61(7):911922. doi:10.1016/j.biopsych.2006.08.025

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Genetic mapping of subsets of patients with fragile X syndro | TACG - Dove Medical Press

Inventum Genetics GmbH and Universitt Marburg agree on a collaboration

The project company of Xlife Sciences AG Inventum Genetics GmbH has signed a collaboration agreement with the Philipps-University of Marburg. In this way, Inventum Genetics has the exclusive opportunity to develop new therapeutic targets using high-quality genetic data.

ZUERICH, SWITZERLAND / ACCESSWIRE / June 22, 2021 / The cooperation between Inventum Genetics and the University of Marburg is a long-term agreement. In a first projects, new therapeutic targets and biomarkers for oncological, neurodegenerative and age-related diseases are be identified using the latest genetic and molecular biological processes. Oliver R. Baumann, CEO der Xlife Sciences, is delighted with the additional prospects for drug development: "All common diseases, like the majority of all oncological, neurodegenerative and age-associated diseases, are multifactorial in cause, not just caused by a singular genetic defect. Rather, multifactorial diseases are characterized by the fact that they are based on (exogenous) environmental factors and (endogenous) genetic risk factors. In this particular project with the University of Marburg, cellular disease mechanisms of multifactorial diseases are to be elucidated. For this purpose, cells are stimulated with exogenous risk factors. It will then be examined how the cells react to it depending on their genetic makeup."

The agreement with the Philipps-University of Marburg gives the university the right to pursue the results achieved in its own research and to industrialize them, provided Inventum Genetics does not use the results itself. In this case, Inventum Genetics would benefit from the royalties generated by the university.

About the Philipps-University Marburg The Institute for Human Genetics at the Faculty of Medicine at the Philipps-University of Marburg, under the leadership of Professor Dr. Johannes Schumacher is well recognized by high-ranking publications in research in the field of human genetics. The institute operates a molecular laboratory with high quality equipment and is therefore able to deal with complex issues in the context of molecular genetic research.

About Inventum Genetics GmbH Inventum Genetics GmbH is a subsidiary of Xlife Sciences AG, which is active in research, development, manufacturing and the sale of medical and biotechnological products, especially in the field of genetics. For more information, please visit: https://www.inventumgenetics.com

About Xlife Sciences AG Xlife Sciences AG is a Swiss company with focus on investing in promising technologies in the life science industry. Xlife Sciences AG is building the bridge from research and development to healthcare markets by supporting researchers and entrepreneurs in positioning, structuring, developing and implementing their concepts. Together with industrial partners or universities, Xlife Sciences AG leads projects through the proof-of-concept phase after an invention disclosure or start-up. Subsequently, the firm focuses on out-licensing or selling the company, often with a combination of a strategic partnership. Xlife Sciences AG offers its investors direct access to the further development of innovative and future-oriented technologies at a very early stage. For more information, please visit: http://www.xlifesciences.ch

For media inquiries:Dennis Lennartz, Head Investor Relations, Xlife Sciences AG, Tel. +41 44 385 84 60, dennis.lennartz@xlifesciences.ch

For scientific inquiries:Dr. Frank Plger, Chief Scientific Officer, Xlife Sciences AG, Tel. +41 44 385 84 62,frank.ploeger@xlifesciences.ch

SOURCE: Xlife Sciences AG

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Xlife Sciences AG: Collaboration with the University of Marburg - BioSpace

MADRID, June 22, 2021 /PRNewswire/ -- We have recently witnessed, once again, a professional athlete suffering a cardiovascular attack during a match. This type of incidence and the possible fatal consequences result from an individual's genetic makeup. Genetic science now makes it possible to know whether a person has an elevated risk to suffer this type of cardiovascular accident and to avoid one of the main causes of death in the world, with more than 17 million deaths each year.

The role of genetics as a diagnostic element has been fundamental for several years, as Dr. Izquierdo, Chief Medical Officer of Veritas Intercontinental, says: "Sudden cardiac death (SCD) is mainly due to coronary pathologies, especially in patients over 40 years old, but in younger patients, such as many high-performance professional athletes, the contribution of genetic factors to the pathogenesis of SCD is a key factor, since we usually find a clear pattern of family inheritance at its origin, such as cardiomyopathies or channelopathies".

To help in the detection and prevention of Cardio Vascular Disease (CVD), Veritas Intercontinental offers the myCardiogenetic service, an innovative Exome sequencing and interpretation service, focused on genes related to hereditary heart diseases.

The analysis includes all genes recommended by the American Heart Association (AHA) analyzing 100 genes based on their relationship with different hereditary heart diseases. The service includes genetic counseling for the prescribing specialist, which is essential for the correct interpretation of the results and clinical management of the patient.

"myCardio,"explains Dr. Luis Izquierdo, "makes it possible to tackle the main types of cardiac disorders of hereditary origin and offers enormously valuable information to avoid the disease or to treat it much more efficiently. Until now, genetic tests related to hereditary heart disease have been very focused on certain pathologies, when it has been shown that there are many interactions between different heart conditions. myCardio allows a comprehensive approach to heart disease, with a new perspective that has been shown to be much more effective".

Advantages

Whole exome sequencing (WES) is the most appropriate tool to address the genetic heterogeneity present in inherited cardiovascular disease. Recent studies show a very significant improvement in diagnostic performance using exome sequencing compared to panels, since a high number of cases in which several mutations are recorded simultaneously are observed. The advantages of the exome are more prominent in those cases in which there is no high clinical suspicion, as well as those in which the patient has been recovered after an episode of sudden death.

The service covers the study of hereditary predisposition to Primary Cardiomyopathies, Metabolic Cardiomyopathies, Channelopathies and Arrhythmias, Syndromes with Vascular Affection, Rasopathies,other syndromes linked to cardiac pathology and other risk factors (Ischemic Heart Disease) such as Familial Hypercholesterolemia.

About Veritas Intercontinental

Veritas Intercontinental was founded in 2018 by Dr. Luis Izquierdo, Dr. Vincenzo Cirigliano and Javier de Echevarra, who have accumulated extensive experience in the field of genetics, diagnostics, and biotechnology, initially linked to Veritas Genetics, a company founded in 2014 by Prof. George Church, one of the pioneers in preventive medicine. Veritas was born with the aim of making genome sequencing and its clinical interpretation available to all citizens as a tool to prevent diseases and improve health and quality of life.

Since its inception, Veritas Intercontinental has led the activity and development of the Veritas market in Europe, Latin America, the Middle East, and Japan; with the aim of making genomics an everyday tool used for proactive healthcare management.

Based on its leadership in the application of preventive genomic medicine (myGenome), Veritas Intercontinental has expanded its offer to other areas such as perinatal medicine (myPrenatal -NIPT- and myNewborn -neonatal screening-), oncology (myCancerRisk), or the mentioned cardiovascular pathologies (myCardio), thus becoming the benchmark in advanced genomics services.

For further informationhttps://www.veritasint.com

Marta Pereiro[emailprotected]+34 915 623 675

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Veritas Intercontinental: Genetics makes it possible to identify cardiovascular genetic risk and prevent cardiac accidents such as those that have...

REYKJAVIK, Iceland, June 18, 2021 /PRNewswire/ -- Scientists from deCODE genetics have developed a predictor based on protein measurements in blood samples that predicts the time to all-cause death better than traditional risk factors.

In a paper published today in Communications Biology, scientists from deCODE genetics, a subsidiary of Amgen, describe how they developed predictor of how much is left of the life of a person.

Using a dataset of ~5000 protein measurements in 22,913 Icelanders, of whom 7,061 died during the study period, the scientists developed a predictor of the time to death that can outperform predictors based on multiple known risk factors. The predictor can identify the 5% at highest risk in a group of 60-80 year olds, where 88% died within ten years and the 5% at lowest risk where only 1% died within ten years.

The scientists explored how individual proteins associate with mortality and various causes of death and found most causes of death to have similar protein profiles. In particular, they found growth/differentiation factor 15 (GDF15), which has been associated with mortality and ageing before, to be an important predictor of all-cause mortality. Furthermore, they found that, on average, participants predicted at high risk of death within a short period of time had less grip strength and performed worse on an exercise tolerance test and a test of cognitive function than those predicted at lower risk.

"The predictor gives a good estimate of general health from a single blood draw," says Thjodbjorg Eiriksdottir scientist at deCODE genetics and author on the paper.

"This is pretty cool but also scary and hopefully somewhat useful", says Kari Stefansson a senior author on the paper . "This shows that our general health is reflected in the plasma proteome. Using just one blood sample per person you can easily compare large groups in a standardized way, for example, to estimate treatment effects in clinical trials."

Based in Reykjavik, Iceland, deCODE is a global leader in analyzing and understanding the human genome. Using its unique expertise in human genetics combined with growing expertise in transcriptomics and population proteomics and vast amount of phenotypic data, deCODE has discovered risk factors for dozens of common diseases and provided key insights into their pathogenesis. The purpose of understanding the genetics of disease is to use that information to create new means of diagnosing, treating and preventing disease. deCODE is a wholly-owned subsidiary of Amgen (NASDAQ: AMGN).

Contact:

Thora Kristin AsgeirsdottirPR and CommunicationsdeCODE geneticsthoraa@decode.is354 894 1909

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Company Codes: NASDAQ-NMS:AMGN

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deCODE genetics: Predicting the probability of death - BioSpace

'If genetic testing is done at the appropriate stage, some diseases can be prevented, cured or managed better.'

The Indian diagnostics industry has been rapidly evolving over the years and its emerged to be a key component of the healthcare segment. The arrival of Covid-19 pandemic pushed the healthcare industry to the sting worldwide by throwing many challenges, and therefore the diagnostic sector too witnessed a large transition during this phase. Whether its about keeping pace with the concept of telemedicine or addressing the change within the consumer psyche, the diagnostic sector has been facing different challenges with the increase of covid cases. As COVID-19 has spread, Indias diagnostic sector has been battling the virus at the forefront. In conversation with Financial Express Neeraj Gupta, Founder and CEO of Genes2me shared his experience and threw light on the challenges, learnings, and therefore the road ahead for the diagnostic businesses in India. Excerpts:

How has the diagnostic sector evolved since the arrival of Covid-19? Being an industry leader, what were some initial challenges you faced?Previously, the molecular diagnostic sector was not harnessed. We have seen that pandemic pushed the healthcare industry to the edge, but Indias diagnostic sector rose to meet the challenges. As COVID-19 has spread, Indias diagnostic sector has been combating the virus at the forefront. Initially, the Indian health care system was not fully prepared for such a massive crisis like COVID-19. We faced challenges regarding imports for raw materials and logistics due to global supply chain disruptions. This is also one of the reasons why we decided to use our expertise in molecular diagnostics and expand the portfolio into IVD manufacturing.

How has Genes2me come to the forefront during the pandemic? Tell us about your journey of delivering 40 Million covid test kits in India to date.

We take pride in the fact that Genes2Me has been working at the front line from the very first day of the pandemic. We developed several IVD kits, including Real-Time PCR Kits, VTM Kit, RNA Extraction Kits, NGS Kits and multiplexed genotyping assays for COVID-19 detection in a quick turnaround time.

Our ViralDtect-II Real-Time PCR Kit for COVID-19 has been a real turning point. It was the first Made in India Real-Time PCR Kit with comprehensive coverage of three genes that are specific to SARS-COV-2.

Also, there have been reports of new strains of SARS-COV-2 being detected. Genes2Me has developed a Unique Mutation Classifier assay that can rapidly differentiate 40 variants between 16 SARS-CoV-2 strains. This can help in the quick genetic screening of large sections of the population.

Genes2Me have been working tirelessly and have delivered more than 40 million COVID-19 testing kits to date. Also, to meet the sudden demand surge of the second Covid wave, we ramped our manufacturing facility from 9million per month to 6 million per week. In fact, during this time, Genes2Me contributed over 20% of the entire Indian testing needs for RT-PCR.

From where the idea of stepping into manufacturing IVD kits came under the Make in India initiative? What have been the challenges and opportunities?

When the pandemic hit us, not many diagnostic labs had the necessary infrastructure or accreditations to offer Covid testing facilities. As the pandemic gathered force, there was not only demand for faster testing but also testing in much higher volumes. The response to that struggle was the idea behind IVD kits under the Make in India initiative.The Indian government has taken progressive steps to boost the capacities of the domestic IVD sector. Genes2Me is also working to collaborate with the government and prestigious medical institutes to offer services on the innovative classifier panel of SARS-COV-2. In this manner, we can all be better prepared to face the challenges posed by this virus frequently changing genetic makeup.

What changes should diagnostic companies bring to fight the pandemic and meet the current market demand?

Post Covid-19, we have seen the entry of many companies into the Molecular Diagnostics Testing and Kit Manufacturing segment. Unfortunately, not many companies have been able to deliver quality genetic solutions in a fast turnaround time. This is evident from the fact that around 10-15 players used to compete in the Tender queries of IVD products till last year. But now, only 4-5 bidders are participating in the Tender queries as most of the companies have failed to satisfy customer expectations of Quality Product.

If you want to build a sustainable diagnostic company, you should maintain Quality Manufacturing and Testing Standards. Genes2Me has responded by building capacities and training faster to keep up with the surge without compromising the sensitivity of Genetic Solutions.

What have been some recent developments and future plans of Genes2me?

Genes2Me is vigorously working to leverage the large installed base of molecular testing platforms across the globe. With the help of our expertise and access to advanced technologies, we have developed several assays for Infectious diseases, Oncology and Reproductive Health in India. In the past, most of these test panels were import-dependent from other countries.

In addition, under the Make in India initiative, we are working to develop diverse nucleic acid research and diagnostics solutions along with NGS reagents for genome sequencing. Again, these solutions were dependent on import from different nations.

Genes2Me has also ramped up Covid-19 testing facilities by installing more infrastructure, hiring manpower and training them meticulously to ensure smooth functioning. Our advanced high throughput Real-Time PCR testing Lab at Gurgaon, Haryana, has an unmatched capacity to perform 8K-10K tests per day.

How do you see the future of Genetic Diagnostics in India?

India has a population of more than 1.26 billion people, with 26 million births occurring every year. This means that the burden of a genetic disease is very high. With the help of genetic diagnostics, many diseases can be predicted with great accuracy. If genetic testing is done at the appropriate stage, some diseases can be prevented, cured or managed better.

Genetics diagnostics in India is on the verge of transformation. There has been widespread awareness and recognition of the increasing incidence of congenital and hereditary genetic diseases in urban India. More and more people are seeking genetic testing and counselling services. Genetic diagnostic in India will evolve from a niche speciality to a wide scope of applications for complex diseases and personal use.

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Genetics diagnostics in India is on the verge of transformation: Neeraj Gupta, Founder and CEO of Genes2me - The Financial Express

Toronto, Ontario - Thursday August, 9 -- Linwood Barclay -- Author Linwood Barclay poses for a picture in Toronto, Thursday August 9, 2018. (Mark Blinch/Globe and Mail)

Mark Blinch/The Globe and Mail

Linwood Barclay had a decades-long career as a newspaper editor and humour columnist before he transitioned to writing thrillers in the early aughts. To call that move a success would be an understatement. Barclays 20 novels, which includes the Promise Falls trilogy along with a memoir about running his familys trailer park north of Peterborough in his youth, and two novels for children have sold millions and been translated into more than 25 languages. Stephen King counts himself a fan.

His latest, Find You First, features cars, genetic testing and not one but two unrelated yet intertwined multimillionaires at opposite ends of the empathy spectrum. One, Jeremy Pritkin, is an uber-creepy Jeffrey Epstein-type philanthropist who regularly invites young girls to his massive Manhattan digs. The other, Miles Cookson, has just been diagnosed with a terminal disease that has a 50-per-cent rate of genetic transmission and is racing to track down the nine adults he fathered decades ago through a sperm bank his plan being to warn them, and to make them his direct heirs. But the plan quickly hits a snag: His unwitting offspring are getting serially knocked off before hes even able to reach them.

The Jeffrey Epstein affair was clearly it sounds wrong to say inspiration, so lets go with spark for this book. How did you think to intertwine it with genetics?

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What sparked the novel was a New York Times piece where someone took photos of all these half siblings who were the product of the same sperm donation, and I thought, thats a heartwarming personal-interest story. But as a thriller writer you think: How could that go horribly wrong? So I was working on that storyline, and when I was starting to plot the book out, the most obvious answer to the mystery was that one of the potential heirs was wiping out the others. And that seemed so obvious that I thought I needed another parallel story that would address the mystery, which is when I started thinking about the Epstein thing.

Have you had your DNA tested?

No. And I dont think I could have written this thriller 15 years ago because you didnt have ads on TV every night saying, Hey, send us a saliva sample! Itll tell you everything about you, and who you could be related to. I looked at this trend more as an opportunity for a story than something I was really curious about doing myself. But my brother had his done, and it didnt reveal anything particularly startling.

Tech is an unavoidable element in modern-day thrillers, just as it is in our lives. Is it something you embrace or just accommodate in your books?

Accommodate. I did an earlier book, Trust Your Eyes, thats a little more involved with tech. It was rooted around Google Street View. There are elements of tech that are very worrisome. If theres any kind of trend that concerns me its been the death, or the decline, of newspapers. Also this kind of embracing of ignorance, and real fake news. The stuff people will believe is so blatantly, obviously not true. Those issues scare me even more than the tech stuff, although the tech stuff plays a role in it because its whats spreading all this disinformation.

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From the vantage point of the 20-novel milestone, what do you feel youre better at? Whats still hard?

Its a little less daunting every time I start, but Ill write a book and make a mistake, or see something I should have done differently, and I think, Okay Ill learn from that for the next book. And I dont make that mistake, but I make a new one, so I find that Im always learning. The trick is to give readers what theyre hoping to get but not give them the same thing you gave them last time. And I dont kill myself doing it the way I used to. I used to try to write 3,000 words a day, and now I do 1,800 to 2,100.

Have you stayed in touch with your readers during this pandemic year?

I have a couple Facebook pages, and Twitter, so I get a lot of feedback, which is nice. Especially in a year when you couldnt go out and see anybody. I always do a U.K. tour and hit Ireland and Scotland, so there was none of that. Writing is a pretty isolating occupation to begin with, so tours and festivals are your one chance to get out and discover that the world is populated.

What parts of the writing process do you like or dislike the most?

I still think finishing is the most fun. There are two parts I really hate. When you send your first draft to your editors its like waiting for tests to come back from the doctor. Is it good news or bad news? And then theres the final reading of page proofs. By that point Im so sick of it. I cant see any mistakes because Im reading what I expect to read, so I never enjoy that.

This book and many of your others have riffed on current events. Do you see any possibilities in a pandemic-lockdown theme?

Ive set next years book in 2022 with the hope that well have moved past this. All Ive done is reference it. My character finds an old mask between his car seats, or some rubber gloves or sanitizer in the glove box. Its such a global event that I think itll end up being incorporated in just about anything that we do, but to actually write a pandemic novel? Theres a guy named Stephen King who wrote a fairly good one back around 1978 or 79, so its kind of been done. The thing is, will we want to read a pandemic novel when were done with this? Ill be happy to forget about it.

Speaking of Stephen King, hes blurbed this book as your best. Do you agree?

It would be rude to argue! Maybe it is. I think its got more momentum than maybe anything else Ive done. It really flies. Trust Your Eyes might still be my favourite, but you know, [King] may be right: This might be it. Maybe I should just quit. But every book you do you hope itll be the best and there are some years where you think, Yeah I pulled it off and others where you think, I can get away with this. Thats the challenge for those of us who write this kind of fiction: Theres an expectation of a book a year.

So whats next? You mentioned a couple of books coming out

Ive done the second draft of next years book, and I wrote a screenplay adaptation for my book Fear the Worst that Jason Priestley wants to star in and produce, and we think we have a director now. But mostly I think I can coast through the summer and then Ill have to get back seriously to writing whatever the next book will be in the fall.

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This interview has been edited and condensed.

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Linwood Barclay emerges from the pandemic to talk about the latest genetic mystery hes penned - The Globe and Mail

Enlarge / On the outside, these heavily engineered bacteria look no different from their normal peers.

Many of the fundamental features of life don't necessarily have to be the way they are. Chance plays a major role in evolution, and there are always alternate paths that were never explored, simply because whatever evolved previously happened to be good enough. One instance of this idea is the genetic code, which converts the information carried by our DNA into the specific sequence of amino acids that form proteins. There are scores of potential amino acids, many of which can form spontaneously, but most life uses a genetic code that relies on just 20 of them.

Over the past couple of decades, scientists have shown that it doesn't have to be that way. If you supply bacteria with the right enzyme and an alternative amino acid, they can use it. But bacteria won't use the enzyme and amino acid very efficiently, as all the existing genetic code slots are already in use.

In a new work, researchers have managed to edit bacteria's genetic code to free up a few new slots. They then filled those slots with unnatural amino acids, allowing the bacteria to produce proteins that would never be found in nature. One side effect of the reprogramming? No viruses could replicate in the modified bacteria.

The genetic code handles translation, during which the information encoded in DNA is made into a functional protein. Key to this process is a group of small RNA molecules called transfer RNAs (or tRNAs). Transfer RNAs have a small, three-base segment that can be matched through base pairing with information carried by DNA. These transfer RNAs can also be chemically linked to a specific amino acid in a process catalyzed by particular enzymes.

That combinationthree specific bases paired with a particular amino acidis the key to translation, i.e., to matching the bases of DNA with a specific amino acid.

A three-base code and four possible bases (A, T, C, and G) yield 64 possible three-base combinations, called codons. Three of those codons signal for translation to be stopped when the end of the protein-coding sequence is reached. That leaves 61 codons for only 20 amino acids. As a result, some amino acids are encoded by two, four, or even six different codons.

That redundancy in the code is what the research teambased in Cambridge, UKtargeted. A few years ago, the researchers edited the entire E. coli genome so that one of the redundant codons were freed up. The research team edited all instances of one of the three stop codons into one of the others so that there were no longer any instances of it in the entire genome. Instead of being used for something, the codon was freed up to be redefined.

The researchers did similar experiments with the codons for the amino acid serine. Instead of leaving six codons that say "serine," the team edited the total down to just four by changing every instance of the two they targeted to a different serine codon.

(That may sound simple, but even a small genome like E. coli's has thousands of each of these codons scattered through millions of base pairs. Editing the genetic code is an impressive technical achievement on its own.)

While the bacteria didn't use the three edited codons, they still could. All the pieces needed to use the codonsthe transfer RNAs, the enzymes that attach amino acids to them, etc.were still present. For reasons that aren't entirely clear, the modified bacteria weren't especially healthy and grew at a slower pace than their unedited source.

For their follow-up work, the researchers evolved the strain to tolerate the modified genetic code better. They exposed the bacteria to mutagens and then grew lots of samples using an automated system that identified when a sample was growing well and kept supplying the sample with fresh food. (Fast-growing bacteria turn whatever they're grown in cloudy, allowing them to be identified.) After a couple of rounds of mutation, near-normal growth was restored.

At that point, the researchers went back and deleted the genes for the transfer RNAs and enzymes that allowed their three edited codons to work. With those changes made, it wasn't that the codons were no longer being usedthey could no longer be used.

Again, this issue slowed down the growth of the bacteria, although it's not clear whyeither some of the deleted genes have other functions or there were codon instances the researchers missed in editing. Regardless, they mutated the bacteria again and selected a strain in which much of the growth had been restored. By the time everything was done, the scientists had a strain that grew about half as well as a normal E. coli. They also had three completely unused codons.

(As an aside, the team also obtained a genome sequence of this final strain to see what mutations had occurred during this process. Although numerous differences were identified, none were obviously associated with the ability to grow with a modified genetic code. The lab has undoubtedly since assigned a few grad students to figure out that conundrum.)

To confirm that the three unused codons were nonfunctional, the researchers infected them with viruses. The proteins encoded by these viruses normally include the unused codons, so this method provides a test of whether the codons' use was truly eliminated.

The bacteria passed the test. No viruses could grow in the engineered strain, even when a mixture of five different viruses were thrown in the culture at the same time. It was clear that in this strain, these codons simply could not be used.

That's what the researchers wanted in the first place (it's fair to say they didn't set out to make virus-resistant bacteria). Now they could start using the three codons for amino acids that aren't naturally used by life on Earth.

The researchers supplied the bacteria with some non-native amino acids, along with the genes for a transfer RNA to attach the amino acids to and an enzyme that would do the attaching. They then started inserting the gene for a nonbacterial protein that could only be translated by using the codons they had redefined and confirmed that the protein was made and that it incorporated these non-natural amino acids. The team even made a version that incorporated three different artificial amino acids, showing that they truly had expanded the genetic code.

The researchers were also able to make strains that used a different set of three artificial amino acids. So it's possible to make a large collection of strains, each specialized to use a different set of artificial amino acids.

The authors didn't go on to demonstrate anything practical, but there are plenty of potential uses for the research. Artificial amino acids can potentially catalyze reactions that aren't possible or efficient with the normal set of 20. And we don't have to necessarily design an enzyme that incorporates the new amino acids; instead, we can simply try to evolve the function in strains with an expanded genetic code.

There's also the possibility for some interesting polymer chemistry. In the chemical reactions that form most polymers, we typically use only a single type of subunit to build the polymer, since you can't control what links with what. But proteins let you build a polymer chain with complete control of the order of each subunit because you can specify the order of amino acids. With an expanded genetic code, we can potentially get molecule-level control over the construction of polymers.

Science, 2021. DOI: 10.1126/science.abg3029 (About DOIs).

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Researchers rewire the genetics of E. coli, make it virus-proof - Ars Technica

Breast cancer is caused by mutations, or damage, to the DNA in breast cells. Exactly what triggers this change is unknown, but many people will spend countless hours trying to figure it out.

What is known is that there are risk factors that may increase your chances of getting breast cancer. Some of them, like age, family history, and dense breasts, cant be changed. Others are determined by lifestyle factors that can often be controlled.

In the United States, its estimated that around 30% of new cancer diagnoses in women will be breast cancer. This makes early detection and possible prevention very important. In this article, well go over the potential causes of breast cancer and what you can do about them.

Breast cancer originates in breast tissue. Its caused by changes, or mutations, in breast cell DNA. These mutations cause cells to grow abnormally and divide quicker than healthy cells do. The abnormal cells accumulate, forming a malignant breast mass, also known as a lump.

Your immune system may be able to successfully fight some abnormal cells. but the ones that continue to grow may spread, or metastasize, throughout the breast to the lymph nodes or other parts of the body.

When breast cancer spreads, the malignant tumors it causes in other places are still referred to as breast cancer.

What exactly triggers DNA changes in breast cells isnt clear. Two people can have the same or similar risk factors, but only one might develop breast cancer.

Age is the most significant risk factor for breast cancer. Most breast cancer cases are diagnosed in people over 55 years old.

But your genetics and external factors, like smoking, also have an impact. Genetic risk factors cant be changed, but lifestyle choices that put you at higher risk can be altered.

Its also likely that for many people, multiple risk factors both genetic and environmental have an impact when several are present.

People born with a vagina are at a significantly higher risk for getting breast cancer than those born without one. According to the Centers for Disease Control and Prevention (CDC), only about 1 in every 100 cases of breast cancer diagnosed in the United States is in a man.

You can inherit a gene mutation that puts you at higher risk for breast cancer from either biological parent. About 5 to 10 percent of all breast cancer cases are caused by hereditary gene mutations. The most common type is a mutation in the BRCA1 or BRCA2 gene.

If you have a BRCA1 or BRCA2 gene mutation, your risk for ovarian cancer is also increased.

There are other inherited gene mutations that can increase your risk as well, including:

If you have several close relatives with breast cancer, you may be more likely to develop it. This is especially true if you have one or more first-degree relatives with breast cancer. A first-degree relative is anyone you share at least 50 percent of your genetics with, like a parent or child.

Having a family history of breast cancer may mean you share the same genetic mutation. But there are other potential explanations here that have nothing to do with genetics.

For example, it may mean you share lifestyle choices that put you at greater risk. It may also be caused by environmental factors, like living in an area where chemical exposure, air pollution, or water pollution levels are high.

You may be more likely to develop ER-positive breast cancer if you began menstruating at a younger age or started menopause later than usual. This is because theres a longer period of time when breast cells are affected by estrogen and possibly, progesterone.

Never having given birth also increases your lifetime exposure to estrogen.

If you have given birth, every 12 months that you nurse your child reduces your chance of getting breast cancer by about 4.3 percent.

Smoking cigarettes and using nicotine products modestly increases the risk for breast cancer. The younger you were when you started smoking, the greater your risk. Smoking also increases your risk to a greater degree if you have a family history of the disease.

The International Agency for Research on Cancer has determined that alcohol is a carcinogen thats causally related to breast cancer risk.

The greater your alcohol intake, the higher your risk may be. But even one drink per day increases risk in both premenopausal and postmenopausal women.

Toxins and chemicals can be found in:

Some toxins are known as endocrine disruptors, or endocrine disrupting compounds. These toxins can mimic the effects of estrogen in the body and may increase breast cancer risk. Endocrine disruptors include:

Certain foods may increase your risk of breast cancer. Foods to limit or avoid include:

Because fat cells produce estrogen, being overweight or obese can be a significant risk factor as is having a sedentary lifestyle, which may contribute to increased weight.

Women whove previously had breast cancer or are postmenopausal have an even higher risk if theyre overweight or are living with obesity.

Hormonal birth control, including the pill, ring, and IUD, may increase your breast cancer risk slightly. This may be greater if you use hormonal birth control for 5 years or more. If you have a family history of breast cancer, your risk may be higher.

Hormone replacement therapy (HRT) poses a much greater risk. HRT isnt recommended for symptom relief of menopause in people who have other risk factors for breast cancer.

Early detection wont stop you from getting breast cancer, but it can help to ensure a better outcome. Talk with a doctor about how often you should get a mammogram. If you have dense breasts, getting regular ultrasounds may also be beneficial.

Adjustments to your lifestyle may also help. These include:

The following tips may aid with recovery and with avoiding breast cancer recurrence:

Breast cancer is caused by mutations in breast tissue cells. The underlying risk factors for breast cancer include genetics, environmental toxins, and lifestyle factors, but a definite cause hasnt been identified.

Make proactive choices to reduce your risk of breast cancer. These include cutting down on smoking and alcohol use, as well as maintaining a healthy weight.

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Breast Cancer Causes: Genetics, Prevention, and More - Healthline