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'Revelatory' study finds a smoking impact that remains after quitting
People who smoked had increased inflammatory responses, but those higher levels were transient, dropping after smoking cessation. But the effects on the adaptive response persisted for many years after quitting, changing the levels of cytokines released after infection or other immune challenges.
First Genetic Clue Why Some People Do Not Get Sick From Covid | Barron's
Out of that group, 136 saw no Covid symptoms two weeks before and after testing positive.
One in five of that group carried at least one copy of an HLA variant called HLA-B*15:01.
Those fortunate enough to have two copies of the gene -- one from their mother, one from their father -- were over eight times more likely to be asymptomatic from Covid than other people, the study said.
A sleep disorder associated with shift work may affect gene function: Going on holiday has a restorative effect on changes in DNA -- ScienceDaily
A total of 32 shift workers participated in the study, of whom 21 suffered from shift work disorder and 11 were in the control group. Dynamic changes to DNA methylation were investigated through a genome-wide analysis during work and after a holiday period.
Changes to DNA methylation which affected gene function were identified in study subjects suffering from a sleep disorder caused by shift work. The findings demonstrated that rest and recovery during holiday periods also resulted in the restoration of DNA methylation in cases where changes had been observed during the work period.
The study proved the dynamic nature of DNA methylation, which was particularly emphasised in the activity of NMDA glutamate receptors. The strongest evidence was gained from the GRIN2C receptor: the methylation level of a specific CpG base pair in the regulatory region was lower during the work period in subjects suffering from shift work disorder. However, this change was reversed after the holiday period.
New clues why gold standard treatment for bipolar disorder doesn't work for majority of patients -- ScienceDaily
"Only one-third of patients respond to lithium with disappearance of the symptoms," says Renata Santos, co-first author on the study and a Salk research collaborator. "We were interested in the molecular mechanisms behind lithium resistance, what was blocking lithium treatment in nonresponders. We found that LEF1 was deficient in neurons derived from nonresponders. We were excited to see that it was possible to increase LEF1 and its dependent genes, making it a new target for therapeutic intervention in BD."
Researchers identify genetic factors that may influence COVID-19 susceptibility -- ScienceDaily
These findings demonstrate a possible association between ACE2 and TMPRSS2 polymorphisms and COVID-19 susceptibility, and indicate that a systematic investigation of the functional polymorphisms these variants among different populations could pave the way for precision medicine and personalized treatment strategies for COVID-19. However, all investigations in this study were performed in general populations, not with COVID-19 patient genetic data. Therefore, Dr. Cheng calls for a human genome initiative to validate his findings and to identify new clinically actionable variants to accelerate precision medicine for COVID-19.
Consuming alcohol leads to epigenetic changes in brain memory centers -- ScienceDaily
n, in mouse models, how acetate -- a byproduct of the alcohol breakdown produced mostly in the liver -- travels to the brain's learning system and directly alters proteins that regulate DNA function. This impacts how some genes are expressed and ultimately affects how mice behave when given environmental cues to consume alcohol. Their findings were published today in Nature.
"It was a huge surprise to us that metabolized alcohol is directly used by the body to add chemicals called acetyl groups to the proteins that package DNA, called histones," said the study's senior author Shelley Berger, PhD, the Daniel S. Och University Professor in the departments Cell and Developmental Biology and Biology, and director of the Penn Epigenetics Institute. "To our knowledge, this data provides the first empirical evidence indicating that a portion of acetate derived from alcohol metabolism directly influences epigenetic regulation in the brain."
Some high-cholesterol genes differ between countries - ScienceBlog.com
They found that the results were broadly consistent across European and Asian groups, with about three quarters of genetic markers applied similarly across the different groups, but only 10% of the genetic markers for triglycerides (the most common type of fat in the body) were implicated in the same cardiovascular risk factors among people from Uganda.
Estonia is using its citizens’ genes to predict disease
“The genetic risk score will be just another tool for doctors. In addition to measuring cholesterol levels, blood pressure, and body mass index, the genetic risk score will be yet another measurement that our prediction algorithm can use,” says Milani. She explains that they’ve already piloted a number of diseases to be diagnosed by the algorithm, but this currently takes place at the biobank, not in the doctor’s office.
“For the genetic information to be used in everyday practice we need to undertake pretty extensive IT developments — which we’re actually starting now. We’re launching the development of automated decision support software for physicians. So when doctors enter various patient data — such as cholesterol level, blood pressure, and smoking status — in the system, then the genetic risk will be calculated by the algorithm, and it’ll provide specific guidance accordingly.” She adds that the final product will be owned by the government, or to be more specific, by the citizens of Estonia.
Gut bacteria may be linked to high blood pressure and depression -- ScienceDaily
The researchers isolated DNA (deoxyribonucleic acid, the carrier of genetic information) from gut bacteria obtained from the stool samples of 105 volunteers. They used a new technique involving artificial-intelligence software to analyze the bacteria, which revealed four distinct types of bacterial genes and signature molecules. Surprisingly, the investigators discovered unique patterns of bacteria from people with 1) high blood pressure plus depression; 2) high blood pressure without depression; 3) depression with healthy blood pressure; or 4) healthy subjects without depression or high blood pressure.
Jogging and five other exercises ward off weight gain despite 'obesity genes' -- ScienceDaily
A new study of 18,424 Han Chinese adults, aged 30 to 70 years, examined the interactions between the individuals' genetics and their self-reported exercise routines. The researchers looked specifically at five measures of obesity, such as body mass index (BMI), body fat percentage and waist-to-hip ratio. They found that regular jogging was the best type of exercise for managing obesity, according to the five measures. Moreover, mountain climbing, walking, power walking, certain types of dancing, and long yoga practices also reduce BMI in individuals predisposed to obesity. Surprisingly, cycling, stretching exercises, swimming and Dance Dance Revolution did not counteract the genetic effects on obesity.
Hippocampus and memory development
The Geneva team has been following 275 patients aged 6 to 35 years for 18 years: a control groups of 135 individuals -- i.e. individuals without genetic problems -- and 140 people with deletion syndrome, including 53 with moderate to severe psychotic symptoms. "They underwent an MRI every three years so that we could observe their brain development," says Valentina Mancini, a researcher in UNIGE's Department of Psychiatry. "This has helped us create a statistical model that measures and compares the development of the hippocampus in both groups of patients." It was discovered that the hippocampus of the group affected by deletion syndrome, although smaller from the beginning, followed a growth curve identical to that of the control group. "This meant that we could hypothesise that the smaller size of the hippocampus originates in utero during its development in the womb." The UNIGE scientists also observed the subfields of the hippocampus in detail, discovering that one of them -- called CA3 -- was not affected by the decrease in size. "This subfield plays a crucial role in the work of memorisation and seems stronger than the other sub-parts," adds professor Eliez.
A one-size-fits-all approach to nutrition doesn't work, even for twins, gene study finds - ABC News
“Genetics may not explain most nutritional differences among people,” said Spector. “Most of this variation that affects our weight, risk of diabetes and heart problems is potentially modifiable for an individual.”
The researchers also analyzed how a person's metabolism may influence food choices, such as if it drives them to prefer savory or sweet foods or vice versa. However, Spector said that it was still unknown "how food preferences relate to food responses, but we do have the data.”
Spector’s study also found that microbiomes differ between identical twins, who shared only about 37% of their gut microbes with each other. By comparison, the study found that unrelated people share about 35% of the same gut microbiota.
After GWAS studies, how to narrow the search for genes? -- ScienceDaily
Borrowing the machine-learning concept of "cross-validation," Benchmarker enables investigators to use the GWAS data itself as its own control. The idea is to take the GWAS dataset and single out one chromosome. The algorithm being benchmarked then uses the data from the remaining 21 chromosomes (all but X and Y) to make predictions about what genes on the single chromosome are most likely to contribute to the trait being investigated. As this process is repeated for each chromosome in turn, the genes that the algorithm has flagged are pooled. The algorithm is then validated by comparing this group of prioritized genes with the original GWAS results.
"You train the algorithm on the GWAS with one chromosome withheld, then go back to that chromosome and ask whether those genes were actually associated with a strong p-value in the original GWAS results," explains Fine. "While these p-values don't represent the exact 'right answers,' they do tell you roughly where some true genetic associations are. The end product is an evaluation of how each algorithm performed."
Owning a dog is influenced by our genetic make-up -- ScienceDaily
"We were surprised to see that a person's genetic make-up appears to be a significant influence in whether they own a dog. As such, these findings have major implications in several different fields related to understanding dog-human interaction throughout history and in modern times. Although dogs and other pets are common household members across the globe, little is known how they impact our daily life and health. Perhaps some people have a higher innate propensity to care for a pet than others." says Tove Fall, lead author of the study, and Professor in Molecular Epidemiology at the Department of Medical Sciences and the Science for Life Laboratory, Uppsala University.
Ancient DNA suggests that some Northern Europeans got their languages from Siberia -- ScienceDaily
"Studying ancient DNA makes it possible to pinpoint the moment in time when the genetic components that we see in modern populations reached the area since, instead of predicting past events based on modern genomes, we are analyzing the DNA of individuals who actually lived in a particular time in the past," Saag explains.
Their data suggest that the Siberian ancestry reached the coasts of the Baltic Sea no later than the mid-first millennium BC -- around the time of the diversification of west Uralic/Finnic languages. It also indicates an influx of people from regions with strong Western hunter-gatherer characteristics in the Bronze Age, including many traits we now associate with modern Northern Europeans, like pale skins, blue eyes, and lactose tolerance.
"The Bronze Age individuals from the Eastern Baltic show an increase in hunter-gatherer ancestry compared to Late Neolithic people and also in the frequency of light eyes, hair, and skin and lactose tolerance," Tambets says, noting that those characteristics continue amongst present-day Northern Europeans.
Schizophrenia: 30 genes under suspicion -- ScienceDaily
Alex Schier's team has now identified 30 genes in these regions and has been able to show that they have concrete effects on the structure and function of the brain as well as on various behavioral patterns. "Of the 132 suspects, we were ultimately able to establish a more precise perpetrator profile for 30 genes," said Schier. "One of the perpetrators is the transcription factor znf536, which controls the development of the forebrain. This brain region influences our social behavior and the processing of stress." The research team not only deciphered the function of the individual genes, but also generated an atlas of all genes with their respective consequences for the brain
Reference genome is threatening dream of personalized medicine - STAT
On March 23, 1997, the then-nascent Human Genome Project placed an ad in a newspaper in Buffalo, N.Y. (site of a project scientist’s lab), seeking volunteers to donate blood from which they would sequence DNA. Through a quirk of whose DNA got processed when, about 70 percent of the reference genome comes from an anonymous man designated RP11, said UW genome scientist Evan Eichler, with the rest from a few score other volunteers. The reference genome is therefore a mashup of the sequences of these everyday people.
As a result, it isn’t a perfectly healthy genome: It has at least 3,556 variants that increase the risk of diseases, including type 1 diabetes and hypertension.
Its most serious shortcoming, however, reflects the fact that 1990s Buffalo was not exactly the United Nations. Its ethnic populations are almost all European — German, Irish, Polish, and others. The reference genome, therefore, is as well. That had long been known, but was largely swept under the rug.
Reference genome is threatening dream of personalized medicine - STAT
In other cases, the reference genome is missing vast quantities of the DNA found in non-Europeans. Computational biologist Steven Salzberg of Johns Hopkins University and colleagues sequenced the genomes of 910 African Americans and measured how many pieces are present in all of them but are missing from the reference genome. Their count: 296,485,284 base pairs — nearly 10 percent of the human genome — they reported last November. One missing fragment is 100,000 base pairs long, and millions are at least 1,000 long.
Serotonin can regulate gene expression inside neurons -- ScienceDaily
The study revolves around DNA and how it works to form each person's individual biological map. Each cell in the body contains two meters of DNA, the blueprint for all functions of all cells in the body. This DNA is wound around spools of histone proteins (proteins that package DNA in the nucleus of cells, and are heavily prone to chemical modifications that aid in the regulation of gene expression) into structures referred to as nucleosomes. When DNA encoding a specific gene is wound tightly within the spool, that gene is less likely to be expressed. When the gene is not wound as tightly, it is more likely to be expressed. This can affect many functions of a given cell.
Serotonin is a chemical that can transmit signals between neurons in the brain and is involved in the regulation of mood. Selective serotonin reuptake inhibitors, known as SSRIs, alter the amounts of serotonin in the brain, which enables mood changes. When small packages of serotonin are released from a neuron, the resulting signals set up a chain reaction of communication between different parts of the brain.
The research team discovered that a protein called tissue transglutaminase 2 can directly attach serotonin molecules to histone proteins (a process called histone serotonylation), which in turn loosens the spool to enable more robust gene expression. Specifically, they found that in developing rodent brains and human neurons, genes near the part of the spool loosened by the serotonin are more likely to be expressed. They also showed that a specific binding complex enables this process.
What controls the tips of our chromosomes? -- ScienceDaily
The researchers also showed that this process is identical both in yeast and in human cells. This means that the regulation of the "S" component has been conserved throughout evolution of species, which somehow reveals the importance of this process for the correct functioning of cells. This opens new avenues to the discovery of therapies capable of dealing with debilitating diseases associated to defects in telomeres. "The unanticipated role of this evolutionary conserved phosphatase is reminiscent of the regulation of the cell cycle by phosphatases that counteract the role of kinases, thus re-establishing the ground state of 'once and only once' cell cycle processes," says the investigator Miguel Godinho Ferreira. "With this work, we now understand better how telomere regulation works, a key process in cancer and ageing," says Jose Escandell, first author of the publication.
How genetic background shapes individual differences within a species: Every genome is different and scientists are beginning to understand what this means for life of an organism -- ScienceDaily
With all this information, Hou was able to scan the genomes of all 1000 yeast isolates and accurately guessed which other strains will act like Sigma or the Sake yeast and be completely reliant on the CYS genes to survive. This is similar to being able to single out, from 1000 patients with the same genetic disorder, those individuals who have a higher chance of developing a more severe form of disease.
Fat cells work different 'shifts' throughout the day -- ScienceDaily
During this unique study seven participants underwent regulated sleep-wake cycles and meal times before entering the laboratory, where they maintained this routine for a further three days.
Participants then experienced a 37- hour 'constant routine' during which time they did not experience daily changes in light-dark, feed-fast and sleep-wake cycles. Biopsies of fat tissue were taken at six hourly intervals and then followed by an analysis of gene expression.
Researchers identified 727 genes in the fat tissue that express their own circadian rhythm, many carrying out key metabolic functions. A clear separation in gene rhythms was identified with approximately a third peaking in the morning and two thirds in the evening.
Could we soon be able to detect cancer in 10 minutes? | Science | The Guardian
Looking for ctDNA has become a viable proposition in recent years because of improvements in DNA sequencing technologies that make it possible to scan fragments and find those few with alterations that may indicate cancer. While other blood-based biomarkers are being investigated, the advantage of ctDNA is that, because it has a direct link to the tumour, it can be very specific at identifying cancer. For that reason, ctDNA is also showing promise as a way to profile and monitor advanced stage cancers, a “liquid biopsy”.
Early detection is a harder problem. Early on, when the tumour is small, there is not as much ctDNA to detect. The women Illumina identified as having cancer were all late, not early stage.
The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated | Genetics in Medicine
Until very recently, the fragmented distribution of patients across institutions hindered the discovery of new rare diseases. Clinicians working with a single, isolated patient could steadily eliminate known disorders but do little more. Families would seek clinicians with the longest history and largest clinic volume to increase their chances of finding a second case, but what does a physician do when N = 1 or if the phenotype is inconsistent across patients? These challenges are driving an increase in the use of NGS. Yet this technological advance presents new challenges of its own. Perhaps the most daunting, in our opinion, is the inability to share sequencing data quickly and universally. Standards and bioinformatic tools are needed that allow for a national repository where families or scientists can bring clinical results and NGS data for comparison. This challenge can be circumvented by tools already created for and by the Internet and social media.
Your genes could impact the quality of your marriage: Specific genes relevant to how partners provide and receive support from each other -- ScienceDaily
"However, what emerged as most relevant to overall marital quality for both partners was genotypic variation among husbands at a specific location on OXTR. Husbands with a particular genotype, which other researchers associated with signs of social deficits, were less satisfied with the support they were provided. Being less satisfied with the support they got from their wives was also associated with being less satisfied with their marriage.
The researchers hope their findings provide the foundation for replication and additional study of OXTR as an enduring determinant of marital functioning, as well as encourage research more broadly evaluating the role of genetic factors in interpersonal processes important to overall marital quality.
"Genes matter when it comes to the quality of marriage, because genes are relevant to who we are as individuals, and characteristics of the individual can impact the marriage," said Mattson. "Our findings were the first to describe a set of genetic and behavioral mechanisms for one possible route of the genetic influence on marriage. In addition, we added to the increasing awareness that the expression of genotypic variation differs greatly depending on context."
Male Y chromosomes not 'genetic wastelands' -- ScienceDaily
Using sequence data generated by new technology that reads long strands of individual DNA molecules, Chang and Larracuente developed a strategy to assemble a large part of the Y chromosome and other repeat-dense regions. By assembling a large portion of the Y chromosome, they discovered that the Y chromosome has a lot of duplicated sequences, where genes are present in multiple copies. They also discovered that although the Y chromosome does not experience crossing over, it undergoes a different type of recombination called gene conversion. While crossing over involves the shuffle and exchange of genes between two different chromosomes, gene conversion is not reciprocal, Larracuente says. "You don't have two chromosomes that exchange material, you have one chromosome that donates its sequence to the other part of the chromosome" and the sequences become identical.