Genetic studies of paired metabolomes

Genetic studies of paired metabolomes

 The GCKD study is an ongoing prospective observational study that enrolled 5,217 adult persons with CKD between 2010 and 2012. Patients regularly seen by nephrologists with eGFR between 30 and 60mlmin1 per 1.73m2 or eGFR >60mlmin1 per 1.73m2 with UACR>300mg per g (or urinary protein/creatinine ratio>500mg per g) were included53. This study used biomaterials collected at the baseline visit, shipped frozen to a central biobank and stored at 80C54. A more detailed description of the study design, standard operating procedures and the recruited study population has been published53,55.Genetic studies of paired metabolomes 

Genetic studies of paired metabolomes
Genetic studies of paired metabolomes

Study design and participants

The GCKD study was registered in the national registry for clinical studies (DRKS 00003971) and approved by local ethic committees of the participating institutions (universities or medical faculties of Aachen, Berlin, Erlangen, Freiburg, Hannover, Heidelberg, Jena, Mnchen and Wrzburg)53. All participants provided written informed consent. For this project, metabolites were quantified from stored EDTA plasma and spot urine. Information on genome-wide genotypes, covariates and metabolites was available for 4,960 (plasma) and 4,912 (urine) persons.

Genotyping and imputation

Genotyping and data cleaning in the GCKD study were conducted as follows5,56. Genomic DNA from GCKD participants was genotyped at 2,612,357 variants using Illumina Omni2.5Exome BeadChip arrays and imputed using minimac3 version 2.0.1 at the Michigan Imputation Server57 and the Haplotype Reference Consortium haplotype version r1.1 and Eagle 2.3 for phasing. On the variant level, SNPs with <96% call rate, imputation quality of r20.3, MAF<1% or deviating from HardyWeinberg equilibrium (P<11010) and all multi-allelic SNPs were removed.

Metabolite identification and quantification

Non-targeted mass spectrometry analysis was performed at Metabolon, and sample preparation was carried out as published by Schlosser et al.5. Automated comparison of the ion features in the experimental samples to a reference library of chemical standard entries (>4,500 purified standards) was used for metabolite identification. Known metabolites reported in this study conformed to confidence level 1 (the highest confidence level of identification) of the Metabolomics Standards Initiative58,59, unless otherwise denoted with an asterisk.

Data cleaning of quantified metabolites

An in-house pipeline was set up for data quality control, filtering and normalization of metabolite concentrations. No plasma specimens and four pairs of urine specimens with a Pearson correlation coefficient greater than 0.9 and differing sample IDs were removed. Four plasma specimens and no urine specimens were removed for >50% missing data. A total of 130 plasma and 131 urine metabolites were removed, as less than 300 genotyped samples were available.Genetic studies of paired metabolomes

Genetic studies of paired metabolomes
Genetic studies of paired metabolomes

Definition of additional variables

In the GCKD study, an IDMS-traceable enzymatic assay (Creatinine Plus, Roche) was used to measure serum creatinine levels, for estimating GFR by means of the CKD-EPI formula61, and to measure urine creatinine levels. The Tina-quant Albumin assay (Roche) was used to measure serum and urine albumin, for adjustment and calculation of the UACR, respectively. The GFR was estimated in the ARIC study from serum creatinine and cystatin C using the CKD-EPI formula62.

Genome-wide association study of metabolite levels

Based on log2-transformed metabolite levels, residuals adjusted for age, sex and the first three genetic principal components were generated (similar to previous mGWAS5,6,56,63,64), with plasma levels additionally adjusted for ln(eGFR) and serum albumin. GWAS analyses of these residuals were performed with SNPTEST version 2.5.2 (, using imputed genotype dosages and linear regression under additive modeling. Statistical significance was defined as genome-wide significance after correcting for multiple testing by a Bonferroni procedure (3.91011=51081,296 plasma traits; 3.61011=51081,401 urine traits).

Heritability estimation

A genetic relationship matrix was calculated from all autosomal SNPs with an imputation quality of r2>0.6 using GCTA-GRM71. GCTA-GREML72 was then used to estimate the proportion of variation in log2-transformed and, in the case of urine, pq-normalized metabolite levels that can be explained by the SNPs for all metabolites that gave rise to an mQTL.Genetic studies of paired metabolomes

Independent SNP selection and statistical fine mapping

We identified independent signals within mQTL using approximate conditional analyses, with LD information estimated from our study sample. The fine-mapping regions of mQTL were aligned within matrices across metabolites, if index SNPs were in LD (r2>0.8). For each mQTL, the GCTA-COJO Slct algorithm version 1.91.6 (ref. 73) was used to identify independent genome-wide significant SNPs (Pconditional<3.91011), using a collinearity cutoff of 0.1. For mQTL with multiple independent SNPs, approximate conditional analyses were carried out conditioning on the other independent SNPs in the region using the GCTA-COJO Cond algorithm to estimate conditional effect sizes. Statistical fine mapping was performed for all independent SNPs per mQTL.

Independent SNP

In loci with a single independent SNP, approximate Bayes factors (ABFs) were calculated from the original GWAS effect estimates using Wakefields formula74 with a standard deviation prior of 1.33. For mQTL with multiple independent SNPs, ABFs were derived from the conditional effect estimates. The SNPs ABF was used to calculate the posterior probability for the variant driving the association signal (PPA, causal variant). Credible sets were calculated by summing the PPA across PPA-ranked variants until the cumulative PPA was >99%. log2-transformed credible set sizes were regressed on the MAFs of independent index SNPs.

Pairwise colocalization tests of plasma and urine mQTL

To examine whether association patterns with metabolites measured in plasma and/or urine are shared across or within matrices, we conducted pairwise colocalization analyses between mQTL. When the windows of 500kb around the index SNPs for two mQTLs overlapped, colocalization was performed within the region of the merged windows using a version of Giambartolomeis colocalization method75 as implemented with the function from the R package gtx ( with default parameters and prior definitions. To visualize the effect sizes and explained variance for colocalizing signals for mQTLs detected for the same metabolite across matrices (Extended Data Fig. 4), we used the R package circlize (ref. 76).


SNP annotation was performed by querying the SNiPA database version 3.4 (released 13 November 2020)13, based on the 1000 Genomes phase 3 version 5 and Ensembl version 87 datasets. The retrieved combined annotation-dependent depletion (CADD) score was based on CADD version 1.3. The Ensembl VEP tool was used for the effect prediction of SNPs. SNiPA was used to collect the following annotations for each index SNP: gene hit or close by, regulated genes, CADD score, SnpEff effect impact (exonic and noncoding), mQTL, pQTL, GWAS Catalog, cis eQTL, disease genes (based on ClinVar, OMIM, HGMD and Drugbank) and UK Biobank associations.

Relation of mQTLs to plasma proteins in trans and phenotypes

We also performed colocalization analyses of mQTLs with disease outcomes and biomarker measurements in the UK Biobank, with two representative kidney function traits and with trans pQTLs using the precomputed pQTL data from Sun et al.79 to gain insights into clinical consequences and potential molecular mediators of mQTLs. Association summary statistics between SNPs and 30 biomarkers from the UK Biobank baseline examination, including the liver function markers AST, ALT, GGT, bilirubin and albumin, were computed using BOLT-LMM80 (application no. 20272) in the same subset of European-ancestry participants as previous studies81.

Human Protein

Precomputed GWAS summary statistics of diseases as ascertained in the UK Biobank and analyzed using phecodes were obtained from (1,403 binary traits) and from (2,325 of 2,989 binary traits82; traits containing job-coding terms were excluded from the analysis).Genetic studies of paired metabolomes

Genetic studies of paired metabolomes
Genetic studies of paired metabolomes


Processing of gene expression data from tissue and cell types

To test for over-representation of plasma or urine mQTL-related genes among those highly expressed in specific tissues and cell types, we compiled bulk and single-cell gene expression (RNA-seq) datasets. These included GTEx version 8 (ref. 78), the Human Liver Cell Atlas85, a single-cell dataset and a single-nucleus dataset from the human kidney86,87, a single-cell dataset from the mouse kidney88, a single-cell dataset from the human intestine89 and a single-nucleus dataset from the kidneys of patients with CKD from the Kidney Precision Medicine Project (KPMP)90.

GO, KEGG, tissue and cell type enrichment analyses

Enrichment testing of the 282 identified genes was performed as follows. The number of independent SNPs per gene was computed using GCKD genotypes (PLINK version 1.90 (ref. 93)), and a database of Entrez gene identifiers based on version 3.8.2 was generated. Gene annotation included the number of independent SNPs per gene, gene length, GO terms94 and KEGG pathways95, as well as being Human Protein Atlas tissue or group enriched96;

Human Protein 

Human Protein Atlas cell type enhanced, enriched or group enriched97; being a VIP gene from PharmGKB (accessed 5 December 2020)98; being a gene with an actionable drug interaction from the Clinical Pharmacogenetics Implementation Consortium (levels A, A/B and B; accessed 13 January 2021)99; and being among the top 10% highly expressed genes in each GTEx version 8 tissue78 and human85,86,87,89,90 and murine cell types88.

100 million random draws

We performed 100 million random draws of an equal number of genes as contained in the respective source list (combined mQTLs, 282; plasma mQTLs, 214; urine mQTLs, 195; plasma-only mQTLs, 87; urine-only mQTLs, 68), matched for deciles of the number of independent SNPs and deciles of gene length and compared any overlap with cell types, tissues and terms with the ones identified for the original source list.

Multiple-testing correction was performed using the BenjaminiHochberg procedure100.Genetic studies of paired metabolomes



A new study asks whether racehorses have reached their genetic peak

A new study asks whether racehorses have reached their genetic peak

for decades there was an apparent paradox in horse racing. The sport is lucrative (Mage, this year’s Kentucky Derby winner, earned his owner $1.9 million) and the fastest horse wins. Horses with good results and a good pedigree are used as breeding stock for the next generation. Horse breeders were armed with a lot of data, a single trait to optimize, and strong incentives to do so. Yet several studies have suggested that despite their best efforts, race times were not improving.

The most common explanation was that, physiologically speaking, it was always more difficult to breed a horse that could run faster than existing horses already do. The modern Thoroughbred racehorse dates back at least three centuries. Perhaps the years of selective breeding had already discovered and exploited almost all the genetic potential of the breeds.

This made no sense to Patrick Sharman, a racing enthusiast and geneticist at the University of Exeter, England. After all, cattle breeding has been going on for hundreds of years, yet it continues to create cows that produce more milk. Artificial selection applied to chickens is still breeding plumper birds. It would be strange, he thought, if racehorses were the one domesticated animal that humans could no longer improve. Then, along with Alastair Wilson, who had once been his Phd supervisor, started digging.

Their first paper was published in 2015 and looked at a much larger dataset of British breeds dating back to the 1800s than other papers. He found that, contrary to accepted wisdom, horses actually got faster. In sprint races, those covered five to seven furlongs (1-1.4 km), the average speed needed to win has increased by about 0.1 percent every year since 1997. Their latest paper, published May 27 in Inheritance, try to gauge how much of that improvement is attributable to genetics. In other words, is the time-, energy- and money-intensive profession of horse breeding worth it?

The answer seems to be yes, although less so than farmers might like. Linking a large performance database, containing nearly 700,000 race times recorded in Britain between 1995 and 2014, to a family tree of over 76,000 horsepower, they found that speed is heritable, albeit weakly, and that breeding he is improving it, but slowly.

The drive is more pronounced for sprints and middle-distance races (812 furlongs). Drs Sharman and Wilson conclude that about 12% of the variation in horse speed at these distances comes down to genetics. (This is roughly the same heritability as neuroticism, extraversion, or lifespan in humans.) And they found that improvements to that genetics accounted for more than half of the speed increase observed over that time period. . The rest, Dr. Sharman says, is likely due to non-genetic factors like better nutrition or veterinary care for better maneuvering technique.

When it comes to long-distance racing, it’s not clear if the times are improving. One reason, says Dr. Sharman, it could be that genes that are good for sprinting don’t necessarily make good endurance athletes. It appears that breeders select for sprint performance because it offers faster commercial returns. Sprinters tend to start racing around the age of two, long-distance horses at three.

Horse breeders can also face other trade-offs. Selecting solely for speed can increase your risk of injury. (Churchill Downs Racecourse, where the Kentucky Derby is run, suspended racing for a month from June 7, after more than a dozen horses had died of injuries in the past six weeks). Temperament also matters: a fast horse is of little use if it is not rideable.

Despite the difficulties, there is also evidence that breeders may be leaving some potency in the gene pool. At least in Britain, says Dr. Sharman, breeders still rely, to some extent, on their professional judgment when evaluating horses. Less intuitive, more objective statistical techniques have transformed other sports, most famously baseball, over the past two decades. Even horse racing may be ripe for its Moneyball moment.

#study #asks #racehorses #reached #genetic #peak

Hereditary cancer advocacy and examination of my genetic heritage

Hereditary cancer advocacy and examination of my genetic heritage

When I received my genetic testing kit in the mail, I quickly opened the package. I was eager to get tested and learn more about my genetic heritage and see if there might be an unknown cancer causing mutation that has been passed down in my family. I felt that as an advocate for hereditary cancer prevention speaking passionately about the importance of knowing and sharing family health history, I needed to be fully tested for the 84 known genes associated with hereditary cancers.

But my excitement turned to a sense of dread as I sat and stared at the kit for several minutes. I was hit with a scary “what if?” I wasn’t really scared for myself; I was afraid for my daughter. What if I carry a germline mutation that I may have passed on to you that would put you at increased risk for cancer?

I say increased risk because she already carries a BRCA2 mutation that she inherited from her late mother. She’s already a provident being monitored for cancers associated with that mutation, and I didn’t want to add any more weight. Inheriting other mutations that increase your risk of cancer can and does happen.

Ever since my late wife was first diagnosed with cancer and tested positive for BRCA2, and especially after my daughter also tested positive for the same mutation, I have wanted to do gene sequencing. It wasn’t that I was overly concerned about carrying a mutation with a cancer risk; after all, there really wasn’t much cancer history on my side of the family. However, my father had survived colon cancer when he was 60, and while he was probably sporadic and not genetic, I wanted to make sure.

But walk into your primary care physician’s office and request a full-panel genetic test for mutations that could cause cancer just because it’s usually met with strong resistance. Even if there is a family history of cancer, many doctors are reluctant to order genetic testing and counseling.

In my late wife’s case, the doctors knew her family’s cancer history for years before her diagnosis, but never suggested genetic testing. Of course, her family’s health history was staggering due to the different types of cancer. However, it should have warranted further investigation. Frustratingly and sadly, 21st century medicine has not yet found its way into all healthcare practitioners’ offices.

Luckily, in my defense, I’ve made great connections with non-profit organizations and individuals. Kathy Baker, executive director of one of those organizations,, helped me get tested. My Faulty Gene is a non-profit organization that helps provide information and assistance to people with a family medical history that suggests genetic testing might be helpful in identifying a cancer risk.

My anxiety about the test didn’t last long. Because of what happened to my wife, I was painfully aware of how not knowing about a genetic mutation can have tragic consequences. So I read the instructions twice to make sure I did everything right, provided my saliva sample and sent it right back.

However, my anxiety returned when I got the email telling me the test was complete. Those “what ifs” punched me in the stomach when I logged on to the results website. Surprisingly, and with a huge sigh of relief, I saw that only one mutation had been detected and it wasn’t related to cancer. It was linked to a metabolic disorder and I only had one copy of the mutation, two copies of the abnormal gene had to be present for the disease to develop.

Since genetic counseling is also important, regardless of the result, I scheduled a meeting to go over my test again. I also want to find out if there are any variants of uncertain meaning (VUS) that I might need to be aware of since the report didn’t mention any VUS information.

Taking the test has given me new insight into why there might be some hesitation about taking the test. Fear of what you might find and what you might have passed on to your children can have a strong effect. But as a phrase often used in the hereditary cancer community states, “knowledge is power.”

For more news on cancer updates, research and education, don’t forget to sign up for CURE newsletters here.

#Hereditary #cancer #advocacy #examination #genetic #heritage

Genetic test leads to correct diagnosis of boy with atypia…

A dozing baby is shown.

Despite having few signs and symptoms of Angelman syndrome (AS), a newborn was eventually diagnosed on genetic testing because of his nonspecific developmental delays and unexplained low muscle tone, according to one case study.

This report is a good example of giving physicians a lower threshold for suspecting and diagnosing AS, the researchers wrote. This can potentially lead to earlier diagnosis and better outcomes for AS patients.

The report, A case study of early diagnosed Angelman syndrome: recognizing atypical clinical presentationswas published in Cureus Journal of Medical Science.

Recommended reading

A dozing baby is shown.

Most Angelman patients diagnosed between 9 months and 6 years of age

Angelman syndrome is a rare genetic disorder characterized by symptoms such as developmental delays, motor problems, speech abnormalities, seizures and excessive excitability, with frequent laughing, smiling and gesturing.

Distinguishing physical signs include coarse (distinctive) facial features, a flat back of the skull, a prominent lower jaw, and a smaller-than-normal head circumference. These features usually develop within the first three years of life. Scoliosis, or curvature of the spine, is also a common feature of Angelman.

Although symptoms typically present between 6 and 12 months of age, most patients are diagnosed between 9 months and 6 years of age, with many cases being mistaken for other conditions with similar symptoms.

Researchers at the University of the Incarnate World School of Osteopathic Medicine in Texas described the rare case of a newborn who showed developmental delays but few signs of Angelman.

Our patient has a relatively rare presentation of AS, wrote the researchers.

The boy was born without complications but experienced a 9.3% weight loss at two days of age. A month later, he was hospitalized due to failure to thrive and inability to gain weight despite being fed on demand with expressed breast milk.

The patient was examined by a pediatric gastroenterologist who found no anatomical or physiological abnormalities of the digestive system. The parents were instructed to use only the formula, which helped the baby gain weight.

Regardless, the boy hasn’t reached developmental milestones for his age at two, four and six months. At two months he was unable to smile socially and at four months he could only partially roll over. Doctors suspected the boy might have developmental delays, so he received physiotherapy and speech therapy.

Recommended reading

An illustration of a woman greeting another person on a computer monitor.

The boy was referred to the neurologist and subjected to genetic testing

At nine months, the boy was diagnosed with global developmental delay and low muscle tone (hypotonia), and at 13 months he was referred to a neurologist.

Coarse facial features were noted on physical examination. However, there was no evidence of other characteristics consistent with Angelman, including protruding tongue, flat skull, prominent lower jaw, small head circumference, tremor-like movements, or excessive laughter.

Despite low muscle tone in his upper and lower extremities, the boy had normal strength and reflexes and a full range of motion. No history of seizures was noted, and MRI scans of the brain showed no signs of abnormalities, such as wasting (atrophy), bleeding, or fluid accumulation.

Seizure onset, which occurs in 75 percent of patients with AS before age three, was also absent in this patient, the team noted.

Genetic testing was ordered due to unexplained low muscle tone, which revealed a genetic mutation that causes Angelman. His family were informed of the diagnosis and future complications, and despite treatment, the boy has made slow progress.

Early diagnosis of AS is difficult due to the nonspecific symptoms and increased likelihood of misdiagnosis with other common genetic conditions, the researchers concluded.

This case study suggests that pediatricians should have a low threshold of suspicion for the diagnosis of AS when children present with nonspecific symptoms such as failure to thrive, hypotonia and global developmental delay, they added.

#Genetic #test #leads #correct #diagnosis #boy #atypia..

Lyric (Formerly ClaimsXten Portfolio) To Add Genetic Testing Edit Module To Its Market-Leading Payment Accuracy Solutions

Lyric (Formerly ClaimsXten Portfolio) To Add Genetic Testing Edit Module To Its Market-Leading Payment Accuracy Solutions

At the end of April, ClaimsXten Portfolio, the market leader in claims modification solutions, became Lyric, with the aim of simplifying the assistance business. Strategic partnership announced today combines Lyric’s market-leading statement editing solution with Concert Genetics machine learning models and proprietary genetic testing market data and will help address pain points for health plans and consumers in the space highly complex genetic testing.

PHILADELPHIA, June 7, 2023 /PRNewswire-PRWeb/ –Partnership with Concert Genetics to Leverage Proprietary Data and Machine Learning to Maximize Claims Payment Accuracy–

Lyric, formerly ClaimsXten Portfolio, has partnered with Concert Genetics (Concert), a leader in end-to-end genetic testing management, to provide solutions to health plan payers seeking to maximize payment accuracy for genetic test claims .


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“Our partnership will bring together machine learning models and proprietary market data,” said Lyric CEO Rajeev Ronanki. “By combining the power of our market-leading editing solution with Concert’s market-leading end-to-end genetic testing edits, we are eliminating complexity in the ever-evolving genetic testing space.”

Adding genetic testing content to Lyric’s payment accuracy offering will help address a costly challenge for health plans and their members, as it is nearly impossible to achieve consistent payment decisions when frequently ordered genetic tests are billed using numerous codes in potentially thousands of combinations.[1],[2] The number of tests, the scope of clinical applications and associated clinical trials are increasing, which can pose a challenge for healthcare professionals and insurers. As a result, the payer, provider and patient experience is often fragmented and frustrating, potentially limiting access to clinically appropriate testing.

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“This partnership is just one example of Lyric’s vision to simplify the support business. We will continue to expand our expertise and innovation, while also forming strategic partnerships with other industry-leading subject matter experts to bring added value to our clients, while minimizing while speed to market. The resulting solution will be a comprehensive playlist of options that best meet the unique needs of our customers,” Ronanki explained.

“Concert Genetics is moving toward a vision where information about genetic testing, including coverage and cost, is readily available at the point of care to support informed clinical decisions and convenient access for patients,” said Rob Metcalf, CEO of Concert Genetics. “We are delighted to partner with Lyric, an organization that is aligned with this vision and deploys the technical infrastructure to link information through to reimbursement decisions.”

For more information on the new genetic testing edit form, please visit:


About Lyrics

Healthcare is complex. When code, transactions and small complexities can lead to big problems and costly errors, transparency is more important than ever.

Lyric combines a flexible software rule engine with a comprehensive library of clinical content to help health plans meet policy management needs and pay claims right the first time. The company’s advanced editing framework effectively enforces health plan, government and industry policy on near real-time demand with interoperability designed and built to accommodate a plan’s mix of products, network infrastructure, and growth. Lyric’s comprehensive product suite includes primary and secondary editing, content and policy management, and other analytics services and solutions.

We’re changing the tone of transparency by simplifying the care business. Visit us at: to learn more about us.

About concert genetics

Concert Genetics is a managed services and software company advancing health by providing the digital infrastructure for reliable and efficient management of genetic testing and precision medicine. Concert’s genetic testing management capabilities leverage a proprietary US market database of clinical genetic testing, market-leading expertise, and a technology platform that supports the ordering, results, coding, coverage, and payment integrity of genetic tests. The following links provide more information on the Concertcoding Standards, Clinical Criteria, and GTU Test ID. Learn more at

[1]Concert Genetics 2022 Genetic Test Price Transparency Report

[2]Concert Genetics 2019 Coding variability in

Genetic Testing

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“This partnership is just one example of Lyric’s vision to simplify the care business. We will broaden our experience and innovation, building partnerships that will result in a comprehensive playlist of options that best meet our customers’ needs,” CEO of Lyric explained Raj Ronanki.

Contact with the media

Amy Churchill, Lyric, 1 7248414450, [email protected],

SOURCE Lyrical

2023 Benzinga. com. Benzinga does not provide investment advice. All rights reserved.

#Lyric #ClaimsXten #Portfolio #Add #Genetic #Testing #Edit #Module #MarketLeading #Payment #Accuracy #Solutions

The coastal family faces a rare genetic condition

The coastal family faces a rare genetic condition

Roya Malaekeh, a mother of three from El Granada, never lets her thoughts wander too far into the future. After her daughter Shadi Bozorginia, who turns 7 this month, was diagnosed with the rare genetic condition of Schaaf-Yang syndrome, Malaekeh has learned to take days and hours as they come.

I’m just looking to maybe look at next week, Malaekeh said. If I go to next year or beyond, there’s a lot more to do that I haven’t done yet and it’s really hard to think about.

Go back home

Roya Malaekeh (right) and son Darian Bozorginia, 3, greet Shadi Bozorginia, 6, as she is being helped off the school bus after a day at school. May 31, 2023. Anna Hoch-Kenney | Revision


Roya works with Darian on using a communication board while Shadi plays with a toy. May 31, 2023. Anna Hoch-Kenney | Revision

#coastal #family #faces #rare #genetic #condition

The genetic structure of Isthmiophora melis populations (Schrank, 1788) (Digenea: Echinostomatidae). Is the diet of the guests important? – Parasites and vectors

The genetic structure of Isthmiophora melis populations (Schrank, 1788) (Digenea: Echinostomatidae).  Is the diet of the guests important?  - Parasites and vectors

Digeneans are one of the most unique and most numerous groups of parasitic flatworms. Their life cycle is complex, with few parthenogenetic generations and only one hermaphrodite [21]. Due to the complexity of the life cycle, these parasites are often subject to various modifications of their life strategies. There are several ways the lifecycle can be changed [10]; however, the modification usually leads to the narrowing of the host spectrum. We can come across the results of numerous studies in the literature on life cycle modifications in digeneans (eg. [22,23,24]). In addition to these interesting alterations, it is also worth noting that the reproduction process occurs both sexually (in the definitive host) and asexually (in the intermediate hosts) in these parasites. Therefore, if we combine these data with the previously mentioned characteristics of digeneous life strategies, we get the set of main factors that could influence the genetic structure of a given population. Furthermore, the genetic structure of fluke populations also depends on the type of life cycle, i.e. allogeneic (semi-aquatic) or autogenous (in an aquatic environment). According to Blasco-Costa and Poulin [8]flukes with an autogenous life cycle express a significantly more pronounced genetic structure than those that leave the aquatic environment in mammalian or bird hosts. Isthmiophora melis it is among the trematodes with an allogeneic life cycle, i.e. having a pulmonary freshwater snail L. stagnalis as the first intermediate host, and freshwater vertebrates (amphibians and fish), as second intermediate host, while sexual reproduction occurs in carnivorous mammals. Our results showed that the genetic structure of I. Melis reflects the typical pattern of such organisms, i.e., reaching the high values ​​of Hd, no statistically significant variation between populations, the negative results of Tajimas d test and star shape of the haplotype network [25]. Therefore, it appears that the main factor influencing the genetic structure of I. Melis it is the biology of the host.

The striped field mouse is a non-synanthropic rodent species, which feeds mainly on plant food. However, some studies have shown that components of animal origin are also found in its diet (e.g. [26,27,28]). Studies conducted in urbanized areas of Warsaw and its surroundings reported a dominant share of invertebrate representatives in the food of A. agriculturaland the presence of vertebrate remains was found in almost 5% of the rodents examined [27]. In the RMP, the water in the ponds is drained periodically, which correlates with the production cycle of the carp, making the tadpoles a readily available food source for rodents (personal observation). The other host analyzed, the American mink, is a species of mustelid native to North America and introduced to Europe. The diet of this species has been analyzed in various studies with different methods, and its composition is probably strongly influenced by extrinsic factors such as habitat, meteorological conditions, seasonality or the abundance of potential prey (eg. [20, 29,30,31,32]); however, the major components are rodents, fish and amphibians. Therefore, this species is among the most common definitive hosts of I. Melis.

As previously reported, the wide range of hosts of I. Meliscombined with various aspects regarding the body size or physiological condition of its hosts (e.g., badger, mink vs striped field mouse), it can cause the parasites to exhibit clearly visible phenotypic plasticity [4], or alternatively, the morphological discrepancies not being due to phenotypic plasticity, can derive from modifications of the life cycle. In this study, we revealed that the intracommunity molecular diversity arose from rodents I. Melis it can be even higher than that of a typical host like the American mink (e.g. WMNP vs. RMP) or can reach a similar value (e.g. BNP, DNP). Of course, these studies could also have been performed with the application of other markers, such as single nucleotide polymorphism (SNP) or microsatellites. However, since the use of nad1 The mtDNA marker showed differences within and between populations, it can be concluded that the chosen methodology was sufficient. The material used in our study was also used in the research conducted by Chibowski et al. [20], in which the authors performed an isotope analysis of the American mink diet obtained from four locations (BNP, DNP, WMNP and NNP). This allowed to compare the composition of the host’s diet and the genetic variability of I. Melis. The results support the hypothesis that in trematodes with an allogeneic life cycle, host biology shapes the genetic structure of the parasites. When wanted.e., not a potential source of I. Melis the infection dominated the diet of the American mink, the genetic diversity of the parasite was at a low level. Conversely, when the diet was dominated by amphibians and, to a lesser extent, fish, the intrapopulation genetic diversity of I. Melis increased. Thus, regional differences in host diet appear to influence the genetic structure of the parasite population. Similar results have been observed in studies by Sharrard-Smith et al. [33]who evaluated the molecular phylogeny and distribution of Opisthorchiidae representatives in otters (Lutra lutra) and mink. The authors showed differences in phylogenies between the two species Metorchis bilis AND Pseudamphistomum truncatum may suggest divergent demographic histories, perhaps reflecting host’s conflicting diets. It is also worth noting that the correlation between the host’s diet and the presence of parasites is an important element necessary to understand the functioning of the food web in the ecosystem.

#genetic #structure #Isthmiophora #melis #populations #Schrank #Digenea #Echinostomatidae #diet #guests #important #Parasites #vectors

Genetic basis of pelvic organ prolapse in the sow

Barn with sows in farrowing stalls

Sow mortality has been a major growing concern for the swine industry, attracting the attention of producers, researchers and industry experts. The trend of increasing mortality rates is being observed globally, posing a serious production and welfare problem for the global swine industry. More importantly, the economic losses associated with sow mortality are substantial. Such losses could be attributed to the opportunity cost of losses of weaned piglets, loss of culled sows or replacement of sows in the production system. Furthermore, such an increase in sow mortality can drastically affect employee morale on the farm and raise employee welfare concerns.

There are a multitude of interacting and time varying factors that are leading to an increase in sow mortality. Nutritional imbalances, changes in management practices, the environment, infectious and non-infectious stressors, and reproductive complications are some factors that may contribute to this growing concern.

One such factor is pelvic organ prolapse, which is characterized by the loss of support from the tissues and muscles of the pelvic floor. This leads to the pelvic organs falling out of their normal position, resulting in protrusion of the pelvic organs, including the rectum, urethra, bladder, cervix, uterus, or vagina. Typically, vaginal, uterine and rectal prolapse are the most prevalent types seen in sows, either in combination or individually.

An industry-wide survey reported the role of multiple factors contributing to the increased risk of POPs in sows and genetics was sought to be one of them. However, there have been conflicting reports in previous years regarding the role of genetics in the susceptibility of sows to POP.

A recent study used pedigree-based records and reported that 22% of phenotypic variation in POP was due to genetics. Our study used the same dataset but advanced further to evaluate and understand the role of genetics in sow susceptibility to POP using genomic information.

This study was conducted using data collected on 30,429 purebred female records (calving and culling) from two multiplier farms located in the Midwestern United States, collected between 2012 and 2022. Of these records, information was available on the genotype of 14,186 sows. Sows were genotyped for 48,075 genetic markers throughout the genome. The overall incidence of POPs was 7.1% for dead and cull sows and was defined as the presence of vaginal, uterine or rectal prolapse or any combination present as it was difficult to distinguish between the three conditions for a farm employee. farm. Overall analyzes were performed as through and parity analyses. Statistical analyzes were conducted to estimate the heritability of POP susceptibility both between and within peers and the genetic correlates of POP susceptibility. Furthermore, a so-called genome-wide association study was performed to identify genomic regions associated with POP susceptibility, followed by functional genomic analyzes of these regions to identify potential genes and biological processes associated with POP susceptibility.

POP susceptibility has been confirmed to have a substantial genetic basis in this population and herds. This indicates that it can be selected against our herds to increase the survival of our sows. POP susceptibility has also been confirmed to have a similar genetic basis in different parities. Genome-wide association studies revealed six regions of the genome that were associated with POP susceptibility, but together they explained only 9% of genetic differences between sows. This means that there are many other genomic regions that contain genes associated with POP susceptibility but have small effects. Functional analyzes also provided detailed insights into several biological processes associated with POP susceptibility, including the role of collagen, estrogen receptor gene, and glycoproteins that are important for calcium/phosphorus homeostasis.

While there is no silver bullet, susceptibility to POP can be reduced by genetic selection because it is substantially heritable, at least in some populations and herds. Therefore, using POP data from such herds, breeders can choose to reduce the POP susceptibility of their lines using procedures similar to those used to select, for example, litter size. Furthermore, with further research, knowledge of the biological pathways discovered to influence POP susceptibility can be used to develop recommendations or targeted management interventions to reduce the incidence of POP in herds worldwide.

Bhatia, V., Stevens, T., Derks, M., Dunkelberger, J., Knol, E., Ross, J., and Dekkers, J. (2023). Identification of the genetic basis of pelvic organ prolapse in the sow. Frontiers In Genetics, 14. doi: 10.3389/fgene.2023.1154713

#Genetic #basis #pelvic #organ #prolapse #sow

The future of genetic engineering: promises and ethical dilemmas

The future of genetic engineering: promises and ethical dilemmas

The future of genetic engineering: promises and ethical dilemmas

Genetic engineering has immense potential to revolutionize various aspects of our lives, from medicine and agriculture to environmental conservation.

This article delves into the future of genetic engineering, exploring the considerable promise it holds for scientific advances and societal benefits. With great power comes great responsibility and ethical dilemmas surround the application of genetic engineering. We will examine these ethical considerations, examining the need for responsible research, regulation and public discourse to ensure that genetic engineering is carried out in a way that aligns with our values ​​and respects the boundaries of ethics.

Advances in genetic engineering


Source: Pirbright

The field of genetic engineering has made great strides in recent years, driven by advances in gene editing technologies such as CRISPR-Cas9. These tools have revolutionized the ability to manipulate genes, allowing scientists to precisely edit and control genetic material. The potential applications are vast, ranging from treating genetic diseases to developing personalized medicine, improving agricultural productivity and conserving endangered species.

Medical discoveries and human health

Genetic engineering offers unprecedented opportunities to address genetic diseases and improve human health.


Source: Drishtiias

With precise gene editing, researchers can potentially correct the genetic mutations responsible for disease. This could lead to the development of breakthrough therapies and even the eradication of some hereditary conditions. However, ethical considerations arise regarding the boundaries of genetic enhancements and the potential risks of unintended consequences.

Ethical dilemmas and social implications

As genetic engineering progresses, ethical dilemmas arise regarding its applications. Questions arise regarding the ethics of human germline editing, the creation of genetically modified organisms (GMOs), and the potential for genetic discrimination. It is critical to balance the desire for scientific progress with concerns about fairness, consensus, and long-term consequences.

Responsible research and regulation

To address the ethical challenges associated with genetic engineering, responsible research practices and effective regulation are essential. Scientific communities must adhere to robust ethical guidelines, including transparent research practices, informed consent, and rigorous safety assessments. At the same time, regulatory frameworks should ensure oversight without stifling innovation, providing a balance between promoting progress and protecting against potential risks.

Public engagement and deliberation

Given the far-reaching implications of genetic engineering, it is vital to involve the public in discussions and decision-making. Societal values, cultural norms, and ethical frameworks must inform the development and implementation of genetic engineering applications. Public engagement initiatives, open dialogues and inclusive decision-making can help shape policies that reflect the collective aspirations and ethical considerations of society.

Navigating the path forward

As we navigate the future of genetic engineering, striking a delicate balance between scientific advancement and ethical responsibility is critical. Collaboration between scientists, policy makers, ethicists and the public is essential to ensure that genetic engineering serves humanity’s best interests. Strong ethical frameworks, transparency, responsible research practices and informed regulations can guide the development and diffusion of genetic engineering technologies.

Breaking barriers into the future

The future of genetic engineering is very promising, offering significant possibilities for advancing medicine, improving agriculture and tackling environmental challenges.


Source: semantic scholar

To fully realize these benefits, it is imperative to address ethical dilemmas and navigate the associated social implications. By prioritizing responsible research, engaging in open public discourse, and implementing effective regulatory measures, we can ensure that genetic engineering is conducted in a way that aligns with our shared values ​​and respects the boundaries of ethics.

#future #genetic #engineering #promises #ethical #dilemmas

Genetic analysis confirms presence of wolf-dog hybrids in India | Weather forecast. com

Representative image: Indian gray wolf pups.  (Molina Khimani/ TOI Jaipur)

Representative image: Indian gray wolf pups.  (Molina Khimani/ TOI Jaipur)

Representative image: Indian gray wolf pups.

(Molina Khimani/ TOI Jaipur)

We’ve all heard the ancient idiom wolf in sheep’s clothing! While this cautionary tale warns of potential treachery, a citizen science initiative in Pune has now spotted such a real-life concoction that it could threaten the entire wolf population in India.

A campaign led by citizen scientists and researchers from the National Center for Biological Sciences (NCBS), Bangalore has confirmed the presence of a wolf-dog hybrid, an individual who is part wolf and part dog for the first time in India.

The earliest known wolfdog hybrids in India

While speculation about wolf-dog hybridization in India has been circulating for several years, until now there has been no conclusive empirical evidence in the form of genome analyses!

It all started in May 2021 when a group of nature enthusiasts led by Siddhesh Bramhankar spotted an outlier looking wolf in a pack near Pune. This wolf-like individual was distinguished by its unusually tawny coat. Observers photographed and documented two such cases. And they left in search of more!

Like true scientists, these science-enthusiastic citizens collected samples along the way. The noninvasive samples included the shed hairs of two individuals, which showed markedly different appearances.

After being tested on dogs, wolves and other genetically known canid species, including jackals and dholes, these samples yielded startling results.

This is the first evidence-based documentation of wolfdog hybridization in the country and also the first time citizens and scientists collaborated on such a discovery, lead researcher Uma Ramakrishnan told the Times of India.

Possible serious implications of hybridization

In a country where millions of dogs are found roaming the streets, they likely end up sharing space with wild wolves, especially since human interference has left the wildlife confined to fragmented habitats.

Having common ancestry, these dogs share a complex dynamic with gray wolves and golden jackals near human-modified landscapes, providing competition and potential for hybridization.

Interestingly, these hybrid individuals of the canine family are fertile. This feature is peculiar because in other mammalian hybrids, such as ligers or tigons (lion-tiger hybrids), at least one sex is usually sterile. Thus, due to the reproductive ability of wolf-dog hybrids, there is a greater propensity for repeated transfer of genetic information between the two.

And it seems that wearing the clothes of other canine members as well is not a good idea for wild wolves.

Wolfdog hybridization may lead to a significant reduction in specific adaptations in wolves that could lead to declines in their populations, the researchers said.

Introgression or mixing of dog genomes with wild wolves and vice versa can also threaten wolf diversity. It can tear apart wolf packs, disrupt their social structure, and push wild wolves into a vortex that could ultimately lead to extinction through increased interbreeding.

Therefore, the researchers have pushed for broader research into how wolf-dog interactions operate under current circumstances to find a roadmap that leads to conservation.

(With contributions from The Times of India)


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#Genetic #analysis #confirms #presence #wolfdog #hybrids #India #Weather #forecast