StemCell Therapy

A study carried out by the University of Malta shows that patients with the fatal neurological condition amyotrophic lateral sclerosis have different causative mutations to patients from Northern Europe.

The DNA results caught us by surprise. The most frequently mutated amyotrophic lateral sclerosis (ALS) genes were flawless in Maltese patients, said the studys lead researcher Ruben Cauchi, Ph.D., a senior lecturer at the University.

Instead, some of the 24 patients included in the study had mutations in genes occasionally associated with ALS including ATXN2, DAO, DCTN1, and ERBB4, among others.

As reported in the European Journal of Human Genetics, three of the 24 cases were familial and 21 were sporadic, with no known family history of the disease. Of the mutations seen in the sporadic cases, 40% were in genes with a previous link to ALS, whereas 60% were not. Only one of the familial cases had a mutation in a known ALS-associated gene.

Although Malta is part of Europe it is geographically and culturally isolated island population of just over 500,000 individuals, which makes it ideal for genetic biobanking studies. The Malta Biobank was set up at the university on the island in 1989 and now contains more than 100,000 samples.

Around 4 years ago, a national ALS registry was set up on the island to collect samples and data about those diagnosed with the condition to help scientists understand the condition better and help contribute to global research studies.

ALS is a rapid neurodegenerative condition with a strong genetic component, which currently has no cure. An effective treatment has proved difficult to develop, with many clinical trials failing over the last 10-15 years. However, research continues with the hope of finding a treatment or cure.

This study, which was carried out in collaboration with the University Medical Centre Utrecht in The Netherlands, sought to discover whether Maltese ALS patients had similar genetics and phenotypic characteristics to patients with the condition from elsewhere.

The researchers found that none of the Maltese patients had mutations in the genes C9orf72, SOD1, TARDBP and FUS, where the most common mutations associated with ALS are located, particularly in patients from a Northern European background. This agrees with other studies of Southern European countries, where rates of these mutations are also lower.

This finding confirms the presence of a NorthSouth gradient in the frequency of mutations within these genes across Europe, write the authors.

As with other populations, almost twice as many men were affected by ALS than women on Malta, although the women who were affected were diagnosed about 5 years earlier than the men at an average age of 59.5 years compared with 64 years. The overall incidence of 2-3 cases per 100,000 people was similar on Malta to elsewhere.

More familial cases of ALS (12.5%) were seen on Malta compared with elsewhere. Normally only 5-10% of cases are familial and 90-95% sporadic.

Our results underscore the unique genetics of the Maltese population, shaped by centuries of relative isolation. We also established that genetic factors play a significant role in causing ALS in Malta, noted Cauchi.

The researchers now plan to search for the disease triggers in the patients in the study who did not have mutations in known ALS-related genes.

Our preliminary data excludes the possibility that these patients have deleterious variants in a set of genes associated with other motor neuron disorders including hereditary ataxias, and hereditary motor and sensory neuropathies, writes the team.

Excerpt from:
Maltese ALS Patients Have Different Genetic Mutations than Northern Europeans - Clinical OMICs News

Experimental design

The teeth used for DNA extraction were obtained with relevant institutional permissions from the Institute of Ethnology and Anthropology of Russian Academy of Sciences (Russia), Cherepovets Museum Association (Russia), and Archaeological Research Collection of Tallinn University (Estonia). DNA was extracted from the teeth of 48 individuals: 3 from Stone Age HGs from western Russia (WeRuHG; 10,800 to 4250 cal BCE), 44 from Bronze Age Fatyanovo Culture individuals from western Russia (Fatyanovo; 2900 to 2050 cal BCE), and 1 from a Corded Ware Culture individual from Estonia (EstCWC; 2850 to 2500 cal BCE) (Fig. 1, data S1, table S1, and text S1). Petrous bones of 13 of the Fatyanovo Culture individuals have been sampled for another project. More detailed information about the archaeological periods and the specific sites and burials of this study is given below.

All of the laboratory work was performed in dedicated aDNA laboratories of the Institute of Genomics, University of Tartu. The library quantification and sequencing were performed at the Institute of Genomics Core Facility, University of Tartu. The main steps of the laboratory work are detailed below.

DNA extraction. The teeth of 48 individuals were used to extract DNA. One individual was sampled twice from different teeth. Apical tooth roots were cut off with a drill and used for extraction because root cementum has been shown to contain more endogenous DNA than crown dentine (62). The root pieces were used whole to avoid heat damage during powdering with a drill and to reduce the risk of cross-contamination between samples. Contaminants were removed from the surface of tooth roots by soaking in 6% bleach for 5 min, then rinsing three times with Milli-Q water (Millipore), and lastly soaking in 70% ethanol for 2 min, shaking the tubes during each round to dislodge particles. Last, the samples were left to dry under an ultraviolet light for 2 hours.

Next, the samples were weighed, [20 * sample mass (mg)] l of EDTA and [sample mass (mg) / 2] l of proteinase K were added, and the samples were left to digest for 72 hours on a rotating mixer at 20C to compensate for the smaller surface area of the whole root compared to powder. Undigested material was stored for a second DNA extraction if need be.

The DNA solution was concentrated to 250 l (Vivaspin Turbo 15, 30,000 MWCO PES, Sartorius) and purified in large-volume columns (High Pure Viral Nucleic Acid Large Volume Kit, Roche) using 2.5 ml of PB buffer, 1 ml of PE buffer, and 100 l of EB buffer (MinElute PCR Purification Kit, QIAGEN).

Library preparation. Sequencing libraries were built using NEBNext DNA Library Prep Master Mix Set for 454 (E6070, New England Biolabs) and Illumina-specific adaptors (63) following established protocols (6365). The end repair module was implemented using 30 l of DNA extract, 12.5 l of water, 5 l of buffer, and 2.5 l of enzyme mix, incubating at 20C for 30 min. The samples were purified using 500 l of PB and 650 l of PE buffer and eluted in 30 l of EB buffer (MinElute PCR Purification Kit, QIAGEN). The adaptor ligation module was implemented using 10 l of buffer, 5 l of T4 ligase, and 5 l of adaptor mix (63), incubating at 20C for 15 min. The samples were purified as in the previous step and eluted in 30 l of EB buffer (MinElute PCR Purification Kit, QIAGEN). The adaptor fill-in module was implemented using 13 l of water, 5 l of buffer, and 2 l of Bst DNA polymerase, incubating at 37C for 30 min and at 80C for 20 min. The libraries were amplified, and both the indexed and universal primers (NEBNext Multiplex Oligos for Illumina, New England Biolabs) were added by polymerase chain reaction (PCR) using HGS Diamond Taq DNA polymerase (Eurogentec). The samples were purified and eluted in 35 l of EB buffer (MinElute PCR Purification Kit, QIAGEN). Three verification steps were implemented to make sure library preparation was successful and to measure the concentration of double-stranded DNA/sequencing librariesfluorometric quantitation (Qubit, Thermo Fisher Scientific), parallel capillary electrophoresis (Fragment Analyzer, Agilent Technologies), and quantitative PCR. One sample (TIM004) had a DNA concentration lower than our threshold for sequencing and was hence excluded, leaving 48 samples from 47 individuals to be sequenced.

DNA sequencing. DNA was sequenced using the Illumina NextSeq 500 platform with the 75base pair (bp) single-end method. First, 15 samples were sequenced together on one flow cell. Later, additional data were generated for some samples to increase coverage.

Mapping. Before mapping, the sequences of adaptors and indexes and poly-G tails occurring due to the specifics of the NextSeq 500 technology were cut from the ends of DNA sequences using cutadapt 1.11 (66). Sequences shorter than 30 bp were also removed with the same program to avoid random mapping of sequences from other species. The sequences were mapped to reference sequence GRCh37 (hs37d5) using Burrows-Wheeler Aligner (BWA 0.7.12) (67) and command mem with reseeding disabled.

After mapping, the sequences were converted to BAM format, and only sequences that mapped to the human genome were kept with samtools 1.3 (68). Next, data from different flow cell lanes were merged and duplicates were removed with picard 2.12 (http://broadinstitute.github.io/picard/index.html). Indels were realigned with GATK 3.5 (69), and lastly, reads with mapping quality under 10 were filtered out with samtools 1.3 (68).

The average endogenous DNA content (proportion of reads mapping to the human genome) for the 48 samples is 29% (table S1). The endogenous DNA content is variable as is common in aDNA studies, ranging from under 1 to around 78% (table S1).

aDNA authentication. As a result of degrading over time, aDNA can be distinguished from modern DNA by certain characteristics: short fragments and a high frequency of CT substitutions at the 5 ends of sequences due to cytosine deamination. The program mapDamage2.0 (70) was used to estimate the frequency of 5 CT transitions.

mtDNA contamination was estimated using the method from (71).This included calling an mtDNA consensus sequence based on reads with mapping quality of at least 30 and positions with at least 5 coverage, aligning the consensus with 311 other human mtDNA sequences from (71), mapping the original mtDNA reads to the consensus sequence, and running contamMix 1.0-10 with the reads mapping to the consensus and the 312 aligned mtDNA sequences while trimming seven bases from the ends of reads with the option trimBases. For the male individuals, contamination was also estimated on the basis of chrX using the two contamination estimation methods first described in (72) and incorporated in the ANGSD software (73) in the script contamination.R.

The samples show 10% CT substitutions at the 5 ends on average, ranging from 6 to 17% (table S1). The mtDNA contamination point estimate for samples with >5 mtDNA coverage ranges from 0.03 to 2.02% with an average of 0.4% (table S1). The average of the two chrX contamination methods of male individuals with average chrX coverage of >0.1 is between 0.4 and 0.87% with an average of 0.7% (table S1).

Kinship analysis. A total of 4,375,438 biallelic single-nucleotide variant sites, with minor allele frequency (MAF) > 0.1 in a set of more than 2000 high-coverage genomes of Estonian Genome Center (EGC) (74), were identified and called with ANGSD (73) command --doHaploCall from the 25 BAM files of 24 Fatyanovo individuals with coverage of >0.03. The ANGSD output files were converted to .tped format as an input for the analyses with READ script to infer pairs with first- and second-degree relatedness (41).

The results are reported for the 100 most similar pairs of individuals of the 300 tested, and the analysis confirmed that the two samples from one individual (NIK008A and NIK008B) were indeed genetically identical (fig. S6). The data from the two samples from one individual were merged (NIK008AB) with samtools 1.3 option merge (68).

Calculating general statistics and determining genetic sex. Samtools 1.3 (68) option stats was used to determine the number of final reads, average read length, average coverage, etc. Genetic sex was calculated using the script sexing.py from (75), estimating the fraction of reads mapping to chrY out of all reads mapping to either X or Y chromosome.

The average coverage of the whole genome for the samples is between 0.00004 and 5.03 (table S1). Of these, 2 samples have an average coverage of >0.01, 18 samples have >0.1, 9 samples have >1, 1 sample have around 5, and the rest are lower than 0.01 (table S1). Genetic sexing confirms morphological sex estimates or provides additional information about the sex of the individuals involved in the study. Genetic sex was estimated for samples with an average genomic coverage of >0.005. The study involves 16 females and 20 males (Table 1 and table S1).

Determining mtDNA hgs. The program bcftools (76) was used to produce VCF files for mitochondrial positions; genotype likelihoods were calculated using the option mpileup, and genotype calls were made using the option call. mtDNA hgs were determined by submitting the mtDNA VCF files to HaploGrep2 (77, 78). Subsequently, the results were checked by looking at all the identified polymorphisms and confirming the hg assignments in PhyloTree (78). Hgs for 41 of the 47 individuals were successfully determined (Table 1, fig. S1, and table S1).

No female samples have reads on the chrY consistent with a hg, indicating that levels of male contamination are negligible. Hgs for 17 (with coverage of >0.005) of the 20 males were successfully determined (Table 1 and tables S1 and S2).

chrY variant calling and hg determination. In total, 113,217 haplogroup informative chrY variants from regions that uniquely map to chrY (36, 7982) were called as haploid from the BAM files of the samples using the --doHaploCall function in ANGSD (73). Derived and ancestral allele and hg annotations for each of the called variants were added using BEDTools 2.19.0 intersect option (83). Hg assignments of each individual sample were made manually by determining the hg with the highest proportion of informative positions called in the derived state in the given sample. chrY haplogrouping was blindly performed on all samples regardless of their sex assignment.

Preparing the datasets for autosomal analyses. The HO array dataset (https://reich.hms.harvard.edu/downloadable-genotypes-present-day-and-ancient-dna-data-compiled-published-papers) was used as the modern DNA background. Individuals from the 1240K dataset (https://reich.hms.harvard.edu/downloadable-genotypes-present-day-and-ancient-dna-data-compiled-published-papers) were used as the aDNA background.

The data of the comparison datasets and of the individuals of this study were converted to BED format using PLINK 1.90 (http://pngu.mgh.harvard.edu/purcell/plink/) (84), and the datasets were merged. Two datasets were prepared for analyses: one with HO and 1240K individuals and the individuals of this study, where 584,901 autosomal SNPs of the HO dataset were kept; the other with 1240K individuals and the individuals of this study, where 1,136,395 autosomal and 48,284 chrX SNPs of the 1240K dataset were kept.

Individuals with <10,000 SNPs overlapping with the HO autosomal dataset were removed from further autosomal analyses, leaving 30 individuals of this study to be used in autosomal analyses. These included 3 from WeRuHG, 26 from Fatyanovo, and 1 from EstCWC (table S1).

Principal components analysis. To prepare for PCA, a reduced comparison sample set composed of 813 modern individuals from 53 populations of Europe, Caucasus, and Near East and 737 ancient individuals from 107 populations was assembled (tables S3 and S4). The data were converted to EIGENSTRAT format using the program convertf from the EIGENSOFT 7.2.0 package (85). PCA was performed with the program smartpca from the same package, projecting ancient individuals onto the components constructed based on the modern genotypes using the option lsqproject and trying to account for the shrinkage problem introduced by projecting by using the option autoshrink.

Admixture analysis. For Admixture analysis (86), the same ancient sample set was used as for PCA, and the modern sample set was increased to 1861 individuals from 144 populations from all over the world (tables S3 and S4). The analysis was carried out using ADMIXTURE 1.3 (86) with the P option, projecting ancient individuals into the genetic structure calculated on the modern dataset due to missing data in the ancient samples. The HO dataset of modern individuals was pruned to decrease linkage disequilibrium using the option indep-pairwise with parameters 1000 250 0.4 in PLINK 1.90 (http://pngu.mgh.harvard.edu/purcell/plink/) (84). This resulted in a set of 269,966 SNPs. Admixture was run on this set using K = 3 to K = 18 in 100 replicates. This enabled us to assess convergence of the different models. K = 10 and K = 9 were the models with the largest number of inferred genetic clusters for which >10% of the runs that reached the highest log likelihood values yielded very similar results. This was used as a proxy to assume that the global likelihood maximum for this particular model was indeed reached. Then, the inferred genetic cluster proportions and allele frequencies of the best run at K = 9 were used to run Admixture to project the aDNA individuals, for which the intersection with the LD pruned modern dataset yielded data for more than 10,000 SNPs, on the inferred clusters. The same projecting approach was taken for all models for which there is good indication that the global likelihood maximum was reached (K3 to 18). We present all ancient individuals in fig. S2 but only population averages in Fig. 2B. The resulting membership proportions to K genetic clusters are sometimes called ancestry components, which can lead to overinterpretation of the results. The clustering itself is, however, an objective description of genetic structure and hence a valuable tool in population comparisons.

Outgroup f3 statistics. For calculating autosomal outgroup f3 statistics, the same ancient sample set as for previous analyses was used, and the modern sample set included 1177 individuals from 80 populations from Europe, Caucasus, Near East, Siberia and Central Asia, and Yoruba as outgroup (tables S3 and S4). The data were converted to EIGENSTRAT format using the program convertf from the EIGENSOFT 5.0.2 package (85). Outgroup f3 statistics of the form f3(Yoruba; West_Siberia_N/EHG/CentralRussiaHG/Fatyanovo/ Yamnaya_Samara/Poland_CWC/Baltic_CWC/Central_CWC, modern/ancient) were computed using the ADMIXTOOLS 6.0 program qp3Pop (87).

To allow chrX versus autosome comparison for ancient populations, outgroup f3 statistics using chrX SNPs were computed. To allow the use of the bigger number of positions in the 1240K over the HO dataset, Mbuti from the Simons Genome Diversity Project (88) was used as the outgroup. The outgroup f3 analyses of the form f3(Mbuti; West_Siberia_N/EHG/CentralRussiaHG/Fatyanovo/ Yamnaya_Samara/Poland_CWC/Baltic_CWC/Central_CWC, ancient) were run both using not only 1,136,395 autosomal SNPs but also 48,284 chrX positions available in the 1240K dataset. Because all children inherit half of their autosomal material from their father but only female children inherit their chrX from their father, then in this comparison chrX data give more information about the female and autosomal data about the male ancestors of a population.

The autosomal outgroup f3 results of the two different SNP sets were compared to each other and to the results based on the chrX positions of the 1240K dataset to see whether the SNPs used affect the trends seen. Outgroup f3 analyses were also run with the form f3(Mbuti; PES001/I0061/Sidelkino, Paleolithic/Mesolithic HG) and admixture f3 analyses with the form f3(Fatyanovo; Yamnaya, EF) using the autosomal positions of the 1240K dataset.

D statistics. D statistics of the form D(Yoruba, West_Siberia_N/EHG/CentralRussiaHG/Fatyanovo/ Yamnaya_Samara/Poland_CWC/Baltic_CWC/Central_CWC; Russian, modern/ancient) were calculated on the same dataset as outgroup f3 statistics (tables S3 and S4) using the autosomal positions of the HO dataset. The ADMIXTOOLS 6.0 package program qpDstat was used (87).

In addition, D statistics of the form D(Mbuti, ancient; Yamnaya_Samara, Fatyanovo/Baltic_CWC/ Central_CWC) and D(Mbuti, ancient; Poland_CWC/Baltic_CWC/ Central_CWC, Fatyanovo) were calculated using the autosomal positions of the 1240K dataset. However, comparing very similar populations directly using D statistics seems to be affected by batch biasesCentral_CWC comes out as significantly closer to almost all populations than Fatyanovo, while this is not the case when comparing less similar Fatyanovo and Yamnaya_Samara. Because of this, the results of D(Mbuti, ancient; Poland_CWC/Baltic_CWC/Central_CWC, Fatyanovo) are not discussed in the main text, but the data are included in table S19.

FST. Weir and Cockerham pairwise average FST (89) was calculated for the dataset used for outgroup f3 and D statistics using the autosomal positions of the HO dataset using a custom script.

qpAdm. The ADMIXTOOLS 6.0 (87) package programs qpWave and qpAdm were used to estimate which populations and in which proportions are suitable proxies of admixture to form the populations or individuals of this study. The autosomal positions of the 1240K dataset were used. Only samples with more than 100,000 SNPs were used in the analyses. Mota, Ust-Ishim, Kostenki14, GoyetQ116, Vestonice16, MA1, AfontovaGora3, ElMiron, Villabruna, WHG, EHG, CHG, Iran_N, Natufian, Levant_N, and Anatolia_N (and Volosovo in some cases indicated in table S15) were used as right populations. Yamnaya_Samara or Yamnaya_Kalmykia was used as the left population representing Steppe ancestry. Levant_N, Anatolia_N, LBK_EN, Central_MN, Globular_Amphora, Trypillia, Ukraine_Eneolithic, or Ukraine_Neolithic was used as the left population representing EF ancestry. In some cases, WHG, EHG, WesternRussiaHG, or Volosovo was used as the left population representing HG ancestry. Alternatively, one-way models between Fatyanovo, Baltic_CWC, and Central_CWC were tested. Also, PES001 was modeled as a mixture of WHG and AfontovaGora3, MA1, or CHG.

To look at sex bias, four models that were not rejected using autosomal data were also tested using the 48,284 chrX positions of the 1240K dataset. The same samples were used as in the autosomal modeling.

ChromoPainter/NNLS. To infer the admixture proportions of ancient individuals, the ChromoPainter/NNLS pipeline was applied (28). Because of the low coverage of the ancient data, it is not possible to infer haplotypes, and the analysis was performed in unlinked mode (option -u). The autosomal positions of the HO dataset were used. Only samples with more than 20,000 SNPs were used in the analyses. Because ChromoPainter (90) does not tolerate missing data, every ancient target individual was iteratively painted together with one representative individual from potential source populations as recipients. All the remaining modern individuals from the sample set used for Admixture analysis were used as donors (tables S3 and S4). Subsequently, we reconstructed the profile of each target individual as a combination of two or more ancient individuals, using the non-negative least square approach. Let Xg and Yp be vectors summarizing the proportion of DNA that source and target individuals copy from each of the modern donor groups as inferred by ChromoPainter. Yp = 1X1 + 2X2 + + zXz was reconstructed using a slight modification of the nnls function in R (91) and implemented in GlobeTrotter (92) under the conditions g 0 and g = 1. To evaluate the fitness of the NNLS estimation, we inferred the sum of the squared residual for every tested model (93). Models identified as plausible with qpAdm with Yamnaya_Samara and Globular_Amphora/Trypillia as sources were used. The resulting painting profiles, which summarize the fraction of the individuals DNA inherited by each donor individual, were summed over individuals from the same population.

DATES. The time of admixture between Yamnaya and EF populations forming the Fatyanovo Culture population was estimated using the program DATES (37). The autosomal positions of the 1240K dataset were used.

Phenotyping. To predict eye, hair, and skin color in the ancient individuals (tables S20 to S22), the HIrisPlex-S variants from 19 genes in nine autosomes were selected (9496), and the region to be analyzed was selected adding 2 Mb around each SNP, collapsing in the same region the variants separated by less than 5 Mb. A total of 10 regions (2 for chromosome 15 and 1 for each of the remaining autosomes) were obtained, ranging from about 6 to about 1.5 Mb. Similarly, to analyze the other phenotype-informative markers (diet, immunity, and diseases), 2 Mb around each variant was selected, and the overlapping regions were merged, for a total of 47 regions (45 regions in 17 autosomes and 2 regions on chrX). For the local imputation, we used a two-step pipeline (97) as follows: (i) variant calling, (ii) first imputation step using a reference panel as much similar as possible to the target samples, (iii) variant filtering, (iv) second imputation step using a larger worldwide reference panel, and (v) final variant filtering. This pipeline has been validated by randomly downsampling a high-coverage Neolithic sample (NE1) (98) to 0.05 and comparing the imputed variants in the low-coverage version with the called variants from the original genome. For a local imputation approach on 2 Mb, we obtained a concordance rate higher than 90% for all the variants, a figure that increased to 99% for frequent variants (MAF 0.3). The variants were called using ATLAS v0.9.0 (99) (task = call and method = MLE commands) (step 1) at biallelic SNPs with a MAF 0.1% in a reference panel composed of more than 2000 high-coverage Estonian genomes (EGC) (74). The variants were called separately for each sample and merged in one VCF file per chromosomal region. The merged VCFs were used as input for the first step of our two-step imputation pipeline [genotype likelihood update; -gl command on Beagle 4.1 (100)], using the EGC panel as reference (step 2). Then, the variants with a genotype probability (GP) less than 0.99 were discarded (step 3), and the missing genotype was imputed with the -gt command of Beagle 5.0 (101) using the large HRC as reference panel (102), with the exception of variants rs333 and rs2430561 [not present in the HRC (Haplotype Reference Consortium)], imputed using the 1000 Genomes as reference panel (step 4) (103). Last, a second GP filter was applied to keep variants with GP 0.85 (step 5). Then, the 113 phenotype-informative SNPs were extracted, recoded, and organized in tables, using VCFtools (104), PLINK 1.9 (http://pngu.mgh.harvard.edu/purcell/plink/) (84), and R (91) (tables S21 and S22). The HIrisPlex-S variants were uploaded on the HIrisPlex webtool (https://hirisplex.erasmusmc.nl/) to perform the pigmentation prediction, after tabulating them according to the manual of the tool. Out of 41 variants of the HIrisPlex-s system, two markers were not analyzed, namely, the rs312262906 indel and the rare (MAF = 0 in the HRC) rs201326893 SNP, because of the difficulties in the imputation of such variants.

The 28 samples analyzed here were compared with 34 ancient samples from surrounding geographical regions from literature, gathering them in seven groups according to their region and/or culture: (i) 3 Western Russian Stone Age HGs (present study); (ii) 5 Latvian Mesolithic HGs (34); (iii) 7 Estonian and Latvian Corded Ware Culture farmers [present study and (27, 34)]; (iv) 24 Fatyanovo Culture individuals (present study); (v) 10 Estonian Bronze Age individuals (28); (vi) 9 Estonian and Ingrian Iron Age individuals (28); (vii) 4 Estonian Middle Age individuals (28). For each variant, an analysis of variance (ANOVA) test was performed between the seven groups, applying Bonferronis correction by the number of tested variants to set the significance threshold (table S20). For the significant variant, a Tukey test was performed to identify the significant pairs of groups.

See the rest here:
Genetic ancestry changes in Stone to Bronze Age transition in the East European plain - Science Advances

Two issues negatively impacting COVID testing are false readings and the turnaround time it takes for results. False positive results can cause undue concern, whereas false negative readings have the potential to unwittingly add to the continued spread of COVID.

The waiting game is especially difficult; its the kind of time that most people dont really have to spare. They must then play the quarantine game which, in addition to the restrictions, often means a loss of income as they wait for their results.

To overcome these hurdles, Huntsville Hospital and Kailos Genetics have teamed up to offer a COVID-19 test option through its Assure Sentinel and Peace of Mind programs. The programs are designed for non-symptomatic individuals who want to know if they are carrying the COVID-19 virus.

Its the second program weve put into place with Huntsville Hospital, said Troy Moore, chief science officer at Kailos, which is headquartered at the HudsonAlpha Institute for Biotechnology. The first program was focused on a return to work or return to school testing, on a routine basis. Then, we learned there were quite a few people that had a son or daughter going back to school or to college, or theyve been around family members during the holidays, or they have a parent they are taking care of.

This is a place where they could go if they have concerns, but not necessarily a known exposure event.

In this partnership, the hospital staff will administer the test, collect samples, and deliver the results. Kailos will process the tests utilizing its Assure Sentinel program which can detect SARS-CoV-2, the virus that causes COVID-19.

Assure Sentinel testing is painless and affordable and can detect viral infections in individuals before they become symptomatic. By reducing the potential for exposure, Sentinel testing helps to minimize the impact in the workplace, as well as in the community.

The best news is the process is a saline swish and gargle the companys ViraWash to provide a viable sample. No long swab going up your nose and it can be easily done in the workplace.

For more information, contact the Huntsville Hospital Clinical Lab at: 256-265-2LAB (2522).

Continued here:
For COVID Peace of Mind - and No Swab Up Your Nose - Huntsville Hospital and Kailos Genetics Roll Out Assure Sentinel - Huntsville Business Journal

ROME (AP) The French doctor who discovered the genetic basis of Down syndrome but spent his career advocating against abortion as a result of prenatal diagnosis has taken his first major step to possible sainthood.

Pope Francis on Thursday approved the heroic virtues of Dr. Jerome Lejeune, who lived from 1926-1994 and was particularly esteemed by St. John Paul II for his anti-abortion stance.

The papal recognition of Lejeunes virtues means that he is considered venerable by the Catholic Church. The Vatican must now confirm a miracle attributed to his intercession for him to be beatified, and a second one for him to be declared a saint.

According to his official biography, Lejeune in 1958 discovered the existence of an extra chromosome on the 21st pair during a study of the chromosomes of a child. It was the first time scientists had found a link between an intellectual disability and a chromosomal anomaly; the condition is now known as trisomy 21.

Although the results of his research should have helped medicine to advance toward a cure, they are often used to identify children carrying these diseases as early as possible, usually with the aim of terminating pregnancy, the Jerome Lejeune Foundation wrote in its biography.

As soon as the pro-abortion laws were drafted in western countries, Lejeune began advocating for the protection of the unborn with Down syndrome: he gave hundreds of conferences and interviews across the globe in defense of life, the group said.

John Paul in 1974 made Lejeune a member of the Vaticans Pontifical Academy of Sciences think tank and later named him the first chairman of the Pontifical Academy for Life, the Holy Sees main bioethics advisory commission.

John Paul visited Lejeunes grave during the Paris World Youth Day in 1997.

Though John Paul made the churchs firm opposition to abortion a hallmark of his quarter-century papacy, Francis too has strongly denounced what he calls todays throwaway culture that considers the weak, disabled or sick disposable. He has likened abortion to hiring a hit man to take care of a problem.

Original post:
French doctor who discovered genetic basis of Down syndrome closer to sainthood - WTNH.com

Kimberly and Kelly Standard, who are twins, assumed that when they became sick with Covid-19 their experiences would be as identical as their DNA.

The virus had different plans.

Early last spring, the sisters from Rochester, Mich., checked themselves into the hospital with fevers and shortness of breath. While Kelly was discharged after less than a week, her sister ended up in intensive care, and spent almost a month in critical condition.

Nearly a year later, the sisters are bedeviled by the divergent paths their illnesses took.

I want to know, Kelly said, why did she have Covid worse than me?

Identical twins offer a ready-made experiment to untangle the contributions of nature and nurture in driving disease. With the help of twin registries in the United States, Australia, Europe and elsewhere, researchers are confirming that genetics can influence which symptoms Covid-19 patients experience.

These studies have also underscored the importance of the environment and pure chance: Even between identical twins, immune systems can look vastly different.

But at least some of the factors that influence the severity of a Covid-19 case are written into the genome. Recent studies suggest that people with type O blood, for example, may be at a slightly lower risk of becoming seriously sick (though experts have cautioned against overinterpreting these types of findings). Other papers have homed in on genes that affect how cells sound the alarm about viruses.

There even seems to be a measurable genetic influence on whether patients experience symptoms like fever, fatigue and delirium, said Tim Spector, an epidemiologist and the director of the TwinsUK registry based at St. Thomas Hospital in London.

Last year, he and his colleagues developed a symptom-tracking app. In a study that has not yet been published in a scientific journal, they reported that genetic factors might account for up to 50 percent of the differences between Covid-19 symptoms.

Still, Dr. Spector said, It would be wrong to think we can answer this if we just crack the genes.

Original post:
Twins with Covid-19 help scientists untangle the diseases genetic roots. - The New York Times

Cameroonian scientist Appolinaire Djikeng, Director of the Centre for Tropical Livestock Genetics ... [+] and Health (CTLGH), holding a chicken.

Cameroonian geneticist Appolinaire Djikeng grew up in a family that depended on livestock for their livelihood, now he is using Africa's livestock genetic diversity to help the 1.3 billion people who depend on livestock for food and income.

Djikeng, the Director of the Centre for Tropical Livestock Genetics and Health (CTLGH), a research alliance with scientific bases in Scotland, Kenya and Ethiopia, says livestock play a critical role in income generation, job creation, gender equity, food production and many other means to improve people's lives.

Djikeng says the focus of CTLGH's efforts is to improve the livestock production systems of smallholder farmers living in low- and middle-income countries, who generally farm less than two hectares and are among the poorest and most marginalized communities.

Djikeng says through the genetics work, smallholder farmers will be able to own animals that are better adapted, more resilient, healthier and able to reach their production potential.

"These animals are less also likely to incur extra inputs, due to poor health or inefficient feed conversion, for the farmers who own them and help mitigate climate change," he said, "Enhancing nutrition through the access to milk, meat and eggs is vital to improve human health and even more critical for infants in their first 1,000 days of life."

Djikeng says his long-standing research interests are centered on genomics, the study of genes and their functions, and specifically on livestock genomics.

"For the last 10 years I have been particularly interested in how genomics can be used to assess and exploit genetic diversity in order to address key agricultural productivity and sustainability challenges, with a focus on farmed animals and crops," he said.

"Our work is not about developing new breeds, " he said, adding that the goal to ensure that existing breeds are more resilient, productive and environmentally sustainable and are able to perform optimally in tropical production systems."

Djikeng believes a reasonable business model for tropical livestock development would be one where a systems approach is considered.

"Under such a model, an important consideration of livestock development must be given on its impact on the environment, deforestation, etcetera," he said, "This is an area where government regulation and incentives should be explored."

Cattle in the village of Idool, near Ngaoundere, Cameroon, Central Africa, Africa

Djikeng says his current work is heavily influenced by growing up in a household economically dependent on small-scale agriculture.

"I was born and grew up in small village in western (French-speaking) Cameroon," he said, adding that his parents farmed on a small piece of land and owned chickens and pigs as assets for income generation.

"You can imagine how very vulnerable my familys situation was, relying on three or four pigs and about 10 chickens to support a range of needs including education and healthcare for myself and my siblings," he said, "Growing up, I wanted to find a job that would give me a stable income so that I did not end up a subsistence farmer like my parents before me."

With the support of his family, he was able to complete his schooling and go to university.

"I wanted to choose a profession that would allow me to support my family and my own parents in the future, so studying medicine was my first option but I realized that advanced biological sciences would be a better path for me," he said, "It was when studying for my PhD that I realized the important link between agricultural development and human health which has led me to work in this area for close to 20 years now."

Another scientist from Cameroon who is making a big impact is Aristide Takoukam.

When Takoukam was in university, he'd never heard of the African Manatee (Trichechus senegalensis) and he didn't know how to swim, but he would go on to become the first person from Cameroon to earn a PhD studying this endangered mammal.

Takoukam would go on to complete his doctorate and become a National Geographic Explorer and founder of the African Marine Mammal Conservation Organization (AMMCO).

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This Scientist Is Harnessing The Rich Genetic Diversity Of African Cattle - Forbes

TEMPLE CITY, Calif., Jan. 06, 2021 (GLOBE NEWSWIRE) -- Fulgent Genetics, Inc. (NASDAQ: FLGT) (Fulgent Genetics or the company), a technology company providing comprehensive testing solutions through its scalable technology platform, today announced that its Chief Financial Officer Paul Kim, and Chief Commercial Officer Brandon Perthuis are scheduled to virtually participate in a presentation at the H.C. Wainwright BIOCONNECT 2021 Conference taking place January 11 to 14, 2021.

A webcast of thepresentation will be available beginning at 6:00 a.m. ET on January 11, 2021 on the Investor Relations section of the Fulgent Genetics website at ir.fulgentgenetics.com, and will be available for 90 days following the conference.

About Fulgent Genetics

Fulgent Genetics proprietary technology platform has created a broad, flexible test menu and the ability to continually expand and improve its proprietary genetic reference library while maintaining accessible pricing, high accuracy and competitive turnaround times. Combining next generation sequencing (NGS) with its technology platform, the Company performs full-gene sequencing with deletion/duplication analysis in an array of panels that can be tailored to meet specific customer needs. In 2019, the Company launched its first patient-initiated product, Picture Genetics, a new line of at-home screening tests that combines the Companys advanced NGS solutions with actionable results and genetic counseling options for individuals. Since March 2020, the Company has commercially launched several tests for the detection of SARS-CoV-2, the virus that causes the novel coronavirus (COVID-19), including NGS and reverse transcription polymerase chain reaction (RT-PCR) - based tests. The Company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for the RT-PCR-based tests for the detection of SARS-CoV-2 using upper respiratory specimens (nasal, nasopharyngeal, and oropharyngeal swabs) and for the at-home testing service through Picture Genetics. A cornerstone of the Companys business is its ability to provide expansive options and flexibility for all clients unique testing needs through a comprehensive technology offering including cloud computing, pipeline services, record management, web portal services, clinical workflow, sequencing as a service and automated lab services.

Investor Relations Contacts:The Blueshirt GroupNicole Borsje, 415-217-2633; nicole@blueshirtgroup.com

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Fulgent Genetics to Participate in the H.C. Wainwright BIOCONNECT 2021 Conference - GlobeNewswire

Cases of eggs from Cal-Maine Foods, Inc., await to be handed out by the Mississippi Department of Agriculture and Commerce employees to several hundred families along with over 1,400 boxes of meat products from Merchants Foodservice and 2,200 gallons of milk from Borden Dairy, at the Mississippi State Fairgrounds in Jackson, Miss., Aug. 7, 2020.

Rogelio V. Solis | AP

Check out the companies making headlines after the bell on Tuesday:

Cal-Maine Foods Cal-Maine Foods reported a surprise profit for its fiscal second quarter, sending the stock up more than 2% after-hours trading. The company posted earnings per share of 25 cents on revenue of $347.3 million. Analysts polled by FactSet expected a loss of 8 cents pre share on revenue of $333.5 million. The company's egg-dozen sales grew by 4.6% on a year-over-year basis.

Myriad Genetics Shares of the biotechnology company rose nearly 2% on news Myriad will explore "strategic alternatives" for its autoimmune business. The company is also restructuring its international operations.

Smart Global Holdings Smart Global posted fiscal first-quarter earnings per share that were better than expected, lifting the computer-memory manufacturer's stock up by 2.4%. Smart Global reported adjusted earnings per share of 78 cents, topping a FactSet estimate of 70 cents per share. The company also issued better-than-expected revenue guidance for the current quarter.

Nektar Therapeutics Nektar shares slipped about 1% after the company announced Dr. Brian Kotzin will take over as interim chief medical officer, effective immediately, replacing current CMO Wei Lin.

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Stocks making the biggest moves after the bell: Cal-Maine Foods, Myriad Genetics & more - CNBC

DUBLIN, Jan. 5, 2021 /PRNewswire/ -- The "Animal Genetics - Global Market Outlook (2019-2027)" report has been added to ResearchAndMarkets.com's offering.

According to this report, the Global Animal Genetics market accounted for $4.48 billion in 2019 and is expected to reach $8.60 billion by 2027 growing at a CAGR of 8.5% during the forecast period. Some of the key factors propelling the growth of the market are growing preference for animal protein, increasing population, and increasing adoption of advanced genetic technologies. However, the shortage of skilled veterinary research professionals is the restraining factor for the growth of the market.

Animal genetics is the study of heredity in animals. It includes the study of colour, genetics, gene expression, and animal breeding for a wide variety of applications and is primarily focused on the passing of traits from one generation to the next.

By live animal, the porcine segment is expected to grow at a significant market share during the forecast period owing to the large consumer base for pork meat, as well as growing penetration of advanced genetic research. Based on geography, North America is anticipated to hold considerable market share during the forecast period which is attributed to the research activities being carried out on animal genetics and the adoption of strategic activities by industry players.

Some of the key players in Animal Genetics Market include Animal Genetics Inc, Cogent, Crv Holding B.V., Alta Genetics Inc, Genus PLC, Neogen Corporation, Inguran LLC, Groupe Grimaud La Corbiere SA, Hendrix Genetics BV, Topigs Norsvin, Vetgen, Ew Group GmbH, Zoetis Inc, Envigo Inc, and Urus.

What the Report offers:

Key Topics Covered:

1 Executive Summary

2 Preface2.1 Abstract 2.2 Stake Holders 2.3 Research Scope 2.4 Research Methodology 2.4.1 Data Mining 2.4.2 Data Analysis 2.4.3 Data Validation 2.4.4 Research Approach 2.5 Research Sources 2.5.1 Primary Research Sources 2.5.2 Secondary Research Sources 2.5.3 Assumptions

3 Market Trend Analysis 3.1 Introduction 3.2 Drivers 3.3 Restraints 3.4 Opportunities 3.5 Threats 3.6 End User Analysis 3.7 Emerging Markets 3.8 Impact of Covid-19

4 Porters Five Force Analysis 4.1 Bargaining power of suppliers 4.2 Bargaining power of buyers 4.3 Threat of substitutes 4.4 Threat of new entrants 4.5 Competitive rivalry

5 Global Animal Genetics Market, By Live Animal 5.1 Introduction 5.2 Canine 5.3 Avian 5.4 Piscine 5.5 Poultry 5.6 Bovine 5.7 Porcine 5.8 Other Live Animals 5.8.1 Goat 5.8.2 Horse 5.8.3 Sheep

6 Global Animal Genetics Market, By Service 6.1 Introduction 6.2 DNA Typing 6.3 Genetic Disease Tests 6.4 Genetic Trait Tests 6.5 DNA Testing 6.6 Other Services 6.6.1 Forensic Testing 6.6.2 Prenatal Testing 6.6.3 Predictive and Presymptomatic Testing 6.6.4 Diagnostic Testing

7 Global Animal Genetics Market, By Genetic Material 7.1 Introduction 7.2 Embryos 7.2.1 Equine Embryos 7.2.2 Bovine Embryos 7.2.3 Other Animal Embryos 7.2.3.1 Porcine Embryos 7.2.3.2 Sheep Embryos 7.2.3.3 Goat Embryos 7.3 Semen 7.3.1 Canine Semen 7.3.2 Porcine Semen 7.3.3 Bovine Semen 7.3.4 Equine Semen 7.3.5 Other Animal Semen 7.3.5.1 Goat Semen 7.3.5.2 Sheep Semen

8 Global Animal Genetics Market, By End User 8.1 Introduction 8.2 Veterinary Hospitals & Clinics 8.3 Research Centers and Institutes 8.4 Diagnostic Centres

9 Global Animal Genetics Market, By Geography 9.1 Introduction 9.2 North America 9.2.1 US 9.2.2 Canada 9.2.3 Mexico 9.3 Europe 9.3.1 Germany 9.3.2 UK 9.3.3 Italy 9.3.4 France 9.3.5 Spain 9.3.6 Rest of Europe 9.4 Asia Pacific 9.4.1 Japan 9.4.2 China 9.4.3 India 9.4.4 Australia 9.4.5 New Zealand 9.4.6 South Korea 9.4.7 Rest of Asia Pacific 9.5 South America 9.5.1 Argentina 9.5.2 Brazil 9.5.3 Chile 9.5.4 Rest of South America 9.6 Middle East & Africa 9.6.1 Saudi Arabia 9.6.2 UAE 9.6.3 Qatar 9.6.4 South Africa 9.6.5 Rest of Middle East & Africa

10 Key Developments10.1 Agreements, Partnerships, Collaborations and Joint Ventures 10.2 Acquisitions & Mergers 10.3 New Product Launch 10.4 Expansions 10.5 Other Key Strategies

11 Company Profiling11.1 Animal Genetics Inc 11.2 Cogent 11.3 Crv Holding B.V. 11.4 Alta Genetics Inc 11.5 Genus PLC 11.6 Neogen Corporation 11.7 Inguran LLC 11.8 Groupe Grimaud La Corbiere SA 11.9 Hendrix Genetics BV 11.10 Topigs Norsvin 11.11 Vetgen 11.12 Ew Group GmbH 11.13 Zoetis Inc 11.14 Envigo Inc 11.15 Urus

For more information about this report visit https://www.researchandmarkets.com/r/gk37es

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

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SOURCE Research and Markets

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Worlwide Animal Genetics Industry to 2027 - Impact Analysis of COVID-19 - PRNewswire

Livestock Improvement Corporation (LIC) say continued investment in gene discovery and genetic analysis technology is allowing their farmer shareholders to improve cow production valued in the millions.

Investment into the understanding of bovine genetics undertaken by LIC scientists indicates farmers could be missing out on production to the tune of up to the tune of up to $10 million each year.

The co-operative spent $16 million on research and development during the 2019/20 season.

The discovery of genetic variations have been made from the farmer-owned co-operative's database of genotyped cows and bulls and validated through on-farm inspections.

LIC chief scientist Richard Spelman says that despite a relatively low frequently, the hidden impacts on production from these variants can be substantial.

Spelman says they are recessive genetic variations, which means an animal has to have two copies to be affected.

"Identifying these animals via Genemark and removing them from the herd as calves will save in lost production and the rearing cost for these animals.

"We estimate this could be worth up to $10 million in lost production each year across the national herd," he says.

"Even having a few of these cows in a herd could equate to significant loss in productivity and profitability."

He says that LIC's continued investment in gene discovery, with the Genemark testing platform, will allow farmers to identify genetic variations in animals as calves, remove them from the herd, and allow them to focus on the rest of their replacements.

Each of the variants exist within the national herd at differing frequencies and all have varying effects on an animal's production.

From spring 2021, all farmers using LIC's Genemark services will automotically be notified at no additional charge if any of their calves are affected by any of the variations.

"We are pleased our combined investment into science and technology has come together to deliver a simple and convenient service for farmers that is likely to save millions in lost production."

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Cow production improved by genetic research and tech - Rural News Group

Ancient people brought the plague to Siberia by about 4,400 years ago, which may have led to collapses in the population there, a new genetic analysis suggests.

That preliminary finding raises the possibility that plague-induced die offs influenced the genetic structure of northeast Asians who trekked to North America starting perhaps 5,500 years ago. If the result holds up, it, along with other newly uncovered insights into human population dynamics in the region, would unveil a more complex ancestry among those ancient travelers than has usually been assumed.

A team led by evolutionary geneticists Glah Merve Kilin and Anders Gtherstrm, both of Stockholm University, extracted DNA from the remains of 40 human skeletons previously excavated in parts of eastern Siberia. Among those samples, DNA from Yersinia pestis, the bacterium that causes plague, was found in two ancient Siberians, the researchers report January 6 in Science Advances. One person lived around 4,400 years ago. The other dated to roughly 3,800 years ago.

Its unclear how the plague bacterium first reached Siberia or whether it caused widespread infections and death, Gtherstrm says. But he and his colleagues found that genetic diversity in their ancient samples of human DNA declined sharply from around 4,700 to 4,400 years ago, possibly the result of population collapse.

Headlines and summaries of the latest Science News articles, delivered to your inbox

The new data coincide with evidence reported in June 2020 in Cell of Y. pestis DNA in two ancient individuals from eastern Siberias Lake Baikal region, dating to around 4,500 years ago.

The plague may well have reached Siberia by roughly 4,500 years ago, at a time when Y. pestis infected people inhabiting other parts of Eurasia (SN: 10/22/15), says evolutionary geneticist Hendrik Poinar of McMaster University in Hamilton, Canada who did not participate in the new study.

But its possible that the ancient Siberians were infected with a version of Y. pestis that wasnt virulent. If so, the bacterium wouldnt have killed enough people to alter the genetic structure of Siberians. Genetic data from only two individuals provides too little evidence to confirm that they possessed a virulent strain of Y. pestis, Poinar says.

The genetic findings do provide a glimpse of a series of previously unknown ancient population shifts in that region. Ancient individuals included in the new research dated from around 16,900 years ago, shortly after the last Ice Age peaked, to 550 years ago. The researchers compared those ancient Siberians DNA to DNA from present-day humans in different parts of the world and to previous samples of ancient human DNA mainly from Europe, Asia and North America. The analyses showed that despite Siberias harsh climate, groups near Lake Baikal and regions further east mixed with various populations in and outside of Siberia from the Late Stone Age up to medieval times.

The two plague-carrying Siberians, in particular, came from regions that had experienced major population transformations during much of the sampled time period, the researchers say. Those events could have included migrations of plague-carrying people from outside Siberia. For instance, the 4,400-year-old skeleton was found just west of Lake Baikal, a region that witnessed the emergence of several distinct genetic groups with roots mainly further to the west and southwest of Lake Baikal between around 8,980 and 560 years ago.

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Plague may have caused die-offs of ancient Siberians - Science News

The pandemic coronavirus SARS-CoV-2 (shown above) mayunder certain conditionsintegrate its genetic material into human cells, confounding COVID-19 diagnostic tests.

By Jon CohenDec. 16, 2020 , 6:30 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

People who recover from COVID-19 sometimes later test positive for SARS-CoV-2, suggesting their immune systems could not ward off a second attack by the coronavirus or that they have a lingering infection. A study now hints at a different explanation in which the virus hides in an unexpected place. The work, only reported in a preprint, suggests the pandemic pathogen takes a page from HIV and other retroviruses and integrates its genetic codebut, importantly, just parts of itinto peoples chromosomes. The phenomenon, if true and frequent, could have profound implications that range from false signals of active infection to misleading results from COVID-19 treatment studies.

The current study only showed this integration in a lab dish, although it also cites published sequence data from humans infected with SARS-CoV-2that suggest it has happened. The authors emphasize that their results dont imply that SARS-CoV-2 establishes permanent genetic residence in human cells to keep pumping out new copies, as HIV does.

Other scientists are divided about the importance of the new work and its relevance to human health, and some are harshly critical. There are open questions that well have to address, saysmolecular biologist Rudolf Jaenisch of the Massachusetts Institute of Technology (MIT), who led the work.

Yet a few veteran retrovirologists are fascinated. This is a very interesting molecular analysis and speculation with supportive data provided, says Robert Gallo, who heads the Institute of Human Virology and looked at the newly posted preprint at Sciences request. I do not think it is a complete story to be certain but as is, I like it and my guess is it will be right.

All viruses insert their genetic material into the cells they infect, but it generally remains separate from the cells own DNA. Jaenischs team, intrigued by reports of people testing positive for SARS-CoV-2 after recovering, wondered whether these puzzling results reflected something of an artifact from the polymerase chain reaction (PCR) assay, which detects specific virus sequences in biological samples such as nasal swabs, even if they are fragmented and cant produce new viruses. Why do we have this positivity, which is now seen all over the place, long after the active infection has disappeared? says Jaenisch, who collaborated with the lab of MITs Richard Young.

To test whether SARS-CoV-2s RNA genome could integrate into the DNA of our chromosomes, the researchers added the gene for reverse transcriptase (RT), an enzyme that converts RNA into DNA, to human cells and cultured the engineered cells with SARS-CoV-2. In one experiment, the researchers used an RT gene from HIV. They also provided RT using human DNA sequences known as LINE-1 elements, which are remnants of ancient retroviral infections and make up about 17% of the human genome. Cells making either form of the enzyme led to some chunks of SARS-CoV-2 RNA being converted to DNA and integrated into human chromosomes, the team reports in their preprint, posted on bioRxiv on 13 December.

If the LINE-1 sequences naturally make RT in human cells, SARS-CoV-2 integration might happen in people who have COVID-19. This could occur in people coinfected with SARS-CoV-2 and HIV, too. Either situation may explain PCR detecting lingering traces of coronavirus genetic material in people who no longer have a true infection. And it could confuse studies of COVID-19 treatments that rely on PCR tests to indirectly measure changes in the amount of infectious SARS-CoV-2 in the body.

David Baltimore, a virologist at the California Institute of Technology who won the Nobel Prize for his role in discovering RT, describes the new work as impressive and the findings as unexpected but he notes that Jaenisch and colleagues only show that fragments of SARS-CoV-2s genome integrate. Because it is all pieces of the coronaviral genome, it cant lead to infectious RNA or DNA and therefore it is probably biologically a dead end, Baltimore says. It is also not clear if, in people, the cells that harbor the reverse transcripts stay around for a long time or they die. The work raises a lot of interesting questions.

Virologist Melanie Ott, who studies HIV at the Gladstone Institute of Virology and Immunology, says the findings are pretty provocative but need thorough follow-up and confirmation. I have no doubt that reverse transcription can happen in vitro with optimized conditions, Ott says. But she notes that SARS-CoV-2 RNA replication takes place in specialized compartments in the cytoplasm. Whether it happens in infected cells and leads to significant integration in the cell nucleus is another question.

Retrovirologist John Coffin of Tufts University calls the new work believable, noting that solid evidence shows that LINE-1 RT can allow viral material to integrate in people, but hes not yet convinced. The evidence of SARS-CoV-2 sequences in people, Coffin says, should be more solid, and the in vitro experiments conducted by Jaenischs team lack controls he would have liked to have seen. All in all, I doubt that the phenomenon has much biological relevance, despite the authors speculation, Coffin says.

Zandrea Ambrose, a retrovirologist at the University of Pittsburgh, adds that this kind of integration would be extremely rare if it does indeed happen. She notes that LINE-1 elements in the human genome rarely are active. It is not clear what the activity would be in different primary cell types that are infected by SARS-CoV-2, she says.

One particularly harsh Twitter critic, a postdoctoral researcher in a lab that specializes in retroviruses, went so far as to call the preprints conclusions a strong, dangerous, and largely unsupported claim. Jaenisch emphasizes that the paper clearly states the integration the authors think happens could not lead to the production of infectious SARS-CoV-2. Lets assume that we can really resolve these criticisms fully, which Im trying to do, Jaenisch says. This might be something not to worry about.

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The coronavirus may sometimes slip its genetic material into human chromosomesbut what does that mean? - Science Magazine

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

Im smaller than most people, said Madison Cain.

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

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

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

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

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

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

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

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

The family started genetic testing, while Madisons symptoms persisted.

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

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

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

Madisons strength paid off.

A break-through finally coming in 2019.

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

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

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

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

Madison has rare gene mutation to the MBTPS1 gene.

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

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

The condition named after two of Oklahomas scientists.

The disorder hinders Madisons bone growth and development.

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

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

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

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

Doctors think that could be because many patients are misdiagnosed.

The mutation can also affect every patient differently.

However, theres hope on the horizon.

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

Now theyre searching for cases across the country.

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

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

Researchers have tested the treatment on mice successfully.

For Madison, this treatment could mean everything.

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

For more information visit the OMRF website.

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

Question: Which genetic syndromes increase the risk of breast cancer?

Many risk factors for breast cancer have been identified, including genetic, environmental, and lifestyle factors. Some are modifiable and others are not. A family history of breast cancer in a first-degree relative is the most widely recognized breast cancer risk factor, but only 5-10% of women diagnosed with breast cancer have a known genetic predisposition. Women with a family history of breast cancer in a mother or sister have a 1.5-3 fold increase in the risk of developing breast cancer.

Multi-panel genetic testing for hereditary breast cancer syndromes is currently not standard for all women diagnosed with breast cancers due to insufficient data regarding interpretation accuracy and its utility. For now, BRCA1/2 testing accounts for half of the detected genetic breast mutations and is recommended in a women with: Personal history of breast cancer diagnosed before the age of 50, multiple female relatives with breast cancer on same side of the family or family history of male breast cancer, multiple breast cancers, both breast and ovarian cancer,with Ashkenazi Jewish heritage.

Those with BRCA mutation are at risk for developing breast cancer (50 to 80%) by age 70 and developing ovarian cancer (40-60%) by age 85. Since 2014, PALB2 (partner and localizer of BRCA2 gene) testing is frequently added to BRCA due to its inherent breast cancer risk of 5 to 9 times the average. Optional genetic panel testing includes PTEN, TP53, ATM, CDH1, CHEK2, NBN, NF1, STK11, and PMS2/MSH2 Lynch syndrome, also known as hereditary non-polyposis colorectal cancer, is a hereditary cancer syndrome, and is associated with multiple types of cancers, particularly colon, ovarian and endometrial/uterine, as well as breast cancers. Women with these mismatch repair genetic mutations (Lynch) may also have a 2-3 fold increase risk of breast cancer compared to the general population.

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Your Cancer Answers: Which genetic syndromes increase the risk of breast cancer? - Lompoc Record

New research published in Nature has revealed important genetic causes of the most severe forms of COVID-19 disease.

Researchers studied over 2,000 severely ill patients with COVID-19, and compared their genomes to those of healthy people from existing population studies in the UK. They found that patients were much more likely to possess variations in a small number of genes that affect anti-viral immune responses and inflammation information that suggests existing drugs could be useful treatments for severe disease.

COVID-19 has been known for almost a year now, but the variation in effects on different people remains baffling: some experience no discernible symptoms at all, others a mild or moderate illness, and some a very distinct, severe and life-threatening illness. Although certain clear risk factors have emerged for the most dangerous forms of the disease, notably older age and certain conditions such as heart disease, diabetes and severe obesity, both within and outside these groups, SARS-CoV-2 infection causes a bewildering and unpredictable range of responses.

Understanding precisely who is and is not at greater risk of dangerous forms of the disease would play a very important role in ongoing efforts to control the disease and prevent the worst effects. It would allow preventative efforts including new vaccines to be directed first towards those at greatest risk. It also offers important clues to the underlying mechanisms that drive the most severe forms of disease, and hence to potential treatments.

It has seemed likely from the beginning that genetic variation between different people accounts for some of the otherwise inexplicable variation in disease severity. It may also account for differing disease susceptibility how likely someone is to become infected; this is the case for many other infectious diseases, though it is less obvious to see and hence to study. Doctors and scientists around the world have thrown themselves into efforts to uncover the genomic factors driving severe disease.

This new paper used DNA samples from over 2,200 patients with severe COVID-19 treated in over 200 intensive care units were obtained from to major research initiatives, the GenOMICC (Genetics Of Mortality In Critical Care) and the ISARIC Coronavirus Clinical Characterisation Consortium 4C studies. Genome sequences were compared with healthy control subject genomes from the UK Biobank to identify areas of the genome where there were significant differences. Findings were checked against samples from a similar number of hospitalised cases from the COVID-19 Host Genetics Initiative.

A handful of important genes involved in severe COVID-19 were identified, of two main types. The first group were genes involved in antiviral defences; the OAS gene helps block replication and spread of the virus, whilst IFNAR2 is involved in the production of an important immune mediator, interferon, which helps to trigger immune responses to viral infections. Weak early responses to infection could help the SARS-CoV-2 virus to spread and grow in the patient.

These discoveries are in line with earlier findings that pinpointed genetic changes that impaired interferon function among severe COVID-19 patients. Whilst giving interferon to critically ill patients has not proved very effective, there is hope that early administration to people with genetic predisposition to poor interferon responses who are infected by the virus might prevent severe disease.

The second group of genes implicated in severe COVID-19 were likely to play a role in the dangerous inflammatory lung damage seen in patients in critical care. These included rare variants in the TYK2, DPP9 and CCR2 genes. TYK2 is involved in controlling immune response; a rare variant that causes excessive inflammation was common among patients. This is a positive finding, since there are already anti-inflammatory drugs that target this particular biological pathway, and could prove to be valuable new treatments. Both DPP9 and CCR2 are also involved in different aspects of inflammatory responses to infection.

The researchers expect that there are other genes that affect the risk of severe disease, and hope to uncover more of these in due course as they analyse genomes additional patients; rarer genetic changes are harder to find and require larger numbers of people in studies. They are particularly interested in additional genetic factors that might account for the increased risk of severe disease seen in certain ethnic groups.

Meanwhile, other researchers continue to employ genome sequencing of the virus itself, rather than human hosts, to aid the battle against COVID-19. The UK government recently announced an additional 12.2 million funding for the COVID-19 Genomics UK (COG-UK) Consortium to continue and expand viral genome sequencing. Combining this information with patient data helps to identify whether the virus is becoming more or less infectious, or dangerous, or amenable to new vaccines all vital information.

Tackling COVID-19 without the insights provided by genomics would be infinitely more difficult like trying to understand the virus and the disease blindfolded and would undoubtedly have hugely slowed the development of vaccines, treatments and other responses to limit the harm caused by the pandemic.

Take a look at our short animation on pandemic in the genomic era

Link:
Further genetic clues to severe COVID-19 - PHG Foundation

Humans come in a variety of heights and genetics play a key role in determining whether you will be short or tall.

Theres much more than just heredity to consider before assuming a person will automatically be the same height as their parents. Medical conditions, hormonal deficiencies, and more can all contribute to how tall you are.

Read on to learn about all of the components that contribute to a persons natural height.

Genetics are among the prominent factors that contribute to how tall youll be.

As a general rule of thumb, your height can be predicted based on how tall your parents are. If they are tall or short, then your own height is said to end up somewhere based on the average heights between your two parents.

Genes arent the sole predictor of a persons height. In some instances, a child might be much taller than their parents and other relatives. Or, perhaps, they may be much shorter.

Such key differences may be explained by other factors outside of your genes that contribute to height.

Aside from genetics, there are other factors to consider that can determine a persons height, especially during childhood and adolescence.

While eating more vegetables wont automatically make you taller, getting adequate nutrition during your growing years is critical in human development, including your height.

A diet based on whole, nutritious foods can ensure you will grow up to the height your genes might dictate. On the flip side, a poor diet could lead to a shorter stature compared to your parents.

Eating healthy isnt so simple for all families. Children of a poor socioeconomic status may be at risk of a lack of access to nutrition, along with poor access to adequate health care. This, in turn, can contribute to a shorter height.

You may notice that boys grow slower than girls at first, due to differences in puberty milestones. Overall though, adult males tend to be an average of 14 centimeters (5.5 inches) taller compared to adult females.

During puberty, hormones are essential for regulating body growth. These include thyroid hormones, human growth hormones, and sex hormones such as testosterone and estrogen.

Any abnormalities in these hormones could alter growth as well as your overall height. Children who develop hypothyroidism (low thyroid) or pituitary gland disorders may experience shorter than average height compared to their parents.

Rarely, hormonal disorders can contribute to being taller than normal. For example, gigantism is caused by too many human growth hormones produced by pituitary gland tumors.

Some conditions present at birth may dictate a persons height. For example, achondroplasia (dwarfism) is a rare bone growth disorder that runs in families.

Another congenital disorder that can cause short stature is known as Turner syndrome. This rare condition causes delays in puberty. Unlike achondroplasia, Turner syndrome doesnt run in families.

Other congenital disorders lead to a taller than normal stature. These include Marfan and Klinefelter syndromes.

Marfan syndrome is caused by connective tissue enlargements, while Klinefelter syndrome occurs when males are born with an additional copy of the X chromosome.

Overall, theres no way you can increase your height. Each person is born with genes that will help dictate how tall they become, but other factors such as inadequate nutrition or medical conditions may alter this outlook.

Hormonal conditions may be the few exceptions. If a lack of thyroid or human growth hormones is detected during childhood, then taking medications may help reverse the effects on height.

However, once you reach adulthood, taking hormonal replacements wont make you taller. At this point, your full height has already been achieved, and taking any medications or supplements wont make a difference.

Its important to focus on good nutrition during childhood, but sticking with these habits will also contribute to your overall health into adulthood and beyond regardless of your height.

Poor posture and lack of exercise can also contribute to poor stature, so correcting these items may help increase your height (or the appearance of it).

Its widely regarded that your genes will dictate how tall you become. However, there are other exceptions to this rule, including your gender, access to nutrition, and any underlying medical or congenital conditions you may have.

See a doctor if you have any concerns about your height, or if you have a child who isnt reaching their growth milestones. They can discuss nutritional issues with you, and they may help rule out the possibility of any hormonal issues.

Continue reading here:
Is Height Genetic? Why and Why Not? - Healthline

A dedicated University of WisconsinMadison clinician, educator, advocate and researcher, Renata Laxova, professor emerita of medical genetics and pediatrics, passed away recently after a brief illness. She was 89.

Laxovas lifelong interests focused on the causes of intellectual and developmental disabilities, prenatal diagnosis of genetic disorders and birth defects, cancer genetics, and above all the relationships between medical professionals and the patients and families they serve. She was especially interested in coping strategies for families in difficult situations.

Renata Laxova

Laxova obtained MD and PhD degrees from the University Medical School in Brno, in what is now the Czech Republic. Initially trained in pediatrics, she later specialized in medical genetics at University College and Guys Hospital in London. She came to the United States in 1975 and joined the UWMadison departments of Pediatrics and Medical Genetics, where she served until she retired in 2000.

A skilled educator, Laxova loved teaching and stressed the importance of making clinical care personal. Understanding that genetics could be an extremely complicated discipline, Laxova worked to build awareness and accessibility through education and experiences. She underscored the importance of the patient perspective and was one of the first on campus to invite parents and families to share with her students their experiences caring for children with genetic conditions or disabilities.

David Wargowski, a clinical geneticist in the Waisman Center Medical Genetic Clinic a clinic and program Laxova helped build says Laxova inspired him to pursue a career in genetics. He first met Laxova as a medical student at UWMadison.

I found human genetics fascinating in college and was excited to have an opportunity to learn about how it applied to the medical care of people with genetic conditions, Wargowski says.

In the mid-1980s, medical genetics was still a field which primarily addressed rare disorders that were off the radar of most physicians.I learned about many of those, but more important to my medical training was learning from Laxovas example that being a good doctor is about more than being knowledgeable. It also means being compassionate and devoted to patients.

Patient care was primary for Laxova. Her innate ability to make connections with patients and learn their story set her apart. She is remembered for asking families during clinical visits, How can we most help you? a sentiment that embodied her commitment to patient advocacy and care that also led to her work on resources and supports for families throughout the state.

Responding to concern that many genetic disorders were going unnoticed and undiagnosed, Laxova helped establish the Genetic Contact Network. Within the network, professionals throughout the state identify people in need of genetic counseling and make referrals. These efforts led to the corresponding Genetic Services Network of outreach clinics and Laxova was a driving force behind the service sites in Green Bay, La Crosse and Eau Claire, among others.

At the Waisman Center, Laxova was in charge of the medical genetics program and clinic program and all of its elements clinical, education and research long before there was a program director, says Wargowski.

In 1976, Laxova was also instrumental in establishing the masters in genetic counseling training program with founding director Joan Burns. The training program was among the first of its kind in the United States and Laxova served as its first medical director, a position she held for more than 20 years. During that time, she helped train hundreds of genetic counselors while treating patients and their families in the Waisman Medical Genetics Clinic.

Casey Reiser, director of the Genetic Counselor Training Program, was herself a student in the third class of genetic counselors. Like Wargowski, Reiser had the opportunity to work with Laxova both as a student and colleague.

She was always animated and enthusiastic when she shared her knowledge with students, says Reiser. Renata was an inspiration, a wonderful mentor, and a beloved friend. She will be missed by many.

While known for the successes of her career, Laxova is also remembered for her experiences escaping both the Holocaust and communism. Laxova twice fled her homeland of the Czech Republic (then known as Czechoslovakia). In the days leading up to World War II, she escaped from the Nazis through safe passage to Britain on the last Kindertransport, which rescued thousands of children from the Holocaust. She returned in 1946.

In the late 1960s, married to her husband Tibor, and as a young mother, doctor and researcher, she once again made her way to Britain to avoid the encroaching Russian communist regime. The couple later moved to Wisconsin, where Tibor, a veterinarian, opened a practice. She joined the faculty of UWMadison in 1975. Her lifes story is chronicled in a poignant memoir dedicated to her grandson titled Letter to Alexander.

Wargowski describes the sentiment felt by many who knew and worked with Laxova.

If you didnt know her, Im sorry you didnt have that chance, he says. She was a remarkably gracious person with an amazing life story. She was absolutely devoted to her patients, her craft and her colleagues, especially those who asked for the opportunity to learn from her. She was a remarkably compassionate person and physician who taught more than genetics. She practiced a love for her patients to which most of us can only aspire, and an intolerance of disparity and discrimination that challenges the most motivated among us.

University Archives has two oral interviews with Renata Laxova from 2004 and 2008. You can access them here: https://search.library.wisc.edu/digital/AMGNC3S2LPJZPN83

More:
Holocaust survivor, geneticist, patient advocate remembered for inspiring others - University of Wisconsin-Madison

The US Food and Drug Administration granted approval yesterday (December 14) for a genetically modified line of pigs that marks the first time a GM animal has been given the regulatory greenlight for both therapeutic development and food consumption, the agency says in a statement. The alteration knocks out alpha-gal, a sugar molecule on the surface of cells, and could help minimize allergic reactions to pork and reduce the risk of organ rejection in transplant patients.

The move represents a a tremendous milestone for scientific innovation, FDA Commissioner Stephen Hahn says in the statement. The FDA strongly supports advancing innovative animal biotechnology products that are safe for animals, safe for people, and achieve their intended results.

Pigs with the genetic modification are known as GalSafe pigs and are made by Revivicor Inc, a subsidiary of the US biotech United Therapeutics. Research in the mid-2010s indicated that the knockout made transplants from the pigs less likely to be rejected by primate recipients.

The director of the FDAs Center for Veterinary Medicine, Steven Solomon, told reporters in a conference call yesterday that developers who want to use GalSafe pigs for therapeutic purposes will still have to seek approval for their applications. I think that people need to be careful, Solomon said, STATreports. Thats why in part, its going to require further evaluation for xenotransplantation, xenograft, or the other activities by the medical products centers and FDA.

As far as food production is concerned, the statement notes that the meat is safe for consumption by the general population, adding that Revivicor intends to sell meat from GalSafe pigs by mail order, rather than in supermarkets.

The agencys evaluation also concluded that GalSafe pigs presented low risk to the environment, with an impact that is no greater than from conventional pigs. It adds that no animal safety concerns were noted for GalSafe pigs beyond those that would be expected in well-managed, commercial swine populations.

Multiple other efforts to develop genetically engineered pigs are underway around the world, including some alterations designed to make pigs grow faster, and others aimed at making the animals more resistant to lethal viruses such as porcine reproductive and respiratory syndrome virus (PRRSV).

See original here:
FDA Clears Genetic Modification in Pigs for Biomedicine and Food - The Scientist

CiBER-seq dissects genetic networks

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

Science, this issue p. eabb9662

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

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

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

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

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

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

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

Genetic Testing to Establish Strong Foothold in Current and Future Healthcare System

The notable rise in the demand for hereditary genetic testing over the past few years is one of the major factors that is expected to fuel the growth of the global genetic analysis services market in the upcoming decade. Technological advancements coupled with the drive to discover new and innovative genetic analysis techniques are set to shape the overall growth trajectory of the global genetic analysis services market during the forecast period. Over the past decade, the genome testing sector has witnessed consistent developments due to which, the global genetic analysis services market is anticipated to expand at an impressive rate during the assessment period.

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Hereditary genetic testing has emerged as ideal, and a rapidly evolving technology within the genetic analysis services market. This is likely to continue, owing to advancements in technology and findings of research activities. The increasing demand for improved and cutting-edge prediction and diagnostic tools and services coupled with surge in demand for disease monitoring is anticipated to play a key role in the overall growth of the global genetic analysis services market during the assessment period.

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Healthcare experts and credible researchers around the world are of the opinion that genetic testing is expected to be the future of the healthcare ecosystem. Advancements in the biomedical field coupled with the notable rise in the number of companies that are developing new genetic-testing kits are expected to augment the global genetic analysis services market during the forecast period. Moreover, as interest levels for precision medicine continues to witness sizeable growth around the world, as a result of which the demand for genetic analysis services is projected to grow at an impressive pace.

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Uptake of Next-generation Sequencing and Multi-gene Tests to Drive Market

Advancements in the genetic technology are likely to play an instrumental role in shaping the growth trajectory of the global genetic analysis services market during the forecast period. Furthermore, due to advancements in technology, the scope of genetic testing has widened by a considerable margin due to which, the demand for genetic analysis services is increasing. While genetic analysis services in the past were largely time-consuming and cumbersome, at present, increasing speed and availability of genomic testing are anticipated to present a plethora of opportunities to the players involved in the current market landscape for genetic analysis services.

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In addition, the gradual shift in the point of access to testing is evolving, as more number of consumers can avail genetic analysis services outside the healthcare setting. Advancements in genetic medicine at the back of advancements in technology are likely to bolster the growth of the global genetic analysis services market during the assessment period.

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Research and Development Activities in Full Swing amid COVID-19 Pandemic

Research and development activities are expected to continue in full swing amid the ongoing COVID-19 pandemic. The significant rise in the demand for genetic counseling services during the ongoing COVID-19 crisis is anticipated to generate consistent revenue for the players involved in the genetic analysis services market. Furthermore, researchers and scientists are increasingly focusing on discovering genetic mechanisms that are required to prevent the spread and transmission of the novel coronavirus disease. Genetic research is estimated to unlock various intricate details of the novel coronavirus, thereby opening up new opportunities for mitigation. The ongoing research pertaining to genetics and its correlation with the ongoing pandemic is expected to provide a detailed and microscopic understanding of the overall cellular mechanisms of the virus.

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Genetic Analysis Services Market: Uptake of Next-generation Sequencing and Multi-gene Tests to Drive Market - BioSpace