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Archive for the ‘Genetics’ Category

Genetics study helps tiger conservation The Shillong Times – The Shillong Times

Saturday, June 20th, 2020

By Natasa Milas

Preserving the tiger population in the Indian subcontinent is a passion with Uma Ramakrishnan, an assistant professor at the National Centre for Biological Sciences (NCBS), Bengaluru, and one of Indias leading scientists. Her work focuses on population genetics and the evolutionary history of mammals.Data from Ramakrishnans work has been used for creating and improving plans for conservation of tigers in a rapidly urbanising India. In 2013, Ramakrishnan and her teams data was used as evidence in the Supreme Court to petition for an underpass for the widened National Highway 7 to enable tiger connectivity between Kanha and Pench tiger reserves in Madhya Pradesh.Ramakrishnan was a 2015-16 Fulbright-Nehru Academic and Professional Excellence Fellow at Stanford University, California. She is the first Indian to win the Parker/Gentry Award, administered by The Field Museum in Chicago in recognition of her work on conservation efforts. Excerpts from an interview:

How did you become interested in population genetics?I was always interested in the natural world and in understanding animal behaviour. I was lucky to grow up on the Indian Institute of Science campus in Bengaluru. My curiosity as a child always extended beyond simply observing the natural world. I asked myself: Why do animals behave the way they do? What is actually transpiring in these animal populations? Early on, I realised that there was a hidden layer of information that we were not considering DNA and genetic variation.After high school, I accompanied my family to Princeton University, USA, where my father was on a sabbatical. There I spent time in a molecular ecology lab and could gain deep insights into biology by understanding this hidden information layer. I knew then that I wanted to use a genetics lens to study wildlife populations.After my studies, I was lucky to get a job at the National Centre for Biological Sciences, part of the Tata Institute of Fundamental Research, Bengaluru. I was their first hire in the ecology and evolution area. Soon after, I got a call from conservation zoologist and tiger expert Ullas Karanth, asking if I was interested in working on tigers and their genetics. My journey over the last 15 years or so at NCBS, understanding tigers and other Indian biodiversity, has been incredibly exciting.

How is your work helping to preserve the tiger population in India?The future of tigers is really in our hands. Thanks to the efforts of the Government of India, several tiger populations have recovered. The viability and future survival of these populations will be contingent on our ability to maintain connectivity between them.I hope our research has and will continue to fill the gap between science, management and policy. We are currently working on an isolated population of tigers in Rajasthan and I hope our research insights will help plan what may be the best way to ensure long-term survival of this population.

How has your experience at the Stanford University as a Fulbright Fellow helped your current work in India?This was a really great opportunity. After nine years at NCBS a sabbatical sounded great. I was outside my comfort zone at Stanford University, the academic mecca for population genetics. Additionally, Stanford is nestled in the San Francisco Bay Area, where many conservation NGOs and start-up companies at the forefront of new genomic technologies are based.The amazing thing about being outside your comfort zone is that its empowering. With colleagues at Stanford, we turned what has typically been a challenge for conservation genetics non-invasive or poor-quality DNA samples into a strength. We asked whether we could develop cheap, reliable and fast methods that used novel genomic technologies to work on poor-quality samples. While there, my colleagues and I set up the Program for Conservation Genomics. Our goal was to provide simple-to-use genetic approaches to on-ground conservationists. We are still working together to make this a reality.

What are some of the biggest challenges in your work?Permissions to work in protected areas are always very challenging. Then, there are the things you really have no influence over. It rains and, well, your samples collected over the next few days are unlikely to have DNA or yield results. Sometimes, we work with large teams or in areas which are very difficult (for example, high elevation), inaccessible or not very politically stable.

What are your future research plans?I would really like to build partnerships with other tiger researchers across Asia. The methods we developed while at Stanford are going to be generalizable across tiger range countries. One of the goals is that everyone across the world can use a common platform for analyses, so that the data is comparable. Critical to this effort, however, is that each country builds an ecosystem to generate and analyze their genetic data on tigers locally.We are working hard to understand the impacts of inbreeding or mating between relatives on small and isolated tiger populations. This is a big ask for a species like tiger, but I am hoping the detailed work we are doing could shed some light on this problem, which is sure to become more common with time.I hope that our research can contribute in whatever small way to reverse biodiversity loss. (SPAN-TWF)

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Genetics study helps tiger conservation The Shillong Times - The Shillong Times

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Biochemical pedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope – Science Advances

Saturday, June 20th, 2020

Abstract

Developmental shifts in stage-specific gene expression can provide a ready mechanism of phenotypic change by altering the rate or timing of ontogenetic events. We found that the high-altitude Tibetan antelope (Panthelops hodgsonii) has evolved an adaptive increase in blood-O2 affinity by truncating the ancestral ontogeny of globin gene expression such that a high-affinity juvenile hemoglobin isoform (isoHb) completely supplants the lower-affinity isoHb that is expressed in the adult red blood cells of other bovids. This juvenilization of blood properties represents a canalization of an acclimatization response to hypoxia that has been well documented in adult goats and sheep. We also found the genomic mechanism underlying this regulatory isoHb switch, revealing how a reversible acclimatization response became genetically assimilated as an irreversible adaptation to chronic hypoxia.

When members of multigene families are developmentally regulated, shifts in the stage-specific expression of individual genes can provide a ready mechanism of phenotypic change by altering the rate or timing of ontogenetic events (heterochrony). For example, retained activity of early-expressed genes in later stages of ontogeny can result in the retention of juvenile characters into adulthood, a well-documented developmental mechanism of phenotypic evolution (1, 2). In extreme cases, deceleration of development can produce a truncation of the ancestral ontogeny, resulting in the juvenilization of the adult-expressed phenotype, a phenomenon known as pedomorphosis.

In jawed vertebrates, the subfamilies of genes that encode the - and -type subunits of tetrameric hemoglobin (Hb) are developmentally regulated such that structurally and functionally distinct 22 Hb isoforms (isoHbs) are expressed during different ontogenetic stages. During mammalian development, different pre- and postnatally expressed isoHbs have evolved different oxygenation properties and perform distinct O2-scavenging/O2-transport tasks during different ontogenetic stages (36). Genetically based shifts in stage-specific isoHb expression could therefore provide a heterochronic mechanism of evolutionary change in respiratory gas transport and aerobic metabolism. Similarly, in humans, hereditary persistence of fetal Hb alleviates the severity of thalassemias and other pathologies affecting the synthesis or stability of adult Hb (7).

Prenatally expressed isoHbs of eutherian mammals typically exhibit substantially higher O2 affinities than adult-expressed isoHbs (3, 5, 6). In anthropoid primates and bovid artiodactyls, expression of a high-affinity fetal isoHb during late stages of prenatal development helps to maintain an O2 affinity difference between fetal and maternal circulations, thereby facilitating O2 transfer across the placental barrier (5, 6). Given that increased Hb-O2 affinity is generally beneficial under conditions of severe hypoxia due to the importance of safeguarding arterial O2 saturation (6, 811), the retention of early isoHb expression into adulthood could provide an effective mechanism of adaptation to chronic O2 deprivation. Consistent with this hypothesis, when adult goats and sheep are exposed to acute hypoxia, they up-regulate a juvenile isoHb at the expense of the normal adult isoHb (12, 13). Here, we report the discovery of a canalized version of this response in the high-altitude Tibetan antelope, Panthelops hodgsonii (Artiodactyla: Bovidae), a champion among mammals in aerobic exercise performance under hypoxia. This species is endemic to the Tibetan Plateau and lives at altitudes of 3600 to 5500 m above sea level. At an altitude of 5500 m, the partial pressure of O2 (PO2) is roughly half the value at sea level, a level of hypoxia that severely compromises aerobic exercise performance in humans and most other mammals (1416). However, at these altitudes, Tibetan antelope can sustain running speeds of >70 km/hour over distances of >100 km (17).

In addition to documenting the phenotypic consequences of developmentally displacing the low-affinity adult isoHb with a higher-affinity juvenile isoHba form of biochemical pedomorphosiswe also found the genomic mechanism by which the up-regulation of the juvenile isoHb became canalized in Tibetan antelope. Specifically, we document how a reversible acclimatization response to acute hypoxiaas observed in modern-day sheep and goatsbecame genetically assimilated as an irreversible adaptation to chronic hypoxia.

We characterized the genomic organization of globin genes in Tibetan antelope and other bovid artiodactyls using published genome assemblies (18). Among mammals, bovid artiodactyls are unusual in that the entire -globin gene cluster has undergone multiple rounds of en bloc duplication involving the same set of pre- and postnatally expressed -type globin genes (Fig. 1) (1921). Cows (Bos taurus) have two duplicated gene blocks, each containing separate paralogs of the -globin gene, A and F, in the 5 and 3 blocks, respectively (Fig. 1). As with other eutherian mammals, the product of A is incorporated into an adult-expressed isoHb, HbA (2A2), whereas the F gene has been recruited for prenatal expression and is incorporated into a fetal isoHb, HbF (2F2) (22). Goats (Capra hircus) and sheep (Ovis aries) have an additional gene block at the 5 end of the cluster that contains a third -globin paralog, C (Fig. 1) (1921). Whereas the A and F genes in goats and sheep have retained the same developmental expression profiles as their respective orthologs in cow, the C gene has been recruited for a new ontogenetic stage of expression during the first few months of neonatal life, and its product is incorporated into a juvenile isoHb, HbC (2C2) (23).

Colored boxes represent individual genes. Labels denote previously annotated C-, A-, and F-globin genes.

The -globin gene cluster of Tibetan antelope appears superficially similar to that of cow in terms of gene content (Fig. 1), suggesting that the Tibetan antelope inherited the same pair of A- and F-containing gene blocks. The alternative hypothesis is that Tibetan antelope inherited the additional en bloc duplication observed in goats and sheep but one of the triplicated gene blocks was secondarily deleted, in which case the sole remaining pair of -globin genes would be represented by one of three possible combinations: A + F (a reversion to the ancestral gene complement observed in cow), C + A, or C + F (Fig. 2, A to C). Either of the latter two combinations would implicate a novel isoHb profile that is not observed in other bovid taxa. To distinguish among these three alternative scenarios, we estimated the phylogeny of bovid C, A, and F genes and the pair of Tibetan antelope -globin paralogs. Estimated phylogenies (Fig. 2D and fig. S1) demonstrate that the 5 and 3 -globin genes of Tibetan antelope are orthologous to bovid C and F, respectively, consistent with the scenario illustrated in Fig. 2B. This result indicates that Tibetan antelope inherited the triplicated set of C-, A-, and F-containing gene blocks observed in goats and sheep (Fig. 1) and that the middle gene block containing A was secondarily deleted. This phylogenetic inference is unambiguously corroborated by patterns of conserved synteny and pairwise sequence matches (Fig. 3), as the C- and F-containing gene blocks of goat and sheep match the 5 and 3 gene blocks in Tibetan antelope. This comparative genomic analysis revealed that a ~45-kb region of the Tibetan antelope -globin gene cluster was deleteda gene region that contained the ortholog of the A gene that encodes the chain of adult Hb in bovids and all other mammals.

Alternative histories of gene deletion in Tibetan antelope yield testable phylogenetic hypotheses: (A) Deletion of C, (B) deletion of A, and (C) deletion of F. (D) Estimated maximum likelihood phylogeny of bovid -type globin genes indicates that Tibetan antelope has retained copies of C and F and that A has been secondarily lost. Bootstrap support values are shown for relevant nodes.

Purple, green, and blue colored boxes represent genes within the C-, A-, and F-gene blocks, respectively. (A) Gray shading denotes percent sequence identity between homologous -globin gene clusters. (B) A ~45-kb chromosomal deletion in the -globin cluster of the Tibetan antelope lineage resulted in secondary loss of the A-containing gene block.

Deletion of the adult A gene in the ancestor of Tibetan antelope effectively truncated the ancestral ontogeny of globin gene expression, such that juvenile HbC completely supplanted HbA in adult red blood cells. Thus, blood-O2 transport in Tibetan antelope has been juvenilized relative to the ancestral phenotype of adult bovids. To examine the effects of this pedomorphic change, we measured the oxygenation properties of purified recombinant Hb from Tibetan antelope and purified native Hbs from adult specimens of 10 other bovid species (Fig. 4 and Table 1). The adult red cells of these other taxa contain HbA alone or in combination with HbC as a minor component (fig. S2). We measured the Hb-O2 affinity of purified total Hb from each bovid species in both the absence (stripped) and presence of 100 mM Cl (in the form of KCl). The stripped treatment provides a measure of intrinsic Hb-O2 affinity, whereas the +KCl treatment provides a measure that is relevant to in vivo conditions in bovid red cells, as Cl ions are the principal allosteric regulators of Hb-O2 affinity (i.e., heme reactivity is modulated oxygenation-linked binding of Cl ions at sites remote from the heme iron) (6, 22, 24). Results of our in vitro experiments revealed that Hb of Tibetan antelope has a substantially higher O2 affinity than that of all other bovid taxa (Fig. 4 and Table 1). Hbs of all taxa were similarly responsive to Cl, as the average P50 (the PO2 yielding 50% Hb-O2 saturation) was 27.1% higher (i.e., Hb-O2 affinity was lower) in the +KCl treatment (Table 1).

O2 tensions at half saturation (P50) for total Hb in the absence (stripped; gray hatched bars) and presence of 0.1 M KCl (black bars) at 37C (pH 7.4) (0.1 mM Hb4). Values are shown as mean P50 SEM (n = 3).

P50 values are reported as means SEM. Cl effect calculated as logP50[+KCl] logP50[stripped].

As a follow-up experiment, we isolated and purified HbC and HbA from two of the bovid species expressing both components, and we measured isoHb-specific O2-binding properties to determine how blood-O2 affinity would be affected by elimination of the major HbA isoHb (as would occur with the deletion of the A gene, leaving juvenile HbC as the sole-remaining isoHb). There was very little among-species variation in the measured O2 affinities of either juvenile HbC or adult HbA (Table 1 and fig. S2), but the O2 affinity of HbC exceeded that of HbA by a consistent margin (average, 10.6 torr) in all species (Table 1 and fig. S2). Moreover, O2 affinity of HbC alone was always substantially higher than that of the composite HbA + HbC mixture (with the two isoHbs present in their naturally occurring relative abundance) (Table 1 and fig. S2), reflecting the fact that the lower affinity HbA is always present as the major isoHb in adult red cells (average HbA/HbC ratio = ~80:20).

The higher Hb-O2 affinity of Tibetan antelope relative to that of other bovid species is entirely attributable to a difference in isoHb composition: They only express the high-affinity HbC instead of jointly expressing HbA and HbC (with the lower-affinity HbA present as the major isoHb). To infer the direction of evolutionary change in isoHb-specific O2 affinities and to reconstruct the phenotypic effect of deleting A-globin (thereby leaving HbC as the sole-expressed isoHb in adult red cells), we reconstructed the ancestral bovid A and C genes as well as their single-copy, preduplication progenitor (AC) (Fig. 5 and fig. S3). Triangulated comparison of O2 affinities of the three recombinantly expressed ancestral isoHbs, AncHb-A, AncHb-C, and AncHb-AC (all of which had identical chains), revealed that the juvenile AncHb-C evolved a slight increase in O2 affinity relative to the estimated ancestral state (represented by AncHb-AC), whereas adult HbA evolved a slight reduction in O2 affinity (Fig. 5). These data indicate that if HbA and HbC were present in a 80:20 ratio in the red cells of the Tibetan antelope ancestor (as in extant bovids), then the deletion of A-globin and the consequent elimination of HbA from the HbA + HbC composite mixture would result in a 13.5% increase in Hb-O2 affinity in the presence of 100 mM Cl (P50 decreased from 18.5 to 16.0 torr). Theoretical and experimental results indicate that an increase in Hb-O2 affinity of this magnitudeif accompanied by a corresponding enhancement of tissue O2 diffusion capacitywould likely translate into a physiologically important enhancement of aerobic exercise performance under hypoxia (6, 811).

(A) Reconstructed ancestral -globin genes (C, A, and AC) of bovids. (B) O2 tensions at half saturation (mean P50 SEM, n = 3) for recombinant ancestral isoHbs in the absence (stripped) and presence of 0.1 M KCl at 37C (pH 7.4) (0.1 mM Hb4). Schematic diagrams show the subunit composition of the three ancestral isoHbs (which have identical chains and structurally distinct chains).

The derived blood phenotype of Tibetan antelope is consistent with the theoretical expectation that an increased Hb-O2 affinity is adaptive under conditions of severe hypoxia (especially in highly athletic species) and is consistent with patterns observed in other high-altitude mammals and birds that maintain especially high rates of aerobic metabolism (2533). In other case studies of high-altitude vertebrates, evolved increases in Hb-O2 affinity have been traced to one or more amino acid substitutions in the and/or chain subunits of the 22 Hb tetramer (6, 3132). Here, we document a unique case in which an evolved change in Hb-O2 affinity has been accomplished via a heterochronic shift in globin gene expression, such that a high-affinity, juvenile isoHb supplants the lower-affinity, adult isoHb. This juvenilization of blood properties represents a novel mode of biochemical adaptation and highlights the utility of heterochrony as an adaptive mechanism, whereby the existing channel of ordinary ontogeny already holds the raw material in a particularly effective state for evolutionary change (2).

There has been debate in the literature regarding the relative importance of regulatory versus coding changes in genetic adaptation (34) and phenotypic evolution in general (3536). In the case of Tibetan antelope, the evolved increase in Hb-O2 affinity was caused by an unusual combination of regulatory and structural changes. Specifically, a marked regulatory switch in protein isoform expression (via truncation of the ancestral ontogeny of globin gene regulation) was caused by a large-scale chromosomal deletion, highlighting the unexpected diversity of genetic mechanisms and substrates of phenotypic evolution.

Frozen erythrocytes from 10 bovid species were provided by the San Diego Zoo Institute for Conservation Research (Uniform Biological Material Transfer Agreement BR2017063). This sample included six species in the subfamily Caprinae (Capra aegagrus cretica, Capra caucasica caucasica, Ovis nivicola, Capra nubiana, Ovis orientalis musimon, and Ovis canadensis nelsoni), two species in the subfamily Alcelaphinae (Damaliscus pygargus phillipsi and Connochaetes gnou), and one species of each from Hippotraginae (Addax nasomaculatus) and Bovinae (Bos gaurus).

RNA was extracted from ~100 l of flash-frozen erythrocytes using an RNeasy Universal Plus Mini kit (QIAGEN). Complementary DNA (cDNA) was synthesized from freshly prepared RNA using SuperScript IV reverse transcriptase (Invitrogen). Gene specific primers were used to amplify the - and -type globin transcripts. Polymerase chain reaction (PCR) reactions were conducted using 1 ml of cDNA template in 0.2-ml tubes containing 25 l of reaction mixture [0.5 l of each deoxynucleotide triphosphate (2.5 mM), 2.5 l of 10 Reaction Buffer (Invitrogen), 0.75 l of 50 mM MgCl2, 1.25 l of each primer (10 pmol/l), 1 l of Taq polymerase (Invitrogen), and 16.75 l of double-distilled H2O], using an Eppendorf Mastercycler Gradient thermocycler. Following a 5-min denaturation period at 94C, the desired products were amplified using a cycling profile of 94C for 30 s, 53 to 65C for 30 s, 72C for 45 s for 30 cycles, followed by a final extension period of 5 min at 72C. Amplified products were run on a 1.5% agarose gel, and bands of the correct size were subsequently excised and purified using Zymoclean Gel DNA recovery columns (Zymo Research). Gel-purified PCR products were ligated into pCR4-TOPO vectors using a TOPO TA Cloning kit and were then transformed into One Shot TOP10 Chemically Competent Escherichia coli (Thermo Fisher Scientific). Three to six transformed colonies were cultured in 5 ml of LB medium, and plasmids were subsequently purified with a GeneJET Plasmid Miniprep kit (Thermo Fisher Scientific). Purified plasmids were sequenced by Eurofins Genomics.

Genomic sequences containing the complete - and -globin gene clusters for the domestic goat (C. hircus), sheep (O. aries), cow (B. taurus), and Tibetan antelope (P. hodgsonii) were obtained from GenBank (table S1). Sequence identity between bovid chromosomal regions containing the -globin gene clusters was calculated using Blastn, and patterns of sequence matching were visualized using Easyfig 2.1 (37). Coding sequences of - and -globin genes were extracted from genomic and cDNA sequences available on GenBank (table S1) and were combined with the newly generated cDNA sequences mentioned above (fig. S3). Sequences were aligned using MUSCLE (38) and were then used to estimate phylogenetic trees. The best fitting codon substitution model and initial tree search were estimated using IQ-TREE with the options -st CODON, -m TESTNEW, -allnni, and -bnni (39, 40). Initial trees were then subjected to 1000 ultrafast bootstrap replicates (41). Bootstrap consensus trees (fig. S1, A and B) were used to estimate ancestral globin sequences using IQ-TREE with the option -asr (figs. S1C and S3). As bovid C-globins are truncated by 9 base pairs (relative to A), the ancestral reconstruction of indels in the -globin gene tree was performed by FastML (42).

Blood samples (~200 l) were added to a 5 volume of ice-cold water and incubated on ice for 30 min to lyse the red blood cells. Samples were centrifuged at 20,000g for 10 min to remove cell debris. Buffer was added to the supernatants to a final concentration of 0.01 M Hepes/0.2 M NaCl (pH 7.4) and passed through a PD-10 desalting column (GE Healthcare) equilibrated with 25 ml of 0.01 M Hepes/0.5 mM EDTA (pH 7.2) to remove intracellular cofactors. Desalted lysates were loaded onto a HiTrap SP cation exchange column (GE Healthcare), and isoHbs were eluted using a linear pH gradient [0.01 M Hepes/0.5 mM EDTA (pH 7.2 to 7.7)]. For each species, a subsample of each isoHb was pooled to create a Total Hb solution. Each Hb solution was then desalted using a PD-10 column (GE Healthcare) equilibrated with 0.01 M Hepes/0.5 mM EDTA (pH 7.4), and eluates were concentrated using the Amicon Ultra-4 Centrifugal Filter Units (Millipore).

O2 equilibrium curves for purified Hb solutions [0.1 mM Hb in 0.1 M Hepes/0.05 M EDTA buffer (pH 7.4)] were measured at 37C using the Blood Oxygen Binding System (Loligo Systems). O2 equilibrium curves were measured in the absence (stripped) and presence of chloride ions (0.1 M KCl). Each Hb solution was sequentially equilibrated with three to five different O2 tensions (PO2) at saturation levels between 30 to 70%, while the absorbance was continually monitored at 430 nm (deoxy peak) and 421 nm (oxy/deoxy isosbestic point) (4345). Hill plots (log[fractional saturation/[1 fractional saturation]] versus logPO2) constructed from these measurements were used to estimate the PO2 at half saturation (P50) and the cooperativity coefficient (n50) from the -intercept and slope of these plots, respectively. O2 equilibrium curves for each Hb solution were measured in triplicate, and P50 is reported as means SEM.

Globin sequences for domestic goat, Tibetan antelope, and the reconstructed ancestral globins were synthesized by GeneArt Gene Synthesis (Thermo Fisher Scientific) after optimizing the nucleotide sequences in accordance with E. coli codon preferences. The synthesized globin gene cassette was cloned into a custom pGM vector system along with the methionine aminopeptidase gene, as described previously (46).

Recombinant Hb expression was carried out in the E. coli JM109 (DE3) strain as described previously (4648). Bacterial cell lysates were then loaded onto a HiTrap Q HP anion exchange column (GE Healthcare), then equilibrated with 20 mM tris/0.5 mM EDTA (pH 8.3), and eluted with a linear gradient of 0 to 0.25 M NaCl. Hb-containing fractions were then loaded on to a HiTrap SP HP cation exchange column (GE Healthcare) and eluted with a linear pH gradient (pH 6.8 to 8.4). Eluted Hb factions were concentrated using the Amicon Ultra-4 Centrifugal Filter Units (Millipore), and oxygenation properties were measured as described above.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

S. J. Gould, Ontogeny and Phylogeny (Harvard Univ. Press, 1977).

S. J. Gould, The Structure of Evolutionary Theory (Harvard Univ. Press, 2002).

J. F. Storz, Hemoglobin: Insights into Protein Structure, Function, and Evolution (Oxford Univ. Press, 2019).

M. H. Blunt, T. H. J. Huisman, The haemoglobins of sheep, in The Blood of Sheep: Composition and Function (Springer, 1975), pp. 155160.

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Biochemical pedomorphosis and genetic assimilation in the hypoxia adaptation of Tibetan antelope - Science Advances

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Despite Recommendations, Genetic Testing Rare Among Those With Autism – Disability Scoop

Saturday, June 20th, 2020

Researchers say that very few people with autism are undergoing the genetic testing they should. (Dreamstime/TNS)

It is widely recommended that individuals with autism receive a battery of genetic tests, but new research finds strikingly few people on the spectrum partaking.

Just 3 percent of those with autism have received both chromosomal microarray and fragile X testing, according to findings from a study published recently in the journal JAMA Psychiatry.

The American Academy of Pediatrics, the American College of Medical Genetics and the American Academy of Child and Adolescent Psychiatry all recommend both assessments in order to determine more precisely what might underlie an individuals symptoms and point to treatment options, the researchers said.

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The study looked at medical records and self-reported information from 1,280 people with autism ranging in age from 1 to 68 between 2013 and 2019. More than 16 percent of the participants said they had received some variety of genetic testing, with 13 percent having undergone fragile X testing and 4.5 percent receiving chromosomal microarray testing. But, the researchers found that only a small number of people were taking both of the recommended tests.

I had the impression that the frequency of recommended genetic testing was not going to be very high based on the patients I encounter clinically, but 3 percent is actually lower than I thought it would be, said Daniel Moreno De Luca, an assistant professor of psychiatry and human behavior at Brown University who worked on the paper.

The study found that genetic testing is more common for those diagnosed in recent years. Among individuals diagnosed with autism between 2010 and 2014, nearly 10 percent said they had received chromosomal microarray testing, which is a more modern offering. But, adults with autism were unlikely to have had any genetic testing.

Researchers behind the study said their findings highlight a disconnect between research and professional recommendations and whats happening in clinical practice.

This paper is really about how you implement clinical genetic tests in the clinical diagnostic setting, said Eric Morrow, an associate professor of biology at Brown and an author of the study. There is rapid progress from research, and then theres the doctor and health systems that need to translate that to clinical practice.

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Human Genetics Market Analysis with Key Players, Applications, Trends and Forecasts to 2026 – Farmers Ledger

Saturday, June 20th, 2020

The Human Genetics market report Added by Market Study Report, LLC, enumerates information about the industry in terms of market share, market size, revenue forecasts, and regional outlook. The report further illustrates competitive insights of key players in the business vertical followed by an overview of their diverse portfolios and growth strategies.

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Human Genetics Market Analysis with Key Players, Applications, Trends and Forecasts to 2026 - Farmers Ledger

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Tiger hair to be used to map striped cats genetic roots – The New Indian Express

Saturday, June 20th, 2020

Express News Service

BENGALURU: A team of researchers from the National Centre for Biological Sciences (NCBS) are using hair shed of tigers to create a genetic database and pedigree of striped cats at Ranthambore Reserve in Rajasthan.

So far, NCBS studied the gene pool using tiger pelts, blood and tissue samples. But now they are using shed hair. In the study titled Are shed hair genomes the most effective non-invasive resource for estimating relationships in the wild? the researchers collected 34 tiger hair samples in Ranthambore during a 256-day study period.

Lead author and research scholar at NCBS Anubhab Khan told TNIE that this was the first-of-its kind of study and the next step of what the team was studying so far. Earlier, tissue and blood samples were used, but getting them was a challenge. We even started direct observation. But since tigers are elusive, we decided to use shed hair for studying genetic database and DNA mapping, he said. Tigers shed hair while scratching, sitting, resting and so on. We found them to be a good sample base for the study. It helped us get precise data because it was also verified with the tissue samples collectedso far.

Spread over an area of 392 sq km, Ranthambore is best known for its tigress Machli (T-16), which died in August 2016. Many, including forest officials, state that most of the tigers in Ranthambore are her lineage and NCBS is studying that.

Khan said two new lineages were reported. In case of T-47, we did not know anything, after the study we found its mother was related to Machli. As for T-24, we have so far found its mothers side has no connection to Machli. Now the fathers side is being studied to draw the family tree, he said. NCBS has around 106 tiger DNA sequences; of these, 100 sequences are from around the world and 60 from India.The researchers are also studying tigers in Similipal National Park, Odisha, and Bandhavgarh National Park, Madhya Pradesh, where many cattle kill cases are reported, with the same method.

What is tiger shed?Like many other mammals, tigers shed their fur or hair once or twice per year. The tiger has a longer winter coat and a shorter summer coat. Hairs are also shed by the bigs cats when they scratch on trees or even while sitting on the ground.

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Tiger hair to be used to map striped cats genetic roots - The New Indian Express

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Genetic rescue of SHANK3 is potential therapy in rare forms of autism spectrum disorder – The Mix

Saturday, June 13th, 2020

A mouse model and previous studies suggest that genetic intervention in SHANK3-related ASD may be most effective earlier in development.

A mouse model and previous studies suggest that genetic intervention in SHANK3-related ASD may be most effective earlier in development.A mouse study by Craig Powell, M.D., Ph.D., and colleagues suggests that early genetic rescue may be a potential therapy in autism spectrum disorder, or ASD. Powell looked at one gene called SHANK3, whose alteration is seen in about 0.5 percent of ASD patients.

The study is published in eNeuro and was highlighted on the ASD news site Spectrum. Powell is professor and chair of the Department of Neurobiology at the University of Alabama at Birmingham and also heads the UAB Civitan International Research Center. The UAB researcher has a longstanding focus on autism, intellectual disability and cognitive dysfunction.

The SHANK3 gene product acts in the brain as a postsynaptic scaffolding protein. A synapse is a gap between two nerve cells where a signal is passed from one nerve to the other. A human brain may have more than 100 trillion synapses in its neuronal circuitry.

Powell and colleagues previously showed that mice deficient in SHANK3 protein have behavioral abnormalities, including repetitive grooming and deficits in social interaction, locomotor activity and rearing. Rearing is standing on hind legs to investigate the surroundings. Some of these behaviors are reminiscent of ASD in humans, which is characterized by deficits in social interaction and communication, restricted interests and repetitive behaviors.

Powells lab and other labs, including Guoping Feng, Ph.D., Massachusetts Institute of Technology, have sought mouse models where a SHANK3 deficit could be reversed early or later in life, to see if that reversal removed some of the behavioral deficits. Powell says his and Fengs labs used different experimental approaches, and their two studies are complementary.

Powells lab used genetic tools to construct mice that had a stop signal inserted into one or both genes for SHANK3, creating heterozygous or homozygous mice for the mutation they call ShankE13. The activation of another inserted gene called Cre-recombinase can excise that stop signal, restoring full function of the mutated SHANK3 gene.

In Fengs mouse model, the SHANK3 gene was activated when the mice were given tamoxifen, which leads to some toxicity, including weight loss. In the Powell mouse model, the Cre-recombinase was negatively controlled by the antibiotic doxycycline; as long as mice were fed doxycycline, the Cre-recombinase was supposed to be shut off. When the doxycycline is stopped, the SHANK3 gene should be restored. Another genetic in the mouse model was supposed to limit reactivation of the SHANK3 gene to the striatum and cerebellum of the brain.

The plan was to activate the Cre-recombinase at different ages and test those mice for changes in ASD-like behaviors.

This elegant approach had two problems, the researchers learned. First, there was more widespread rescue of the SHANK3 gene in the brain than expected, including in the cortex. Second, the doxycycline control was leaky, allowing expression of the Cre-recombinase even as the mice were fed the antibiotic. Thus, Powell and colleagues were only able to look at the effect of early developmental genetic reversal of ShankE13, occurring about embryonic day 18.

Still, as Powell told Spectrum, It is important to publish experiments that do not work out exactly as planned.

Craig Powell, M.D., Ph.D.In a wide variety of behavioral tests, the researchers found that early genetic restoration of SHANK3 rescued a variety of behaviors that included repetitive grooming and social, locomotor, and rearing deficits.

The social tests included the amount of social interaction with another mouse; social recognition memory, where a test mouse was introduced to another mouse, and then reintroduced three days later; and social novelty exploration, which compares the amount of time spent with a novel caged mouse versus an inanimate object.

The locomotor tests included placing mice in a novel cage with minimal bedding and measuring how much they freely explored over two hours. In a different series of tests, the mice as expected showed no changes in anxiety-related behaviors. That lack of change in anxiety in mutant and rescued mice had also been shown in previous work.

Overall, Powell said, our studies suggest early genetic rescue as a potential genetic therapy for ASD-like behaviors in ASD associated with SHANK3 deletion or mutation. Taken together with previously published studies, genetic intervention in SHANK3-related ASD may be most effective earlier in development.

Co-authors with Powell for the study, Early restoration of Shank3 expression in Shank3 knockout mice prevents core ASD-like behavioural phenotypes, are Thomas C. Jaramillo, Jeremy M. Reimers, Christine O. Escamilla and Shunan Liu, University of Texas Southwestern Medical Center, Dallas; and Zhong Xuan, UAB Department of Neurobiology.

Powell moved to UAB from the Southwestern Medical Center in 2018. At UAB, Powell holds the Virginia B. Spencer Endowed Professorship in Neuroscience.

Support came from National Institutes of Health grants HD069560 and HD069560-S1, Autism Speaks, an Autism Science Foundation Pre-doctoral Fellowship, The Hartwell Foundation, gifts from Clay Heighten and Debra Caudy, and BRAINS for Autism.

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Global Genetic Testing Market Forecasts for Applications and Technologies 2020-2024, Updated in Light of Impact of COVID-19 Pandemic -…

Saturday, June 13th, 2020

The "Genetic Testing. Global Market Forecasts for Applications and Technologies. Updated for COVID-19 Pandemic impact with Executive and Consultant Guides 2020 to 2024" report has been added to ResearchAndMarkets.com's offering.

This report explores how the large genetic testing cancer segment has been impacted by COVID-19. Genetic Blizzard is creating a confusing array of new tests. Will all newborns receive Whole Genomic Sequencing at birth? What has happened to Direct to Consumer?

The role of genetics in health and disease is just now being understood. This new knowledge, combined with lower pricing is driving the Genetic Testing industry to record growth. New drugs may only work for people with a certain genetic makeup, and this too is driving the Genetic Testing Industry. The traditional genetic testing market is growing in volume and growing in the breadth of tests creating a new life for the industry. The report forecasts the market size out to 2024. The report includes detailed breakouts for 14 countries and 5 regions.

Predictive Diagnostics? Pharmacogenomic Testing? Direct to Consumer? Find out about the technology in readily understood terms that explain the jargon. What are the issues? Find the opportunities and pitfalls. Understand growth expectations and the ultimate market forecasts for the next five years.

Key Topics Covered:

1. Introduction and Market Definition

1.1 Genetic Testing Definition in This Report

1.2 The Genomics Revolution

1.3 Market Definition

1.4 U.S. Medical Market and laboratory Testing - Perspective

2. Market Overview

2.1 Market Participants Play Different Roles

2.2 Genetic Tests -Types, Examples and Discussion

2.3 Industry Structure

2.4 Market Shares of Key Genetics Players - Analysis

3. Market Trends

3.1 Factors Driving Growth

3.2 Factors Limiting Growth

3.3 Instrumentation and Automation

3.4 Diagnostic Technology Development

4. Genetic Testing Recent Developments

5. Profiles of Key Companies

6. Global Market Size

6.1 Global Market by Country

6.2 Global Market by Application

6.3 Global Market by Technology

7. Market Sizes by Application

7.1 Newborn Testing Market

7.2 NIPT Market

7.3 Predictive Testing Market

7.4 Oncology Testing Market

7.5 DTC Testing Market

7.6 Other Testing Market

8. Global Genetic Testing Market by Technology

9. The Future of Genetic Testing

For more information about this report visit https://www.researchandmarkets.com/r/jp4uin

About ResearchAndMarkets.com

ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200610005299/en/

Contacts

ResearchAndMarkets.comLaura Wood, Senior Press Managerpress@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470For U.S./CAN Toll Free Call 1-800-526-8630For GMT Office Hours Call +353-1-416-8900

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Global Genetic Testing Market Forecasts for Applications and Technologies 2020-2024, Updated in Light of Impact of COVID-19 Pandemic -...

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International Albinism Awareness Day celebrates those with rare genetic condition – Down To Earth Magazine

Saturday, June 13th, 2020

Made To Shine the chosen theme for this years International Albinism Awareness Day celebrates the achievements of those who have albinism

International Albinism Awareness Day is observed every year on June 13 to highlight the rights of those born with albinism and increase awareness of the genetic condition. The theme gains significance this year since the novel coronavirus disease (COVID-19) pandemic has resulted in the spread of misinformation against those who have albinism.

The physical appearance of those with albinism is often conflated with erroneous beliefs and myths influenced by superstition, something that furthers marginalisation and social exclusion, leading to stigma and discrimination.

In some countries, those with the genetic condition have been stigmatised and accused for spreading COVID-19, something that does not have a basis in scientific fact.

Killings, attacks, bullying and discrimination continue against people with albinism.

This day, hence, serves as a reminder that people with albinism continue to defy odds, overcome hurdles and face injustice with resilience.

Made To Shine the chosen theme for this years International Albinism Awareness Day celebrates the achievements and successes of individuals with albinism worldwide.

It is also a call for solidarity with those who have albinism and the challenges they face.

Albinism a rare disease, according to the National Institutes of Health is characterised by a lack of melanin pigment in skin, hair and eyes. Those with albinism are vulnerable to sun exposure, something that increases chances of skin cancer and severe visual impairment.

An albino crocodile in Odisha's Bhitarkanika National Park Photo: Ashis Senapati

The condition is still not fully understood, socially or medically. Both parents must carry the gene for their child to have the condition.

Even though the parents carry the gene, they may not show any physical signs of the condition, said Sudhashree Pattanaik, a noted dermatologist from Odisha.

One out of every 17,000 people across the world have albinism. Africa and Europe have the greatest number of those with albinism.

In India, there are around 200,000 who have albinism. The Union government is yet to conduct a census to account for those who have albinism, said Amarbara Biswal, a human rights activist.

In 2013, the United Nations Human Rights Council adopted a resolution that called for the prevention of discrimination against individuals with albinism.

The UN General Assembly proclaimed June 13 to be International Albinism Awareness Day on December 18, 2014, with it being observed for the first time in 2015.

Widespread among animals

An albino turtle at Rushikulya beach in Odishas Ganjam district Photo: Ashis Senapati

Albinism is widespread among animals as well and is caused by the absence of melanin in their bodies, said Sudhakar Kar, a noted herpetologist and former wildlife researcher in Odishas forest and wildlife department.

A baby albino crocodile was found in Odishas Bhitarkanika National Park in 1975. After her birth, forest officials kept the reptile in a pond at a crocodile rearing centre within the park.

The female baby crocodile was named gori (white) because of its colour. In 2012, forest officials discovered another albino crocodile in Bhitarkanika and kept the reptile in a pen as well, according to Kar.

An albino Olive Ridley turtle laid eggs during arribada (mass nesting) at Rushikulya beach in Odishas Ganjam district in March this year, said Basudev Tripathy, a noted turtle researcher and Deputy Director of the Zoological Survey of India. Albino sea turtles are extremely rare, he added.

Rabindranath Sahu the secretary of the Rushukulya Sea Turtle Protection Committee discovered the albino turtle, according to him.

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International Albinism Awareness Day celebrates those with rare genetic condition - Down To Earth Magazine

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COVID-19 Genetic PCR Tests Give False Negative Results if Used Too Early – Diagnostic and Interventional Cardiology

Saturday, June 13th, 2020

June 10, 2020 In a new study, Johns Hopkins researchers found that testing people for SARS-CoV-2 (COVID-19) too early in the course of infection is likely to result in a false negative test, even though they may eventually test positive for the virus.[1] This is important to understand since many hospitals are using these COVID tests to screen patients before imaging exams, diagnostic testing or procedures.

The report found even a week after infection, one in five people who had the virus had a negative test result. The findings was published in the May 13 issue of Annals of Internal Medicine.

A negative test, whether or not a person has symptoms, doesnt guarantee that they arent infected by the virus, said Lauren Kucirka, M.D., Ph.D., M.Sc., obstetrics and gynecology resident at Johns Hopkins Medicine. How we respond to, and interpret, a negative test is very important because we place others at risk when we assume the test is perfect. However, those infected with the virus are still able to potentially spread the virus.

Kucirka said patients who have a high-risk exposure should be treated as if they are infected, particularly if they have symptoms consistent with COVID-19. This means communicating with patients about the tests shortcomings. One of several ways to assess for the presence of SARS-CoV-2 infection is a method called reverse transcriptase polymerase chain reaction (RT-PCR). These tests rapidly make copies of and detect the viruss genetic material. However, as shown in tests for other viruses such as influenza, if a swab misses collecting cells infected with the virus, or if virus levels are very low early during the infection, some RT-PCR tests can produce negative results. Since the tests return relatively rapid results, they have been widely used among high-risk populations such as nursing home residents, hospitalized patients and healthcare workers. Previous studies have shown or suggested false negatives in these populations.

For the new analysis, Johns Hopkins Medicine researchers reviewed RT-PCR test data from seven prior studies, including two preprints and five peer-reviewed articles. The studies covered a combined total of 1,330 respiratory swab samples from a variety of subjects including hospitalized patients and those identified via contact tracing in an outpatient setting.

Using RT-PCR test results, along with reported time of exposure to the virus or time of onset of measurable symptoms such as fever, cough and breathing problems, the researchers calculated the probability that someone infected with SARS-CoV-2 would have a negative test result when they had the virus infection. In the published studies, healthcare providers collected nasal and throat samples from patients and noted the time of virus exposure or symptom onset and sample collection.

From this data, the Johns Hopkins researchers calculated daily false-negative rates, and have made their statistical code and data publicly available so results can be updated as more data are published.

The researchers estimated that those tested with SARS-CoV-2 in the four days after infection were 67 percent more likely to test negative, even if they had the virus. When the average patient began displaying symptoms of the virus, the false-negative rate was 38 percent. The test performed best eight days after infection (on average, three days after symptom onset), but even then had a false negative rate of 20 percent, meaning one in five people who had the virus had a negative test result.

We are using these tests to rule out COVID-19, and basing decisions about what steps we take to prevent onward transmission, such as selection of personal protective equipment for healthcare workers, Kucirka explained. As we develop strategies to reopen services, businesses and other venues that rely on testing and contact tracing, it is important to understand the limitations of these tests.

Ongoing efforts to improve tests and better understand their performance in a variety of contexts will be critical as more people are infected with the virus and more testing is required. The sooner people can be accurately tested and isolated from others, the better we can control the spread of the virus, the researchers said.

Another John Hopkins study in March found the average incubation period for COVID-19 was approximately five days.[2] This was originally used as a guide by some in developing quarantine guidelines. However, this new study shows that test COVID PCR test results are not reliable for a firm diagnosis until well after a week of infection.

Additional authors include Denali Boon, Stephen Lauer, Oliver Layendecker and Justin Lessler and of Johns Hopkins.

Funding for the study was provided by the National Institute of Allergy and Infectious Diseases (R01AI135115 and T32DA007292), the Johns Hopkins Health System and the U.S. Centers for Disease Control and Prevention (NU2GGH002000).

Reference:

1. Lauren M. Kucirka, Stephen A. Lauer, Oliver Laeyendecker, et al. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain ReactionBased SARS-CoV-2 Tests by Time Since Exposure. Annuals of Internal Medicine. May 13, 2020. doi.org/10.7326/M20-1495.

2. Stephen A. Lauer, Kyra H. Grantz, Qifang Bi, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020 Mar 10 : M20-0504. Published online 2020 Mar 10. doi: 10.7326/M20-0504.

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COVID-19 Genetic PCR Tests Give False Negative Results if Used Too Early - Diagnostic and Interventional Cardiology

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Blood type might boost immunity to COVID-19, genetic website says – SILive.com

Saturday, June 13th, 2020

STATEN ISLAND, N.Y. -- An "O" blood type could provide some level of immunity against the coronavirus (COVID-19), according to a study by the genetic website 23andMe.

Preliminary information from more than 750,000 participants in the study suggests that the "O" blood type appears to be protective against the virus when compared to all other blood types, according to a blog on the genetic website.

Comparing the research participants who reported that they tested positive for COVID-19 to those who tested negative, our researchers identified a variant in the ABO gene associated with a lower risk, according to the genetic website.

People with that blood type could be 9-to-18% less likely to test positive for COVID-19, according to the genetic website.

Among healthcare workers and others repeatedly exposed to the virus, "O" blood type is similarly protective, but the proportion of cases within strata is higher, according to 23andMe.

Whether the "O" blood is positive or negative is not a significant factor in immunity or severity of illness for those who become infected, according to the genetic website.

The genetic website referenced some similar results from other studies in China, Italy and Spain.

Numerous other studies have reported that the ABO blood group plays a role in both susceptibility and severity for COVID-19 (refs: 1, 2, 3), the genetic website said. And we know from other studies that the ABO blood group can play a direct role in other types of infections by serving as receptors, or co-receptors for microorganisms, parasites, and viruses. The preliminary findings from 23andMes data are also notable because of the link between COVID-19 blood clotting, and cardiovascular disease.

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Blood type might boost immunity to COVID-19, genetic website says - SILive.com

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Researchers uncover the arks of genetic diversity in terrestrial mammals – Jill Lopez

Saturday, June 13th, 2020

Maximizing the protection of life on Earth requires knowledge of the global patterns of biodiversity at multiple dimensions, from genetic diversity within species, to species and ecosystem diversity. Yet, the lack of genetic sequences with geographic information at global scale has so far hindered our ability to map genetic diversity, an important, but hard to detect, biodiversity dimension.

In a new study, researchers from the Universities of Copenhagen and Adelaide have collected and georeferenced a massive amount of genetic data for terrestrial mammals and evaluated long-standing theories that could explain the global distribution of genetic diversity. They found that regions of the world rich in deep evolutionary history, such as Northern Andes, the Eastern Arc Mountains, Amazonia, the Brazilian Atlantic forest, the central America jungles, sub-Saharan Africa and south-eastern Asia are also strongholds of genetic diversity. They also show that the relatively stable climate in these regions during the past 21'000 years contributes significantly to this intraspecific richness.

"Genetic diversity within species is a critical component of biodiversity, playing two important roles at the same time. It reflects species evolutionary history and defines their capacity to adapt under future environmental change. However, and despite the predictions of major biodiversity theories, the actual global distribution of genetic diversity remained, so far, a mystery. Recent collective efforts to populate public databases with genetic sequences and their localities allowed us to evaluate these theories and generate the first global maps of genetic diversity in terrestrial mammal assemblages", says Spyros Theodoridis, Postdoctoral Researcher at the Center for Macroecology, Evolution and Climate, GLOBE Institute, and lead author of the study.

"The tropics, and more specifically tropical mountain regions, host large amounts of the global pool of genetic diversity. These arks of biodiversity are under a high pressure today due to climate and land-use change. The conservation of genetic diversity in these areas should be a priority in on-going conservation efforts", says David Nogues-Bravo, the senior author of the study and Associate Professor at the University of Copenhagen.

The study also evaluated the effects of climate change during the last 21'000 years in shaping current patterns of genetic diversity. Regions of the world that experienced less severe change in temperature and precipitation harbor higher levels of genetic diversity, potentially due to reduced population extinctions. It also suggests that past inter-annual precipitation variability contributes to higher genetic diversity possibly through population adaptive divergence.

"While we show that areas of high genetic diversity tend to occur in regions where climates have remained relatively unchanged during past periods of global-scale climate change, many of these regions are forecast to experience major climate disturbances in the near future. Unfortunately, this is likely to lead to a loss of genetic diversity in many biodiversity hotspots", says Damien Fordham, Associate Professor at The University of Adelaide's Environment Institute and a coauthor of the study.

"The identified correlations of genetic diversity with evolutionary history and past climate change allowed us to develop predictive models at global scale, particularly in regions that lack sufficient data, such as the tropics. These predictions constitute a first step towards filling major gaps of knowledge for genetic diversity, and can inform and be further validated by field-work campaigns in data-poor regions of the Earth", says Carsten Rahbek, head of the Center for Macroecology, Evolution and Climate.

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UK was inundated by new coronavirus cases from abroad, genetic analysis reveals – ITV News

Saturday, June 13th, 2020

Forget the UK's "patient zero", new cases of coronavirus were pouring into the country by the hundreds each week during March, helping to explain why our outbreak grew so large so quickly, new analysis of virus genomes reveals.

The study also finds the vast majority of cases arrived in the UK from mainland Europe at a time when much of our travel advice was focused on Asia.

The finding reinforces the conclusion of leading scientists like Professor Neil Ferguson on Wednesday that many lives could have been saved if the lockdown had happened sooner.

Scientists from the UK - Coronavirus Genomics Consortium - have been collecting the genetic sequences of more than 25,000 virus samples from UK cases of the virus.

Because the virus makes copying errors in its genetic code as it reproduces, it slowly mutates as time passes.

They used the changes in the virus genome to build a family tree of the SARS-CoV-2 virus from its origin in China to more than 7,000,000 confirmed human cases worldwide.

"The coronavirus evolves at around two-and-a-half mistakes a month and over the period of an outbreak that results in many different genomes of many different types being detectable," says Nick Loman, Professor of microbial genomics at the University of Birmingham and a member of the UK-COG.

They used their data on the virus' family trees, combined with data on travel patterns to the UK at the time to map where new cases of Covid-19 were coming from.

The majority (34%) came from Spain, a similar number (28%) from France, 14% from Italy, although these cases made up the bulk of early infections in February and 23% from other countries.

The bulk of cases - more than 80% - arrived in the UK between February 28 and March 29.

The UK implemented lockdown on March 23.

On Wednesday, Prof Ferguson told a committee of MPs "had we introduced lockdown measures a week earlier, we would have reduced the final death toll by at least a half".

The data also shows that while major public gatherings like football matches and the Cheltenham festival could have been important for spreading the virus, so many people were brining the virus into the country at the time, these events alone weren't significant drivers of our outbreak.

The study also found, that as our outbreak grew, the UK itself became a source of spread elsewhere.

It reveals the majority of cases contributing to Iceland's outbreak originated in the UK.

But the real benefit of sequencing Covid-19 genomes could be yet to come.

Now the numbers of infections has declined, its possible to use the virus' family tree to better trace and track new infections based on how related they are to one another.

"It's a very powerful tool," says Prof Loman.

"This allows us to look backwards and say, were all these cases at a particular gathering, is there an association with travel."

Coronavirus: Everything you need to know

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Scots parents’ heartache as baby with rare genetic condition will not live long enough to go to school – Daily Record

Saturday, June 13th, 2020

His bright, blue eyes shine with happiness but behind his smile lies heartache for little Rowan Packers parents.

For the one-year-old tot will not survive long enough to even go to school.

Little Rowan has a rare condition called Tay-Sachs Disease, a genetic condition which causes progressive damage to the nervous system.

It affects just one in 320,000 babies although it is more common within the Ashkenazi Jewish population of Eastern Europe where one in 3500 babies are born with it.

The family do not think there are Ashkenazi antecedents on either side and Rowans brother and sister Aaron, seven, and Gracie, five, do not have the condition.

Mum Deborah McDonald, 26, and delivery driver dad Aaron Packer, 25, had never even heard of the condition before Rowan was diagnosed.

Deborah, who trained as a nurse for a time, said: Id heard about other genetic conditions but never this one. It was an absolute shock.

Student Deborah, studying for an honours degree in integrated health and social care, had a normal pregnancy with Rowan. With her other two pregnancies she suffered life-threatening pre-eclampsia and they were born nine weeks early.

But Rowan wasnt born until 39 weeks.

However, Deborah, who has the immune disease lupus which can cause damage to organs and as well as causing miscarriages, had always felt there was something very different about the pregnancy because Rowan hardly moved.

But she said: He looked absolutely perfect when he was born and all the routine tests came back fine.

He weighed 5lb 15oz the biggest of all the couples babies, with Aaron only 3lb 3oz and Gracie a tiny 2lb 14oz.

She said: He was maybe about four months when we realised he wasnt trying to turn over. We were doing exercises on the mat with him but he didnt have the urge to do it.

His eyesight was always a bit strange. He never focused on a person or an object.

Rowan wasnt progressing like a normal child at all.

He had a string of tests but when a cherry dot was spotted on the retina during eyetest it pretty much confirmed the diagnosis.

Deborah said: It is just mad. This thing can be in families for years and years but the chances of meeting a partner who also has the gene are quite slim, particularly in somewhere the size of Scotland.

We only know of one other child in Scotland with it, a little boy in Aberdeen, and his mum has been helping me with answers and advice. He is maybe three or four and is unresponsive.

It is hard knowing no matter what you do, Rowan will not survive. If it was cancer there may have been a chance but there is nothing that can be done for him.

Rowan, who turned one on May 24, can only eat pureed food and his movement is just like a newborn.

Deborah said: He can smile and laugh. But that will go. He will never be able to sit unaided or roll over and he cant put any pressure on his feet.

If he is not lying down, he is in his chair if we are not lifting him. His wee muscles just dont work and anything that he can do just now will be lost. Even any automatic responses will go away.

At the end, he will be completely unaware of anything. The body just stops functioning.

The couple are desperate to move to a bigger home. At the moment they are in a two-bed private let in Mosspark, Glasgow, as they wait for a Glasgow Housing Association medical property to become available.

The family need a bigger house so Rowan can have a proper hospital bed and a hoist for when he grows too big for his mum to carry.

Deborah said: We have been bidding for medical properties but we have lost out to people who have been on the list longer.

GHA said they are doing all they can to help the Packers find a home that suits their needs.

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Scots parents' heartache as baby with rare genetic condition will not live long enough to go to school - Daily Record

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Direct-to-consumer Disease Risk and Health Genetic Test Market Growth Prospects, Revenue, Key Vendors, Growth Rate and Forecast To 2026 – Jewish Life…

Saturday, June 13th, 2020

Direct-to-consumer Disease Risk and Health Genetic Test Market Overview

The Direct-to-consumer Disease Risk and Health Genetic Test market report presents a detailed evaluation of the market. The report focuses on providing a holistic overview with a forecast period of the report extending from 2018 to 2026. The Direct-to-consumer Disease Risk and Health Genetic Test market report includes analysis in terms of both quantitative and qualitative data, taking into factors such as Product pricing, Product penetration, Country GDP, movement of parent market & child markets, End application industries, etc. The report is defined by bifurcating various parts of the market into segments which provide an understanding of different aspects of the market.

The overall report is divided into the following primary sections: segments, market outlook, competitive landscape and company profiles. The segments cover various aspects of the market, from the trends that are affecting the market to major market players, in turn providing a well-rounded assessment of the market. In terms of the market outlook section, the report provides a study of the major market dynamics that are playing a substantial role in the market. The market outlook section is further categorized into sections; drivers, restraints, opportunities and challenges. The drivers and restraints cover the internal factors of the market whereas opportunities and challenges are the external factors that are affecting the market. The market outlook section also comprises Porters Five Forces analysis (which explains buyers bargaining power, suppliers bargaining power, threat of new entrants, threat of substitutes, and degree of competition in the Direct-to-consumer Disease Risk and Health Genetic Test) in addition to the market dynamics.

Get Sample Copy with TOC of the Report to understand the structure of the complete report @ https://www.marketresearchintellect.com/download-sample/?rid=274030&utm_source=JLN&utm_medium=888

Leading Direct-to-consumer Disease Risk and Health Genetic Test manufacturers/companies operating at both regional and global levels:

Direct-to-consumer Disease Risk and Health Genetic Test Market Scope Of The Report

This report offers past, present as well as future analysis and estimates for the Direct-to-consumer Disease Risk and Health Genetic Test market. The market estimates that are provided in the report are calculated through an exhaustive research methodology. The research methodology that is adopted involves multiple channels of research, chiefly primary interviews, secondary research and subject matter expert advice. The market estimates are calculated on the basis of the degree of impact of the current market dynamics along with various economic, social and political factors on the Direct-to-consumer Disease Risk and Health Genetic Test market. Both positive as well as negative changes to the market are taken into consideration for the market estimates.

Direct-to-consumer Disease Risk and Health Genetic Test Market Competitive Landscape & Company Profiles

The competitive landscape and company profile chapters of the market report are dedicated to the major players in the Direct-to-consumer Disease Risk and Health Genetic Test market. An evaluation of these market players through their product benchmarking, key developments and financial statements sheds a light into the overall market evaluation. The company profile section also includes a SWOT analysis (top three companies) of these players. In addition, the companies that are provided in this section can be customized according to the clients requirements.

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Direct-to-consumer Disease Risk and Health Genetic Test Market Research Methodology

The research methodology adopted for the analysis of the market involves the consolidation of various research considerations such as subject matter expert advice, primary and secondary research. Primary research involves the extraction of information through various aspects such as numerous telephonic interviews, industry experts, questionnaires and in some cases face-to-face interactions. Primary interviews are usually carried out on a continuous basis with industry experts in order to acquire a topical understanding of the market as well as to be able to substantiate the existing analysis of the data.

Subject matter expertise involves the validation of the key research findings that were attained from primary and secondary research. The subject matter experts that are consulted have extensive experience in the market research industry and the specific requirements of the clients are reviewed by the experts to check for completion of the market study. Secondary research used for the Direct-to-consumer Disease Risk and Health Genetic Test market report includes sources such as press releases, company annual reports, and research papers that are related to the industry. Other sources can include government websites, industry magazines and associations for gathering more meticulous data. These multiple channels of research help to find as well as substantiate research findings.

Table of Content

1 Introduction of Direct-to-consumer Disease Risk and Health Genetic Test Market

1.1 Overview of the Market1.2 Scope of Report1.3 Assumptions

2 Executive Summary

3 Research Methodology of Verified Market Research

3.1 Data Mining3.2 Validation3.3 Primary Interviews3.4 List of Data Sources

4 Direct-to-consumer Disease Risk and Health Genetic Test Market Outlook

4.1 Overview4.2 Market Dynamics4.2.1 Drivers4.2.2 Restraints4.2.3 Opportunities4.3 Porters Five Force Model4.4 Value Chain Analysis

5 Direct-to-consumer Disease Risk and Health Genetic Test Market, By Deployment Model

5.1 Overview

6 Direct-to-consumer Disease Risk and Health Genetic Test Market, By Solution

6.1 Overview

7 Direct-to-consumer Disease Risk and Health Genetic Test Market, By Vertical

7.1 Overview

8 Direct-to-consumer Disease Risk and Health Genetic Test Market, By Geography

8.1 Overview8.2 North America8.2.1 U.S.8.2.2 Canada8.2.3 Mexico8.3 Europe8.3.1 Germany8.3.2 U.K.8.3.3 France8.3.4 Rest of Europe8.4 Asia Pacific8.4.1 China8.4.2 Japan8.4.3 India8.4.4 Rest of Asia Pacific8.5 Rest of the World8.5.1 Latin America8.5.2 Middle East

9 Direct-to-consumer Disease Risk and Health Genetic Test Market Competitive Landscape

9.1 Overview9.2 Company Market Ranking9.3 Key Development Strategies

10 Company Profiles

10.1.1 Overview10.1.2 Financial Performance10.1.3 Product Outlook10.1.4 Key Developments

11 Appendix

11.1 Related Research

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We Werent Going To Give Up: Family Celebrates Progress Of 1-Year-Old With Rare Genetic Disorder – CBS Denver

Saturday, June 13th, 2020

DENVER (CBS4) A one-year-old girl is growing stronger after being diagnosed a rare genetic condition. Payton Calvillo was diagnosed with Hypophosphatasia, which can cause bones and teeth to be extremely weak. Her family was told before she was even born she likely wouldnt survive.

My boys had been asking for a baby sister for a long time, laughed Ahna Calvillo, Paytons mom. They were sure she was a girl.

When Ahna was pregnant with their third child, she and her husband Riley went to an ultrasound appointment, to find out their babys sex. They were told they were having a little girl, but things didnt look good.

She just was like, These babys bones, they are bent and they are fractured in some places, Ahna said, tearing up. We just had two healthy boys and that was the last thing I expected. Was there something to be wrong with our baby girl?

Ahna said they immediately saw a specialist to learn more about the babys condition. However, it was so rare, doctors had a tough time diagnosing what was wrong.

Along the journey there were a lot of different diagnoses because they really didnt know what we were dealing with, Ahna said.

Staff with Rocky Mountain Hospital for Children in Denver began to help the Calvillo family. Cathy Brunson is a genetic counselor at the hospital, and said this condition usually impacts adults or older children.

Its a condition that can affect definitely bones but also the teeth, Brunson said. This was the first time I had seen it prenatally, especially to this degree.

Based on studies around the world, often babies like Payton require significant support upon delivery and some children can experience additional skeletal malformations, breathing difficulty and diminished muscle tone.

Doctors told the Calvillo family, because the babys bones were so weak, she likely wouldnt make it through birth. Ahna said, they decided to continue to pregnancy and keep their faith.

We werent going to give up on Payton. Payton hadnt given up at that point and we werent going to give up on her, Ahna told CBS4s Makenzie OKeefe. We just started praying.

After weeks of ultrasounds, at 39 weeks Ahna had a C-section to bring Payton into the world. She said if she heard her little girl cry, she knew she made it through birth without her chest collapsing.

She started crying and only had some rib fractures but no broken bones, Ahna said. She was, she was a miracle.

When Payton was born, x-rays show her bones were extremely bowed. She began treatment when she was just 6 days old and at a 6-week follow-up with an orthopedic specialists at Rocky Mountain Hospital for Children, they found no new fractures and improvement in her bowing legs.

At 12 months of age, baby Payton is weight bearing and her development milestones are on track.

The tricky part now is she has this condition and now what are we going to do for her, for the rest of her life, Brunson said.

Ahna and Riley say, seeing Payton grow up and get stronger has been a joy.

Ive been so excited to see her do all the things, to crawl and to walk, Ahna said. And shes not a low-key baby. She loves to keep up with her brothers.

The Calvillo family said it was a tough road, but seeing all the families facing tough diagnoses at the hospital too, was heartbreaking. They hope their story of not giving up when they were told she wouldnt make it early on, gives others hope.

We just want to bring encouragement, Ahna said. Shes a miracle, and shes a joy.

Ahna was also recently diagnosed with the same genetic condition, and is waiting to be enrolled in a clinical trial to receive the same medication as her baby.

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We Werent Going To Give Up: Family Celebrates Progress Of 1-Year-Old With Rare Genetic Disorder - CBS Denver

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When Cancer Cells Cant Make Their Own Fat, They Eat Whats Around Them – SciTechDaily

Saturday, June 13th, 2020

A switch in cancer fat metabolism from production to import could be exploited for therapy, researchers say. Credit: National Institutes of Healthy Public LIbrary

Cancer cells rewire their metabolism to compensate for a halt in fat production by importing more fat molecules from their environment.

Knowing what cancer will do next could lessen the likelihood of it becoming resistant to treatment. A new U of T study investigates how cancer adapts its metabolism to potentially overcome therapies still in development.

Several clinical trials have failed because metabolism is such an adaptive process by which cancer cells gain drug resistance, says Michael Aregger, a co-lead author and Research Associate working with Jason Moffat, Professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research, who co-led the work. If you know how cells are able to adapt to perturbations, maybe we can target them more specifically to avoid resistance from developing.

If you know how cells are able to adapt to perturbations, maybe we can target them more specifically to avoid resistance from developing Michael Aregger, Research Associate

The research was also led by Brenda Andrews and Charles Boone, University Professor and Professor of molecular genetics at the Donnelly Centre, respectively, and Chad Myers, a Professor of computer science at the University of Minnesota-Twin Cities.

The study, published this week in the journal Nature Metabolism, is the first to investigate global changes in cancerous cells as they adapt to a shortfall of critical nutrients such as fat molecules, or lipids, which make up the cells outer envelope.

When cancer cells are unable to make their own lipids, they gobble them up from their environment to ensure a steady supply of these essential building blocks, the study found. Lipids also serve as fuel and chemical signals for communication between cells, among other roles.

The switch in metabolism could be bad news for drugmakers seeking to target cancer by reducing its lipid reserves. In particular, drugs that inhibit an enzyme called FASN, for fatty acid synthase, involved in an early step of lipid synthesis, are being explored in patient trials. Fatty acids are precursors of larger lipid molecules and their production is increased in many cancers thanks to elevated FASN levels, which are also associated with poor patient prognosis.

The U of T study suggests that the effectiveness of FASN inhibitors could be short-lived owing to cancers ability to find another way to procure lipids.

Because FASN is upregulated in many cancers, fatty acid synthesis is one of the most promising metabolic pathways to target says Keith Lawson, a co-lead author and PhD student in Moffats lab enrolled in the Surgeon-Scientist Program at the Faculty of Medicine. Given that we know there is a lot of plasticity in metabolic processes, we wanted to identify and predict ways in which cancer cells can potentially overcome the inhibition of lipid synthesis.

To block fatty acid synthesis, the researchers employed a human cell line from which the FASN coding gene was removed. Using the genome editing tool CRISPR, they deleted from these cells all ~18,000 or so human genes, one by one, to find those that can compensate for the halt in lipid production. Such functional relationships are also referred to as genetic interactions.

Data analysis, performed by Maximilian Billmann, a co-lead author and a postdoctoral fellow in Myers lab at Minnesota-Twin Cities, revealed hundreds of genes that become essential when cells are starved of fat. Their protein products clustered into well-known metabolic pathways through which cells hoover up dietary cholesterol and other lipids from their surroundings.

Cells intake of cholesterol has become textbook knowledge since it was discovered half a century ago, winning a Nobel Prize and inspiring the blockbuster drug statin and many others. But the new study found that one component of this process remained overlooked all this time.

The gene encoding it was only known as C12orf49, named after its location on chromosome 12. The researchers re-named the gene LUR1, for lipid uptake regulator 1, and showed that it helps switch on a set of genes directly involved in lipid import.

This was a big surprise to us that we were able to identify a new component of the process we thought we knew everything about, says Aregger. It really highlights the power of our global genetic interaction approach that allowed us to identify a new player in lipid uptake in a completely unbiased way.

By a remarkable coincidence, two groups working independently in New York and Amsterdam also linked C12orf49 to lipid metabolism, lending further support for the genes role in this process. The New York team published their findings in the same journal issue as Moffat and colleagues.

Inhibiting LUR1, or other components of lipid import, along with FASN could lead to more effective cancer treatments. Such combination therapies are thought to be less susceptible to emerging drug resistance because the cells would have to simultaneously overcome two obstaclesblocked lipid production and importwhich has a lower probability of occurring.

Therapeutic context that comes out of our work is that you should be targeting lipid uptake in addition to targeting lipid synthesis and our work highlights some specific genes that could be candidates, says Lawson.

Reference: Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism by Michael Aregger, Keith A. Lawson, Maximillian Billmann, Michael Costanzo, Amy H. Y. Tong, Katherine Chan, Mahfuzur Rahman, Kevin R. Brown, Catherine Ross, Matej Usaj, Lucy Nedyalkova, Olga Sizova, Andrea Habsid, Judy Pawling, Zhen-Yuan Lin, Hala Abdouni, Cassandra J. Wong, Alexander Weiss, Patricia Mero, James W. Dennis, Anne-Claude Gingras, Chad L. Myers, Brenda J. Andrews, Charles Boone and Jason Moffat, 1 June 2020, Nature Metabolism.DOI: 10.1038/s42255-020-0211-z

The research was supported by the Canadian Institutes for Health Research, Ontario Research Fund, Canada Research Chairs Program and the U.S. National Institutes of Health.

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New Research Reveals the Function of Genetic Pathway for Reproductive Fitness in Flowering Plants – Newswise

Saturday, June 13th, 2020

Newswise ST. LOUIS, MO, June 11, 2020 Small RNAs are key regulators involved in plant growth and development. Two groups of small RNAs are abundant during development of pollen in the anthers a critical process for reproductive success. A research collaboration has demonstrated the function of a genetic pathway for anther development, with this pathway proven in 2019 work to be present widely in the flowering plants that evolved over 200 million years ago. The research team was led by Blake Meyers, Ph.D., member, Donald Danforth Plant Science Center and professor, Division of Plant Sciences, University of Missouri, and Virginia Walbot, Ph.D., Professor of Biology, Stanford University. Their findings, Dicer-like 5deficiency confers temperature-sensitive male sterility in maize were published in the journal,Nature Communications.

Unexpectedly, their research uncovered an environmentally sensitive male sterile phenotype. By using mutants and knocking out one of the pathways, the research team produced plants that failed to make pollen, but when they lowered the temperature, they found they could recover full male fertility. This ability to turn on or turn off pollen production in different conditions could be useful for seed production. The team could also attribute the function of this pathway in anther development, an observation previously missing but important. These results are important companions to a previously published discovery, which described the evolutionary distribution of the pathway across flowering plants, 24-nt reproductive phasiRNAs are broadly present in angiosperms,also published in the journalNature Communications.

Putting these two discoveries together, we can understand the role these molecules play is important for full male fertility in maize, plus, the pathway first evolved with flowering plants, said Meyers. Understanding the genetic mechanisms by which flowers develop is important for improving crop yields and breeding better varieties, particularly for making the high-yielding hybrid crops that support modern agriculture.

The research team will continue to work to understand why there is an environmentally-sensitive response to changes in this pathway, and what exactly is the molecular mechanism that leads to this male sterility in the absence of this small RNA pathway. Work in a separately funded project is examining if modulation of this pathway could be used to regulate pollen development in other crops, for the improvement of seed production and crop yield.

The authors include co-first authors, Chong Teng, Ph.D., postdoctoral associate in the Meyers lab and Han Zhang, Ph.D. former postdoctoral associate in the Walbot lab. Also contributing were Kun Huang, Ph.D., postdoctoral associate in the Meyers lab, and Reza Hammond, Ph.D., former graduate student in the Meyers lab. The work is funded by the National Science Foundation.

About The Donald Danforth Plant Science Center Founded in 1998, the Donald Danforth Plant Science Center is a not-for-profit research institute with a mission to improve the human condition through plant science. Research, education and outreach aim to have impact at the nexus of food security and the environment, and position the St. Louis region as a world center for plant science. The Centers work is funded through competitive grants from many sources, including the National Institutes of Health, U.S. Department of Energy, National Science Foundation, and the Bill & Melinda Gates Foundation. Follow us on Twitter at@DanforthCenter.

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Is Applied Genetic Technologies (AGTC) Stock Outpacing Its Medical Peers This Year? – Yahoo Finance

Saturday, June 13th, 2020

Investors focused on the Medical space have likely heard of Applied Genetic Technologies (AGTC), but is the stock performing well in comparison to the rest of its sector peers? One simple way to answer this question is to take a look at the year-to-date performance of AGTC and the rest of the Medical group's stocks.

Applied Genetic Technologies is one of 888 companies in the Medical group. The Medical group currently sits at #1 within the Zacks Sector Rank. The Zacks Sector Rank considers 16 different groups, measuring the average Zacks Rank of the individual stocks within the sector to gauge the strength of each group.

The Zacks Rank is a proven system that emphasizes earnings estimates and estimate revisions, highlighting a variety of stocks that are displaying the right characteristics to beat the market over the next one to three months. AGTC is currently sporting a Zacks Rank of #2 (Buy).

Within the past quarter, the Zacks Consensus Estimate for AGTC's full-year earnings has moved 11.64% higher. This signals that analyst sentiment is improving and the stock's earnings outlook is more positive.

Our latest available data shows that AGTC has returned about 15.71% since the start of the calendar year. At the same time, Medical stocks have gained an average of 0.21%. This means that Applied Genetic Technologies is outperforming the sector as a whole this year.

Looking more specifically, AGTC belongs to the Medical - Biomedical and Genetics industry, which includes 382 individual stocks and currently sits at #34 in the Zacks Industry Rank. This group has gained an average of 8.10% so far this year, so AGTC is performing better in this area.

AGTC will likely be looking to continue its solid performance, so investors interested in Medical stocks should continue to pay close attention to the company.

Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free reportApplied Genetic Technologies Corporation (AGTC) : Free Stock Analysis ReportTo read this article on Zacks.com click here.Zacks Investment Research

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Is Applied Genetic Technologies (AGTC) Stock Outpacing Its Medical Peers This Year? - Yahoo Finance

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The History Of Lynching From Trees: Where did it come from …

Tuesday, June 9th, 2020

Chev

But the Original Jews did NOT challenge Jesus, it was Jews such as the National group that stemmed from a movement prior to the time of Jesus. The Hellene Movement. So, Jesus was challenged by mixed-bred movement of people that were elevated above the Original Jews!!!

Therefore, they were probably telling the truth in that they had never been oppressed in Egypt.

YOU DO NOT UNDERSTAND WHAT THE PROBLEM WAS DURING THAT TIME! Geez!

You shouldn't be so quick to assume what I do and do not understand....lol.

I know there was a struggle between the Sadducees and Pharisees during the time of Jesus.What you're calling the Hellene Movement for the Jews to become more like the Greeks was led by the Pharisees -who were Persian overseers sent to Jersusalem to monitor the Jews when they returned from exile.

The Sadducees (sons of Zadok) wanted to maintain the religion the Moses gave them when he civilized them but the Pharisees wanted to move them more in line with the rest of the Caucasians called Gentiles or Greeks.

Get outta here! That was the book you used as a reference

Go back and look at my quotes.You will find NO QUOTE of me referencing a "Hebrew Standard Version".

I say there is the Hebrew Bible, and the various English translations like King James, American Revised, ect.....

The date of that translation was hundreds of years prior to the scriptures translated just before the time of the CRUSADES, of which became the basis for the

KJV which was translated by Hebrew Israelites.

YOur version is NOT received by Christians today for specific reasons.

But, I will add that I do know some of the terms you referenced is in an Ethiopian version [GEEZ]. But however, scholars today

do NOT agree with those terms for major reasons. and today, the people speak Amharic.

I'm not sure what you mean by "my" version.I don't have too much faith in ANY of them.....lol.But when discussing (or in this case arguing...lol) the Bible I like to get the PURIST source possible to find out exactly what the authors meant, so I usually used the HEBREW Bible.

I haven't quoted from the Hebrew Bible on this site because I have to post the text of it along with the translation and I'm not sure how to do that here.The texts is in both Hebrew and English letters.But that's the one I read from and use the most.

No. The very reference you quoted states that LOT was deceived; he had no idea.

OK?Whether he KNEW it or not, INCEST was still performed!

I said according to the Bible INCEST was commited, I didn't say Lot was willing to do it or started it or loved it or enjoyed it or was tricked into it....I said according to the Bible he DID it.And again, you can't find ANY scriptures where the Kenaani, Kemeti, Sumarian, or other Original peoples committed incest......drunk or sober.

Today, there are numerous findings that attest to the violence in that land byway of the Canaanites. They were BAAL PRIEST, that means HEADHUNTERS

Baal was a Kenaani deityZedek was anotherSalem (of which Jersusalem was named after) was another.

Most of these deities had "priests" or "Kohens" who served them in their dedicated temples.That doesn't mean they were killing people or cutting off heads for them.Melchizedek of the Bible was a Canaanite priest who came out to meet Abraham, was HE a head hunter?

As I told you before, the Kenaani were a very sexual people and this usually means violence was kept to a minimum.What credible source can you reference to say that the priests of Baal were headhunters?

The only record we have of people KILLING others and even chopping off heads (in the case of David) for their "god" are the Israelites who went around slaughtering the Original peoples of the land in the name of Yahweh....according to the Bible.

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Bestselling, Award Winning, New and Classic Books for …

Tuesday, June 9th, 2020

Mar/Apr 2020 | Jan/Feb 2020 | Nov/Dec 2019 | Sep/Oct 2019 | Jul/Aug 2019 | May/Jun 2019

Books Coming Out in the Next 6 Months and Beyond Books Published in the Last 60 Days The Most Critically Acclaimed Books of the Past 40 Years Top 150 Recommended African-American Childrens Books More Lists of Books

Bestselling Books for the Year 100 Essential Black Books Top 100 Selling Publisher Imprints Visit our Book Reviews Section 100 Bestselling Books of All-Time The Top 10 Books in 100 Different Categories 100 Bestselling Books of All Time Black-Owned Publishing Companies Favorite 100 Titles of the 20th Century The QBR 100 Essential Black Books Favorite 100 Titles of the 21sth Century (list being compiled now, cast your vote) Go On Girl! Book Clubs Complete Reading List (1991 2020) The Coffee Will Make You Black Book Clubs Reading List (19982006, and 2010) The Power List BestSelling Books (Spring 2013 to Spring 2015) Get Your Book on AALBC.com

We track all of the Black winners of the National Book Awards, Pulitzer Prize, Carter G. Woodson Award, Coretta Scott King Award, and many more. Winners of these awards are factored into our formula for determining The Most Critically Acclaimed Books of the Past 40 Years.

The Coffee Will Make You Black is AALBCs online book club. Check out our reading list and participate in discussions that take place over the course of a month. There is no commitment or pressure; just enjoy.

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