Category Archives: Human Genetics

Abstract

In less than 25 y, the field of animal genome science has transformed from a discipline seeking its first glimpses into genome sequences across the Tree of Life to a global enterprise with ambitions to sequence genomes for all of Earths eukaryotic diversity [H. A. Lewin etal., Proc. Natl. Acad. Sci. U.S.A. 115, 43254333 (2018)]. As the field rapidly moves forward, it is important to take stock of the progress that has been made to best inform the disciplines future. In this Perspective, we provide a contemporary, quantitative overview of animal genome sequencing. We identified the best available genome assemblies in GenBank, the worlds most extensive genetic database, for 3,278 unique animal species across 24 phyla. We assessed taxonomic representation, assembly quality, and annotation status for major clades. We show that while tremendous taxonomic progress has occurred, stark disparities in genomic representation exist, highlighted by a systemic overrepresentation of vertebrates and underrepresentation of arthropods. In terms of assembly quality, long-read sequencing has dramatically improved contiguity, whereas gene annotations are available for just 34.3% of taxa. Furthermore, we show that animal genome science has diversified in recent years with an ever-expanding pool of researchers participating. However, the field still appears to be dominated by institutions in the Global North, which have been listed as the submitting institution for 77% of all assemblies. We conclude by offering recommendations for improving genomic resource availability and research value while also broadening global representation.

The first animal genome sequence was published 23 y ago (1). The 97 millionbasepair (bp) (Mb) Caenorhabditis elegans genome assembly ushered in a new era of animal genome biology where genetic patterns and processes could be investigated at genome scales. As genome assemblies have accumulated for an increasingly diverse set of species, so too has our knowledge of how genomes vary and shape Earths biodiversity (e.g., refs. 2 and 3). Major shifts in genome availability and quality have been driven by two key events. First, the invention of high-throughput, short-read sequencing provided an economical means to generate millions of reads for any species from which sufficient DNA could be obtained. These 100-bp short reads could be assembled into useful, albeit fragmented, genome assemblies. Later, the rise of long-read sequencing allowed for similarly economical generation of reads that are commonly orders of magnitude longer than short reads, resulting in vastly more contiguous genome assemblies (4).

We have now entered an era of genomic natural history. Building on 250 y of natural history efforts to describe and classify the morphological diversity of life on Earth, we are gaining a complementary genomic perspective of Earths biodiversity. However, a baseline accounting of our progress toward a complete perspective of Earths genomic natural historywhere every species has a corresponding, reference-quality genome assembly availablehas not been presented. This knowledge gap is particularly important given the momentum toward sequencing all animal genomes, which is being driven by a host of sequencing consortia. For instance, the Vertebrate Genomes Project seeks to generate high-quality assemblies for all vertebrates (5), the Bird10K project seeks to generate assemblies for all extant birds (6), the i5K project plans to produce 5,000 arthropod genome assemblies (7), the Earth BioGenome Project aims to sequence all eukaryote genomes (8), and the Darwin Tree of Life project plans to sequence genomes for all eukaryotes in Britain and Ireland (https://www.darwintreeoflife.org/).

In this Perspective, we curated, quantified, and summarized genomic progress for a major component of Earths biodiversity: kingdom Animalia (Metazoa) and its roughly 1.66 million described species (9). We show that as of June 2021, 3,278 unique animals have had their nuclear genome sequenced and the assembly made publicly available in the National Center for Biotechnology Information (NCBI) GenBank database (10). This translates to 0.2% of all animal species. When viewed through the lens of major clades, massive disparities exist. For instance, 32 times more assemblies are available for chordates than arthropods (Fig. 1).

Variation in taxonomic richness and genome availability, quality, and assembly size across kingdom Animalia in GenBank (as of 28 June 2021). Taxonomic groups are clustered by phylogeny following ref. 11. Only groups with 30 or more available assemblies as of January 2021 are shown with the exception of Hominidae (n = 5 assemblies). In the tree, bold group names represent phyla and naming conventions follow those of the NCBI database. Of 34 recognized animal phyla, 10 do not have a representative genome sequence. (A) The total number of described species for each group following Zhang (9) and the references therein. (B) Genomic representation among animal groups for 3,278 species with available genome assemblies. Bars represent the magnitude of the observed minus the expected number of genomes given the proportion that each group comprises of described animal diversity. Significance was assessed with Fishers exact tests and significantly under- or overrepresented groups (P < 0.05) are denoted with asterisks. Gray numbers indicate the total number of species with available genome assemblies for each group. The number of available assemblies is not mutually exclusive with taxonomy; that is, a carnivore genome assembly would be counted in three categories (order Carnivora, class Mammalia, phylum Chordata). (C) The percentage of described species within a group with an available genome sequence (bars) and the percentage of those assemblies that have corresponding annotations (red circles). For many groups (e.g., arthropods), only a fraction of a percent of all species have an available genome assembly, making their percentage appear near zero. (D) Assembly size for all animal genome assemblies, grouped by taxonomy. (E) Contig N50 by taxonomic group. The sequencing technology used for each assembly is denoted by circle fill color: short-read (blue), long-read (yellow), or not provided (gray). In D and E, each circle represents one genome assembly and a few notable or outlier taxa are indicated with gray text.

To construct a database of the best available genome assembly for all animals, we downloaded metadata from GenBank for all kingdom Animalia taxa using the summary genome function in v.10.9.0 of the NCBI Datasets command-line tool on 4 February 2021. Next, we used the TaxonKit (12) lineage function to retrieve taxonomic information for each taxid included in the genome metadata. To gather additional data for each assembly (e.g., sequencing technology), we used a custom web scraper script. Both this web scraper script and the scripts used to download and organize the metadata are available in this studys GitHub repository (https://github.com/pbfrandsen/metazoa_assemblies). We later supplemented this initial dataset with a second round of metadata acquisition on 28 June 2021. For the full dataset, we hand-refined the NCBI taxonomy classifications to subdivide our dataset into three categories: species, subspecies, or hybrids (Dataset S1). If replicate assemblies for a taxon were present, we defined the best available assembly as the one with the highest contig N50 (the midpoint of the contig distribution where 50% of the genome is assembled into contigs of a given length or longer).

We filtered our data in several ways: We removed subspecies (unless they were the only representative for a species), hybrids, and assemblies that were shorter than 15.3 Mb [the smallest confirmed assembly size for a metazoan to date (13)] or had a contig N50 less than 1 kilobase (Kb). We also culled assemblies that were unusually short (i.e., 1 to 2.5 Mb) with information in their descriptions that indicated they were not true nuclear genome assemblies (e.g., exon capture). In total, we culled 407 assemblies based on the above criteria. The remaining assemblies were classified as short-read, long-read, or not provided if only short reads (e.g., Illumina) were used, any long-read sequences (e.g., PacBio) were used, or no information was available. We defined a species as having gene annotations available if any assembly for that taxon also had annotations in GenBank. When the best available assembly did not have annotations included or when multiple assemblies had annotations, we retained the annotations for the assembly with the highest contig N50. Finally, we used the submitting institution for each assembly as a surrogate for the institution that led the genome assembly effort. Using these data, we classified assemblies to a country, region (Africa, Asia, Europe, Middle East, North America, Oceania, South America, Southeast Asia), and the Global North (e.g., Australia, Canada, Europe, United States) or Global South (e.g., Africa, Asia including China, Mexico, Middle East, South America).

To test if clades were under- or overrepresented in terms of genome availability relative to their species richness, we compared the observed number of species with assemblies with the expected total for the group. We obtained totals for the number of described species overall and for each group from previous studies, primarily from Zhang (9) and the references therein. We assessed significance between observed and expected representation with Fishers exact tests (alpha = 0.05). We tested for differences in distributions of contig N50 or assembly size between short- and long-read genomes with Welchs t tests. For both display (i.e., Fig. 1) and analysis, we subdivided the dataset into the lowest taxonomic level that still contained 30 or more assemblies as of January 2021 (with the exception of hominids, which were given their own category due to their exceptionally high genomic resource quality).

Genome assemblies were available for 3,278 species representing 24 phyla, 64 classes, and 258 orders (Fig. 2A and Dataset S1). The dataset was exceptionally enriched for the phylum Chordata (which includes all vertebrates) with 1,770 assemblies for the group (54% of all assemblies) despite chordates comprising just 3.9% of animal species (P, Fishers < 1e-5; Fig. 1). Conversely, arthropods were underrepresented with 1,115 assemblies (34% of the dataset) for a group that comprises 78.5% of animal species (P, Fishers < 1e-5; Fig. 1). However, not all arthropods were underrepresented; five insect clades were overrepresented (Apidae [bees], Culicidae [mosquitoes], Drosophila [fruit flies], Formicidae [ants], and Lepidoptera [butterflies and moths]; all P, Fishers < 1e-3; Fig. 1). Collectively, of the 59 animal taxonomic groups included in our dataset, 14 groups were underrepresented, 17 were represented as expected, and 28 were overrepresented (primarily chordates; Fig. 1). Ten phyla had no publicly available genome sequence (Fig. 1). Over the 17-y GenBank genome assembly record, animal assemblies have been deposited at a rate of 0.52 species assemblies per day. Over the most recent year, however, this rate increased eightfold to 4.07 assemblies per day. If the most recent rate were maintained, all currently described animals would have a genome assembly available by 3136. To achieve this goal by 2031 instead, an average of 165,614 novel animal genomes would need to be sequenced and assembled each year (112 times faster than the rate for the most recent year).

Genome availability for kingdom Animalia versus taxonomic descriptions and over time. (A) The proportion of described taxonomic groups versus the number with sequenced genome assemblies from phyla to species. The gray plot (Right) is a zoomed-in perspective of the higher taxonomy-level categories in the full plot (Left). For genus through phylum, the number of described categories is based on the NCBI taxonomy. For species, the total number described is from Zhang (9). (B) The timeline of genome contiguity versus availability for animals according to the GenBank publication date (x axis; C). A rise in assembly contiguity has been precipitated by long-read sequencing. Particularly contiguous assemblies for a given time period are labeled. (C) The number of animal genome assemblies deposited in GenBank each month since February 2004. Several notable events are labeled. When specific dates are indicated, those (and the assemblies referred to) are included within that months total. For B and C, it is important to note that when a genome assembly is updated to a newer version, its associated date is also updated. Thus, the date associated with many early animal assemblies [e.g., C. elegans (1)] has shifted to be more recent with updates.

The average animal genome assembly was 1.02 gigabases (Gb) in length (SD 1.21 Gb) with a contig N50 of 2.26 Mb (SD 25.16 Mb; Fig. 1 D and E). Two animal genome assemblies were 25 Gb longer than all other assembliesthe axolotl [32.4 Gb (14)] and Australian lungfish [34.6 Gb (15)] (Fig. 1D). The smallest genome assembly in the dataset, the mite Aculops lycopersici, was over 1,000 times smaller, spanning just 32.5 Mb (16). Still smaller is the 15.3 Mb assembly of the marine parasite Intoshia variabili, which has the smallest animal genome currently known (13). But, since the I. variabili assembly was not available in GenBank as of June 2021, it was not included in our dataset.

Contiguity varied dramatically across groups. For instance, hominid assemblies (family Hominidae, n = 5) were the most contiguous with an average contig N50 of 24.2 Mb. Bird assemblies (class Aves, n = 515) were also highly contiguous (mean contig N50 = 1.4 Mb) despite being so numerous (and accumulating over a long period of time). On the other end of the spectrum, jellyfish and related species (phylum Cnidaria) exhibited some of the least contiguous genome assemblies with a mean contig N50 of 0.18 Mb (n = 65; Fig. 1E). Roughly 34% of animals with genome assemblies had corresponding annotations in GenBank but annotation rates differed substantially among groups (Fig. 1C). For example, the rate of arthropod annotations (22.3%) lags behind that for chordates (41.3%); however, much of this disparity appeared to be driven by the low and high annotation rates of butterflies and moths (order Lepidoptera) and birds (class Aves), respectively. Of 445 assemblies, just 6.5% of lepidopteran assemblies in GenBank have corresponding annotations versus 72.8% of birds (n = 519 assemblies; Fig. 1C). Notably, since most gene models are based on sequence similarity to known functional genes and not functional data, the true rate of annotation is likely even lower than reported here.

Animal genome assemblies have been contributed by researchers at institutions on every continent with permanent inhabitants, including 52 countries. From a regional perspective, institutions in North America (n = 1,331), Europe (n = 972), and Asia (n = 828) collectively accounted for 95.5% of all assemblies (Fig. 3A). And, nearly 70% of all animal genome assemblies have been submitted by researchers in just three countries: United States (n = 1,275), China (n = 676), and Switzerland (n = 317) (Fig. 3A). When countries were grouped by their inclusion in the Global North or South, similarly stark patterns emerged. Researchers affiliated with institutions in the Global North contributed roughly 75% of animal genome assemblies (Fig. 3B). From a taxonomic perspective, researchers at North American institutions have contributed the most insect and mammal assemblies, European researchers have contributed the most fish assemblies, and Asian researchers have contributed the most bird assemblies (Fig. 3A). The first assembly in GenBank from the Global North was deposited in 2004 and the first assembly from the Global South was deposited in 2011 (Fig. 3C). Since then, the number of assemblies deposited each year has steadily risen, with the proportions from the Global North and South staying relatively constant (Fig. 3C).

Where animal genome assemblies have been produced around the world according to the submitting institutions in GenBank. (A) For each geographic region, total numbers of genome assemblies are shown by dark circles with white lettering. This total is further broken down by country and taxon. For regions where more than four countries have contributed assemblies (e.g., Europe), an Other category represents all other countries. The same applies to all assemblies that are not insects, birds, fish, or mammals in the taxon plots. Countries are color-coded by assignment to the Global North or South. (B) The total number of genome assemblies contributed by countries in the Global North (e.g., United States, Europe, Australia) versus the Global South (e.g., Africa, South America, China, Mexico, Middle East). (C) The rate of genome assembly deposition by major sources in the Global North (Europe, United States) and Global South (China, Southeast [SE] Asia) as well as all other countries collectively in each (Other).

Use of long reads in genome assemblies and availability of key metadata also differ with geography. For assemblies deposited since 2018, researchers from the Global South have used long reads slightly more frequently than those from the Global North (25.7% versus 20.2%; Fig. 4A). However, researchers from the Global North were far less likely to report the types of sequence data used (19.9% of assemblies for the Global North versus 1.4% of assemblies for the Global South; Fig. 4A). Much of this difference appears to be driven by genome assemblies deposited by researchers at European institutions (Fig. 4B). This gap in metadata may reflect an issue with data mirroring between the European Nucleotide Archive (ENA) and GenBank. For instance, many new genome assemblies being generated by the United Kingdom, for example, are part of the Wellcome Sanger Institutes Darwin Tree of Life project, which is generating exceptionally high quality assemblies using long-read sequencing and depositing them into the ENA (Fig. 5). One region (Oceania) and three countries (Australia, Finland, India) reported long reads being used in more than 50% of deposited assemblies (Fig. 4 B and C).

Sequencing technologies used around the world (A) between the Global North versus Global South, (B) among regions, and (C) among countries. To limit bias due to the limited availability of long-read sequencing technologies before 2017 (Fig. 2B), only assemblies deposited on or after 1 January 2018 were included in the analysis and in C only countries that deposited five or more assemblies during the focal period (January 2018 to June 2021) are shown.

Examples of major contributors of genome assemblies for (A) butterflies (order Lepidoptera), (B) birds (class Aves), and (C) fish (primarily class Actinopterygii). Major contributors were defined as any consortium, organization, or project that has deposited more than 5% of all assemblies for butterflies and birds or 2.5% of all assemblies for fish.

Animal genome sequencing has dramatically progressed in the last 25 y. In that span, the field has moved from sequencing the first nuclear genome for any animal (1)a landmark achievementto targeting the generation of genome assemblies for all of Earths eukaryotic biodiversity (8). Here, we provided a contemporary perspective on progress toward this goal for the 1.6 million species in the animal kingdom (9). We showed that while tremendous progress has been made, major gaps and biases remain both in terms of taxonomic and geographic representation, at least within the most commonly used database of genomic resources, GenBank. For instance, a major bias exists in favor of vertebrates which are vastly overrepresented relative to their total species diversity (Fig. 1 AC). From the perspectives of biomedicine and human evolution, this bias is reasonable since humans are vertebrates. However, from a basic research perspective, particularly as it relates to genomic natural history and an overarching goal to sequence all animal genomes, there is a need to taxonomically diversify sequencing efforts.

At the highest taxonomic levels, 10 animal phyla still have no genomic representation. To illustrate the scale of this disparity versus other groups and the unique biology that is being overlooked, genome assemblies are available for 685 ray-finned fishes (class Actinopterygii) but none exists for phylum Nematomorpha, an 2,000-species clade of parasitic worms whose presence can dramatically alter energy budgets of entire stream ecosystems (17). Another phylum without genomic representationLoriciferawas first described in 1983 (18). This group of small, sediment-dwelling animals includes the only examples of multicellular species that spend their entire life cycles under permanently anoxic conditions (19). Loriciferans accomplish this feat by foregoing the energy-producing mitochondria found in virtually all animals in favor of hydrogenosome-like organelles akin to those found in prokaryotes inhabiting anaerobic habitats (19). Clearly, there is much to discover in terms of genomic diversity and functional biology in clades yet to be sampled.

A few select countriesprimarily the United States, several European nations, and Chinahave led the sequencing of the vast majority of animal genome assemblies (Fig. 3A). Aside from China, all of these countries are within the Global North. This pattern of geographic bias raises two potential issues for representation in animal genome science. First, the researcher population of animal genome sequencing likely does not reflect the global population. Second, sampling biases may exist toward the regions where most of the genome sequencing is occurring. Some of this bias is intentional and reflects funding goals for a given region. For instance, the Darwin Tree of Life project seeks to sequence the genomes of all 70,000 eukaryotic species living in Britain and Ireland. Still, however, similar to how sampling biases can yield skewed understanding of the natural world in other disciplines (e.g., ref. 20), so too could bias toward specific ecoregions, habitats, or other classifications skew genomic insight.

Inherently linked with questions of representation in animal genome science is the specter of parachute science (or helicopter research)the practice where international scientists, typically from wealthy nations, conduct studies in other countries that are often poorer without meaningful communication nor collaborations with local people (21). Parachute science has a long history in ecological research, and signatures of these practices have been observed for genome sciences. For instance, Marks etal. (22) found that the majority of plant genome assemblies for species that are native to South America and Africa were sequenced off-continent by researchers at European, North American, or Asian institutions. Given the sheer number of animal genome assemblies that have been submitted by a small number of countries and institutions, a similar pattern likely exists for animal genomes. However, to properly assess this issue, parsing authorship to quantify collaboration, at a minimum, would need to occur and this approach would still overlook key aspects of representation that need to be considered (e.g., if a researcher from the Global South is working at an institution in the Global North).

For the purpose of biological discovery, not all genome assemblies are created equal. As long-read sequencing technologies have matured, so too has the quality of assemblies being generated (4). In the last year alone, the largest ever animal genome assembly was deposited [Australian lungfish (15)] as well as the most complete human genome to date, a telomere-to-telomere assembly (23). Still, many species in GenBank only have low-quality assemblies available (i.e., contig N50 < 100 Kb with no corresponding gene annotations; Fig. 1). Since fragmentation and/or poor or missing gene annotations reduce the research value of an assembly, genome quality is important, particularly when the end goal is resource development for a broader community. As of April 2021, the Earth BioGenome Project sought assembly quality of 6.C.Q40 (https://www.earthbiogenome.org/assembly-standards) for reference genomes, where 6 refers to a 1e-6 contig N50 (i.e., 1 Mb). In our dataset, 568 assemblies (17.3%) reach this contiguity standard. And that number drops to 271 assemblies (8.3%) when contig N50 1 Mb and deposited gene annotations are both required. For reference, the C above refers to chromosomal scale scaffolding and Q40 to a less than 1/10,000 error rate. Neither of these metrics were assessed in this study.

Independent research laboratories, institutions, and consortia have contributed genome assemblies on both ends of the quality spectrum (Fig. 5). For example, among butterflies (order Lepidoptera), a bimodal quality distribution is being primarily driven by contributions made in 2021 by two submitting institutions, the Florida Museum of Natural History (e.g., ref. 24) and the Wellcome Sanger Institute (Fig. 5A). When viewing genome assembly contributions holistically across the animal Tree of Life, it is clear that two consortiathe Vertebrate Genomes Project (5) and the Darwin Tree of Life, part of the Wellcome Sanger Institutewarrant specific recognition for contributing exceptional genomic resources relative to closely related species (Fig. 5).

While animal genome science has dramatically matured in recent years, the field still rests on the cusp of massive change. Thousands of genome assemblies are now available for a wide range of taxa, a resource that can empower unprecedented scales of genomic comparison. Simultaneously, multiple consortia are building momentum toward their goals and generating some of the highest-quality genome assemblies ever produced. The field is also diversifying, with researchers around the world, particularly from the Global South, leading a rising number of efforts. These ongoing advances will yield higher-quality, more globally representative genome data for animals. As we collectively build toward this new genomic future, we offer recommendations to improve assembly quality and accessibility while also continuing to increase representation within the discipline.

The quality of a genome assembly is likely the most important factor dictating its long-term value. Genome assembly quality, however, is difficult to define. Here, we propose a holistic view on genome assembly quality that generally echoes the guidelines proposed by the Earth BioGenome Project and other consortia. Briefly, assemblies should reach minimum levels of contiguity (e.g., contig N50 > 1 Mb) and accuracy in order to be considered a reference that will likely not need to be updated for most applications. At a minimum, assemblies should also include high-quality gene annotations that perhaps take advantage of standardized pipelines [e.g., NCBI Eukaryotic Genome Annotation Pipeline (25)] to maximize compatibility across taxa. We recommend the field further improve the quality of genome assembly resources in two ways. First, refining and expanding the coordinated deposition of genome assemblies will improve the usability of the resources and reproducibility of analyses. It will also reduce duplications of effortthat is, when a group sequences a genome that has already been producedan issue that is likely to become increasingly common.

To refine and expand coordinated resource deposition, we recommend the continued use of GenBank (10) or one of the other archives that are members of the International Nucleotide Sequence Database Collaborationthe ENA and DNA Database of Japanas the central repositories for genome assemblies and their metadata given their tripartite data-sharing agreement. Next, we call on genetic archive administrators, consortia, and independent researchers to collectively improve the metadata submitted with each assembly and the mirroring of data across repositories. Too many assemblies lack basic information about the sequence data and methods used (e.g., Fig. 4) and, with the difficulty of linking assemblies to published studies (if available), it can be challenging or impossible to find this information. Further, an expansion of the metadata associated with each assemblyideally to make more of the categories required and expand demographic datawould make efforts to quantify geographic representation, for instance, far more straightforward. Alternatively, the metadata associated with genome assembly accessions could be integrated with existing efforts like the Genomic Observatories Metadatabase [GeOMe (26)]. Furthermore, a set of minimum quality characteristics for a genome assembly may need to be defined. A number of exceptionally low quality genome assemblies (e.g., with contig N50 values shorter than 1 Kb) that often cover only a small fraction of the expected total genome sequence length for a given group are present in GenBank. The presence of these assemblies raises the question: Where is the inflection point between resource quality and value to other researchers versus diluting the resources of a shared repository?

For our second recommendation, we amplify and expand the message of Buckner etal. (27) and Thompson etal. (28): Genome science needs specimen vouchers. Vouchers serve as a key physical link between taxonomy and molecular insight. Rarely, however, are vouchers referenced in publications of genome assemblies; only 11% of vertebrate assemblies included such a reference as of January 2020 (27). While vouchers represent a physical reference for assessing taxonomic classification or morphological variation, a properly stored voucher could also provide a long-term source of material for future resource improvement. If a physical specimen cannot be deposited, photographs and/or genomic DNA should be deposited in its place (e.g., ref. 29). Tied to the metadata discussion above, additional fields should be added to GenBank genome assembly accessions to directly link the assembly to a specimen, photo, or genomic DNA that has been deposited elsewhere.

Though geographic representation in animal genome science has improved in recent years, the discipline appears far from properly reflecting the global researcher pool. This issue is almost certainly multifaceted, likely stemming from a lack of infrastructure (e.g., fewer high-throughput sequencing platforms in developing countries), fewer resources for expensive molecular research, and a corresponding lack of training in genome data analysis. To bridge this gap and to empower a more diverse discipline, the nations and institutions that are devoting large amounts of resources to animal genome sequencing (e.g., China, United Kingdom, United States), and the researchers within those countries, should continue to develop meaningful collaborations with researchers within countries where their focal species reside (30). These meaningful collaborationswhere all parties are valued for their expertise and involved in decision makingimprove the science through transfer of local knowledge, provide a means for local researchers to expand their skillset and network while raising their scholarly profile, and, most importantly, can effectively end the practice of parachute science (30). Within-continent (or -country) initiatives also have transformative potential for people and genome research. For instance, the African-led effort to sequence 3 million African genomes over the next 10 y (the 3MAG project) will yield massive investment in African genomics, an incredible resource for understanding the full scope of human genetic diversity, and a new generation of African genome scientists (31). While focused on human genetics, the infrastructure and expertise that arise from the 3MAG project will no doubt translate to other taxa in the coming years.

A practical justification also exists for increasing representation in genome science, particularly as we seek to generate genome assemblies for every animal on Earth. The Global South is home to the bulk of the worlds biodiversity (32) and, as such, researchers in these regions have greater access to key habitats and specimens. Thus, it behooves everyone, including researchers in the Global North, to deepen collaborations with peers in the Global South while also helping to build indigenous capacity for collection, storage, and sequencing of new specimens.

Animal genome science continues to grow and expand at an exceptional rate. The coming years will surely see thousands, and perhaps tens of thousands, of new genome assemblies from across the Tree of Life, technological and analytical improvements, and some of the largest-scale and most in-depth studies of animal genome biology conducted to date. However, if we are to realize the ambitious goals of efforts like the Earth BioGenome Projecta self-described biological moonshotthe rate and mean quality of animal genome assembly production will have to increase by roughly two orders of magnitude. Regardless of rates and timelines, however, perhaps the most important goal for the future of animal genome science is that we empower a more diverse, representative researcher community in parallel with the generation of new resources.

All study data are included in the article and/or supporting information.

S.H. and J.L.K. were supported by NSF Award OPP-1906015. We thank Guangfeng Song, Eric Cox, and Anne Ketter from the Datasets development team at the NCBI for their responsiveness and receptiveness to improving this valuable tool for data science.

Author contributions: S.H., J.L.K., and P.B.F. designed research; S.H. and P.B.F. performed research; S.H. and P.B.F. analyzed data; and S.H., J.L.K., and P.B.F. wrote the paper.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2109019118/-/DCSupplemental.

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Toward a genome sequence for every animal: Where are we now? - pnas.org

Flash isnt your average puppy. A yellow Labrador, named after one of the first British guide dogs from 1931, she is playful, affectionate, and loves learning new commands. Flash is enrolled in an elaborate program herself, one that takes two years and nearly $50,000 to train her to become a guide dog for the blind and visually impaired. Her temporary caregiver Melanie will make sure she maintains a healthy routine: twice-daily walks in different environments, a train ride here, a trip to a mall there to get used to other people. But Melanie has already accomplished one of her most important tasks: When Flash was five months old, she swabbed the puppys cheek and mailed the saliva away to a team of researchers that is trying to decipher the link between dog genetics, health, and behavior.

Around half of the dogs that are bred for guiding dont end up doing that work because of health or behavioral problems. Modern dogs suffer from many genetic diseases, a side effect of keeping breeds separate and selecting them for desirable traits. Some of these purebreds might have the right looks, but not the right temperament, to become a working dog. But what if breeders could predict what makes a good guide dog and select against undesired traits, ensuring they arent passed on to the next generation?

More than 500 traits analogous to human genetic conditions have been described in dogsboth species can suffer from cancer, eye disease, or dysplasia of the hip, to name a few. Cheap DNA tests for canines can screen for changes, known as mutations, in a single gene. The causes of many other conditions, however, are more complex. They can be linked to multiple genes or to environmental factors like exercise, food, dust, or mold spores. We definitely want to get a handle on complex traits, says Tom Lewis, head of canine genetics at Guide Dogs. The charity breeds around 1,000 puppies a year, which spend their first year in the homes of volunteers before entering formal training.

Before joining Guide Dogs in January, Lewis worked at the Animal Health Trust and the Kennel Club in the United Kingdom, where he studied the genetic risk of hip dysplasia in breeds registered with the club. Dysplasia is one of the hereditary conditions that can be difficult to diagnose and treat. It is a malformation of the hip joint that develops during growth, though traumatic injury, being overweight, or lacking muscle strength can worsen the condition. For example, puppies raised in homes with hardwood flooring may build less muscle mass in their legsthey cant get traction on the floor, and slip and slide around, which is hard on their little joints. The constant pain can eventually turn into lameness and arthritis in grown dogs, making them unsuitable for guiding or assisting people with disabilities.

Good health is key for guide dogs, but temperament is just as important. They need to lead their owners around obstacles and other people while staying calm and obedient. They need to resist chasing after squirrels or getting too excited when meeting other dogs. Not every breed has what it takes. For example, the typical cocker spaniel is intelligent, affectionate, and a great option for families, but it is also too excitable. Even if you give them the same training, you would never expect a spaniel to be a guide dog. They're far too temperamentally unsuited, and that's probably a genetic thing, says Lewis.

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Is There a Genetic Link to Being an Extremely Good Boy? - WIRED

After years of researching the SON gene,Erin Eun-Young Ahn, Ph.D., may have found the cause behind an extremely rare disease.

After years of researching the SON gene, Erin Eun-Young Ahn, Ph.D., may have found the cause behind an extremely rare disease.(Photography: Nik Layman)Since the early 2000s, Erin Eun-Young Ahn, Ph.D., associate professor in theUniversity of Alabama at BirminghamDepartment of PathologysDivision of Molecular & Cellular Pathology, has been studying the SON protein and gene. The SON gene makes a protein, also called SON, that is required for the body to develop and grow normally. While Ahn is one of the worlds leading experts on the SON gene, she had no idea that her work would ultimately help determine the cause behind an extremely rare disease known as Zhu-Tokita-Takenouchi-Kim syndrome.

ZTTK syndrome is a severe multi-system developmental disorder characterized by delayed psycho-motor development and intellectual disability. Common clinical features of ZTTK include intellectual and developmental delays, brain malformations, muscle abnormalities and facial asymmetry. Little is known about this disease, including its cause, until Ahn discovered that ZTTK syndrome is the result of a genetic mutation of the SON gene.

Ahns journey began in 2014 when a physician from California contacted her about a pediatric patient who suffered from developmental and intellectual disabilities. These included late milestones in language and cognitive processing. Ahn has published research showing that SON function is important in the RNA editing step, called RNA splicing. RNA delivers instructions to cells from DNA on which proteins to produce. The physician found Ahns postdoctoral research publication and reached out for help.

The patient underwent standard genetic testing panels and tests for gene mutations on known genes, which all came back normal. Finally, the doctors ran exome sequencing a test developed in the last decade that can identify more undiscovered variants in an unbiased way. They found that the only gene mutation this patient had was in the SON gene.

This was the first finding of this specific gene mutation in humans, Ahn said. We knew that SON is overexpressed in several types of cancer cells, but we didnt know whether the mutations in the DNA sequence of the SON gene that cause loss-of-function really existed in the human patient. It was really eye opening.

Ahn made a case report on this single patient, showing how in cancer there is an overproduction of SON, and with an underproduction, there are developmental and intellectual delays like those present in the first patient. The journal to which she submitted the work suggested she locate other cases. With the assistance of a website tracking undiagnosed diseases and a database of gene mutations, Ahn found a few more incidents indicating DNA sequence changes in the SON gene. She reached out to those patients physicians and the involved researchers in the U.S. and Europe, finding they had the same symptoms as her original pediatric patient.

We went from one case to five cases, Ahn said. And a few months after that, the information began to spread rapidly. Clinicians and genetic counselors started talking, and the information became international.

Ahns group eventually analyzed clinical symptoms of 20 patients who carry mutations in the SON gene. They also conducted experiments using the cells obtained from the patients and demonstrated that an insufficient amount of the SON protein leads to defective RNA splicing in patients, which in turn causes abnormal brain development and metabolism. Their findings were published in the journal,American Journal of Human Genetics, in September 2016. The publication played a major role in designating this new disease caused by SON mutations as ZTTK syndrome.

Typically, the human body houses two copies of the SON gene, and Ahn found that those with ZTTK have one copy of the normal SON gene and one copy of the mutated SON gene. This mutation in the SON gene means that the body cannot produce as much of the SON protein needed for its cells to develop properly. This lack of cell development leads to the developmental and intellectual delays found in patients with this disease. There are currently no reported cases of mutations found in both copies of the SON gene, which suggests that mutations in both copies may be extremely detrimental to human development.

The mutations show up during development but are not inherited from the parents, which is why awareness of the syndrome by clinicians is key to connecting patients with resources, Ahn said. They have to talk to their doctor and a genetic counselor and get the exome sequencing done to get the diagnosis.

In her role as one of the worlds primary researchers on the SON gene, Ahn became a point of contact for patients and their families, connecting families all over the world. This led to the establishment of a Facebook group for the syndrome, which now has more than 245 members. Last year, several of the parents of children, together with Ahn, created theZTTK SON-Shine Foundationthat showcases personal stories of families learning how to live with this syndrome.

We developed the ZTTK SON-Shine Foundation, because we wanted to create a sense of community among people affected by this disease so they do not feel isolated, Ahn said. This is a way that parents of children with ZTTK can help and share information with each other in hopes of improving the quality of life for every patient with ZTTK syndrome.

In addition to connecting families with this challenging rare disease, the foundation hopes to spread awareness of the syndrome to clinicians in particular.

One of the goals of the ZTTK SON-Shine Foundation is making a network of clinicians and researchers who can share their expertise to help the families affected by this syndrome, Ahn said. Exome sequencing reports typically indicate the results in scientific terms, but when patients receive those, they dont understand what that means. So, I often provide the families with an explanation of what these genetic codes mean in laymans terms, so that they can have a clear understanding. I am very grateful that I have opportunities to help the patients and families.

Ahn is no longer alone in the study of ZTTK, but working with researchers across the globe on different manifestations of this syndrome in patients, from issues ranging from bone development to kidney function to metabolism and the immune system.

We hope some part of our finding will contribute to a medical treatment, Ahn says, And we know our findings can provide them with information. We dont know whether we can find a cure, but if we know more about how SON mutation affects patients metabolism, kidney issues, bone structure, neurological features, and immune system, we can do a lot for patient care and prevention and alleviate their symptoms.

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UAB researcher shines light on a rare disease that causes developmental and intellectual delays - The Mix

c/o Caroline Pitton

One of the best known faces to students even before they enroll at the University, Caroline Pittons 22 smiling face framed by her famous bangs is plastered on the wall of the admissions office, where she can frequently be found when she is not working in a research lab, TAing, or singing. The Argus caught up with Pitton to talk about her time on campus and her future beyond it.

The Argus: Why do you think you were nominated to be a WesCeleb?

Caroline Pitton: I was genuinely so surprised when you told me cause I dont think I know enough people to be a WesCeleb. I feel like I just walk around and recognize most people that pass me, but I think I have a very public-facing job. I work as a senior interviewer in the Office of Admission, and Ive worked in admissions since literally the first week of my freshman year. I used to plan WesFest and Open House, and now I talk to prospective students a lot. That job is the most fun place to work on campus. Everyone who works there is so outgoing and friendly. I also TA a lot so if you took intro bio or intro chem or some French classes, chances are youve seen me as your TA.

A: What are your majors?

CP: Im a biology and French double major with an informatics and modeling minor. I came into Wesleyan knowing I wanted to do biology, and then my pre-major advisor was a French professor and that was a happy accident. Then, I did my minor almost completely by accident. One day [I] was talking to another bio major and figured out that Id done five of the six credits for [the modeling] minor.

A: Did you speak French prior to coming to Wes?

CP: My moms entire extended family lives in France. They do not speak English whatsoever, so she spoke to me in French when I was a baby, and that kind of tapered off, especially when my brother was born and life got wild. I went to a French and English school and all of the kids who went there only spoke French, so I really had to learn how to speak, to communicate with my classmates. I wasnt super invested in the study of French language and culture until I got a couple years into college and I realized how fun it is to speak another language and think about cultures that arent those that youve grown up in.

A: How did you know you wanted to be a bio major?

CP: I was really supported in my science classes in middle and high school. I thought I might want to be a math major at some point but I took intro bio as a freshman in my first semester. I went in and I was like, I think I wanna be a bio major, but if I hate intro bio, its okay to change my mind. I loved it, but I think its not a given that biology majors like intro bio [because] our intro bio curriculum is challenging and fast-paced and intense. Every bio class Ive taken since then Ive liked even more. Its my favorite academic discipline in the world. I could talk your ear off about biology. Thats what I want to do academically and career-wise in the future. Biology is what I want to think about every day.

A: Have you had a favorite class or professor at Wesleyan?

CP: My favorite professor at this university is Professor Joe Coolon in the Biology department. Hes my research advisor. Ive been in his lab since I was a sophomore and we study genomics in fruit flies and yeast. He is one of the best teachers and academic mentors I could ever ask to have. Every time I talk to him, he makes me so excited about science. He has this really infectious energy. He always wants to know whats going on, with my work but also with my life and with my future plans. And he creates a really fun lab environment where everyone works together really well and is genuinely friends in and outside of the work environment.

A: What are you researching?

CP: I spent my whole junior year and the summer after my junior year researching a system in fruit flies that we can use to turn on and off the expression of specific genes, which is very niche. But I looked at this one system and I did a lot of bioinformatics analysis and then I finished that project over the summer, and now Im working on a few other projects. They all have to do with what happens when we expose fruit flies to different environmental toxins, like pesticides, and what happens in the fruit fly genome. Like, which genes get turned on? Do some genes turn on more than other genes? Do they turn off? How do those genes interact?

A: What else are you involved with on campus?

CP: Up until this semester, I sang with Onomatopoeia, the acapella group. I had to take a step back from that this semester, but that was one of the most formative and most fun parts of my college experience. I also music directed two shows for Second Stage my freshman and sophomore years. The friends that I made doing theater and acapella, I still hold so closely.

A: You mentioned that you started working in admissions the first week of [your first] year. How did that happen?

CP: I walked on campus and I was like, okay, I need to find a work-study job. And they have a job fair with a table for admissions. I was like, that seems like a fun place to work. As a [first year], its one of the only offices at Wesleyan that you are aware exists because its the office that you interact with before you are a student. I literally just filled out an application for a random job, which happened to be the intern job, which is event planning mostly. I met a lot of really cool people through it, and working in the Office of Admission gives you a really nice support network of other students, but also the professional adult staff that work there. Going to work three times a week and seeing the same people and having office chit-chat and building those relationships that still exist three years later was really stabilizing.

A: What are your plans after graduation?

CP: Im going to be a research associate in a lab at the Dana Farber Cancer Institute in Boston. Im working in a lab that studies the genetics and genomics of blood cancers. Im also really lucky that I found a job this early. Its a lot of biology concepts that I learn about and I practice in my undergraduate lab and classes, but its applied to medicine and to people in a way that we dont do at Wesleyan, which is really exciting to me as someone that wants to work more in medical research and human genetics in the future.

A: How do you think your friends would describe you?

CP: They make fun of me for how much I talk about flies, but also people know me as having bangs. So when we have conversations about how my housemates describe each other to people that dont know us, I am the short one with bangs who works in admissions.

A: Did you ever not have bangs?

CP: I have quite literally never not had bangs. At my first haircut where I had a substantial amount of hair, my mom said, I think bangs would be cute. And I was two years old, and now Im 21 and I still have bangs. I considered growing them out during COVID-19, but then I had an identity crisis. And I was like, Im gonna come back for my junior year in a mask and Im not gonna have bangs. No one will recognize me; the bangs have to stay.

A: Do you have a favorite Wesleyan story?

CP: One that really stuck with me, especially during COVID-19, was in February of 2020. Ono and Slender James threw a kegcert, which is a concert with a keg in a Fauver. It was the weekend before spring break and it was probably the most fun concert that wed ever done in anyones memory of people that were in Ono at the time. The singing, I think, was good, but it was more like, the energy was really exciting and it was a packed Fauver. All of our friends were there and were screaming and people were dancing. I remember finishing that concert and everyone in Ono was like, That was so fun. We have to do that again. Then obviously we all went home and [didnt come] back. I think for a long time, especially last year when no one was socializing, that was something that I really held onto as being like the last real party that I had been to. And it was such funthere was nothing bad about that night.

A: What are you most proud of in your time at Wes?

CP: Im really proud of how I pushed myself out of my comfort zone to try new things during my time at Wesleyan. I didnt become complacent. I mentioned doing student theater. I had never done theater before college. That was totally out of my comfort zone, and Im so glad I did it. I had so much fun and I learned a lot. Same with research. I didnt think I wanted to do research and then I tried it, and now its literally what Im doing for a job next year. And same with the French major. I had never thought of myself as a humanities person, and now I read French literature.Im proud that I didnt box myself into only doing one thing and how much I got to learn from my peers at Wesleyan. I think that other students are what make this place so special. Im glad that I really took advantage of getting to know everyone around me.

This interview has been edited for length and clarity.

Hallie Sternberg can be reached at hsternberg@wesleyan.edu.

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WesCeleb Caroline Pitton '22: The Short One with Bangs Who Works in Admissions - Wesleyan Argus

Study showed the potential of Alphataxin, an orally available, small-molecule drug that elevates tumor-infiltrating CD4+ T cells to treat renal cancer

STONY BROOK, N.Y.--(BUSINESS WIRE)-- Alpha-1 Biologics, a biotherapeutics company developing innovative treatments for cancers and immune deficiencies, today announced that positive data was published in frontiers in Oncology demonstrating Alphataxin, a small molecule that elevates circulating and tumor-infiltrating CD4+ T cells, suppressed kidney cancer and suppressed metastasis in mice. Orally available Alphataxin, is the first and only drug in development to increase formation of CD4+ helper T cells. Immune checkpoint inhibitor therapy, the vanguard of cancer therapy, promotes the ability of CD8+ T cells to kill tumor cells. However, CD8+ T cells are unable to kill tumor cells in the absence of chemical mediators secreted by CD4+ helper T cells. The data showed that Alphataxin treatment is efficacious as a monotherapy in kidney cancer in mice and enhances anti-PD-1 immune checkpoint inhibitor therapy, with the potential to expand the number of human cancer patients who respond to checkpoint inhibitor therapy.

Cynthia L. Bristow, PhD, CEO of Alpha-1 Biologics said, We are excited to announce this positive pre-clinical data, which showed that Alphataxin, orally delivered in combination with an injected immune checkpoint inhibitor, may provide a powerful approach that can produce long-term remission in kidney cancer and other T cell-responsive tumors. Alphataxin as a monotherapy and in combination with anti-PD-1 immune checkpoint inhibitor therapy significantly suppressed tumor growth in a mouse model of kidney cancer and significantly elevated the number of circulating and tumor-infiltrating CD4+ T cells.

In the study, following implantation of mouse kidney tumor cells within the kidney of mice, combination treatment of Alphataxin and anti-PD-1 therapy resulted in 100% elimination of tumor growth. Moreover, in mice implanted with ten times more tumor cells into the kidney, doubling the Alphataxin dose in combination treatment with anti-PD-1 led to 100% elimination of tumors in one-third of mice and 81% suppression of tumor growth in the remaining two-thirds of mice. Both anti-PD-1 and Alphataxin monotherapy showed decreased tumor growth as compared with untreated mice. Lung metastasis was present in monotherapy but eliminated in combination-treated mice.

The study also investigated the effects of Alphataxin on the immune system in healthy mice. The data showed that Alphataxin increased the normally circulating numbers of CD4+ T cells, Pre-T cells, and CD4/CD8 ratio indicating that Alphataxin acts to increase the formation of CD4+ helper T cells.

This combination treatment of Alphataxin with an anti-PD-1 therapy addresses a high unmet medical need in patients with kidney cancer who have very low survival rates. The 5-year survival rate for patients with renal adenocarcinoma undergoing anti-PD-1 treatment is estimated to be 27.7%. However, despite the efficacy of checkpoint inhibitors in promoting the cytotoxic activities of tumor infiltrating CD8+ T cells, approximately 87% of cancer patients do not respond to immune checkpoint therapy, said Dr. Bristow. Kidney cancer is often not diagnosed until after metastasis, a disease stage for which there are few effective treatment options; however, recent promising advances demonstrate that easily accessible blood-based tests provide early detection, and this means that Alphataxin has the potential to be transformative in providing long lasting remission in kidney cancer.

Ron Winston, President, Institute for Human Genetics and Biochemistry said, We are pleased with these pre-clinical results, which have further increased our confidence in the promising potential of Alphataxin to treat cancers and immune deficiencies. Based on this positive data, the company plans to raise additional capital to rapidly advance the Alphataxin development program.

The full article in frontiers in Oncology can be accessed here: Alphataxin, a Small-Molecule Drug That Elevates Tumor-Infiltrating CD4+ T Cells, in Combination With Anti-PD-1 Therapy, Suppresses Murine Renal Cancer and Metastasis.

About Alphataxin

Alpha-1 Biologics discovered that the protein alpha-1 proteinase inhibitor (1PI, alpha-1 antitrypsin) regulates the number of circulating CD4+ T cells by stimulating the locomotion of Pre-T cells. The orally available small-molecule drug Alphataxin acts as a surrogate for 1PI in this pathway. The Company is focused on the development of Alphataxin, which suppressed tumor growth in a mouse model of kidney cancer. Alphataxin, in combination with anti-PD-1 antibody, significantly elevated circulating and tumor-infiltrating CD4+ T cells. Because orally available Alphataxin is the first and only drug developed to increase CD4+ T cells, Alphataxin is eligible for FDA Breakthrough Designation. In combination with anti-PD-1, Alphataxin is a powerful therapeutic method that provides long-term remission in kidney cancer in mice and is being tested in other T cell-responsive cancer models.

About Alpha-1 Biologics

Alpha-1 Biologics was founded by Cynthia L. Bristow, PhD, in 2011 for the purpose of developing patented therapeutics related to the generation of immune cells from stem cells within the body to treat immunodeficiency with disease applications including immune cell replenishment in cancer therapy, HIV/AIDS, patients with inherited deficiency of 1PI, and in the most prevalent cause of immune deficiency, malnutrition. The research to discover a therapy to elevate the number of CD4+ helper T cells was inspired by a desire to provide treatment for HIV-infected childhood orphans in subSaharan Africa. The idea for how to develop a therapy was discovered by comparing HIV-infected patients with healthy individuals. In two clinical trials using FDA-approved 1PI therapy, the number of CD4+ T cells were increased in HIV-infected patients and in uninfected healthy volunteers. Based on those studies, the Company is focused on developing orally available drugs to stimulate locomotion of helper T cells and Pre-T cells to treat cancer and immune deficiency. The discoveries at the core of Alpha-1 Biologics therapeutic approach resulted from basic research conducted by Dr. Bristow and supported for many years by the non-profit research organization, Institute for Human Genetics and Biochemistry (IHGB) funded by the Harry Winston Research Foundation.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211208005360/en/

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Alpha-1 Biologics Announces Positive Data Published in frontiers in Oncology on Alphataxin in Combination with Anti-PD-1 Therapy that Suppressed...

Published on December 10, 2021

SKMCs Dr. Shaden Abdelhadi shares the story of her prolific career and how support from SEHA is helping women working in healthcare achieve their dreams

Abu Dhabi Health Services Company (SEHA), the UAEs largest healthcare network, is continuing with its efforts to propel the careers of young and ambitious female doctors.

Setting an example of perseverance and sheer determination, coupled with excellence in her field, is Dr. Shaden Abdelhadi, FRCP (Edin), FAAD is an internationally trained Emirati Pediatric Dermatologist specializing in human genetic skin disorders at the Genetic Pediatric Dermatology Unit at Sheikh Khalifa Medical City (SKMC), part of SEHA.

Dr. Abdelhadi said: To women in medicine, I urge you to continue persevering, irrespective of the challenges you may encounter. Forge ahead and never lose sight of the patients whose health we strive to better every single day. I consider myself supremely lucky to have received the right support during my career. I joined SEHA in 2005 as a Staff Physician in the Department of Medicine at SKMC. The tremendous support I have received in terms of training, access to opportunities and resources, played a major contributing role in where I stand today as a dermatologist.

One of the most respected medical professionals working in her area of expertise, Dr. Abdelhadi acknowledges how education has shaped her career. I consider it an absolute privilege to have had such an extensive education. From becoming a Department of Health (DoH) Specialist through the Arab Board Dermatology Residency Program at SKMC in 2012, to gaining clinical training experience at the Childrens Hospital of Washington University in Seattle, and St. Thomas Hospital in London, every step has added a new dimension to my clinical understanding.

Gaining the Postgraduate Belgium Board Certificate in Pediatric Dermatology (2017) and the Interdisciplinary Board Certificate in Human Medical Genetics (2018) were both challenges that bolstered my self-confidence. In my line of work, real-world experience is an absolute necessity, and I am truly grateful for having received it through my fellowships with the Royal College of Physicians, Edinburgh; American Academy of Dermatology; European Academy of Dermatology and Venereology; and the European Society of Pediatric Dermatology.

Dr. Abdelhadi is currently a member of the International Society of Pediatric Dermatology and a member of the Editorial Board of Dermatologic Therapy, one of Europes leading scientific publications. She was recently elected to the UAE Dermatology Specialty Committee, which is leading the future of postgraduate education in dermatology in the UAE.

Despite having reached the zenith of professional success, Dr. Abdelhadi maintains there is no greater joy than to teach. What use is a wealth of knowledge if one isnt willing to share it? I am currently an Assistant Professor of Dermatology at the College of Medicine and Health Sciences, Khalifa University in Abu Dhabi, and a core faculty member at the Arab Board Dermatology Residency Program at SKMC. I thrive on the discussions I have with my students; it keeps adding a fresh perspective to my understanding of medicine.

I am passionate about disseminating national and international education in the treatment of pediatric dermatology and pediatric genetic skin diseases. In my opinion, medical education never ceases, you must constantly keep yourself updated. Since 2016, I have been the co-founder and Vice President of several annual international pediatric dermatology conferences precisely for this reason.

Dr. Abdelhadi is a leading figure in helping SEHA deliver excellence in healthcare. She has been instrumental in efforts to have the Arab Board Dermatology Residency Program at SKMC accredited by the American Council for Graduate Medical Education (ACGME), making it the worlds second US accredited dermatology residency program outside the USA. Furthermore, she also set up the UAEs first Multidisciplinary Epidermolysis Bullosa Center.

Speaking about the immense support she has received at SEHA, Dr. Abdelhadi said: SEHA has played a key role in my training and supported my ambition of becoming a uniquely specialized physician. With SEHA being a leader in medical education, I believe I can work closely with the National Institute of Health Sciences in better planning the medical specialties and sub-specialties the UAE needs.

Dr. Abdelhadis route to success, however, has not been without challenges, with slow and bureaucratic processes, changing priorities and decisions all hurdles that needed to be overcome.

There is no success without challenges, she said. To all the budding female doctors in the region, I hope my journey serves as a reminder that nothing is impossible if you have enough perseverance.

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Inspiring Young Female Doctors in the UAE and Beyond - APN News

Stress affects up to 90% of people, and we know it harms our mental and physical well-being.

Stress can impact the activity and function of our genes. It does this via epigenetic changes, which turn on and off certain genes, though it doesnt change the DNA code.

But why do some people respond worse to stress, while others seem to cope under pressure?

Previous research has identified having strong social support and a sense of belonging are robust indicators of physical and mental health.

Social support means having a network you can turn to in times of need. This can come from natural sources such as family, friends, partners, pets, co-workers and community groups. Or from formal sources such as mental health specialists.

My new study, published today in the Journal of Psychiatric Research, shows for the first time that these positive effects are also observed on human genes.

Having supportive social structures buffers and even reverses some of the harmful effects of stress on our genes and health, via the process of epigenetics.

The findings suggest the DNA we are born with is not necessarily our destiny.

Read more: How chronic stress changes the brain and what you can do to reverse the damage

Our genes and our environment contribute to our health.

We inherit our DNA code from our parents, and this doesnt change during our life. Genetics is the study of how the DNA code acts as a risk or protective factor for a particular trait or disease.

Epigenetics is an additional layer of instructions on top of DNA that determines how they affect the body. This layer can chemically modify the DNA, without changing DNA code.

The term epigenetics is derived from the Greek word epi which means over, on top of.

Read more: Explainer: what is epigenetics?

This extra layer of information lies on top of the genes and surrounding DNA. It acts like a switch, turning genes on or off, which can also impact our health.

Epigenetic changes occur throughout our lives due to different environmental factors such as stress, exercise, diet, alcohol, and drugs.

For instance, chronic stress can impact our genes via epigenetic changes that in turn can increase the rate of mental health disorders such as post-traumatic stress disorder (PTSD), depression and anxiety.

New technologies now allow researchers to collect a biological sample from a person (such as blood or saliva) and measure epigenetics to better understand how our genes respond to different environments.

Measuring epigenetics at different times allows us to gain insight into which genes are altered because of a particular environment.

Read more: Extreme stress in childhood is toxic to your DNA

My study investigated both positive and negative factors that drive a persons response to stress and how this changes the epigenetic profiles of genes.

Certain groups of people are more likely to face stress as a part of their routine work, such as emergency responders, medical workers and police officers.

So, my research team and I recruited 40 Australian first year paramedical students at two points in time before and after exposure to a potentially stressful event. The students provided saliva samples for DNA and filled out questionnaires detailing their lifestyle and health at both points in time.

We investigated epigenetic changes before and after exposure to stress, to better understand:

We found stress influenced epigenetics and this in turn led to increased rates of distress, anxiety, and depressive symptoms among participants.

However, students who reported high levels of perceived social support showed lesser levels of stress-related health outcomes.

Students with a strong sense of belonging to a group, organisation, or community dealt much better with stress and had reduced negative health outcomes following exposure to stress.

Both these groups of students showed fewer epigenetic changes in genes that were altered as a result of stress.

The COVID pandemic has created heavy psychological and emotional burdens for people due to uncertainty, altered routines and financial pressures.

In Australia, the rates of anxiety, depression and suicide have soared since the start of the pandemic. One in five Australians have reported high levels of psychological distress.

The pandemic has also made us more isolated, and our relationships more remote, having a profound impact on social connections and belonging.

My study highlights how family and community support, and a sense of belonging, influence our genes and act as a protective factor against the effects of stress.

In such unprecedented and stressful times, its vital we build and maintain strong social structures that contribute to good physical and mental well-being.

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Stress is a health hazard. But a supportive circle of friends can help undo the damaging effects on your DNA - The Conversation AU

"By establishing iHope Genetic Health, we are expanding our commitment to ensure that the benefits derived from whole-genome sequencing are available to as many people as possible, as quickly as possible, regardless of disease, geography or income," said Francis deSouza, Chief Executive Officer at Illumina. "By unlocking the power of the human genome, we can find answers for these patients where no others can, and dramatically change lives."

Through this flagship program, Illumina will enable Genetic Alliance, a global nonprofit focused on advancing genetics to benefit human health, to create networks of clinics, and laboratories equipped with the necessary genome technology to provide precision genomic diagnoses to patients suffering from rare genetic disease.As part of this program, Genetic Alliance will also partner with pharmaceutical, technology companies and care providers to support patient access to data, therapeutic interventions, and ongoing supportive care.

"Since our inception in 1986, Genetic Alliance's mission has been to realize a world in which those affected by genetic disease are diagnosed and offered interventions to alleviate their suffering," said Genetic Alliance CEO, Sharon Terry. "As the mother of two children, diagnosed with a genetic condition, I can't rest until we build equitable systems to meet the needs of all who experience the diagnostic odyssey. In iHope Genetic Health we recognize the place of individuals, families, and communities to prioritize and solve the problems they face, consistent with their own values and culture."

iHopeTM Genetic Health will build upon the success of Illumina's existing iHope efforts, further extending the reach of the program and enabling clinical laboratories and care centers throughout the world to test patients impacted by rare disease and other genetic health conditions. Genetic disease affects over 300 million individuals worldwide, the vast majority of whom are children. In high income countries these patients often remain undiagnosed for up to seven years, while in low- and middle-income geographies, many families never know the cause of their child's suffering. Further enabling access will help reduce the psychological stress and loss of income that many families endure.

"The success of the Human Genome Project has revolutionized medicine by enabling treatments that precisely target disease-causing changes in DNA," said National Institutes of Health Director Francis S. Collins, M.D., Ph.D. "While the cost of genome sequencing has dropped precipitously over the past decade, it remains cost-prohibitive for many. I applaud Genetic Alliance for launching this important initiative to improve access to this life-changing technology. Access to medicine should always be a right, not a privilege."

To ensure support for patients throughout their diagnostic and care journey iHope Genetic Health will be supported by a network of disease advocacy, technology, pharmaceutical and clinical support organizations.

"We have a moral imperative to help genetic disease patients who need a diagnosis," said Ryan Taft, PhD, Illumina's iHope lead and Vice President, Scientific Research."iHope Genetic Health will change the trajectory of genomic medicine worldwide, helping patients who may have otherwise been invisible. Our vision is a genome for every patient that needs one, and a network of partners who will help them on every part of their journey to better health."

iHope Genetic Health will begin reviewing applications for clinical whole genome sequencing programs in February 2022. For more information please visit ihopegenetichealth.org.

About IlluminaIllumina is improving human health by unlocking the power of the genome. Our focus on innovation has established us as the global leader in DNA sequencing and array-based technologies, serving customers in the research, clinical and applied markets. Our products are used for applications in the life sciences, oncology, reproductive health, agriculture and other emerging segments. To learn more, visitwww.illumina.comand connect with us onTwitter,Facebook,LinkedIn,Instagram, andYouTube.

About Genetic AllianceGenetic Alliance, a nonprofit organization founded in 1986, is a leader in deploying high-tech and high-touch programs for individuals, families, and communities to transform health systems by being responsive to the real needs of people in their quest for health. The Alliance comprises 10,000 organizations, 2,000 of which are disease and patient advocacy foundations, and include community health programs, employee wellness programs, local nonprofits, religious institutions, and community-specific programs to grow and expand their reach and mission. For more information, visit geneticalliance.org.

Use of forward-looking statements This release contains forward-looking statements that involve risks and uncertainties, including the expectation for lower costs related to the storing and managing of genomic data costs. Among the important factors that could cause actual results to differ materially from those in any forward-looking statements are: (i) challenges inherent in developing and launching new products and services; (ii) our ability to successfully manage partnerships; (iii) our ability to deploy new products, services, and applications, especially in developing markets; and (iii) the acceptance by customers and other stakeholders of our newly launched products or services, which may or may not meet our and their expectations once deployed, together with other factors detailed in our filings with the Securities and Exchange Commission, including our most recent filings on Forms 10-K and 10-Q, or in information disclosed in public conference calls, the date and time of which are released beforehand. We undertake no obligation, and do not intend, to update these forward-looking statements, to review or confirm analysts' expectations, or to provide interim reports or updates on the progress of the current quarter.

Contacts For Illumina:

InvestorsBrian Blanchett858.291.6421[emailprotected]

MediaDr. Karen BirminghamEMEA: +44 7500 105665US: 646.355.2111[emailprotected]

For Genetic Alliance:[emailprotected]

SOURCE Illumina, Inc.

https://www.illumina.com

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Illumina and Genetic Alliance Launch $120 Million Global Initiative to Increase Equity and Improve Outcomes for Families Impacted by Genetic Disease -...

Matthew L. Meyerson, MD, PhD, is constantly curious, both about the world and the people around him and as one of the top cancer researchers on the planet, he has a talent for elevating younger scientists, turning obstacles into discoveries, and sensing future research opportunities.

Matthew L. Meyerson, MD, PhD, is constantly curious, both about the world and the people around him. As one of the top cancer researchers on the planet, he has a talent for elevating younger scientists, turning obstacles into discoveries, and sensing future research opportunities.

Hes not afraid to try something completely different. As a freshman at Harvard University, he spent a summer on a farm, baling hay and building a cow pen the farmer called Harvard Yard. He spent his senior year in Japan, studying in a lab at Kyoto University.

That genuine sense of wonder, and wander, started when he was a child growing up in Philadelphia, Pennsylvania. Thats when Meyerson discovered the work of famed architect R. Buckminster Fuller, inventor of the geodesic dome. Fuller was a university professor emeritus at the University of Pennsylvania for the final 10 years of his life. Before his death in 1983, Fuller wrote about how technology can transform peoples lives and emphasized the role of creativity, starting in childhood.

I think its important to have a sense of wonder, and its also important to look at things and say, You know, theres always a limit to our knowledge, said Meyerson, who was named the second most influential scientist in the world in all fields of science by Thomson Reuters in 2014.

There are a lot of things that we think are true, he said. And even though theres a lot of evidence that theyre true, [the truth] ends up being different.

In Meyersons office at Dana-Farber Cancer Institute, his desk is covered with photos of friends and his family, including his wife, Sandra Meyerson, a primary care pediatrician also on the Harvard Medical School faculty, and their 4 children, Sophia, 30; Olivia, 27; Jacob, 25; and Phoebe, 20. On the wall is artwork from his sister-in-law, a drawing of what looks like a tree but is actually a set of lungs, reflecting his work on the genetics of human lung carcinomas.

Im not so sure Biz Markie isnt not one of the dopest to ever grip the mic.

Meyerson received his MD in 1993 and PhD in 1994 from Harvard University. Prior to joining Dana-Farber in 1998, he completed a residency in clinical pathology at Massachusetts General Hospital and a research fellowship with the legendary Robert Weinberg, PhD, at Whitehead Institute in Cambridge, Massachusetts. In the early 1980s, Weinberg discovered the first human cancer-causing gene, the RAS oncogene. By 1986, he and his team also isolated the first known tumor-suppressor gene, the retinoblastoma gene. And in 1997, Meyerson and Christopher M. Counter, PhD, identified the telomerase catalytic subunit gene.

From 2006 through 2015, Meyerson was a principal investigator for The Cancer Genome Atlas (TCGA), a landmark program aimed at comprehensive cancer genome characterization. TCGA was a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute based at the Broad Institute of Massachusetts Institute of Technology and Harvard. He served as cochair of the lung cancer disease working group, and his projects have identified many mutated genes in lung cancer.

He says that his work on lung cancer mutations in the EGFR gene has been his most impactful discovery to date. EGFR mutations occur mostly in nonsmokers who develop lung cancer, helping investigators understand why the disease develops in what should be a low-risk population.

Like many discoveries, Meyerson says it kind of happened by good fortune. In 2003, he was working with fellow Harvard researchers William Sellers, MD, and Bruce E. Johnson, MD, the 2018 Giants of Cancer Care award winner trying to identify mutations in lung cancer that could be targeted therapeutically.

They had lung cancer samples from a group of Japanese patients including women who had lung cancer but werent smokers. It turned out half of them had the EGFR mutation. Further studies with Sellers, Johnson and Pasi A. Jnne, MD, PhD, this years Giants of Cancer Care award winner in the lung cancer category, showed that those with the mutation responded well to therapy.

There was already a drug out theregefitinib [Iressa], an EGFR inhibitorbut people didnt really know what patients it worked on or why it worked, Meyerson said. The study really answered the question and helped us target therapy.

It led to much improved EGFR inhibitors, and it led to this whole wave of discovery in lung cancer. There are now literally dozens of targeted inhibitors that are in use for lung cancer and more coming all the time. So it was just a huge impact on the field.

Research in lung cancer has expanded since Meyerson first started in the field in the late 1990s. He says he was frustrated by the stigma of the disease and the limited number of treatments available. Now, because more patients survive, theres more support for research.

The people who really push for research in the field are the survivors. They know about the disease, they know how bad it is, and theyre still here, he said.

Although most of Meyersons research has been in lung cancer, his lab has also studied microbes that cause human cancer. Comparing the genomes from 9 colon tumors with normal tissue from the same patient led to a major discovery in 2011: colorectal cancer tissue contains high levels of several types of bacteria, most notably Fusobacterium nucleatum. Now Meyerson and colleagues are trying to understand whether these bacteria cause colon cancer as part of the NCI/ Cancer Research UKs Cancer Grand Challenges.

Meyerson is also excited about his labs work on telomeres and mortal and immortal cells, a project that spans all types of cancer. In normal cells, telomeres protect the DNA from mutating and eventually stop the cell from dividing. But mutations in cancer cells occur outside the gene that controls how much of the telomerase enzyme is made. Although this discovery is 25 years old, there still isnt a drug that inhibits that mutation. Yet.

My lab has [started working] on a project in this area, [so] Im hoping that will change in the next few years, he said.

Meyerson started working in a laboratory while still in high school and says he thought doing research would be easierthat hed start working on something and figure it out. He learned, instead, that doing scientific research is like constructing a skyscraper.

If you look at building a skyscraper, most of the time is spent digging out and structuring and shoring up the foundation. And then when you actually erect the steel frame, it goes really fast, he said. Research is like that; youve got to do a huge amount of preparation before you actually answer a scientific question.

You might have to build the experimental system, or if its a human disease, you have to collect the patient samples. And sometimes thats weeks or months, but sometimes its years. Sometimes it takes many years.That balance and the need for all the prep work, that was a surprise to me.

As a student, graduate student, and postdoctoral researcher, Meyerson learned that each lab had its own style. Some lab directors gave students a very specific project with a limited scope of responsibilities. Others gave students more independence, which also came with greater risks for the lab director.

In his own lab, Meyerson gets to know students as individuals so that he can best match them with projects and partners.

Rameen Beroukhim, MD, PhD, is an associate professor at Harvard Medical School, an associate professor at Dana-Farber Cancer Institute, and an attending physician at Brigham and Womens Hospital. He joined the Meyerson lab after he heard Meyerson give a lecture about attempts to understand the cancer genome. Beroukhim ended up working as a postdoctoral fellow with Meyerson from 2005 to 2010 and eventually opened his own lab.

Back then we really didnt know so much about the cancer genome, but I thought, Well, mutations are the essential forces that drive cancer, so really understanding them would be a way of understanding cancer from the ground up, Beroukhim said. At the time, he was using single nucleotide polymorphism arrays, but those arrays had been developed to genotype people to figure out [inherited alterations]but he was applying them to cancers to understand which cancers had lost certain parts of their genomes and where those parts of the genome had been lost. That seemed like an elegant way to try to understand the genome that was different from how other people had attacked the situation.

Beroukhim says Meyerson is unusual as a mentor because of his social skills, both in and outside the lab. He makes a lot of effort not only to connect with his trainees, but also help them network with colleagues and promote their work. Off the top of his head, Beroukhim could name 5 of Meyersons former research fellows who are now faculty members at Dana-Farber, as well as others at Cornell University and Columbia University.

Matthew has a great way of sort of seeing the future and whats going to be interesting in the futurelooking at research that will be informative and where people will be interested, not just now, but in years to come, Beroukhim noted.

Meyerson says many people might be surprised by the social nature of the science field and how many ideas develop not as an independent eureka moment, but as part of a conversation. I think a lot of that scientific progress is thinking together and discovering together, and maybe thats a piece that people havent fully understood, that isnt always fully captured.

Regarding pursuing an education or a career, Meyerson tells his students the same thing he tells his children. I would say its important to find your own way. Find what you like doing, what suits you personally, he advised.

After 4 decades working as a researcher, Meyerson says hes gotten better at delegating and taking some time for his family. As a child growing up outside Philadelphia, he would collect rocks and minerals from Wissahickon Creek, and he has continued this habit throughout his travels. When his mother moved out of his childhood home, he took ownership of boxes of collected rocksand his wife created a collectors shelf for him.

To escape from the noise of Boston and the intensity of the lab, Meyerson and his wife recently bought a country home in Vermont where they cant see their neighbors. The quiet suits him, as does the chaos.

Just like with his research, Meyerson enjoys trying something new and exciting.

I like it a lot. Its funnyI tend to like everything, he said. I dont know if [thats] unusual or not, but I look for new things. I like the variety."

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A new collaborative effort aims to cure HIV using a novel block-lock-excise approach and is backed by a $26.5 million grant from the National Institutes of Health. The multidisciplinary group of researchers, known as the HIV Obstruction by Programmed Epigenetics Collaboratory, is being led by scientists at Gladstone Institutes, Scripps Research, and Weill Cornell Medicine.

The biggest hurdle to curing HIV has been the viruss ability to hide a reservoir of latent copies within immune cells. Up to now most viable cure efforts have aimed at reactivating that virus reservoir in order to kill it with antiretroviral therapy an approach called shock and kill or kick and kill. Unfortunately, those approaches havent been able to wake every single copy of the latent virus (at least not without also bringing about severe side effects).

The HOPE Collaboratory is taking a fundamentally different approach to targeting HIV than what everyone else has been trying, Dr. Melanie Ott, director of the Gladstone Institute of Virology and program director for the collaboratory, explained in a press statement.

The new alternative tactic, block-lock-excise, targets latent HIV without reactivating it. The inspiration for this tactic arose from the fact that researchers have found ancient viruses that are integrated into the human genome but are no longer active or viable.

The central concept behind [this] strategy is inspired by the way our cells naturally cope with the remnants of ancient retroviruses that have integrated into our genetic material during evolution, said Cedric Feschotte, one of the investigators and professor of molecular biology and genetics at Cornells College of Agriculture and Life Sciences.

Feschotte studies these so-called endogenous retroviruses, which make up about 8 percent of modern humans DNA.

Identifying which proteins are used by our immune cells to lock up endogenous retroviruses opens the way to developing new repressive molecules that can target HIV and lock it permanently, Feschotte said. The concept is exciting, and it makes sense. We want to accelerate what evolution has already achieved with thousands of relatives of HIV previously defeated and buried in every human[s] cells.

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The researchers have also found that these ancient inactive viruses are missing several elements that HIV contains. Theyve identified two elements in particular, one a sequence of DNA and the other a protein called Tat, which are necessary for latent HIV to reactivate and begin replicating again.

We have shown that blocking Tat with certain drug-like small molecules can lock HIV in its dormant stage, and this block stays in place for some time, even if antiretroviral therapy is interrupted, said Susana Valente, also a principal investigator and associate professor of immunology and microbiology at Scripps Research. With the block and lock approach, we basically want to push HIV into becoming like a harmless, ancient virus.

The pharmaceutical solution would block the Tat protein and alter the structure of the virus, making it harder for other proteins to access the HIV genes and potentially turn them on. This could prevent the virus from awakening and reactivating. That would keep HIV from returning even after someone goes off antiretroviral treatment.

The idea is not only to lock HIV so it cannot replicate without using drugs, but essentially to throw away the key, keeping it locked away forever, unable to do any more harm, Valente said.The excise part of the new approach uses recent advances in genome editing. By employing CRISPR/Cas9 genome-editing technology, researchers could delete the remnant HIV hiding in the DNA of immune cells. That would eliminate all traces of HIV and any chance of the virus rebounding.

The collaborators are drawn from 12 institutions around the globe, three pharmaceutical companies, clinical groups in Africa and Brazil providing data and samples from people living with HIV, and the San Francisco AIDS Foundation, which will bring insights and perspectives from people living with HIV.

Its absolutely key that this is a multi-institutional and multidisciplinary approach, said Gladstones Danielle Lyons, program manager for the HOPE Collaboratory. Bringing together this diverse group of people with expertise across various disciplines is what will really drive the discovery of a cure for HIV.

The HOPE Collaboratory is one of 10 groups awarded a five-year grant under the Martin Delaney Collaboratories program, the flagship program on HIV cure research at the NIH.

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Science Discovers Another Avenue That Could Lead to an HIV Cure - Yahoo News