International Human Genome Sequencing Consortium Research Articles

Gut Microbiome and Psoriasis - A Possible Link to be explored

Dear editor. Just over 30 years ago, the US National Center for Human Genome Research, today known as the National Human Genome Research Institute, was established in the United States, with the ambitious goal of sequencing all 3 million nitrogenous bases in the human genome. In simple terms, it represented the determination of the exact order of DNA bases, determining the segments of human genetic material from blood samples from healthy individuals [1]. More than 2000 researchers from many countries participated in the project in a global joint effort (Universities and Research Centers, mostly from the USA, United Kingdom, France, Germany, Japan, and China, which represented the International Human Genome Sequencing Consortium)

Green Day: An Interview with NHGRI Director Eric Green

Green Day: An Interview with NHGRI Director Eric Green

The dark proteome: translation from noncanonical open reading frames.

Omics-based technologies have revolutionized our understanding of the coding potential of the genome. In particular, these studies revealed widespread unannotated open reading frames (ORFs) throughout genomes and that these regions have the potential to encode novel functional (micro-)proteins and/or hold regulatory roles. However, despite their genomic prevalence, relatively few of these noncanonical ORFs have been functionally characterized, likely in part due to their under-recognition by the broader scientific community. The few that have been investigated in detail have demonstrated their essentiality in critical and divergent biological processes. As such, here we aim to discuss recent advances in understanding the diversity of noncanonical ORFs and their roles, as well as detail biologically important examples within the context of the mammalian genome.

A natural laboratory to elucidate the evolution of endogenous‐exogenous retroviral interactions

The advent of whole genome sequencing has revealed much about the genomes of animals including the relatively large percentage of the genome consisting of endogenous retroviruses (ERV; International Human Genome Sequencing Consortium, 2001). An ERV arises when a retrovirus integrates into a host germ cell genome through normal infection processes. Germline infections can be transmitted to offspring through Mendelian inheritance and at times become fixed elements of the host genome (Weiss, 2006). At their inception, these endogenized retroviruses maintain all the functions of their exogenous progenitors and can produce infectious virus (Figure 1). Mutations in the ERV randomly accumulate over time and can lead to the loss of the deleterious effects. In addition, the ERV can provide benefits to the host often via limiting exogenous viral infections (Chiu and VandeWoude, 2020a). However, most of these endogenous viruses are evolutionary relics representing historical infections and have no contemporary exogenous virus. This limits the opportunities to understand the evolution of ERVs and their interactions with exogenous viruses. In this issue of Molecular Ecology, Quigley et al. (2020) use a novel approach to show that koala retrovirus (KoRV) is undergoing endogenization along a geographic gradient with a variety of exogenous variants dispersed across the landscape. This system provides an opportunity to further elucidate the complex mechanisms in which endogenous and exogenous viruses interact and follow the evolution of an ERV in real time.

Interview Prompts to Uncover Mathematical Knowledge for Teaching: Focus on Providing Written Feedback

IntroductionMathematical knowledge that is specifically connected to the work of teaching has been investigated empirically and theoretically, leading to a significant progression of its conceptualization. In particular, Ball, Thames, and Phelps (2008) developed a practice-based theory of content knowledge for teaching and introduced mathematical knowledge for teaching (MKT) as the mathematical knowledge needed to carry out the work of teaching mathematics. Such knowledge has been studied by examining teaching practice, such as job analysis (Ball & Bass, 2003) and by developing its measurement (Hill, Schilling, & Ball, 2004). MKT has been identified as important in teaching mathematics (Lewis & Blunk, 2012) and in student achievement (Hill, Rowan, & Ball, 2005; Rockoff, Jacob, Kane, & Staiger, 2011).Research on MKT has been conducted with practices of teaching that are prominent in mathematics classrooms, though not all practices. Ma (1999), for example, used four items with some exceptional tasks of teaching and mathematical demands, but did not include all topics and practices in and from teaching. Items developed by the University of Michigan include substantial tasks of teaching, but not a sufficiently organized approach to mathematical topics and teaching practice.1 Ball et al. (2008) emphasized a practice-based approach to study content knowledge for teaching. While introducing their conceptualization about such special knowledge, they focused on several and seminal practices of teaching, such as presenting mathematical ideas, responding to students' why questions, choosing and developing useable definitions. Nonetheless, the conceptualization has not yet been broadened to explore all practices or all topics in terms of MKT. In other words, these studies do not cover the extensive terrain of mathematical demands in teaching across contexts. For sustainable and elaborated development of the study of MKT, the mathematical demands entailed in teaching now needs to be explored systemically using a clear and comprehensive map of the practice of teaching, mathematics, features of learners, and national or international curriculum or grade levels.How MKT is studied has yet to receive sufficient attention. Ball and her colleagues studied MKT with a set of analytic tools they developed, using their wide range of experiences and disciplinary backgrounds, for coordinating mathematical and pedagogical perspectives (Ball et al., 2008; Thames, 2009). However, their experiences have not been shared in terms of researching MKT. A robust, reliable, and consistent study of MKT can be expected with an appropriate and good method. Substantial areas of mathematical demands in different practices of teaching still call for investigations from many researchers. Like the collaborative work on the Human Genome Project (International Human Genome Sequencing Consortium, 2001; Naidoo, Pawitan, Soong, Cooper, & Ku, 2011), research on MKT would need cooperative work for elaborate and systematic conceptualization. A major prerequisite for such collective work is the identification of a method to research MKT. If relevant methods of studying MKT are specified, research of MKT will be powerfully advanced. To systemically research MKT, a comprehensive method needs to be specified.To address the problems, the current study focuses on both using interviews as a comprehensive way to study and measure MKT and researching mathematical demands in providing written feedback, which is an unexamined teaching practice. It does so by building on lessons from the interview prompts used in Ball (1988) and Ma (1999) and on items used to measure MKT (Ball, Bass, & Hill, 2004). Specifically, this paper explores the ways in which interview prompts are developed and used to provide the content and character of MKT, and what, through the use of such interview prompts, might be learned. Particularly, what is entailed mathematically and pedagogically in providing written feedback? …

Evolutionary paradox of immunity.

Evolutionary paradox of immunity.

Nutrigenomics, Mass Media and Commercialization Pressures

In 2004, the International Human Genome Sequencing Consortium published its scientifi c description of the fi nished human genome sequence containing 20,000 to 25,000 protein-coding genes. 1 The Human Genome Project (HGP), through political rhetoric and publicity, was portrayed as an end in itself, which, in the near term, would produce an explosion of new genomics products, services and therapeutics. Most have yet to materialize and some of those that have, especially in the area of genetic testing targeted directly at consumers, raise considerable ethical, regulatory and legitimacy issues. In particular, the fi eld of nutrigenomics illustrates many of these concerns in the context of direct-to-consumer (DTC) advertising and delivery of genetic testing services, related products (such as nutritional supplements) and associated media coverage. This article presents preliminary data from a study of how the media translate knowledge about nutrigenomics to the public. Specifi cally, we are interested in whether media coverage of nutrigenomics is of suffi cient quality for the public to understand the risks and benefi ts associated with genetic testing. We have considered three main sources of information: peerreviewed science journals, media coverage and, more briefl y, promotional material from nutrigenomic company websites. A fuller understanding of the media’s role has policy implications as countries deal with regulating the provision of genetic testing services and the sale of nutritional supplements and personalized diet plans. It also has implications for regulating commercial representations of nutrigenomics, especially DTC advertising by genetic testing companies and the claims they can make about health benefi ts.

A possible future for the pharmaceutical industry.

A possible future for the pharmaceutical industry.

The 1000 Genomes Project: paving the way for personalized genomic medicine.

The 1000 Genomes Project: paving the way for personalized genomic medicine.

Scientists See Promise and Challenges in Translating Genomics to the Clinic

LIKE MANY PATIENTS,PIONEERING GEnetic researcher JamesWatsonhad ahardtimetoleratingthe -blockers he was taking to control hypertension. “They put me to sleep,” he said during a February symposiumat theNational InstitutesofHealth(NIH).Butunlikemost patients, Watson was able to deduce the causeof this adverseeffectbyexamining his genes. One of the first human beings to undergo whole-genome sequencing (WheelerDAetal.Nature.2008;45[7189]: 872-876), Watson found that he carried a certain genetic variant that made him aslowmetabolizerof thedrug.Soheand his physician reduced his dose, and he is now able to control his blood pressure without such adverse effects. “That was very useful,” Watson said. But much of the information he gained fromhavinghisentiregenomesequenced wasnotsouseful,henoted.Forexample, he found that he was heterozygous for a host of harmful genes and homozygous for a gene variant that is associated with a disease involving a malfunctioning genomerepairmechanismthatwouldhave prevented him from living to his current age. “So I didn’t think about it,” he quipped. Watsonsharedhispersonalexperience with genomics during a symposium hosted by the NIH to commemorate the 10-yearanniversaryof thepublicationof the first data from the Human Genome Project(HGP)(InternationalHumanGenome Sequencing Consortium. Nature. 2001;409[6822]:860-921)andtoexamine the future of genomics. Other scientists whospokeat theeventdiscussedtheprogressthathasbeenmadeinthepastdecade and the challenges yet to be overcome. DATA EXPLOSION In just a decade, the HGP and the genomic techniques that have stemmed from it have sparked an explosion of information that has proved useful to basic and clinical scientists.

Discovery of the "RNA continent" through a contrarian's research strategy

The International Human Genome Sequencing Consortium completed the decoding of the human genome sequence in 2003. Readers will be aware of the paradigm shift which has occurred since then in the field of life science research. At last, mankind has been able to focus on a complete picture of the full extent of the genome, on which is recorded the basic information that controls all life. Meanwhile, another genome project, centered on Japan and known as the mouse genome encyclopedia project, was progressing with participation from around the world. Led by our research group at RIKEN, it was a full-length cDNA project which aimed to decode the whole RNA (transcriptome) using the mouse as a model. The basic information that controls all life is recorded on the genome, but in order to obtain a complete picture of this extensive information, the decoding of the genome alone is far from sufficient. These two genome projects established that the number of letters in the genome, which is the blueprint of life, is finite, that the number of RNA molecules derived from it is also finite, and that the number of protein molecules derived from the RNA is probably finite too. A massive number of combinations is still involved, but we are now able to understand one section of the network formed by these data. Once an object of study has been understood to be finite, establishing an image of the whole is certain to lead us to an understanding of the whole. Omics is an approach that views the information controlling life as finite and seeks to assemble and analyze it as a whole. Here, I would like to present our transcriptome research while making reference to our unique research strategy.

Genetics terminology for respiratory physicians

Genes affect our susceptibility to almost all diseases, from the rare single gene disorders such as cystic fibrosis to common multifactorial disorders such as asthma. They also influence our response to specific therapies. Scientific advances in genetics, starting with projects such as the mapping of the human genome [International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004; 431: 931-945] are likely to improve healthcare in the coming decades. Internationally, government initiatives have been established to address strategies to implement these changes [NHS Genetics White Paper. "Our Inheritance - Our Future": Realising the potential of Genetics in the NHS. UK: Department of Health 2003; Family Health History Initiative. National Human Genome Research Institute and Office of Surgeon General, Department of Health and Human Services. 2004]. A knowledge of basic genetic principles and familiarity with genetic 'jargon' associated with new technologies will be important for those practicing in this era of 'genomic medicine' [Collins FS, Green ED, Guttmacher AE, Guyer MS. A vision for the future of genomics research. Nature 2003; 422; April 24; 835-847]. The aim of this article is to review genetic terminology using examples from paediatric respiratory medicine.

Analysis of Complex Disease Association and Linkage Studies Using the University of California Santa Cruz Genome Browser

The sequencing of the human genome, the identification of common single-nucleotide polymorphisms (SNPs) and haplotype blocks, and advances in microarray technology have enabled the study of complex diseases at a level of detail not previously imaginable. These have aided in the design and analyses of association and linkage studies of many complex diseases including cardiovascular disease. Recent technological advances have enabled the undertaking of large-scale genome-wide association studies (GWAS) that can assay hundreds of thousands of polymorphic sites on hundreds to thousands of individuals to find genomic regions associated with disease. Although results from these experiments enable the identification of smaller regions of association compared with previous studies, as with all linkage and association studies, there is the need for the further investigation of regions of interest for the causal genes or variants. The purpose of this review is to present a detailed demonstration as to how publicly available resources can be used to easily guide more detailed research into genomic regions of interest identified in linkage and association study data. Large-scale projects, such as the Human Genome Sequencing project,1,2 have generated large volumes and varieties of annotated genomic data necessitating the development of Internet-based tools to organize and make practically available these public data. One important tool in human disease research is the web-based graphical genome browsers that use the human genome sequence as the framework on which to organize genomic annotations, providing various ways for researchers to view and extract important information. Currently, there are 3 human genome browsers that have been developed for public use: (1) the National Center for Biotechnology Information (NCBI) Map Viewer3; (2) the University of California Santa Cruz (UCSC) Genome Browser4; and (3) the European Bioinformatics Institute’s Ensembl system.5 Although these genome browsers share common features and …

Closing gaps in the human genome with fosmid resources generated from multiple individuals

The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome.

Further delineation of interstitial chromosome 6 deletion syndrome and review of the literature

Interstitial deletions of chromosome 6q are a relatively rare finding. Deletions have ranged from the loss of a single band to larger deletions spanning multiple bands. The clinical phenotype varies, but some features commonly seen include cardiac anomalies, hypotonia, facial dysmorphism and mental retardation. To further delineate the syndrome, we report an infant with facial dysmorphism, ectrodactyly and tetralogy of Fallot owing to interstitial deletion 6q16.1-6q22.32. On array comparative genomic hybridization analysis, the deletion spanned from the 93 377 323rd base to the 127 650 582nd base on chromosome 6 [coordinates are based on Human Mar. 2006 (hg18) assembly of International Human Genome Sequencing Consortium]. A literature review identified 16 additional cases with overlapping interstitial deletions of chromosome 6q between q13 and q23.1. Genotype-phenotype correlations are considered.

ENCODE: More genomic empowerment

ENCODE: More genomic empowerment

The evolution of genomes and language

The evolution of genomes and language

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.

How Many New Genes Are There?

How Many New Genes Are There?

DNA sequence and analysis of human chromosome 8

The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.