New strategy to uncover structural variations of human genomes

full-text ►New strategy to uncover structural variations of human genomes: "New Strategy to Uncover Structural Variations of Human Genomes

ScienceDaily (July 26, 2011) — A new study on single-nucleotide resolution structural variations (SVs) of an Asian and African genome was recently published online in Nature Biotechnology. This study was performed by BGI (previously known as the Beijing Genomics Institute), and demonstrates that whole genome de novo assembly could serve as a new solution for developing a more comprehensive SV map of individuals.

With the rapid development of genomics, more and more experts focus upon the studies of human genome variations by identification and annotation of SNPs in the context of structure, function, and disease. However, recent studies have shown that there are a large number of SVs that have been discovered in the human genome putatively having equal or greater functional impacts than SNPs.

Although many methods have been used to characterize SVs in previous studies, each may have some disadvantages due to technological limitations and the complexity of SVs, making it necessary to find a high accuracy detection method to identify and characterize SVs of human genomes.

"The research focusing on SVs is a real challenge," said Yingrui Li, Director of Science and Technology Department at BGI and the co-lead author of the study, "The study was confronted with many difficulties at the start, such as alignment accuracy, rearranged structure (non-linear), breakpoint recovery, and background noises."

"As a solution," he explained, 'researchers discovered a novel pipeline for detecting SVs in Whole Genome Assembly with a lower cost and faster speed." Based on large-scale genome assembly data from next-generation sequencing technologies, small and intermediate size homozygous SVs (1- 50kbp) can be detected, including insertions, deletions, inversions, and complex rearrangements with precise breakpoints and genotypes previously difficult to define by other approaches.

Through this new method, researchers identified 277,243 SVs, ranging from 1bp to 23kbp in assembled regions of both genomes. Meanwhile, the researchers performed validation using computational and experimental methods and the results indicated a high accuracy of detection. They also carried out characterization of genome-wide patterns of these SVs on different genomic features and studied their potential biological impacts. Profiling using 106 individuals of the 1000 Genomes Project indicates that the extent of diversity in SVs between individuals exceeds that of SNPs. These findings demonstrate whole genome de novo assembly could serve as a new solution to a more comprehensive SV map.

"Here we provide a new method, at a relatively low cost and high speed, to establish in greater detail the presence and patterns of SVs in different genomes, and the results have a high accuracy and a wider range of length spectrum coverage in comparison with previous methods," said Honglong Wu, bioinformatician at BGI and one senior author of the study.

Furthermore, researchers reported, SVs are more individual-specific than SNPs, which may play a significant role underlying the phenotypic differences between individuals. "This study makes us understand we need to consider all kinds of genetic variations and potential differences in their impacts on disease and various other phenotypes in medical genomics studies in the future." added Yingrui Li.

Professor Jun Wang, Executive Director of BGI, said, "With further progresses in de novo assembling by new technologies, assembly-based approaches will be of greater importance and potentially an ultimate solution to SV determination. The study of SVs is likely to attract even more attention in the future."

This study also reveals that de novo assembly can develop more complete personal genomes than resequencing based mapping. Researchers recommend using de novo sequencing technology to decode many more human genomes in the future.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Beijing Genomics Institute.

Journal Reference:

1. Yingrui Li, Hancheng Zheng, Ruibang Luo, Honglong Wu, Hongmei Zhu, Ruiqiang Li, Hongzhi Cao, Boxin Wu, Shujia Huang, Haojing Shao, Hanzhou Ma, Fan Zhang, Shuijian Feng, Wei Zhang, Hongli Du, Geng Tian, Jingxiang Li, Xiuqing Zhang, Songgang Li, Lars Bolund, Karsten Kristiansen, Adam J de Smith, Alexandra I F Blakemore, Lachlan J M Coin, Huanming Yang, Jian Wang, Jun Wang. Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly. Nature Biotechnology, 2011; DOI: 10.1038/nbt.1904

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Structural variation in two human genomes mapped a... [Nat Biotechnol. 2011] - PubMed result

Structural variation in two human genomes mapped a... [Nat Biotechnol. 2011] - PubMed result: "Nat Biotechnol. 2011 Jul 24. doi: 10.1038/nbt.1904. [Epub ahead of print]

Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly.
Li Y, Zheng H, Luo R, Wu H, Zhu H, Li R, Cao H, Wu B, Huang S, Shao H, Ma H, Zhang F, Feng S, Zhang W, Du H, Tian G, Li J, Zhang X, Li S, Bolund L, Kristiansen K, de Smith AJ, Blakemore AI, Coin LJ, Yang H, Wang J, Wang J.

Source

1] BGI-Shenzhen, Shenzhen, China. [2].

Abstract

Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation.

PMID:
21785424
[PubMed - as supplied by publisher]

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Massive Project to Study the Link between Genetics and Health - Technology Review

full=text ►Massive Project to Study the Link between Genetics and Health - Technology Review: "Biomedicine
Massive Project to Study the Link between Genetics and Health

Kaiser Permanente has compiled the genetic and medical data of 100,000 of its members.

* Tuesday, July 26, 2011
* By Emily Singer


Most health insurers are wary of genetics because, in most cases, it's not yet clear how a particular genetic variation influences an individual's health, or whether it should affect their care.

Now Kaiser Permanente, the nation's largest nonprofit health plan, has announced that it's finished the first phase of a massive project to compile genetic, medical, and environmental information for 100,000 of its members. Researchers also analyzed the length of participants' telomeres—a molecule structure at the tip of the chromosome that has been linked to aging. This represents the largest telomere study to date.

The resulting data, gathered in collaboration with the University of California, San Francisco, will soon be available to outside researchers who study how different genetic and environmental factors influence disease. It took about 15 months for the team to collect and analyze the genomes of 100,000 people ranging in age from 18 to 107. The team used gene microarrays—small chips designed to quickly detect hundreds of thousands of genetic variations across the genome.

While genetic studies have been done on this scale before, they focused on one or a few diseases, such as diabetes and heart disease. The Kaiser project is unusual in that it includes years of comprehensive medical information—including blood-test results, medications, and other conditions—in the form of electronic health records. (Kaiser was one of the earliest adopters of electronic medical records in the United States.)
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'The computerized data goes back 15 years,' says Neil Risch, a statistical geneticist at UCSF who co-led the study. 'It's not like we have 100,000 blood-pressure measurements—it's closer to a million.' By combining that information with prescriptions, for example, researchers could examine how genetics influence blood pressure and the effectiveness of medication.

Researchers will also incorporate environmental data, such as air-quality and water-quality records, based on knowledge of where participants lived and when.

Because the average age of the participants in the study is 65, 'we think some of the most interesting initial questions will relate to aging,' says Cathy Schaefer, executive director of the Kaiser Permanente Program on Genes, Environment, and Health, and a co-leader on the project. 'Specifically, are there genetic and environmental influences that lead to people living to a ripe old age without serious problems?'

Researchers will continue to follow participants as long as they continue to receive health care from Kaiser. They can examine, for example, how accurately telomere length can predict longevity or healthy aging.

Genetic studies such as these have often raised privacy issues—the concern is that individual participants could be identified and their data misused. In this case, because the health-plan provider is involved in the research, the fear is that Kaiser could use genetic information to alter rates or drop some members. But this type of discrimination is outlawed by the Genetic Information Non-Discrimination Act, passed in 2008. In addition, research participants' information has special protection under the Health Insurance Portability and Accountability Act.

Patrick Taylor, a fellow at Harvard Law School's Center for Health Law Policy, Biotechnology, and Bioethics, says he is not concerned about privacy issues in this case, in part because the project has oversight from the National Institutes of Health. (The project was funded by a two-year $24.8 million grant from the NIH.) In addition, Kaiser has a long history of commitment to its members, says Taylor, who has studied the organization.

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Research Activities, August 2011: Announcements: Signups soar for AHRQ's popular CME courses

Research Activities, August 2011: Announcements: Signups soar for AHRQ's popular CME courses: "Announcements
Signups soar for AHRQ's popular CME courses

One hundred years ago, students could enter dozens of medical schools after completing less than 4 years of high school. Even Harvard Medical School admitted some students without an undergraduate degree. With a few notable exceptions, most medical training was considered mediocre. And if you wanted to continue your formal studies after medical school, you were on your own.

For today's health professionals, getting into college is competitive. But education doesn't stop—and can't stop—with a degree. Continuing education isn't an extra. It's a requirement.

In 2010, the Agency for Healthcare Research and Quality (AHRQ) began offering Continuing Medical Education/Continuing Education (CME/CE) credits through its Effective Health Care Program. Free credit classes are available to physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other health professionals. Content for the courses comes from comparative effectiveness reviews, which provide systematic appraisals of scientific evidence on common conditions such as arthritis, high cholesterol, and diabetes. The reviews are part of the growing field of patient-centered outcomes research, also called comparative effectiveness research, which evaluates the benefits and harms of treatment options.

The Program's first CME/CE modules were created by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine. In 2011, with funding from the American Recovery and Reinvestment Act, the Agency expanded online courses through a contract with PRIME Education, Inc., a medical education provider. In addition, Total Therapeutic Management provides in-person accredited CME/CE to clinicians in their offices.

'We didn't know what to expect when we first started,' said Kathleen Moreo, R.N., president of PRIME. 'We found that clinicians seek this type of unbiased education.' Indeed, within 60 days of its first CME/CE modules being released, PRIME issued more than 1,000 CME/CE certificates.

Every person who receives a certificate also participates in a post-test. Michael Fordis, M.D., director of the Eisenberg Center, said 'We found that 95 percent of clinicians who complete the CME find them relevant to their practice and about 55 percent find them very relevant.'

This isn't surprising to Frank Urbano, M.D., medical director of care coordination at Cooper University Hospital in Camden, NJ. He recently completed a course comparing treatments for patients with type 2 diabetes. 'A lot of CME courses come from commercial interests,' said Dr. Urbano. 'They tend to be focused on one particular disease or treatment. The AHRQ classes give you a chance to look at what's out there to treat a condition and how the treatments compare. It gives you an objective measure.'

AHRQ's free CME/CE classes give clinicians another choice to keep current. For more information, go to http://www.ce.effectivehealthcare.ahrq.gov�or the AHRQ main site: http://www.effectivehealthcare.ahrq.gov, and select the link to CME/CE courses.

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Effects of Rift Valley Fever, United States | CDC EID::Volume 17, Number 8–August 2011

full-text ►Effects of Rift Valley Fever, United States | CDC EID: "EID Journal Home > Volume 17, Number 8–August 2011
Volume 17, Number 8–August 2011
Online Report
Potential Effects of Rift Valley Fever in the United States

David M. Hartley, Jennifer L. Rinderknecht, Comments to Author Terry L. Nipp,1 Neville P. Clarke,1 Gary D. Snowder,1 and the National Center for Foreign Animal and Zoonotic Disease Defense Advisory Group on Rift Valley Fever2
Author Affiliations: Georgetown University, Washington, DC, USA (D.M. Hartley); National Institutes of Health, Bethesda, MD, USA (D.M. Hartley); National Center for Foreign Animal and Zoonotic Disease Defense, College Station, Texas, USA (T. L. Nipp, J. L. Rinderknecht, G. D. Snowder); and Texas &M University, College Station (N.P. Clarke)

Suggested citation for this article
Workshop Summary

Rift Valley fever virus (RVFV) has been the cause of disease outbreaks throughout Africa and the Arabian Peninsula, and the infection often results in heavy economic costs through loss of livestock. If RVFV, which is common to select agent lists of the US Department of Health and Human Services and the US Department of Agriculture, entered the United States, either by accidental or purposeful means, the effects could be substantial. A group of subject matter experts met in December 2009 to discuss potential implications of an introduction of RVF to the United States and review current modeling capabilities. This workshop followed a similar meeting held in April 2007. This report summarizes the 2 workshop proceedings. Discussions primarily highlighted gaps in current economic and epidemiologic RVF models as well as gaps in the overall epidemiology of the virus.

Foreign Animal and Zoonotic Disease Defense Workshops

The potential effects on both human and animal health and the US economy from foreign animal and zoonotic disease (FAZD) threats is clear. The National Center for Foreign Animal and Zoonotic Disease Defense (FAZD Center) was founded in April 2004 to defend the United States from FAZD threats. One such threat is the accidental or deliberate introduction of Rift Valley fever virus (RVFV). This article reports on 2 FAZD Center workshops (in April 2007 and November 2009) that reviewed the status of US vulnerability to RVF and mitigation modeling and identified information and technology gaps. Workshop discussion centered on relevant biology and management strategies to include in RVF epidemiologic models, important effects to include in economic models of RVF consequences, and ways to integrate epidemic and economic models. Each major topic of discussion is summarized below.

Disease Cycle

RVFV is transmitted to livestock and human hosts primarily by biting vectors and handling of infected animals by persons. In Africa and the Arabian Peninsula, competent vectors include numerous Aedes and Culex spp. mosquitoes. Recent competence studies have found that competent vectors in both genera exist in the United States (1). Field observations indicate that RVFV is vertically maintained during dry periods in the eggs of floodwater Aedes spp. mosquitoes, although transovarial transmission has not been observed in laboratory experiments (2). Workshop participants recommended that an earlier hypothesis regarding an RVFV sandfly/rodent cycle be studied further (3,4). Given the hardiness of Aedes spp. eggs, which have been found to remain viable in African soil for years, if RVFV were to be introduced into the United States, eradicating it may be difficult or impossible (5). Climatic, environmental, and ecologic factors such as the creation of larval mosquito habitat by above-normal amounts of rainfall are well-known antecedent events for African outbreaks, but the timing and interaction of these variables in the United States are unknown. Participants also noted that human morbidity and mortality rates in the United States may be different from those observed in rural Africa.

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Suggested Citation for this Article

Hartley DM, Rinderknecht JL, Nipp TL, Clarke NP, Snowder GD; National Center for Foreign Animal and Zoonotic Disease Defense Advisory Group. Potential effects of Rift Valley fever in the United States. Emerg Infect Dis [serial on the Internet]. 2011 Aug [date cited]. http://www.cdc.gov/EID/content/17/8/101088.htm

DOI: 10.3201/eid1708.101088

Comments to the Authors

Please use the form below to submit correspondence to the authors or contact them at the following address:

Jennifer Rinderknecht, National Center for Foreign Animal and Zoonotic Disease Defense (FAZD Center), 1500 Research Pkwy, Suite B130, College Station, TX77843-2129, USA; email: jlrinderknecht@ag.tamu.edu

ASFV p72 Genotype IX in Domestic Pigs | CDC EID::Volume 17, Number 8–August 2011

full-text ►ASFV p72 Genotype IX in Domestic Pigs | CDC EID: "EID Journal Home > Volume 17, Number 8–August 2011
Volume 17, Number 8–August 2011
Dispatch
African Swine Fever Virus p72 Genotype IX in Domestic Pigs, Congo, 2009

Carmina Gallardo, Comments to Author Raquel Anchuelo, Virginia Pelayo, Frédéric Poudevigne, Tati Leon, Jacques Nzoussi, Richard Bishop, Covadonga Pérez, Alejandro Soler, Raquel Nieto, Hilario Martín, and Marisa Arias

Author affiliations: Centro de Investigación en Sanidad Animal, Valdeolmos, Madrid, Spain (C. Gallardo, V. Pelayo, C. Pérez, A. Soler, R. Nieto, H. Martín, M. Arias); International Livestock Research Institute, Kabete, Nairobi, Kenya (R. Anchuelo, R. Bishop); United Nations Food and Agriculture Organization, Bamako, Mali (F. Poudevigne); and Conseiller à l'Elevage du Ministre de l'Agriculture et de l'Elevage, Brazzaville, Republic of the Congo (T. Leon, J. Nzoussi)

Suggested citation for this article

Abstract
African swine fever virus p72 genotype IX, associated with outbreaks in eastern Africa, is cocirculating in the Republic of the Congo with West African genotype I. Data suggest that viruses from eastern Africa are moving into western Africa, increasing the threat of outbreaks caused by novel viruses in this region.

African swine fever (ASF) is a serious disease of domestic pigs caused by a DNA arbovirus (African swine fever virus [ASFV]) belonging to the family Asfaviridae (1). Its highly contagious nature and ability to spread over long distances make it 1 of the most feared diseases of pigs; it causes devastating effects on pig production as manifested in the Caucasus since its introduction from southeastern Africa during 2007 (2). Considerable spread of ASF has been reported in western Africa during the past 20 years, and, except for in Côte d'Ivoire, the disease remains endemic (3). Because discernible ASFV serotypes are lacking, the field strains are grouped genetically by using sequencing of the C-terminus of the p72 protein, which discriminates 22 genotypes (4,5). Genotype I is historically associated with outbreaks in western Africa, whereas viruses from southern and eastern Africa have higher heterogeneity, with all 22 known genotypes having been recorded within the region (5–7).

The Republic of the Congo, located in western-central sub-Saharan Africa, shares borders with the Cabinda enclave of Angola, the Democratic Republic of the Congo, Central African Republic, Cameroon, and Gabon. The last ASF outbreaks in Congo were reported to the World Organization for Animal Health (OIE) during 2003. Since then, the disease has been officially declared endemic but without quantitative data. Sampling and characterization of currently circulating field strains from this region of western-central Africa are needed to fully understand virus spread and maintenance. Such data will have implications for regional control in western Africa.

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Suggested Citation for this Article

Gallardo C, Anchuelo R, Pelayo V, Poudevigne F, Leon T, Nzoussi J, et al. African swine fever virus p72 genotype IX in domestic pigs, Congo, 2009. Infect Dis [serial on the Internet]. 2011 Aug [date cited]. http://www.cdc.gov/EID/content/17/8/101877.htm

DOI: 10.3201/eid1708.101877

Comments to the Authors

Please use the form below to submit correspondence to the authors or contact them at the following address:

Carmina Gallardo, Centro de Investigación en Sanidad Animal (CISA-INIA), Ctra Algete el Casar s/n. Valdeolmos, Madrid, Spain; email: gallardo@inia.es

Confirmation of Norovirus Outbreaks | CDC EID::Volume 17, Number 8–August 2011

full-text ►Confirmation of Norovirus Outbreaks | CDC EID: "EID Journal Home > Volume 17, Number 8–August 2011
Volume 17, Number 8–August 2011
Dispatch
Specimen Collection and Confirmation of Norovirus Outbreaks1

Melissa S. Plantenga, Beletshachew Shiferaw, William E. Keene, Christianne Biggs, James M. Terry, LaDonna Grenz, and Paul R. Cieslak Comments to Author
Author affiliation: Oregon Department of Human Services, Portland, Oregon, USA

Suggested citation for this article

Abstract
We evaluated data from gastroenteritis outbreaks in Oregon to assess sensitivity of stool testing for norovirus and determine number of specimens needed to confirm norovirus as the cause. Norovirus can be readily confirmed if 3–6 specimens are collected any time <7 days after onset of diarrhea and for almost that long after symptoms resolve.

One goal of any outbreak investigation is to identify the causative pathogen (1). In a recent analysis of foodborne disease outbreaks in the United States during 2006, only 49% had a confirmed causative pathogen (2). A review of foodborne disease outbreaks investigated in the 10-site Foodborne Disease Active Surveillance Network during 1998–1999 found that an etiologic agent was identified for only 29% (3). The major limitation in identifying etiologic agents was a lack of specimens; no stool specimens were collected in two thirds of the unconfirmed outbreaks.

In Oregon, outbreaks of illness are reportable to public health authorities, who investigate to determine the causative pathogen and means of transmission and to implement control measures accordingly. Obtaining stool specimens within 3 days of onset has been recommended (4), but carrying out this recommendation is frequently not feasible.

Since 1999, specimens from case-patients in outbreaks of acute gastroenteritis have been tested for norovirus at the Oregon State Public Health Laboratory. Noroviruses are a group of related, nonenveloped, single-stranded RNA viruses that cause acute gastroenteritis in humans. We reviewed Oregon data to assess the sensitivity of stool testing for norovirus at different times after illness onset and to determine the number of specimens needed to ensure a high probability of confirming a norovirus outbreak.

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Suggested Citation for this Article

Plantenga MS, Shiferaw B, Keene WE, Biggs C, Terry JM, Grenz L. Speciman collection and confirmation of norovirus outbreaks. Emerg Infect Dis [serial on the Internet]. 2011 Aug [date cited]. http://www.cdc.gov/EID/content/17/8/101815.htm

DOI: 10.3201/eid1708.101815

1Preliminary report presented at the 2004 International Conference on Emerging Infectious Diseases, February 29–March 3, 2004, Atlanta, Georgia, USA (abstract no. 244).

Comments to the Authors

Please use the form below to submit correspondence to the authors or contact them at the following address:

Paul R. Cieslak, Acute and Communicable Disease Prevention, 800 NE Oregon St, Suite 772, Portland, OR 97232, USA; email: paul.r.cieslak@state.or.us