Monthly Archives: February 2017

The genetic material of an organism encodes the instructions that guide its development. These codes are not written in stone; they can change or mutate any time during the life of the organism. Single changes in the code can occur spontaneously, as a mutation, causing developmental problems.

Others, as an international team of researchers has discovered, are too numerous to be explained by random mutation processes present in the general population. When such multiple genetic changes occur before or early after conception, they may inform scientists about fundamental knowledge underlying many diseases. The study appears in Cell.

"As a part of the clinical evaluation of young patients with a variety of developmental issues, we performed clinical genomic studies and analyzed the genetic material of more than 60,000 individuals. Most of the samples were analyzed at Baylor Genetics laboratories," said lead author Pengfei Liu, assistant professor of molecular and human genetics Baylor College of Medicine and assistant laboratory director of Baylor Genetics. "Of these samples, five had extreme numbers of genetic changes that could not be explained by random events alone."

The researchers looked at a type of genetic change called copy number variants, which refers to the number of copies of genes in human DNA. Normally we each have two copies of each gene located on a pair of homologous chromosomes.

"Copy number variants in human DNA can be compared to repeated or missing paragraphs or pages of text in a book," said senior author James R. Lupski, Cullen Professor of Molecular and Human Genetics at Baylor. "For instance, if one or two pages are duplicated in a book it could be explained by random mistakes. On the other hand, if 10 different pages are duplicated, you have to suspect that it did not happen by chance. We want to understand the basic mechanism underlying these multiple new copy number variant mutations in the human genome."

The researchers call this phenomenon multiple de novo copy number variants. As the name indicates, the copy number variants are many and new (de novo). The latter means that the patients carrying the genetic changes did not inherit them from their parents because neither the mother nor the father carries the changes.

In this rare phenomenon, the copy number variants are predominantly gains duplications and triplications rather than losses of genetic material, and are present in all the cells of the child. The last piece of evidence together with the fact that the parents do not carry the alterations suggest that the extra copies of genes may have occurred either in the sperm or the egg, the parent's germ cells, and before or very early after fertilization.

"This burst of genetic changes happens only during the early stages of embryonic development and then it stops," Liu said. "Interestingly, despite having a large number of mutations, the young patients present with relatively mild neurological problems."

The researchers are analyzing more patient samples looking for additional cases of multiple copy number variants to continue their investigation of what may trigger this rare phenomenon.

"We hope that as more researchers around the world learn about this and confirm it, the number of cases will increase," Liu said. "This will improve our understanding of the underlying mechanism and of why and how pathogenic copy number variants arise not only in developmental disorders but in cancers."

This discovery was made possible in great measure thanks to the breadth of genetic testing performed and genomic data available at Baylor Genetics laboratory.

"The diagnostics lab Baylor Genetics is one of the pioneers in this new era of clinical genomics-supported medical practice and disease gene discovery research," Lupski said. "They are developing the clinical genomics necessary to foster and support the Precision Medicine Initiative of the National Institutes of Health, and generating the genomics data that further drives human genome research."

Using state-of-the art technologies and highly-trained personnel, Baylor Genetics analyzes hundreds of samples daily for genetic evaluation of patients with conditions suspected to have underlying genetic factors potentially contributing to their disease. Having this wealth of information and insight into the genetic mechanisms of disease offers now the possibility of advancing medicine and basic research in ways that were not available before.

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Striking Number of Genetic Changes Can Occur Early in Human Development - Laboratory Equipment

Two researchers from a UCLA clinical site explained the genetic approach to diagnosing rare diseases to about 50 UCLA students and faculty members Monday.

In honor of Rare Disease Day, Stanley Nelson and Christina Palmer, principal investigators of a UCLA clinical site, discussed how UCLA participates in the Undiagnosed Diseases Network. UCLA is one of seven clinical sites in the UDN, a network of researchers who study rare diseases and introduce further research possibilities based on a team science approach.

Team science is a collaborative research approach that is based on the overall contribution of the network, which includes clinicians, scientists, genetic counselors and other experts, Palmer said. For example, clinical sites such as UCLA provide patient evaluations while other sites act as laboratory cores that provide DNA sequencing.

Under the UDN, UCLA has worked with 63 patients with rare diseases. The network approach allows patients and physicians to seek out other individuals within the network who may be working with the same disease, Nelson said.

Lab investigations can also address a broad spectrum of rare diseases and increase the speed of testing for disease-specific concerns, Nelson said.

Palmer said patients must go through a comprehensive application process to be evaluated by the UDN. Each patient has to demonstrate that their rare disease has gone through extensive prior evaluation and submit other medical information.

Palmer added some diseases the UCLA researchers study include neurological diseases.

Nelson said the UDN uses genome sequencing in their research, which is done at UCLA prior to clinical evaluation. Sequencing patients DNA before evaluating them can present ethical limitations.

This can overwhelm patients with variants that might not be clinically relevant, Palmer said. There exists a potential for unnecessary tests and possible risks with related procedures, (and) patients wait longer for clinical visit.

Researchers gather phenotypes physical characteristics of participants from medical records, not in-person evaluations, Nelson said. Unlike other disorder researchers, who group patients with similar characteristics, UCLA researchers do not intentionally gather patients with similar phenotypes.

Palmer said clinical evaluations start after genome sequencing. Evaluations take one to five days and may include consultations with specialists and other medical tests.

As a clinical site, UCLA does not focus on treatment or symptom management of rare diseases, Nelson said. Although UCLA researchers aim to diagnose patients, doing so is difficult and not necessarily included in the patient follow-up.

About 70 percent of the patients UCLA is working with are children. Researchers have diagnosed five of 35 completed cases.

Siena Salgado, a third-year human biology and society student who attended the talk, said she had previously studied the sociological impacts of the UDNs structure. She said she was interested in the possible ethical implications of the UDNs genetic-based approach.

Michael Gorin, an ophthalmology and human genetics professor who attended the event, said he thinks the UDN becomes a compensatory process that catches up to other countries with health care systems that already have vested interests in genetic diseases.

The psychological benefit for patients to know why they have a disease is powerful, Gorin said. To be able to tell someone we know what genetic variance is causing this disease, even if we cant treat it removes guilt, uncertainty (and) gives people hope.

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UCLA researchers describe methods for diagnosing diseases using genetics - Daily Bruin

CAMBRIDGE, MA - Elsevier, a world-leading provider of scientific, technical and medical information products and services, today announced the publication of an updated edition of its valuable reference, Genetics and Evolution of Infectious Diseases, edited by Michel Tibayrenc. This book is aimed at controlling and preventing neglected and emerging worldwide diseases that are a major cause of global morbidity, disability and mortality. Using an integrated approach, the book discusses the constantly evolving field of infectious diseases and their continued impact on the health of populations, especially in resource-limited areas of the world. At the same time, Elsevier announced five additional immunology, virology and microbiology books.

Genetics and Evolution of Infectious Diseases, Second Edition looks at the worldwide human immunodeficiency virus (HIV) pandemic, increasing antimicrobial resistance, and the emergence of many new bacterial, fungal, parasitic and viral pathogens. With contributions from leading authorities, the book includes developments in the field of infectious disease since it was last published in 2010. It demonstrates how the economic, social and political burden of infectious diseases is most evident in developing countries which must confront the dual burden of death and disability due to infectious and chronic illnesses.

Learn more about infectious disease genomics in this sample chapter.

Michel Tibayrenc, M.D., Ph.D., has worked on the evolution of infectious diseases for more than 35 years. He is a director of research emeritus at the French Institut de Recherche pour le Dveloppement (IRD) Montpellier, France, and the founder and principal organizer of the international congresses MEEGID (molecular epidemiology and evolutionary genetics of infectious diseases). The author of more than 200 international papers, Dr, Tibayrenc has been the head of the unit of research "genetics and evolution of infectious diseases" at the IRD research center for 20 years. With his collaborator, Jenny Telleria, he is the founder and scientific adviser of the Bolivian Society of Human Genetics. Dr. Tibayrenc has won the prize of the Belgian Society of Tropical Medicine (1985), and the medal of the Instituto Oswaldo Cruz, Rio de Janeiro (2000), for his work on Chagas disease. A fellow of the American Association for the Advancement of Science, he is the founder and editor-in-chief of the Elsevier journal, "Infection, Genetics and Evolution."

The six new immunology, virology and microbiology titles are:

In order to meet content needs in immunology, virology and microbiology, Elsevier uses proprietary tools to identify the gaps in coverage of the topics. Editorial teams strategically fill those gaps with content written by key influencers in the field, giving students, faculty and researchers the content they need to answer challenging questions and improve outcomes. These new books, which will educate the next generation of immunologists and virologists, and provide critical foundational content for information professionals, are key examples of how Elsevier is enabling science to drive innovation.

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'Genetics and Evolution of Infectious Diseases' Announces Updates - Broadway World