Category Archives: Human Genetics

PUBLIC RELEASE DATE:

28-Apr-2014

Contact: Anne-Julie Ouellet anne-julie.ouellet@icm-mhi.org 514-376-3330 x2700 Montreal Heart Institute

A study published today in Nature Genetics has revealed mutations that could have a major impact on the future diagnosis and treatment of many human diseases. Through an international collaboration, researchers at the Montreal Heart Institute (MHI) were able to identify a dozen mutations in the human genome that are involved in significant changes in complete blood counts and that explain the onset of sometimes severe biological disorders.

The number of red and white blood cells and platelets in the blood is an important clinical marker, as it helps doctors detect many hematological diseases and other diseases. Doctors can also monitor this marker to determine the effectiveness of therapy for certain pathologies.

"Complete blood counts are a complex human trait, as the number of cells in the blood is controlled by our environment and the combined expression of many genes in our DNA," explained Dr. Guillaume Lettre, a study co-author, an MHI researcher, and an Associate Professor at the Faculty of Medicine at Universit de Montral.

In collaboration with their colleagues at the University of Washington in Seattle and the University of Greifswald in Germany, these MHI researchers analyzed the DNA of 6,796 people who donated specimens to the MHI Biobank by looking specifically at segments of DNA directly involved in protein function in the body. They specifically identified a significant mutation in the gene that encodes erythropoietin, a hormone that controls the production of red blood cells. "Subjects who carry this mutation in their DNA have reduced hemoglobin levels and a 70% greater chance of developing anemia," explained Dr. Lettre. The scientists also identified a mutation in the JAK2 gene, which is responsible for a 50% increase in platelet counts and, in certain cases, for the onset of bone marrow diseases that can lead to leukemia. Dr. Jean-Claude Tardif, Director of the MHI Research Centre, Full Professor at the Faculty of Medicine at Universit de Montral, and a study co-author, added that "after reviewing pre-existing clinical data from the MHI Biobank, we observed that these donors also had a higher risk of having a stroke during their lifetime."

Dr. Lettre believes that these findings are very encouraging, as they suggest that the experimental approach used in the study can be applied to other human diseases. "Thanks to the existing genetic data and wealth of other clinical information available from the MHI Biobank, we will be able to identify other rare genetic variations that may impact the risk of cardiovascular disease and open the door to the development of new therapies."

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About the MHI Biobank: https://www.icm-mhi.org/en/research/infrastructures-services/mhis-hospital-biobank

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Identification of genetic mutations involved in human blood diseases

A study published today in Nature Genetics has revealed mutations that could have a major impact on the future diagnosis and treatment of many human diseases. Through an international collaboration, researchers at the Montreal Heart Institute (MHI) were able to identify a dozen mutations in the human genome that are involved in significant changes in complete blood counts and that explain the onset of sometimes severe biological disorders.

The number of red and white blood cells and platelets in the blood is an important clinical marker, as it helps doctors detect many hematological diseases and other diseases. Doctors can also monitor this marker to determine the effectiveness of therapy for certain pathologies.

"Complete blood counts are a complex human trait, as the number of cells in the blood is controlled by our environment and the combined expression of many genes in our DNA," explained Dr. Guillaume Lettre, a study co-author, an MHI researcher, and an Associate Professor at the Faculty of Medicine at Universit de Montral.

In collaboration with their colleagues at the University of Washington in Seattle and the University of Greifswald in Germany, these MHI researchers analyzed the DNA of 6,796 people who donated specimens to the MHI Biobank by looking specifically at segments of DNA directly involved in protein function in the body. They specifically identified a significant mutation in the gene that encodes erythropoietin, a hormone that controls the production of red blood cells. "Subjects who carry this mutation in their DNA have reduced hemoglobin levels and a 70% greater chance of developing anemia," explained Dr. Lettre. The scientists also identified a mutation in the JAK2 gene, which is responsible for a 50% increase in platelet counts and, in certain cases, for the onset of bone marrow diseases that can lead to leukemia. Dr. Jean-Claude Tardif, Director of the MHI Research Centre, Full Professor at the Faculty of Medicine at Universit de Montral, and a study co-author, added that "after reviewing pre-existing clinical data from the MHI Biobank, we observed that these donors also had a higher risk of having a stroke during their lifetime."

Dr. Lettre believes that these findings are very encouraging, as they suggest that the experimental approach used in the study can be applied to other human diseases. "Thanks to the existing genetic data and wealth of other clinical information available from the MHI Biobank, we will be able to identify other rare genetic variations that may impact the risk of cardiovascular disease and open the door to the development of new therapies."

Story Source:

The above story is based on materials provided by Montreal Heart Institute. Note: Materials may be edited for content and length.

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Genetic mutations involved in human blood diseases identified

Stem Cell Therapy | Genetics and Rheumatoid Arthritis
What do genes have to do with arthritis? No... not those kinds of genes... these kinds of jeans. Genetics can explain why infections can trigger rheumatoid arthritis Appearing in Science Codex...

By: Nathan Wei

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Stem Cell Therapy | Genetics and Rheumatoid Arthritis - Video

The most likely wild chicken ancestor, photographed in India.

More than 10,000 years ago, our ancestors began to expand their organization offood productionpurposefully promoting certain plants and animals they found tasty or useful. Over time, they domesticated those species, inserting human preferences into the process of natural selection.

We know today that agriculture and domesticated species arose separately in different regions around the world. Grains, beans, and livestock appear to be some of the earliest species domesticated in Southwest Asia, for example. But many questions remain about why humans shifted from hunting and gathering to agriculture and how the process of domesticatingspecies unfoldeda process that, in cases like wheat and rice, appears to have taken more than a thousand years.

A special section in this weeks Proceedings of the National Academy of Sciencesdelvedinto what science has discovered about domestication and how toprovide answers to ourremaining questions about the lives of prehistoric people and their relationship with the plants and animals around them.

In one of the examples explored inPNAS, scientists turned to chickens in their search for answers to an age old question.

It's not the questionyoure probably thinking of. The jurys still out on which came first, as well as motivations for road crossing. Instead, scientists were looking to see if certain traits commonly found in modern chickenswere the same traits selected for whenancient humans beganthe domestication process.

To study the origins of these traits, the scientists compared the DNA in modern chickens to samples obtainedfrom archeological sites ranging from 200 years BC to the 18th century.

In chickens, traits that are considered hallmarks of domestication include yellow skin. This iscommonly found in most modern breeds, and it is caused by a recessive allele inthe gene that breaks down orange-yellow compounds known as carotenoids. However, its absent in the chicken's primary ancestor, the Red Jungle Fowl, which still lives in Asia and looks a lot like a chicken. Another key trait associated with domestication is a mutation in a thyroid hormone receptorthe jungle fowl lacks it, but almost all modern chicken breeds have it.

In the past, many researchers concluded that these traits must have been selected long ago by our ancestors as they first domesticated chickens. But the in-depth genetic analysis showed that they onlybecame common in chicken breeds relatively recentlywithin the past couple hundred years.

The significance here goes far beyond chicken genetics. Its so tempting to trust neat little evolutionary storiesall the chickens have the same hormonal mutation, that must have been one of the things our ancestors selected for long, long agowhen it very well might be random chance. The genetic process of domestication cant just be assumed from modern data.

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Reading human history using ancient chicken DNA and chili peppers

Dive into Human Genetics
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By: stasundr

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Dive into Human Genetics - Video

Women Shaping a Better Tomorrow: Penn Association of Alumnae 100th Anniversary Colloquium
Women Shaping a Better Tomorrow: 100th Anniversary Colloquium featuring University of Pennsylvania Alumnae Faculty Thursday, October 10, 2013 1) Dr. Beverly Willis Emanuel, CW #39;62, GR #39;72 "Using...

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Women Shaping a Better Tomorrow: Penn Association of Alumnae 100th Anniversary Colloquium - Video

PUBLIC RELEASE DATE:

24-Apr-2014

Contact: Sid Dinsay sid.dinsay@mountsinai.org 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

A substantial proportion of risk for developing autism spectrum disorders (ASD), resides in genes that are part of specific, interconnected biological pathways, according to researchers from the Icahn School of Medicine at Mount Sinai, who conducted a broad study of almost 2,500 families in the United States and throughout the world. The study, titled "Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders," was first published online in the American Journal of Human Genetics on April 24.

ASD affects about one percent of the population in the United States and is characterized by impairments in social interaction and communication, as well as by repetitive and restricted behaviors. ASD ranges from mild to severe levels of impairment, with cognitive function among individuals from above average to intellectual disability.

Previously, ASD has been shown to be highly inheritable, and genomic studies have revealed that that there are various sources of risk for ASD, including large abnormalities in whole chromosomes, deletions or duplications in sections of DNA called copy number variants (CNVs), and even changes of single nucleotides (SNVs) within a gene; genes contain instructions to produce proteins that have various functions in the cell.

The researchers reported numerous CNVs affecting genes, and found that these genes are part of similar cellular pathways involved in brain development, synapse function and chromatin regulation. Individuals with ASD carried more of these CNVs than individuals in the control group, and some of them were inherited while others were only present in offspring with ASD.

An earlier study, results of which were first published in 2010, highlighted a subset of these findings within a cohort of approximately 1,000 families in the U.S. and Europe; this larger study has expanded that cohort to nearly 2,500 families, each comprising "trios" of two parents and one child. By further aggregating CNVs and SNVs (the latter identified in other studies), Mount Sinai researchers discovered many additional genes and pathways involved in ASD.

"We hope that these new findings will help group individuals with ASD based upon their genetic causes and lead to earlier diagnosis, and smarter, more focused therapies and interventions for autism spectrum disorders," said first author Dalila Pinto, PhD, Assistant Professor of Psychiatry, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. Dr. Pinto is a Seaver Foundation Faculty Fellow, and a member of the Mindich Child Health & Development Institute, the Icahn Institute for Genomics and Multiscale Biology, and the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai; other Mount Sinai researchers on this study include Mafalda Barbosa, Graduate Student in Psychiatry; Xiao Xu, PhD, Postdoctoral Fellow in Psychiatry; Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center and Associate Professor of Psychiatry and Pediatrics; and Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, Vice Chair for Research in Psychiatry, and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences.

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Genetic alterations in shared biological pathways as major risk factor for ASD

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Newswise (NEW YORK April 24) A substantial proportion of risk for developing autism spectrum disorders (ASD), resides in genes that are part of specific, interconnected biological pathways, according to researchers from the Icahn School of Medicine at Mount Sinai, who conducted a broad study of almost 2,500 families in the United States and throughout the world. The study, titled Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders, was first published online in The American Journal of Human Genetics on April 24.

ASD affects about one percent of the population in the United States and is characterized by impairments in social interaction and communication, as well as by repetitive and restricted behaviors. ASD ranges from mild to severe levels of impairment, with cognitive function among individuals from above average to intellectual disability.

Previously, ASD has been shown to be highly inheritable, and genomic studies have revealed that that there are various sources of risk for ASD, including large abnormalities in whole chromosomes, deletions or duplications in sections of DNA called copy number variants (CNVs), and even changes of single nucleotides (SNVs) within a gene; genes contain instructions to produce proteins that have various functions in the cell.

The researchers reported numerous CNVs affecting genes, and found that these genes are part of similar cellular pathways involved in brain development, synapse function and chromatin regulation. Individuals with ASD carried more of these CNVs than individuals in the control group, and some of them were inherited while others were only present in offspring with ASD.

An earlier study, results of which were first published in 2010, highlighted a subset of these findings within a cohort of approximately 1,000 families in the U.S. and Europe; this larger study has expanded that cohort to nearly 2,500 families, each comprising trios of two parents and one child. By further aggregating CNVs and SNVs (the latter identified in other studies), Mount Sinai researchers discovered many additional genes and pathways involved in ASD.

We hope that these new findings will help group individuals with ASD based upon their genetic causes and lead to earlier diagnosis, and smarter, more focused therapies and interventions for autism spectrum disorders, said first author Dalila Pinto, PhD, Assistant Professor of Psychiatry, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. Dr. Pinto is a Seaver Foundation Faculty Fellow, and a member of the Mindich Child Health & Development Institute, the Icahn Institute for Genomics and Multiscale Biology, and the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai; other Mount Sinai researchers on this study include Mafalda Barbosa, Graduate Student in Psychiatry; Xiao Xu, PhD, Postdoctoral Fellow in Psychiatry; Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center and Associate Professor of Psychiatry and Pediatrics; and Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, Vice Chair for Research in Psychiatry, and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences.

This study was jointly supported through the main funders of the International Autism Genome Project: Autism Speaks, the Health Research Board (Ireland), the Hillbrand Foundations, the Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research.

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Newswise (SALT LAKE CITY)A computational tool developed at the University of Utah (U of U) has successfully identified diseases with unknown gene mutations in three separate cases, U of U researchers and their colleagues report in a new study in The American Journal of Human Genetics. The software, Phevor (Phenotype Driven Variant Ontological Re-ranking tool), identifies undiagnosed illnesses and unknown gene mutations by analyzing the exomes, or areas of DNA where proteins that code for genes are made, in individual patients and small families.

Sequencing the genomes of individuals or small families often produces false predictions of mutations that cause diseases. But the study, conducted through the new USTAR Center for Genetic Discovery at the U of U, shows that Phevors unique approach allows it to identify disease-causing genes more precisely than other computational tools.

Mark Yandell, Ph.D, professor of human genetics, led the research. He was joined by co-authors Martin Reese, Ph.D., of Omicia Inc., an Oakland, Calif., genome interpretation software company, Stephen L. Guthery, M.D., professor of pediatrics who saw two of the cases in clinic, a colleague at the MD Anderson Cancer Center in Houston, and other U of U researchers. Marc V. Singleton, a doctoral student in Yandells lab, is the first author.

Phevor represents a major advance in personalized health care, according to Lynn B. Jorde, Ph.D., U of U professor and chair of human genetics and also a co-author on the study. As the cost of genome sequencing continues to drop, Jorde expects it to become part of standardized health care within a few years, making diagnostic tools such as Phevor more readily available to clinicians.

With Phevor, just having the DNA sequence will enable clinicians to identify rare and undiagnosed diseases and disease-causing mutations, Jorde said. In some cases, theyll be able to make the diagnosis in their own offices.

Using Phevor in Clinic

Phevor works by using algorithms that combine the probabilities of gene mutations being involved in a disease with databases of phenotypes, or the physical manifestation of a disease, and information on gene functions. By combining those factors, Phevor identifies an undiagnosed disease or the most likely candidate gene mutation for causing a disease. It is particularly useful when clinicians want to identify an illness or gene mutation involving a single patient or the patient and two or three other family members, which is the most common clinical situation for undiagnosed diseases.

Yandell, the lead developer of the software, describes Phevor as the application of mathematics to biology. Phevor is a way to try to get the most out of a childs genome to identify diseases or find disease-causing gene mutations, Yandell said.

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Software Identifies Gene Mutations in 3 Undiagnosed Children

PUBLIC RELEASE DATE:

22-Apr-2014

Contact: Phil Sahm phil.sahm@hsc.utah.edu 801-581-2517 University of Utah Health Sciences

(SALT LAKE CITY)A computational tool developed at the University of Utah (U of U) has successfully identified diseases with unknown gene mutations in three separate cases, U of U researchers and their colleagues report in a new study in The American Journal of Human Genetics. The software, Phevor (Phenotype Driven Variant Ontological Re-ranking tool), identifies undiagnosed illnesses and unknown gene mutations by analyzing the exomes, or areas of DNA where proteins that code for genes are made, in individual patients and small families.

Sequencing the genomes of individuals or small families often produces false predictions of mutations that cause diseases. But the study, conducted through the new USTAR Center for Genetic Discovery at the U of U, shows that Phevor's unique approach allows it to identify disease-causing genes more precisely than other computational tools.

Mark Yandell, Ph.D, professor of human genetics, led the research. He was joined by co-authors Martin Reese, Ph.D., of Omicia Inc., an Oakland, Calif., genome interpretation software company, Stephen L. Guthery, M.D., professor of pediatrics who saw two of the cases in clinic, a colleague at the MD Anderson Cancer Center in Houston, and other U of U researchers. Marc V. Singleton, a doctoral student in Yandell's lab, is the first author.

Phevor represents a major advance in personalized health care, according to Lynn B. Jorde, Ph.D., U of U professor and chair of human genetics and also a co-author on the study. As the cost of genome sequencing continues to drop, Jorde expects it to become part of standardized health care within a few years, making diagnostic tools such as Phevor more readily available to clinicians.

"With Phevor, just having the DNA sequence will enable clinicians to identify rare and undiagnosed diseases and disease-causing mutations," Jorde said. "In some cases, they'll be able to make the diagnosis in their own offices."

Phevor works by using algorithms that combine the probabilities of gene mutations being involved in a disease with databases of phenotypes, or the physical manifestation of a disease, and information on gene functions. By combining those factors, Phevor identifies an undiagnosed disease or the most likely candidate gene mutation for causing a disease. It is particularly useful when clinicians want to identify an illness or gene mutation involving a single patient or the patient and two or three other family members, which is the most common clinical situation for undiagnosed diseases.

Yandell, the lead developer of the software, describes Phevor as the application of mathematics to biology. "Phevor is a way to try to get the most out of a child's genome to identify diseases or find disease-causing gene mutations," Yandell said.

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Applying math to biology: Software identifies disease-causing mutations in undiagnosed illnesses