Baboon genome sequence reveals evolutionary diversification - (Wednesday, January 30, 2019)
Rapidly increasing efforts to generate whole genome sequences for many vertebrate species are providing a significantly improved understanding of the biological differences among animals across the tree of life. In a new study published in Science Advances, an international multi-institutional research team, led by the Human Genome Sequencing Center at Baylor College of Medicine, reports novel results describing the genome sequences and evolutionary history of six Papio baboon species. This work sheds new light on the fundamental biological processes that generate new species and has implications for the origin of our own species, Homo sapiens.
Baboon populations are widespread across sub-Saharan Africa, and various researchers have conducted extensive analyses of the behavior, morphology and ecology of these species, leading to a detailed understanding of how they have thrived in their respective environments. However, far less is known about how each of the six baboon species arose and became distinct from the others.
“Baboons have long attracted scientific attention because they evolved within the same sub-Saharan African habitat in which early human ancestors arose. The behavioral and ecological differences among baboons make them an excellent model for investigating how a socially complex, highly adaptable primate lineage diversifies over time. In this new work, we show that baboon diversification and evolution was a more complex and reticulated process than was previously recognized,” said Dr. Jeffrey Rogers, associate professor in the Human Genome Sequencing Center at Baylor and lead author on the paper.
Distinct stages in infant microbiome development identified - (Wednesday, October 24, 2018)
In the largest clinical microbiome study in infants reported to date, a team led by researchers at Baylor College of Medicine explored the sequence of microbial colonization in the infant gut through age 4 and found distinct stages of development in the microbiome that were associated with early life exposures. Published in the journal Nature, their report and an accompanying report led by the Broad Institute are the result of extensive analysis of data collected from a cohort of participants involved in the TEDDY diabetes study.
The TEDDY study (The Environmental Determinants of Diabetes in the Young) study has been collecting data for 10 years with the goal of understanding what triggers type 1 diabetes in children at increased genetic risk for the disease. Researchers at six clinical centers in the U.S., Sweden, Finland, and Germany, as well as the Data Coordinating Center at the University of South Florida, have gathered monthly stool samples and data from more than 8,600 children who are genetically susceptible to type 1 diabetes. From this cohort, researchers at Baylor College of Medicine sequenced and analyzed 12,005 stool samples that were collected from 903 children between three and 46 months of age to further understand what the microbiome looks like early in life.
“We know that the first few years of life are important for microbiome establishment. You are born with very few microbes, and microbial communities assemble on and in your body through those first years of your life,” said Dr. Joseph Petrosino, director of the Alkek Center for Metagenomics and Microbiome Research and professor and interim chair of molecular virology and microbiology at Baylor. “In this study, we took a closer look in this amazing cohort at the establishment of the microbiome over the first few years of life and the early life exposures associated with that sequence of events.”
In collaboration with the Human Genome Sequencing Center at Baylor, state-of-the-art sequencing of both RNA and DNA was applied to uncover the complete genetic makeup of all microbes. Upon analysis of these data, Petrosino and his team determined that the developing gut microbiome undergoes three distinct phases of microbiome progression:
- Developmental phase (3 to 14 months of age)
- Transitional phase (15 to 30 months of age)
- Stable phase (31 to 46 months of age)
“This information is useful for any future microbiome studies looking at an infant cohort for scientific discovery and potential intervention purposes. The idea that we can stratify the development phases in this manner may give researchers additional resolution to reveal differences that could potentially be disease-associated,” Petrosino said.
New test gives better risk prediction for heart attack, stroke - (Thursday, July 5, 2018)
Knowing your risk factors is key when it comes to preventing heart attack and stroke, and now researchers at Baylor College of Medicine have found that testing a specific type of triglyceride may be a better indicator for predicting risk of cardiovascular disease and stroke compared to just traditional risk factors.
The findings, which also point to a potential new treatment target to help prevent cardiovascular disease, appear in the latest issue of the Journal of the American College of Cardiology.
Using data from the long-term, ongoing Atherosclerosis Risk in Communities (ARIC) study, designed to investigate the causes of atherosclerosis and its clinical outcomes, researchers added remnant lipoprotein cholesterol (RLP-C) and low-density lipoprotein triglycerides (LDL-TG) to the Pooled Cohort Equation, a 10-year risk prediction tool. The RLP-C levels didn’t add any extra information. However, when LDL-TG levels were added, the researchers found that the levels of LDL-TG predicted not only heart attack but also stroke.
Researchers also observed that a genetic variant of APOE, known as APOE2, was found to have the strongest association with both RLP-C and LDL-TG. It was associated with higher RLP-C but lower levels of LDL-TG.
Sequencing for ARIC was carried out at the Baylor College of Medicine Human Genome Sequencing Center.
Researchers of Newly Discovered European Cavefish Awarded Genome Sequencing Grant - (Wednesday, June 27, 2018)
Dr. Fritz Sedlazeck of the Baylor College of Medicine Human Genome Sequencing Center and Dr. Arne Nolte of the Institute for Biology and Environmental Sciences at the University of Oldenburg, Germany, have been awarded the 2018 Plant and Animal SMRT® Grant. This grant provides the researchers access to the PacBio Sequel System at GENEWIZ, as well as the materials needed and bioinformatics support to conduct comparative genomic sequencing on the newly discovered European cavefish.
The pale loach, which belongs to the genus Barbatula, was discovered in 2015 by diver Joachim Kreiselmaier in the Danube-Aach underground karst system in Southern Germany. Sedlazeck and Nolte will join efforts with Dr. Jasminca Behrmann-Godel of the Limnological Institute of the University of Konstanz to further understand the evolution of this cavefish.
The outcome of this study will enable us to understand the initial steps that lead to the evolution of cave animals and impact our understanding of how multiple phenotypes evolve among vertebrates.
"This grant enables us to establish the genome assembly of the European cavefish and identify genetic variants from its surface-water ancestors," said Sedlazeck. "We are fascinated by changes in the sensory system and pale pigmentation of the fish and we will compare its genomic makeup with the Mexican cavefish which is an important model organism in developmental biology. The outcome of this study will enable us to understand the initial steps that lead to the evolution of cave animals and impact our understanding of how multiple phenotypes evolve among vertebrates."
Novel structure found in ‘antennae’ of light-sensing neuron - (Wednesday, June 13, 2018)
Scientists at Baylor College of Medicine and Radboud University Medical Center in the Netherlands have discovered that the antennae-like structures on light-sensing neurons, called photoreceptors, have a unique feature not observed in the ‘antennae’ or cilia of other types of cells. The study, published in the Journal of Cell Biology, reveals that this novel functional zone plays a structural role that is essential for the function of the photoreceptors and also helps explain why mutations on certain cilia proteins, although present throughout the body, only affect cilia on photoreceptors, causing non-syndromic blindness.
“Practically all cells in the body have a single cilium called the primary cilium that seems to allow cells to sense their environment. The primary cilia on photoreceptors, for instance, specialize in sensing light,” said first author Rachayata Dharmat, graduate student of molecular and human genetics in the lab of Dr. Rui Chen.
“Our lab focuses on understanding the molecular mechanisms and gene variants underlying human retinal disease,” said Chen, professor of molecular and human genetics and in the Human Genome Sequencing Center as well as member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.
Previous work in the Chen lab discovered that the SPATA7 gene is expressed in all primary cilia in the body, but, surprisingly, when this gene mutated, only the primary cilia in photoreceptors were affected. The photoreceptors lose their ability to function causing visual impairment. Why this happens is what this group tried to answer.
The presence of this unique distal zone exclusively in the cilia of photoreceptors also explains the biological mystery of non-syndromic blindness observed in both patients and mouse models… .
Using state-of-the-art super-resolution microscopy (STORM) coupled with cryo-electron tomography and genetic models, the researchers discovered that when SPATA7 was present, SPATA7-binding proteins localized throughout the connecting cilium. But in the absence of SPATA7, the binding proteins concentrated at the base of the cilium in a region closest to the body of the neuron, the researchers called it the proximal region, leaving a distal region empty of SPATA7-binding proteins. Chen, Dharmat and their colleagues also observed that proteins that did not bind to SPATA7 always localized in the proximal region, both when SPATA7 was present and absent.
“Cilia in other cell types also have SPATA7, but these cilia do not have a distal region in the transition zone like the one we discovered in cilia of photoreceptors, therefore they are not affected when SPATA7 is mutated,” Dharmat said.
“The presence of this unique distal zone exclusively in the cilia of photoreceptors also explains the biological mystery of non-syndromic blindness observed in both patients and mouse models, that loss of certain transition zone proteins only causes degeneration of cilia in photoreceptors without affecting the cilia on other cell types,” Dharmat said.
Scientists Want to Sequence the DNA Of Every Species On Earth - (Wednesday, May 9, 2018)
Dr. Stephen Richards, associate professor at the Baylor Collge of Medicine Human Genome Sequencing Center, joined Craig Cohen on Houston Public Media's "Houston Matters" program to discuss the Earth BioGenome Project, an initative to sequence all 1.5 million eukaryote species on Earth.
"It's a big project; there's going to be a lot of data," said Richards regarding the proposed 10-year international undertaking. "We think now because the cost of sequencing has dropped so much that the overall cost to do this on planet Earth would be about the same or even less than it was to do the human genome the first time."
Xia-Gibbs Syndrome study led to new patient registry - (Friday, May 4, 2018)
Researchers at the Human Genome Sequencing Center at Baylor College of Medicine have conducted a study of 20 individuals with Xia-Gibbs Syndrome, a rare condition that has symptoms of severe developmental delay, sleep apnea, delayed speech and generalized upper body weakness, and have established a registry to collect genetic and other clinical information from patients with the condition.
As discovered in 2014 by a team led by Dr. Richard Gibbs, professor and director of the Human Genome Sequencing Center at Baylor, Xia-Gibbs Syndrome is the result of new changes within the AT-Hook DNA Binding Motif Containing 1 gene (AHDC1). The new study, which appears in the American Journal of Medical Genetics, shows that the gene is more susceptible to mutations than previously known.
The registry, which is private and HIPAA protected, is the next step in identifying and studying the full spectrum of the disorder. The current group of 30 enrollees in the registry learned about the study through their doctors, social media, including a private Facebook page for families affected by Xia-Gibbs Syndrome, or elsewhere on the internet.
“We know of about nearly 70 families worldwide, and roughly half of these are participating in the registry thus far,” said Dr. Yunyun Jiang, postdoctoral associate in the Human Genome Sequencing Center and lead author on the study.
As more patients join the registry, accompanying laboratory work aims to understand the full range of underlying molecular changes that cause the symptoms of Xia-Gibbs Syndrome.
When we fully understand how this gene damage causes Xia-Gibbs Syndrome, we can begin the path to a cure.
“We recently encountered a patient who is more than 50 years old, which is remarkable because this condition is typically only identifiable in children,” said contributing author Dr. David Murdock, assistant professor of molecular and human genetics at Baylor and assistant director of the clinical lab in the Human Genome Sequencing Center. “When we fully understand how this gene damage causes Xia-Gibbs Syndrome, we can begin the path to a cure.”
Current work in the Human Genome Sequencing Center is focused on whether mild mutations lead to a more mild form of the disorder, as well as the construction of animal models to help study the condition.
“Given the rarity of this disease, scientists and physicians are seldom able to gather all the information about a group like this. It is something that has really been lacking in the field,” said Gibbs, corresponding author on the study and also the Wofford Cain Chair and Professor in Molecular and Human Genetics at Baylor. “With the growth of the registry and future mouse model studies, there is hope that we will get to the bottom of this one.”
Other contributors to this work include Drs. Amy McGuire, James Lupski, Jennifer Posey, Michael Khayat, Fan Xia, Qingchang Meng and Mullai Murugan, all with Baylor, Luis Sanchez-Pulido and Chris Ponting with the University of Edinburgh, and Jill Hunter with Texas Children’s Hospital.
This work was supported by the National Human Genome Research Institute, the Texas Institute for Advanced Studies at Texas A&M, the UK Medical Research Council, and by a private donation.
PacBio Blog Interviews Baylor’s Fritz Sedlazeck on New Long-Read Algorithms - (Monday, April 30, 2018)
A PacBio blogger reached out to Dr. Fritz Sedlazeck of Baylor's Human Genome Sequencing Center to learn more about a newly published article appearing in Nature Methods, "Accurate detection of complex structural variations using single-molecule sequencing." Lead author Sedlazeck discusses two new tools designed for use with long-read sequencing data, the NGMLR aligner and Sniffles structural variant caller.
Scientists seek to sequence genomes of all known species - (Monday, April 23, 2018)
Ever since the completion of the Human Genome Project, scientists have become increasingly interested in sequencing the genomes of more cultures and populations of humans, as well as various species of animals and organisms to better understand evolution, adaptability and disease susceptibility. In what is perhaps the most ambitious biological proposal since the initial Human Genome Project, an international group of researchers, including researchers from Baylor College of Medicine, seek to sequence every known species that calls planet Earth home. The perspective piece on the project, called the Earth BioGenome Project, appears in the journal Proceedings of the National Academy of Sciences.
The unprecedented initiative aims to sequence each of the roughly 1.5 million species of eukaryotes – all living organisms with a clearly defined nucleus – that have been described in modern science, although there are estimated to be upward of 15 million species, most of which have yet to be identified.
“There are several reasons, both philosophical and practical, as to why this global initiative is a crucial one,” said Dr. Stephen Richards, associate professor in the Human Genome Sequencing Center at Baylor. “The Earth BioGenome Project will demonstrate the value of life on earth, provide a comprehensive understanding of the primary genetic data of life, reveal insights into future novel therapies and drug development and connect the large population of urban humans to the ecosystems that exist, and may be in jeopardy, across the world.”