Predicting genes that can cause disease due to the production of truncated or altered proteins that take on a new or different function, rather than those that lose their function, is now possible thanks to an international team of researchers, including researchers from Baylor College of Medicine, that has developed a new analytical tool to effectively and efficiently predict such candidate genes. The tool allowed the researchers to identify 252 candidate ‘disease genes.’ Some of these genes had already been studied in other labs where it was shown that they most likely cause disease by producing defective proteins, which supports the effectiveness of this novel tool. The study appears in the American Journal of Human Genetics. “Genes can cause disease because of mutations that result in loss-of-function; that is when the gene is not producing the protein it encodes. But genes also can cause disease when mutations result in the production of a defective protein with a new function – a gain-of-function mutation – that may interfere with the function of the normal protein,” said corresponding author Dr. Claudia M.B. Carvalho, assistant professor of molecular and human genetics at Baylor College of Medicine. ”This is an incredible example of what a fantastic benchtop experimental scientist and a terrific computational scientist can do when they put their intellects together and study the wonderful BigData generated by the Baylor College of Medicine Human Genome Sequencing Center,” said senior author Dr. Jim Lupski, Cullen Professor of Molecular and Human Genetics at Baylor, principal investigator at the Baylor Hopkins Center for Mendelian Genomics and faculty with the Baylor genetics and genomics graduate training program.
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.
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. Dr. Fritz Sedlazeck "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."
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… . Rachayata Dharmat 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.