Project description:Blood samples from patients with myeloid malignancies were analyzed using whole exome sequencing (WES). Data set from genotyping by microarray of the same samples has been deposited in ArrayExpress under accession number E-MTAB-1845 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1845/).
Project description:Single Gland Whole-exome sequencing: building on our prior description of multi-region WES of colorectal tumors and targeted single gland sequencing (E-MTAB-2247), we performed WES of multiple single glands from different sides (right: A and left: B) of two tumors in this study (tumor O and U) on the illumina platform using the Agilent SureSelect 2.0 or illumina Nextera Rapid Capture Exome kit (SureSelect or NRCE, as indicated in the naming of fastq files). Colorectal Cancer Xenograft Whole-exome sequencing: The HCT116 and LoVo Mismatch-Repair-deficient colorectal adenocarcinoma cell lines were obtained from the ATCC and cultured under standard conditions. For both cell lines, a single âfoundingâ cell was cloned and expanded in vitro to ~6M cells. Two aliquots of ~1M cells were subcutaneously injected into opposite flanks (right and left) of a nude mouse and tumors allowed to reach a size of ~1B cells (1cm3) before the animal was sacrificed. Tumor tissue was collected separately from the right and left lesions and DNA was extracted for WES using the illumina TruSeq Exome kit or Nextera Rapid Capture Exome expanded Kits (Truseq or NRCEe), as was DNA from the first passage population (a polyclonal tissue culture for HCT116 and a polyclonal xenograft sample for LoVo), which were employed as a control to study mutation accumulation in culture and post xenotransplantation.
Project description:Whole exome sequencing (the SureSelectXT Mouse All Exon Kit) was done on leukemias from NP23-NHD13 double transgenic mice with strain background designated “C57Bl6-NIH”.
Project description:Canine tachycardia-induced cardiomyopathy caused by several weeks of rapid ventricular pacing is a well-established animal model of congestive heart failure. However, little is known about the underlying changes in gene expression that occur in the canine myocardium after the induction of heart failure. This project aims to compare expression profiles in left ventricular free wall samples from control dogs and dogs with pacing-induced heart failure on the custom MuscleChip. Keywords: other
Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
Project description:The inherent diversity of canines is closely intertwined with the unique color patterns of each dog population. These variations in color patterns are believed to have originated through mutations and selective breeding practices that occurred during and after the domestication of dogs from wolves. To address the significant gaps that persist in comprehending the evolutionary processes that underlie the development of these patterns, we generated and analyzed deep-sequenced genomes of 113 Korean indigenous Jindo dogs that represent five distinct color patterns to identify the associated mutations in CBD103, ASIP, and MC1R. The degree of linkage disequilibrium and estimated allelic ages consistently indicate that the black-and-tan dogs descend from the first major founding population on Jindo island, compatible with the documented literature. We additionally demonstrate that black-and-tan dogs, in contrast to other color variations within the breed, exhibit a closer genetic affinity to ancient wolves from western Eurasia than those from eastern Eurasia. Lastly, population-specific genetic variants with moderate effects were identified, particularly in loci associated with traits underlying body size and behavioral variations, potentially explaining the observed phenotypic diversity based on coat colors. Overall, comparisons of whole genome sequences of each coat color population diverged from the same breed provided an unprecedented glimpse into the properties of evolutionary processes maintaining variation in Korean Jindo dog populations that were previously inaccessible.