Browsing by Author "Omer, Arina"

Now showing 1 - 4 of 4
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    Chromatin alternates between A and B compartments at kilobase scale for subgenic organization
    (Springer Nature, 2023) Harris, Hannah L.; Gu, Huiya; Olshansky, Moshe; Wang, Ailun; Farabella, Irene; Eliaz, Yossi; Kalluchi, Achyuth; Krishna, Akshay; Jacobs, Mozes; Cauer, Gesine; Pham, Melanie; Rao, Suhas S. P.; Dudchenko, Olga; Omer, Arina; Mohajeri, Kiana; Kim, Sungjae; Nichols, Michael H.; Davis, Eric S.; Gkountaroulis, Dimos; Udupa, Devika; Aiden, Aviva Presser; Corces, Victor G.; Phanstiel, Douglas H.; Noble, William Stafford; Nir, Guy; Di Pierro, Michele; Seo, Jeong-Sun; Talkowski, Michael E.; Aiden, Erez Lieberman; Rowley, M. Jordan; Center for Theoretical Biological Physics
    Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all active promoters and distal enhancers localize in the A compartment, even when flanking sequences do not. Furthermore, we find that the TSS and TTS of paused genes are often segregated into separate compartments. We then identify diffuse interactions that radiate from CTCF loop anchors, which correlate with strong enhancer-promoter interactions and proximal transcription. We also find that these diffuse interactions depend on CTCF’s RNA binding domains. In this work, we demonstrate features of fine-scale chromatin organization consistent with a revised model in which compartments are more precise than commonly thought while CTCF loops are more protracted.
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    Chromosome-length genome assembly and structural variations of the primal Basenji dog (Canis lupus familiaris) genome
    (Springer Nature, 2021) Edwards, Richard J.; Field, Matt A.; Ferguson, James M.; Dudchenko, Olga; Keilwagen, Jens; Rosen, Benjamin D.; Johnson, Gary S.; Rice, Edward S.; Hillier, La Deanna; Hammond, Jillian M.; Towarnicki, Samuel G.; Omer, Arina; Khan, Ruqayya; Skvortsova, Ksenia; Bogdanovic, Ozren; Zammit, Robert A.; Aiden, Erez Lieberman; Warren, Wesley C.; Ballard, J. William O.; Center for Theoretical and Biological Physics
    Basenjis are considered an ancient dog breed of central African origins that still live and hunt with tribesmen in the African Congo. Nicknamed the barkless dog, Basenjis possess unique phylogeny, geographical origins and traits, making their genome structure of great interest. The increasing number of available canid reference genomes allows us to examine the impact the choice of reference genome makes with regard to reference genome quality and breed relatedness.
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    The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology
    (Oxford University Press, 2023) Ballard, J. William O.; Field, Matt A.; Edwards, Richard J.; Wilson, Laura A.B.; Koungoulos, Loukas G.; Rosen, Benjamin D.; Chernoff, Barry; Dudchenko, Olga; Omer, Arina; Keilwagen, Jens; Skvortsova, Ksenia; Bogdanovic, Ozren; Chan, Eva; Zammit, Robert; Hayes, Vanessa; Aiden, Erez Lieberman; Center for Theoretical and Biological Physics
    One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed.We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog.These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney.
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    The Australian dingo is an early offshoot of modern breed dogs
    (AAAS, 2022) Field, Matt A.; Yadav, Sonu; Dudchenko, Olga; Esvaran, Meera; Rosen, Benjamin D.; Skvortsova, Ksenia; Edwards, Richard J.; Keilwagen, Jens; Cochran, Blake J.; Manandhar, Bikash; Bustamante, Sonia; Rasmussen, Jacob Agerbo; Melvin, Richard G.; Chernoff, Barry; Omer, Arina; Colaric, Zane; Chan, Eva K. F.; Minoche, Andre E.; Smith, Timothy P. L.; Gilbert, M. Thomas P.; Bogdanovic, Ozren; Zammit, Robert A.; Thomas, Torsten; Aiden, Erez L.; Ballard, J. William O.; Center for Theoretical Biological Physics
    Dogs are uniquely associated with human dispersal and bring transformational insight into the domestication process. Dingoes represent an intriguing case within canine evolution being geographically isolated for thousands of years. Here, we present a high-quality de novo assembly of a pure dingo (CanFam_DDS). We identified large chromosomal differences relative to the current dog reference (CanFam3.1) and confirmed no expanded pancreatic amylase gene as found in breed dogs. Phylogenetic analyses using variant pairwise matrices show that the dingo is distinct from five breed dogs with 100% bootstrap support when using Greenland wolf as the outgroup. Functionally, we observe differences in methylation patterns between the dingo and German shepherd dog genomes and differences in serum biochemistry and microbiome makeup. Our results suggest that distinct demographic and environmental conditions have shaped the dingo genome. In contrast, artificial human selection has likely shaped the genomes of domestic breed dogs after divergence from the dingo.