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UFGI Publications Round-Up Week 10/17

Genomic Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit.

Author information: Azarian T1,2, Maraqa NF3,4, Cook RL1,2, Johnson JA2,5, Bailey C3, Wheeler S3, Nolan D2,5, Rathore MH3,4, Morris JG Jr2,6, Salemi M2,5.

1College of Public Health and Health Professions and College of Medicine, Department of Epidemiology, University of Florida, Gainesville, FL, United States of America.
2Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States of America.
3Infectious Diseases and Immunology, Wolfson Children’s Hospital, Jacksonville, FL, United States of America.
4University of Florida Center for HIV/AIDS Research, Education and Service, University of Florida, College of Medicine, Jacksonville, FL, United States of America.
5Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States of America.
6Division of Infectious Diseases, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, United States of America.

Journal: PLoS One

Date of e-pub: October 2016

Abstract: Despite infection prevention efforts, neonatal intensive care unit (NICU) patients remain at risk of Methicillin-resistant Staphylococcus aureus (MRSA) infection. Modes of transmission for healthcare-associated (HA) and community-associated (CA) MRSA remain poorly understood and may vary by genotype, hindering the development of effective prevention and control strategies. From 2008-2010, all patients admitted to a level III NICU were screened for MRSA colonization, and all available isolates were spa-typed. Spa-type t008, the most prevalent CA- genotype in the United States, spa-type t045, a HA- related genotype, and a convenience sample of strains isolated from 2003-2011, underwent whole-genome sequencing and phylodynamic analysis. Patient risk factors were compared between colonized and noncolonized infants, and virulence and resistance genes compared between spa-type t008 and non-t008 strains. Epidemiological and genomic data were used to estimate MRSA importations and acquisitions through transmission reconstruction. MRSA colonization was identified in 9.1% (177/1940) of hospitalized infants and associated with low gestational age and birth weight. Among colonized infants, low gestational age was more common among those colonized with t008 strains. Our data suggest that approximately 70% of colonizations were the result of transmission events within the NICU, with the remainder likely to reflect importations of “outside” strains. While risk of transmission within the NICU was not affected by spa-type, patterns of acquisition and importation differed between t008 and t045 strains. Phylodynamic analysis showed the effective population size of spa-type t008 has been exponentially increasing in both community and hospital, with spa-type t008 strains possessed virulence genes not found among t045 strains; t045 strains, in contrast, appeared to be of more recent origin, with a possible hospital source. Our data highlight the importance of both intra-NICU transmission and recurrent introductions in maintenance of MRSA colonization within the NICU environment, as well as spa-type-specific differences in epidemiology.

 

 

HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

Author information: Lamers SL1, Rose R1, Maidji E2, Agsalda-Garcia M3, Nolan DJ4, Fogel GB5, Salemi M6, Garcia DL7, Bracci P7, Yong W8, Commins D9, Said J8, Khanlou N8,Hinkin CH10, Sueiras MV11, Mathisen G12, Donovan S12, Shiramizu B3, Stoddart CA2, McGrath MS13, Singer EJ11.

1Bioinfoexperts, LLC, Thibodaux, Louisiana, USA.
2Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.
3The University of Hawaii, Department of Tropical Medicine, Medical Microbiology & Pharmacology and Hawaii Center for AIDS, Honolulu, Hawaii, USA.
4Bioinfoexperts, LLC, Thibodaux, Louisiana, USA The University of Florida Emerging Pathogens Institute, Department of Pathology and Laboratory Medicine, Gainesville, Florida, USA.
5Natural Selection, Inc., San Diego, California, USA.
6The University of Florida Emerging Pathogens Institute, Department of Pathology and Laboratory Medicine, Gainesville, Florida, USA.
7The AIDS and Cancer Specimen Resource, San Francisco, California, USA University of California, San Francisco, Department of Medicine, San Francisco, California, USA.
8National Neurological AIDS Bank, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA David Geffen School of Medicine and Olive View-UCLA Medical Center, Department of Pathology and Laboratory Medicine, Los Angeles, California, USA.
9University of Southern California Keck School of Medicine, Los Angeles, California, USA.
10National Neurological AIDS Bank, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA UCLA School of Medicine, Department of Psychiatry & Biobehavioral Sciences, Los Angeles, California, USA.
11National Neurological AIDS Bank, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA David Geffen School of Medicine and Olive View-UCLA Medical Center, Department of Neurology, Los Angeles, California, USA.
12National Neurological AIDS Bank, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
13The AIDS and Cancer Specimen Resource, San Francisco, California, USA University of California, San Francisco, Department of Medicine, San Francisco, California, USA MMcGrath@php.ucsf.edu.

Journal: Journal of Virology

Date of e-pub: September 2016

Abstract: HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis.

IMPORTANCE:

It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, “Where is HIV hiding?” A well-studied HIV reservoir is “resting” T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since <2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV(+) participants who died while on cART and identified that >50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants’ tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence.

 

 

HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

Author information: Rose R1, Lamers SL1, Nolan DJ2, Maidji E3, Faria NR4, Pybus OG4, Dollar JJ5, Maruniak SA5, McAvoy AC5, Salemi M5, Stoddart CA3, Singer EJ6, McGrath MS7.

1Bioinfoexperts, LLC, Thibodaux, Louisiana, USA.
2Bioinfoexperts, LLC, Thibodaux, Louisiana, USA Department of Pathology, Immunology and Laboratory Medicine and the Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
3Department of Medicine, University of California at San Francisco, San Francisco, California, USA.
4Department of Zoology, University of Oxford, Oxford, United Kingdom.
5Department of Pathology, Immunology and Laboratory Medicine and the Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
6National Neurological AIDS Bank, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
7The AIDS and Cancer Specimen Resource, University of California at San Francisco, San Francisco, California, USA Departments of Laboratory Medicine, Pathology, and Medicine, University of California at San Francisco, San Francisco, California, USA MMcGrath@php.ucsf.edu.

Journal: Journal of Virology

Date of e-pub: September 2016

Abstract: While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread.

IMPORTANCE:

Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV(+) cART(+) individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies.

 

 

Factors affecting the success of a large embryo transfer program in Holstein cattle in a commercial herd in the southeast region of the United States.

Author information: Ferraz PA1, Burnley C2, Karanja J3, Viera-Neto A4, Santos JE4, Chebel RC5, Galvão KN6.

1Escola de Medicina Veterinária, Universidade Federal da Bahia, Salvador, BA, Brazil.
2Southern Embryo, Athens, Georgia, USA.
3North Florida Holsteins, Bell, Florida, USA.
4Department of Animal Sciences, University of Florida, Gainesville, Florida, USA.
5Department of Animal Sciences, University of Florida, Gainesville, Florida, USA; Department of Large Animal Clinical Sciences, University of Florida, Gainesville, Florida, USA.
6Department of Large Animal Clinical Sciences, University of Florida, Gainesville, Florida, USA; D. H. Barron Reproductive and Perinatal Biology Research Program, University of Florida, Gainesville, Florida, USA. Electronic address: galvaok@ufl.edu.

Journal: Theriogenology

Date of e-pub: October 2016

Abstract: The objectives of this study were to evaluate factors affecting in vivo embryo production and pregnancy per embryo transfer (P/ET) in Holstein cattle in the southeast region of the United States. Data from a total of 516 embryo collections and 10,297 ETs performed from 2011 to 2014 were available. For embryo production, the effects of donor parity (nulliparous [N], primiparous [P], multiparous [M]), average temperature-humidity index (THI) at embryo collection, days in milk at embryo collection, occurrence of calving problems, and occurrence of metritis postpartum were evaluated. For P/ET, the effects of donor parity (N or parous), recipient parity (N, P, and M), embryo type (fresh, frozen, IVF, and IVF-frozen), embryo developmental stage (4-7), embryo quality (1-3), recipient estrous cycle day at ET (6-9), average THI at ET, days in milk at ET, milk yield at ET, occurrence of calving problems (abortion, dystocia, twins, fetal death, or retained placenta), and occurrence of metritis postpartum were evaluated. Pregnancy was diagnosed at 41 ± 3 days of gestation. Continuous and binary data were analyzed using the MIXED and GLIMMIX procedures of SAS, respectively. Parity affected embryo production; M had greater number and percentage of unfertilized embryos and lesser percentage of viable embryos than P and N. Recipient parity, embryo type, embryo stage, embryo quality, estrous cycle day at ET, and THI at ET affected P/ET. There was an interaction between recipient parity and THI at ET. P/ET was greater for N than P and greater for P than M, greater for fresh embryos than others, greater for stage 7 than others, greater for quality 1 than 2 and greater for quality 2 than 3, and greater for ET on estrous cycle Day 7 and 8 than 6. P/ET was decreased for THI ≥80 in N and THI ≥72 in P and M. Calving problems and metritis also affected P/ET in P and M and was lesser for cows that had calving problems and metritis. In conclusion, embryo production was affected by donor parity, and P/ET was affected by embryo type, embryo stage, embryo quality, recipient estrous cycle day at ET, THI, calving problems, and metritis.

 

 

The complex evolutionary history of big-eared horseshoe bats (Rhinolophus macrotis complex): insights from genetic, morphological and acoustic data.

Author information: Sun K1, Kimball RT2, Liu T1, Wei X1, Jin L1, Jiang T1, Lin A1, Feng J1.

1Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, Changchun, China.
2Department of Biology, University of Florida, Gainesville, Florida, United States of America.

Journal: Science Reports

Date of e-pub: October 2016

Abstract: Palaeoclimatic oscillations and different landscapes frequently result in complex population-level structure or the evolution of cryptic species. Elucidating the potential mechanisms is vital to understanding speciation events. However, such complex evolutionary patterns have rarely been reported in bats. In China, the Rhinolophus macrotis complex contains a large form and a small form, suggesting the existence of a cryptic bat species. Our field surveys found these two sibling species have a continuous and widespread distribution with partial sympatry. However, their evolutionary history has received little attention. Here, we used extensive sampling, morphological and acoustic data, as well as different genetic markers to investigate their evolutionary history. Genetic analyses revealed discordance between the mitochondrial and nuclear data. Mitochondrial data identified three reciprocally monophyletic lineages: one representing all small forms from Southwest China, and the other two containing all large forms from Central and Southeast China, respectively. The large form showed paraphyly with respect to the small form. However, clustering analyses of microsatellite and Chd1 gene sequences support two divergent clusters separating the large form and the small form. Moreover, morphological and acoustic analyses were consistent with nuclear data. This unusual pattern in the R. macrotis complex might be accounted for by palaeoclimatic oscillations, shared ancestral polymorphism and/or interspecific hybridization.

 

 

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

Author information: Jin Y1,2, Andersen G1, Yorgov D3, Ferrara TM1, Ben S1, Brownson KM1, Holland PJ1, Birlea SA1,4, Siebert J5, Hartmann A6, Lienert A6, van Geel N7, Lambert J7, Luiten RM8, Wolkerstorfer A8, Wietze van der Veen JP8,9, Bennett DC10, Taïeb A11, Ezzedine K11, Kemp EH12, Gawkrodger DJ12, Weetman AP12, Kõks S13, Prans E13, Kingo K14, Karelson M14, Wallace MR15, McCormack WT16, Overbeck A17, Moretti S18, Colucci R18, Picardo M19, Silverberg NB20,21, Olsson M22, Valle Y23, Korobko I23,24, Böhm M25, Lim HW26, Hamzavi I26, Zhou L26, Mi QS26, Fain PR1,2, Santorico SA1,3,27, Spritz RA1,2.

1Human Medical Genetics and Genomics Program, University of Colorado School of Medicine, Aurora, Colorado, USA.
2Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
3Department of Mathematical and Statistical Sciences, University of Colorado Denver, Denver, Colorado, USA.
4Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado, USA.
5CytoAnalytics, Denver, Colorado, USA.
6Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
7Department of Dermatology, Ghent University Hospital, Ghent, Belgium.
8Netherlands Institute for Pigment Disorders, Department of Dermatology, Academic Medical Centre University of Amsterdam, Amsterdam, the Netherlands.
9Department of Dermatology, Medical Centre Haaglanden, The Hague, the Netherlands.
10Molecular and Clinical Sciences Research Institute, St. George’s, University of London, London, UK.
11Centre de Référence des Maladies Rares de la Peau, Department of Dermatology, Hôpital St.-André, Bordeaux, France.
12Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
13Department of Pathophysiology, University of Tartu, Tartu, Estonia.
14Department of Dermatology, University of Tartu, Tartu, Estonia.
15Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA.
16Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
17Lumiderm, Madrid, Spain.
18Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
19Laboratorio Fisiopatologia Cutanea, Istituto Dermatologico San Gallicano, Rome, Italy.
20Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
21Pediatric and Adolescent Dermatology, St. Luke’s-Roosevelt Hospital Center, New York, New York, USA.
22International Vitiligo Center, Uppsala, Sweden.
23Vitiligo Research Foundation, New York, New York, USA.
24Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
25Department of Dermatology, University of Münster, Münster, Germany.
26Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA.
27Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.

Journal: Nature Genetics

Date of e-pub: October 2016

Abstract: Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine 

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