Visit the Genetics & Genomics Graduate Program Homepage
Comments are off

UFGI Publications Round-Up Week 7/18/2016

Genome-wide association mapping and pathway analysis of leukosis incidence in a US Holstein cattle population.

Author information: Abdalla EA1,2, Peñagaricano F3,4, Byrem TM5, Weigel KA6, Rosa GJ1,7.
1Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53705, USA.
2Department of Animal Science, University of Benghazi, Benghazi, 21861, Libya.
3Department of Animal Sciences, University of Florida, Gainesville, FL, 32611, USA.
4University of Florida Genetics Institute, University of Florida, Gainesville, FL, 32611, USA.
5Antel BioSystems, Inc., Lansing, MI, 48910, USA.
6Department of Dairy Science, University of Wisconsin-Madison, Madison, WI, 53706, USA.
7Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Journal: Animal Genetics

Date of e-pub: April 19, 2016

Abstract: Bovine leukosis virus is an oncogenic virus that infects B cells, causing bovine leukosis disease. This disease is known to have a negative impact on dairy cattle production and, because no treatment or vaccine is available, finding a possible genetic solution is important. Our objective was to perform a comprehensive genetic analysis of leukosis incidence in dairy cattle. Data on leukosis occurrence, pedigree and molecular information were combined into multitrait GBLUP models with milk yield (MY) and somatic cell score (SCS) to estimate genetic parameters and to perform whole-genome scans and pathway analysis. Leukosis data were available for 11 554 Holsteins daughters of 3002 sires from 112 herds in 16 US states. Genotypes from a 60K SNP panel were available for 961 of those bulls as well as for 2039 additional bulls. Heritability for leukosis incidence was estimated at about 8%, and the genetic correlations of leukosis disease incidence with MY and SCS were moderate at 0.18 and 0.20 respectively. The genome-wide scan indicated that leukosis is a complex trait, possibly modulated by many genes. The gene set analysis identified many functional terms that showed significant enrichment of genes associated with leukosis. Many of these terms, such as G-Protein Coupled Receptor Signaling Pathway, Regulation of Nucleotide Metabolic Process and different calcium-related processes, are known to be related to retrovirus infection. Overall, our findings contribute to a better understanding of the genetic architecture of this complex disease. The functional categories associated with leukosis may be useful in future studies on fine mapping of genes and development of dairy cattle breeding strategies.


On the widespread capacity for, and functional significance of, extreme inbreeding in ferns.

Author information: Sessa EB1, Testo WL2, Watkins JE Jr3.
1Department of Biology, University of Florida, Box 118525, Gainesville, FL 32611, USA.
2Department of Plant Biology, University of Vermont, 111 Jeffords Hall, 63 Carrigan Drive, Burlington, VT, 05405, USA.
3Biology Department, Colgate University, 129 Ho Science Center, 13 Oak Drive, Hamilton, NY, 13346, USA.

Journal: The New Phytologist

Date of e-pub: April 20, 2016

Abstract: Homosporous vascular plants utilize three different mating systems, one of which, gametophytic selfing, is an extreme form of inbreeding only possible in homosporous groups. This mating system results in complete homozygosity in all progeny and has important evolutionary and ecological implications. Ferns are the largest group of homosporous land plants, and the significance of extreme inbreeding for fern evolution has been a subject of debate for decades. We cultured gametophytes in the laboratory and quantified the relative frequencies of sporophyte production from isolated and paired gametophytes, and examined associations between breeding systems and several ecological and evolutionary traits. The majority of fern species studied show a capacity for gametophytic selfing, producing sporophytes from both isolated and paired gametophytes. While we did not follow sporophytes to maturity to investigate potential detrimental effects of homozygosity at later developmental stages, our results suggest that gametophytic selfing may have greater significance for fern evolution and diversification than has previously been realized. We present evidence from the largest study of mating behavior in ferns to date that the capacity for extreme inbreeding is prevalent in this lineage, and we discuss its implications and relevance and make recommendations for future studies of fern mating systems.


A social-ecological systems approach for environmental management.

Author information: Virapongse A1, Brooks S2, Metcalf EC3, Zedalis M4, Gosz J5, Kliskey A6, Alessa L7.
1Center for Resilient Communities, University of Idaho, Moscow, ID 83844, USA; Tropical Conservation and Development, Center for Latin American Studies, University of Florida, Gainesville, FL 32611, USA. Electronic address:
2Madison River Group LLC, Ashburn, VA 20148, USA.
3College of Forestry and Conservation, University of Montana, Missoula, MT 59182, USA.
4Heritage Program, Payette National Forest, United States Forest Service, McCall, ID 83638, USA.
5Department of Forest, Rangeland, and Fire Science, University of Idaho, Moscow, ID 83844, USA.
6Center for Resilient Communities, University of Idaho, Moscow, ID 83844, USA.
7Center for Resilient Communities, University of Idaho, Moscow, ID 83844, USA; International Arctic Research Center, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.

Journal: Journal of Environmental Management

Date of e-pub: April 28, 2016

Abstract: Urgent environmental issues are testing the limits of current management approaches and pushing demand for innovative approaches that integrate across traditional disciplinary boundaries. Practitioners, scholars, and policy-makers alike call for increased integration of natural and social sciences to develop new approaches that address the range of ecological and societal impacts of modern environmental issues. From a theoretical perspective, social-ecological systems (SES) science offers a compelling approach for improved environmental management through the application of transdisciplinary and resilience concepts. A framework for translating SES theory into practice, however, is lacking. In this paper, we define the key components of an SES-based environmental management approach. We offer recommendations for integrating an SES approach into existing environmental management practices. Results presented are useful for management professionals that seek to employ an SES environmental management approach and scholars aiming to advance the theoretical foundations of SES science for practical application.


Assignment of function to a domain of unknown function: DUF1537 is a new kinase family in catabolic pathways for acid sugars.

Faculty author: Zhang X1, Carter MS1, Vetting MW2, San Francisco B1, Zhao S3, Al-Obaidi NF2, Solbiati JO1, Thiaville JJ4, de Crécy-Lagard V4, Jacobson MP3, Almo SC2,Gerlt JA5.
1Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
2Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461;
3Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158;
4Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611;
5Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801

Journal: Proceedings of the National Academy of Sciences

Date of e-pub: July 11, 2016

Abstract: Using a large-scale “genomic enzymology” approach, we (i) assigned novel ATP-dependent four-carbon acid sugar kinase functions to members of the DUF1537 protein family (domain of unknown function; Pfam families PF07005 and PF17042) and (ii) discovered novel catabolic pathways for d-threonate, l-threonate, and d-erythronate. The experimentally determined ligand specificities of several solute binding proteins (SBPs) for TRAP (tripartite ATP-independent permease) transporters for four-carbon acids, including d-erythronate and l-erythronate, were used to constrain the substrates for the catabolic pathways that degrade the SBP ligands to intermediates in central carbon metabolism. Sequence similarity networks and genome neighborhood networks were used to identify the enzyme components of the pathways. Conserved genome neighborhoods encoded SBPs as well as permease components of the TRAP transporters, members of the DUF1537 family, and a member of the 4-hydroxy-l-threonine 4-phosphate dehydrogenase (PdxA) oxidative decarboxylase, class II aldolase, or ribulose 1,5-bisphosphate carboxylase/oxygenase, large subunit (RuBisCO) superfamily. Because the characterized substrates of members of the PdxA, class II aldolase, and RuBisCO superfamilies are phosphorylated, we postulated that the members of the DUF1537 family are novel ATP-dependent kinases that participate in catabolic pathways for four-carbon acid sugars. We determined that (i) the DUF1537/PdxA pair participates in a pathway for the conversion of d-threonate to dihydroxyacetone phosphate and CO2 and (ii) the DUF1537/class II aldolase pair participates in pathways for the conversion of d-erythronate and l-threonate (epimers at carbon-3) to dihydroxyacetone phosphate and CO2 The physiological importance of these pathways was demonstrated in vivo by phenotypic and genetic analyses.


Patterns of abiotic niche shifts in allopolyploids relative to their progenitors.

Author information: Blaine Marchant D1,2, Soltis DE1,2,3, Soltis PS2,3.
1Department of Biology, University of Florida, Gainesville, FL, 32611, USA.
2Florida Museum of Natural History, Gainesville, FL, 32611, USA.
3Genetics Institute, University of Florida, Gainesville, FL, 32611, USA.

Journal: The New Phytologist

Date of e-pub: July 11, 2016

Abstract: Polyploidy has extensive genetic, physiological, morphological, and ecological ramifications. While the patterns underlying the genetic and morphological consequences of polyploidy are being rapidly elucidated, the effects on ecological niche are still largely unknown. This study investigated 13 allopolyploid systems in North America (10 ferns and three angiosperms) using digitized natural history museum specimens. The abiotic niches of the allopolyploids were compared with those of their diploid progenitors using ecological niche modeling, niche analyses, and multivariate analyses. We identified four patterns of niche shifts through our analyses: niche expansion, niche contraction, niche intermediacy, and niche novelty. The classification of these shifts depended on the amount of niche overlap and breadth between the polyploid and progenitors. The most common niche shift was niche intermediacy in which the polyploid inhabited a geographic range between that of the progenitors and had a high degree of niche overlap. Each polyploid had at least partial geographic sympatry and abiotic niche overlap with one of its progenitors, suggesting that biotic and/or microclimate factors may play a larger role in polyploid establishment than previously hypothesized. This study provides a baseline for future comparisons of the diverse outcomes of genome merger and duplication on abiotic niche preference.


An external validation of models to predict the onset of chronic kidney disease using population-based electronic health records from Salford, UK.

Author information: Fraccaro P1,2,3, van der Veer S2,3, Brown B1,2,3, Prosperi M2,3,4, O’Donoghue D5, Collins GS6, Buchan I1,2,3, Peek N7,8,9.
1NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre, Institute of Population Health, The University of Manchester, Manchester, UK.
2Health eResearch Centre, Farr Institute for Health Informatics Research, Manchester, UK.
3Centre for Health Informatics, Institute of Population Health, The University of Manchester, Vaughan House, Portsmouth St, Manchester, M13 9GB, UK.
4Department of Epidemiology, University of Florida, Gainesville, FL, USA.
5Renal Clinic, Salford Royal NHS Trust, Salford, UK.
6Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK.
7NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre, Institute of Population Health, The University of Manchester, Manchester, UK.
8Health eResearch Centre, Farr Institute for Health Informatics Research, Manchester, UK.
9Centre for Health Informatics, Institute of Population Health, The University of Manchester, Vaughan House, Portsmouth St, Manchester, M13 9GB, UK.

Journal: BioMed Central: Medicine

Date of e-pub: July 12, 2016

Abstract: Chronic kidney disease (CKD) is a major and increasing constituent of disease burdens worldwide. Early identification of patients at increased risk of developing CKD can guide interventions to slow disease progression, initiate timely referral to appropriate kidney care services, and support targeting of care resources. Risk prediction models can extend laboratory-based CKD screening to earlier stages of disease; however, to date, only a few of them have been externally validated or directly compared outside development populations. Our objective was to validate published CKD prediction models applicable in primary care.
We synthesised two recent systematic reviews of CKD risk prediction models and externally validated selected models for a 5-year horizon of disease onset. We used linked, anonymised, structured (coded) primary and secondary care data from patients resident in Salford (population ~234 k), UK. All adult patients with at least one record in 2009 were followed-up until the end of 2014, death, or CKD onset (n = 178,399). CKD onset was defined as repeated impaired eGFR measures over a period of at least 3 months, or physician diagnosis of CKD Stage 3-5. For each model, we assessed discrimination, calibration, and decision curve analysis.
Seven relevant CKD risk prediction models were identified. Five models also had an associated simplified scoring system. All models discriminated well between patients developing CKD or not, with c-statistics around 0.90. Most of the models were poorly calibrated to our population, substantially over-predicting risk. The two models that did not require recalibration were also the ones that had the best performance in the decision curve analysis.
Included CKD prediction models showed good discriminative ability but over-predicted the actual 5-year CKD risk in English primary care patients. QKidney, the only UK-developed model, outperformed the others. Clinical prediction models should be (re)calibrated for their intended uses.


Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study.

Author information: Langballe R1, Mellemkjær L2, Malone KE3, Lynch CF4, John EM5,6, Knight JA7,8, Bernstein L9, Brooks J8, Andersson M10, Reiner AS11, Liang X11, Woods M11, Concannon PJ12; WECARE Study Collaborative Group, Bernstein JL11.
1Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
2Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
3Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4University of Iowa, Iowa City, IA, USA.
5Cancer Prevention Institute of California, Fremont, CA, USA.
6Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
7Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
8University of Toronto, Dalla Lana School of Public Health, Toronto, Canada.
9Beckman Research Institute of the City of Hope, Duarte, CA, USA.
10Department of Oncology at Rigshospitalet, Copenhagen, Denmark.
11Memorial Sloan Kettering Cancer Center, New York, NY, USA.
12University of Florida Genetics Institute, Gainesville, FL, USA.

Journal: Breast Cancer Research

Date of e-pub: July 12, 2016

Abstract: Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics.
The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models.
Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53-1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1-4 years (RR = 0.59; 95 % CI = 0.45-0.77) and 5-9 years (RR = 0.73; 95 % CI = 0.56-0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies.
Our findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed.

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 

About the Author