Paul Brennan

Summary

Affiliation: Cardiff University
Country: UK

Publications

  1. ncbi request reprint Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells
    Paul Brennan
    Section of Infection and Immunity, Tenovus Building, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XX Wales, UK
    Oncogene 21:1263-71. 2002
  2. doi request reprint STAT1 contributes to the maintenance of the latency III viral programme observed in Epstein-Barr virus-transformed B cells and their recognition by CD8+ T cells
    James E McLaren
    Department of Medical Biochemistry, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    J Gen Virol 90:2239-50. 2009
  3. pmc Latent membrane protein 1 inhibits Epstein-Barr virus lytic cycle induction and progress via different mechanisms
    Stuart Prince
    Section of Infection and Immunity, University of Wales College of Medicine, Cardiff CF14 4XX, United Kingdom
    J Virol 77:5000-7. 2003
  4. pmc Co-operative membrane disruption between cell-penetrating peptide and cargo: implications for the therapeutic use of the Bcl-2 converter peptide D-NuBCP-9-r8
    Catherine L Watkins
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Mol Ther 19:2124-32. 2011
  5. pmc Genetic modification of primary chronic lymphocytic leukemia cells with a lentivirus expressing CD38
    Laurence Pearce
    Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK
    Haematologica 95:514-7. 2010
  6. pmc Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant
    Stefan Siebert
    Section of Infection and Immunity, Wales College of Medicine, Cardiff University, Cardiff, UK
    Arthritis Rheum 52:1287-92. 2005
  7. ncbi request reprint Epstein-Barr virus induces a distinct form of DNA-bound STAT1 compared with that found in interferon-stimulated B lymphocytes
    James McLaren
    Department of Medical Biochemistry and Immunology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    J Gen Virol 88:1876-86. 2007
  8. doi request reprint Quantitative nuclear proteomics reveals new phenotypes altered in lymphoblastoid cells
    Paul Brennan
    Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
    Proteomics Clin Appl 3:359-69. 2009
  9. doi request reprint Proteomics-based strategies to identify proteins relevant to chronic lymphocytic leukemia
    Suliman A Alsagaby
    Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom
    J Proteome Res 13:5051-62. 2014
  10. doi request reprint Development and characterization of a physiologically relevant model of lymphocyte migration in chronic lymphocytic leukemia
    Elisabeth Walsby
    Cardiff Chronic Lymphocytic Leukemia Research Group, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom
    Blood 123:3607-17. 2014

Collaborators

Detail Information

Publications48

  1. ncbi request reprint Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells
    Paul Brennan
    Section of Infection and Immunity, Tenovus Building, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XX Wales, UK
    Oncogene 21:1263-71. 2002
    ..These data describe a mechanism by which PI3K plays a role in B-lymphocyte growth and suggests that a pathway from PI3K to D-type cyclin expression may provide diagnostic or treatment opportunities...
  2. doi request reprint STAT1 contributes to the maintenance of the latency III viral programme observed in Epstein-Barr virus-transformed B cells and their recognition by CD8+ T cells
    James E McLaren
    Department of Medical Biochemistry, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    J Gen Virol 90:2239-50. 2009
    ..These results suggest that STAT1 is involved in maintaining the latency III viral program observed in transformed B cells and regulating immunorecognition by EBV-specific T cells...
  3. pmc Latent membrane protein 1 inhibits Epstein-Barr virus lytic cycle induction and progress via different mechanisms
    Stuart Prince
    Section of Infection and Immunity, University of Wales College of Medicine, Cardiff CF14 4XX, United Kingdom
    J Virol 77:5000-7. 2003
    ..These findings indicate that in B cells EBV self-limits its lytic cycle via three distinct LMP1-mediated mechanisms...
  4. pmc Co-operative membrane disruption between cell-penetrating peptide and cargo: implications for the therapeutic use of the Bcl-2 converter peptide D-NuBCP-9-r8
    Catherine L Watkins
    Welsh School of Pharmacy, Cardiff University, Cardiff, UK
    Mol Ther 19:2124-32. 2011
    ..For delivery of therapeutic peptides the work emphasizes that key amino acids in cargo, located several residues away from the cell-penetrating sequence, can significantly influence their cellular uptake and mode of action...
  5. pmc Genetic modification of primary chronic lymphocytic leukemia cells with a lentivirus expressing CD38
    Laurence Pearce
    Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK
    Haematologica 95:514-7. 2010
    ..This high level of transduction of all the CLL cell samples tested demonstrates the utility of this technique which should prove applicable for the introduction and analysis of other genes in these non-dividing cells...
  6. pmc Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant
    Stefan Siebert
    Section of Infection and Immunity, Wales College of Medicine, Cardiff University, Cardiff, UK
    Arthritis Rheum 52:1287-92. 2005
    ....
  7. ncbi request reprint Epstein-Barr virus induces a distinct form of DNA-bound STAT1 compared with that found in interferon-stimulated B lymphocytes
    James McLaren
    Department of Medical Biochemistry and Immunology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    J Gen Virol 88:1876-86. 2007
    ..STAT1 is serine-phosphorylated downstream of PI3K and MEK in LCLs and this modification restricts IFN-stimulated STAT1-DNA binding. These data suggest that EBV induces a distinct form of DNA-bound STAT1 in virus-infected cells...
  8. doi request reprint Quantitative nuclear proteomics reveals new phenotypes altered in lymphoblastoid cells
    Paul Brennan
    Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
    Proteomics Clin Appl 3:359-69. 2009
    ..Importantly, we have also identified new regulators of transcription and changes in ribonuclear proteins that may contribute to the increased cell size and immortalisation of lymphoblastoid cells. ..
  9. doi request reprint Proteomics-based strategies to identify proteins relevant to chronic lymphocytic leukemia
    Suliman A Alsagaby
    Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom
    J Proteome Res 13:5051-62. 2014
    ..Myosin-9 exhibited reduced expression in CLL samples from high-risk patients. This study shows the usefulness of proteomic approaches, combined with transcriptomics, to identify disease-related proteins. ..
  10. doi request reprint Development and characterization of a physiologically relevant model of lymphocyte migration in chronic lymphocytic leukemia
    Elisabeth Walsby
    Cardiff Chronic Lymphocytic Leukemia Research Group, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom
    Blood 123:3607-17. 2014
    ..01). Taken together, our data provide evidence for a novel, dynamic, and tractable in vitro model of lymphocyte migration and confirm that CD49d is a critical regulator of this process in CLL. ..
  11. ncbi request reprint Susceptibility of B lymphocytes to adenovirus type 5 infection is dependent upon both coxsackie-adenovirus receptor and alphavbeta5 integrin expression
    Ciaran Richardson
    Infection and Immunity, Henry Wellcome Research Building, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    J Gen Virol 86:1669-79. 2005
    ..The work identified a strategy for engineering B cells to become susceptible to adenovirus infection and showed that such a strategy could be useful for the introduction of genes to alter lymphoblastoid-cell gene expression...
  12. doi request reprint Defining the prognosis of early stage chronic lymphocytic leukaemia patients
    Chris Pepper
    School of Medicine, Cardiff University, Cardiff, UK
    Br J Haematol 156:499-507. 2012
    ..ZAP-70 expression and FISH were not independent prognostic markers in early stage disease and can be omitted at diagnosis but FISH analysis should be undertaken at disease progression to direct treatment strategy...
  13. doi request reprint Cellular uptake, distribution and cytotoxicity of the hydrophobic cell penetrating peptide sequence PFVYLI linked to the proapoptotic domain peptide PAD
    Catherine L Watkins
    Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3NB Wales, UK
    J Control Release 140:237-44. 2009
    ..Primary human leukaemia cells were more similar to KG1a cells than HeLa cells, suggesting the relative sensitivity of leukaemia cells to these peptides could be exploited in vivo...
  14. doi request reprint NF-kappaB as a prognostic marker and therapeutic target in chronic lymphocytic leukemia
    Chris Pepper
    School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK
    Future Oncol 5:1027-37. 2009
    ....
  15. doi request reprint Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers
    Chris Pepper
    Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom
    Blood 112:3807-17. 2008
    ..The close correlation between Mcl-1 expression and V(H) gene mutation status, CD38 expression, and ZAP-70 expression offers a biologic explanation for their association with adverse prognosis...
  16. doi request reprint The novel nuclear factor-kappaB inhibitor LC-1 is equipotent in poor prognostic subsets of chronic lymphocytic leukemia and shows strong synergy with fludarabine
    Saman Hewamana
    Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom
    Clin Cancer Res 14:8102-11. 2008
    ..Here we elucidated the mechanism of action of LC-1, evaluated its relative cytotoxicity in prognostic subsets, and investigated its potential synergistic interaction with fludarabine...
  17. pmc A novel Cdk9 inhibitor preferentially targets tumor cells and synergizes with fludarabine
    Elisabeth Walsby
    Cardiff CLL Research Group, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
    Oncotarget 5:375-85. 2014
    ..Our data present a strong rationale for the development of cdk9 inhibitors such as CDKI-73 as anticancer therapeutics. ..
  18. doi request reprint Targeting transcription factors for therapeutic benefit
    Paul Brennan
    Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK
    Mol Biosyst 4:909-19. 2008
    ..This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of cancer...
  19. ncbi request reprint Analysis of human tumour necrosis factor receptor 1 dominant-negative mutants reveals a major region controlling cell surface expression
    Ceri A Fielding
    Infection and Immunity, University of Wales College of Medicine, Henry Wellcome Research Institute, Heath Park, Cardiff CF14 4XX, UK
    FEBS Lett 570:138-42. 2004
    ..The increased dominant-negative activity correlates with increased cell surface expression. The membrane proximal region is the most important region of the receptor for restricting expression...
  20. doi request reprint Rel a is an independent biomarker of clinical outcome in chronic lymphocytic leukemia
    Saman Hewamana
    Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom
    J Clin Oncol 27:763-9. 2009
    ..We recently demonstrated the biologic importance of the nuclear factor kappa B (NF-kappaB) subunit Rel A in chronic lymphocytic leukemia (CLL) and hypothesized that Rel A DNA binding would have prognostic significance in this disease...
  21. doi request reprint Gene and protein responses of human lung tissue explants exposed to ambient particulate matter of different sizes
    Bastiaan Hoogendoorn
    Department of Primary Care and Public Health, Neuadd Meirionnydd, School of Medicine, Heath Park, Cardiff, UK
    Inhal Toxicol 24:966-75. 2012
    ..It is necessary to understand causal pathways driving the observed health effects, particularly if they are differentially associated with particle size...
  22. pmc Epstein-Barr virus regulates STAT1 through latent membrane protein 1
    Ciaran Richardson
    Infection and Immunity, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom
    J Virol 77:4439-43. 2003
    ..The increase in STAT1 expression is mediated by the C-terminal activating region 1 (CTAR-1) and/or CTAR-2 domains of LMP-1 and is inhibited by mutant IkappaB, demonstrating a role for NFkappaB in LMP-1-mediated STAT1 expression...
  23. doi request reprint Bicarbonate-dependent serine/threonine protein dephosphorylation in capacitating boar spermatozoa
    Fahima A Alnagar
    Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK
    J Androl 31:393-405. 2010
    ..Together, this provides direct evidence for more complex S/T phosphorylation dynamics than has been previously described for sperm undergoing capacitation...
  24. pmc Proliferation and interleukin 5 production by CD8hi CD57+ T cells
    Lee K Chong
    Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK
    Eur J Immunol 38:995-1000. 2008
    ....
  25. pmc Impaired lymphoid chemokine-mediated migration due to a block on the chemokine receptor switch in human cytomegalovirus-infected dendritic cells
    Magdalena Moutaftsi
    Section of Infection and Immunity Department of Medicine, University of Wales College of Medicine, Cardiff, United Kingdom
    J Virol 78:3046-54. 2004
    ....
  26. pmc Epstein-Barr virus represses the FoxO1 transcription factor through latent membrane protein 1 and latent membrane protein 2A
    Angharad M Shore
    Medical Biochemistry and Immunology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, United Kingdom
    J Virol 80:11191-9. 2006
    ..Expression of the EBV genes for latent membrane protein 1 and latent membrane protein 2A decreases FoxO1 expression. Thus, our data elucidate distinct mechanisms for the regulation of the proapoptotic transcription factor FoxO1 by EBV...
  27. pmc Epstein-Barr virus LMP1 blocks p16INK4a-RB pathway by promoting nuclear export of E2F4/5
    Naoko Ohtani
    Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK
    J Cell Biol 162:173-83. 2003
    ..These results reveal a novel activity of LMP1 and increase an understanding of how viral oncoproteins perturb the p16INK4a-RB pathway...
  28. pmc LY294002 and rapamycin co-operate to inhibit T-cell proliferation
    Elaine M Breslin
    Infection and Immunity, Wales College of Medicine, Cardiff University, Henry Wellcome Research Building, Heath Park, Cardiff CF14 XX
    Br J Pharmacol 144:791-800. 2005
    ..4. These data indicate that PI3K regulates T-cell proliferation in response to diverse stimuli, and suggest that combinations of inhibitors, perhaps isoform-selective, may be useful as alternative immunosuppressive therapies...
  29. ncbi request reprint Meta- and pooled analyses of GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes and risk of head and neck cancer
    Mia Hashibe
    International Agency for Research on Cancer, Lyon, France
    Cancer Epidemiol Biomarkers Prev 12:1509-17. 2003
    ....
  30. ncbi request reprint Statin use and risk of lymphoid neoplasms: results from the European Case-Control Study EPILYMPH
    Joan Fortuny
    Servei d Epidemiologia i Registre del Cancer, Institut Catala d Oncologia, Gran Via Km 2 7, 08907 L Hospitalet de Llobregat, Autonomous University of Barcelona corrected Barcelona, Catalonia, Spain
    Cancer Epidemiol Biomarkers Prev 15:921-5. 2006
    ..Statins, drugs used to treat dyslipidemia, may have anticancer properties. We have evaluated lymphoma risk associated with regular statin use in an international case-control study...
  31. ncbi request reprint Dose-specific meta-analysis and sensitivity analysis of the relation between alcohol consumption and lung cancer risk
    Jeffrey E Korte
    Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, Lyon, France
    Am J Epidemiol 155:496-506. 2002
    ..At lower levels, any associations observed appear to be explained by confounding...
  32. ncbi request reprint Second primary cancers in thyroid cancer patients: a multinational record linkage study
    Thekkepat C Sandeep
    Metabolic Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
    J Clin Endocrinol Metab 91:1819-25. 2006
    ..Thyroid cancer can also arise as a second primary neoplasm after other cancers...
  33. ncbi request reprint Risk of second cancer among women with breast cancer
    Lene Mellemkjaer
    Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
    Int J Cancer 118:2285-92. 2006
    ....
  34. ncbi request reprint Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review
    Rayjean J Hung
    Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France
    Am J Epidemiol 162:925-42. 2005
    ..Recommendations for future studies include pooling of individual data to facilitate evaluation of multigenic effects and detailed analysis of effect modification by environmental exposure...
  35. ncbi request reprint Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy
    Min Shen
    International Agency for Research on Cancer, Lyon, France
    Cancer Epidemiol Biomarkers Prev 12:1234-40. 2003
    ..Similarly, the XRCC1 codon 399 polymorphism also had a protective effect on bladder cancer among heavy smokers. The XPD polymorphism was not, however, associated with bladder cancer risk...
  36. ncbi request reprint Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies
    Jay D Hunt
    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA, USA
    Int J Cancer 114:101-8. 2005
    ..Inhaled tobacco smoke is clearly implicated in the etiology of RCC, with a strong dose-dependent increase in risk associated with numbers of cigarettes smoked per day and a substantial reduction in risk for long-term former smokers...
  37. ncbi request reprint Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe
    Rayjean J Hung
    IARC, Lyon, France
    Cancer Res 66:8280-6. 2006
    ..However, a definite conclusion can only be drawn on replication by different studies among individuals who are highly exposed to IR...
  38. ncbi request reprint The XRCC3 Thr241Met polymorphism and breast cancer risk: a case-control study in a Thai population
    Suleeporn Sangrajrang
    Research Division, National Cancer Institute, Bangkok, Thailand
    Biomarkers 12:523-32. 2007
    ..48, 95% CI 0.82-2.69). Our findings suggest that the XRCC3 Thr241Met polymorphism is likely to play a modifying role in the individual susceptibility to breast cancer among Thai women as already shown for women of European ancestry...
  39. ncbi request reprint Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma
    Patrick J Hayden
    Durkan Leukaemia Laboratories, Department of Haematology, Institute of Molecular Medicine, Trinity College Dublin, Ireland
    Hum Mol Genet 16:3117-27. 2007
    ..015). This SNP is located in the 3'-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma...
  40. ncbi request reprint Polymorphisms in three base excision repair genes and breast cancer risk in Thai women
    Suleeporn Sangrajrang
    Research Division, National Cancer Institute, Bangkok, 10400, Thailand
    Breast Cancer Res Treat 111:279-88. 2008
    ..26-2.82). In conclusion, our data suggest that Thai women with a certain XRCC1 diplotype or homozygous for two or three variant alleles of XRCC1, OGG1, and APEX1 are likely to have an increased susceptibility to breast cancer...
  41. ncbi request reprint Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells
    Matthew A Burchill
    Center for Immunology, Cancer Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
    J Immunol 171:5853-64. 2003
    ....
  42. doi request reprint The NF-kappaB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target
    Saman Hewamana
    Department of Haematology, School of Medicine, Cardiff University, Cardiff, United Kingdom
    Blood 111:4681-9. 2008
    ..001, r(2) = 0.3), implicating Rel A in fludarabine resistance. Taken together, these data indicate that Rel A represents an excellent therapeutic target for this incurable disease...
  43. pmc Obesity and hypertension in an Iranian cohort study; Iranian women experience higher rates of obesity and hypertension than American women
    Hossein Bahrami
    Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
    BMC Public Health 6:158. 2006
    ..We determined the prevalence of overweight, obesity, and hypertension in a large cohort of Iranians and compared age-adjusted rates with the rates in the US...
  44. pmc Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium
    Silvia de Sanjose
    Unit of Infections and Cancer, Catalan Institute of Oncology, Institut d Investigacio Biomedica de Bellvitge, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública, Barcelona, Spain
    Clin Gastroenterol Hepatol 6:451-8. 2008
    ..We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin's lymphoma (NHL) subtypes after HCV infection...
  45. ncbi request reprint A common coding variant in CASP8 is associated with breast cancer risk
    Angela Cox
    Sheffield University Medical School, Sheffield S10 2RX, UK
    Nat Genet 39:352-8. 2007
    ..02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies...
  46. ncbi request reprint Second primary malignancies in females with primary fallopian tube cancer
    Annika Riska
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland
    Int J Cancer 120:2047-51. 2007
    ..The clustering of cancers of the lung and bladder in PFTC patients may suggest shared smoking aetiology. The excess of colorectal and breast cancers after PFTC may indicate a genetic aetiology...
  47. ncbi request reprint Associations between ocular melanoma and other primary cancers: an international population-based study
    Ghislaine Scelo
    International Agency for Research on Cancer IARC, Lyon, France
    Int J Cancer 120:152-9. 2007
    ..The high SIR found for liver cancer may be explained by misclassification bias. Common etiological factors may be involved in ocular and prostate cancers...
  48. ncbi request reprint Inherited predisposition of lung cancer: a hierarchical modeling approach to DNA repair and cell cycle control pathways
    Rayjean J Hung
    IARC, 150 cours Albert Thomas, F 69372 Lyon Cedex 08, France
    Cancer Epidemiol Biomarkers Prev 16:2736-44. 2007
    ..In particular, further investigation of OGG1, MGMT, and CHEK2 focusing on the genetic regions where the present markers are located or the haplotype blocks tightly linked with these markers might be warranted...