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1.  Characterizing Genetic Variants for Clinical Action 
Genome-wide association studies, DNA sequencing studies, and other genomic studies are finding an increasing number of genetic variants associated with clinical phenotypes that may be useful in developing diagnostic, preventive, and treatment strategies for individual patients. However, few common variants have been integrated into routine clinical practice. The reasons for this are several, but two of the most significant are limited evidence about the clinical implications of the variants and a lack of a comprehensive knowledge base that captures genetic variants, their phenotypic associations, and other pertinent phenotypic information that is openly accessible to clinical groups attempting to interpret sequencing data. As the field of medicine begins to incorporate genome-scale analysis into clinical care, approaches need to be developed for collecting and characterizing data on the clinical implications of variants, developing consensus on their actionability, and making this information available for clinical use. The National Human Genome Research Institute (NHGRI) and the Wellcome Trust thus convened a workshop to consider the processes and resources needed to: 1) identify clinically valid genetic variants; 2) decide whether they are actionable and what the action should be; and 3) provide this information for clinical use. This commentary outlines the key discussion points and recommendations from the workshop.
PMCID: PMC4158437  PMID: 24634402
genomic medicine; clinical actionability; database; electronic health records (EHR); pharmacogenomics; DNA sequencing
2.  ECG Response of Koalas to Tourists Proximity: A Preliminary Study 
PLoS ONE  2009;4(10):e7378.
Koalas operate on a tight energy budget and, thus, may not always display behavioral avoidance reaction when placed in a stressful condition. We investigated the physiological response of captive koalas Phascolarctos cinereus in a conservation centre to the presence of tourists walking through their habitat. We compared, using animal-attached data-recorders, the electrocardiogram activity of female koalas in contact with tourists and in a human-free area. One of the koalas in the tourist zone presented elevated heart rate values and variability throughout the recording period. The remaining female in the exhibit area showed a higher field resting heart rates during the daytime than that in the isolated area. In the evening, heart rate profiles changed drastically and both the koalas in the exhibit and in the tourist-free zones displayed similar field resting heart rates, which were lower than those during the day. In parallel, the autonomic nervous systems of these two individuals evolved from sympathetic-dominant during the day to parasympathetic-dominant in the evening. Our results report ECG of free-living koalas for the first time. Although they are preliminary due to the difficulty of having sufficient samples of animals of the same sex and age, our results stress out the importance of studies investigating the physiological reaction of animals to tourists.
PMCID: PMC2757916  PMID: 19823679
4.  A HapMap harvest of insights into the genetics of common disease 
The Journal of Clinical Investigation  2008;118(5):1590-1605.
The International HapMap Project was designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases. This expectation has been amply fulfilled with just the initial output of genome-wide association studies, identifying nearly 100 loci for nearly 40 common diseases and traits. These associations provided new insights into pathophysiology, suggesting previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. In addition, HapMap-based discoveries have shed new light on the impact of evolutionary pressures on the human genome, suggesting multiple loci important for adapting to disease-causing pathogens and new environments. In this review we examine the origin, development, and current status of the HapMap; its prospects for continued evolution; and its current and potential future impact on biomedical science.
PMCID: PMC2336881  PMID: 18451988
5.  Expression of Mammaglobin, B305D, GABAπ and B726P and elevation of Mammaglobin protein in the peripheral blood of women with untreated breast cancers 
Clinical chemistry  2004;50(11):2069-2076.
The aim of this study was to analyze the utility of a mammaglobin multigene RT-PCR assay and a mammaglobin sandwich ELISA to detect peripheral blood samples of breast cancer patients.
Experimental Design
Peripheral blood samples of 147 untreated Senegalese women with biopsy confirmed breast cancer were collected. The samples were tested for mammaglobin and 3 breast cancer associated gene transcripts using a multigene real-time RT-PCR assay and for secreted mammaglobin protein using a sandwich ELISA format. Patient information regarding demographic and clinical staging of disease was also collected.
In 77 % of the breast cancer blood samples a positive expression signal was found using the multigene RT-PCR assay detecting mammaglobin and three complementary transcribed genes. 50 samples from healthy female donors tested negative. Circulating mammaglobin protein was found in 68 % of the breast cancer sera, whereas 38 % showed significantly elevated protein levels in comparison to a mixed control population. Statistical correlations were found between the detection of mammaglobin protein in serum, presence of mammaglobin mRNA expressing cells in blood, stage of disease and tumor size.
The multigene mammaglobin RT-PCR assay and mammaglobin sandwich ELISA could be valuable tools to detect metastatic disease and to monitor therapeutic efficiency. Both assays together provided a diagnostic sensitivity of 83 %. Use of the multigene RT-PCR increased detection sensitivity from 61 to 77 % in comparison to mammaglobin expression alone.
PMCID: PMC1482781  PMID: 15375015
multigene RT-PCR; circulating tumor cell detection; breast cancer
6.  Potential Serological Use of a Recombinant Protein That Is a Replica of a Mycobacterium tuberculosis Protein Found in the Urine of Infected Mice 
The recent availability of numerous well-characterized Mycobacterium tuberculosis recombinant proteins has revived interest in the serological diagnosis of tuberculosis. Several promising results have been reported, particularly when more than one antigen is used in the test. However, thus far these antigens have not been used in routine diagnostic tests because they lack sufficient sensitivity. In addition, with the exception of one antigen, most recombinant M. tuberculosis proteins do not identify the majority of tuberculosis patients coinfected with human immunodeficiency virus (HIV). Here, we report a newer M. tuberculosis protein that is a promising candidate for increasing the sensitivity of the serological tests, in particular for patients coinfected with HIV. The protein was found in the urine of mice during the early stages of infection with M. tuberculosis (10 to 14 days), thus suggesting that the antigen is abundantly released during the in vivo growth of the mycobacterium. Reverse genetics was used to produce the recombinant protein, which we named U1 (for urine protein 1). Using a conventional enzyme-linked immunosorbent assay (ELISA), antibody to U1 could be detected in 60% of patients with pulmonary tuberculosis with no signs of coinfection with HIV (n = 83). Conversely, anti-U1 antibody was detected in 87% of the sera from tuberculosis patients coinfected with HIV (n = 47). Out of 12 HIV-infected nontuberculosis patients' sera, 9 did not react with U1 and three sera gave borderline ELISA signals (signal/cutoff of ≤1.75). These results suggest that the high efficiency of U1 in identifying tuberculosis patients coinfected with HIV may be related to abundant release of this protein during the initial phase of the HIV coinfection. The immediate availability of the antigen at a time point in which the patient's immune system is still competent would lead to a secondary immune response to U1 that persists for months in the patient's serum.
PMCID: PMC371208  PMID: 15013976

Results 1-6 (6)