Journal•ISSN: 1945-0257
Genetic Testing and Molecular Biomarkers
Mary Ann Liebert, Inc.
About: Genetic Testing and Molecular Biomarkers is an academic journal published by Mary Ann Liebert, Inc.. The journal publishes majorly in the area(s): Population & Genotype. It has an ISSN identifier of 1945-0257. Over the lifetime, 1896 publications have been published receiving 20057 citations. The journal is also known as: Genetic testing and molecular biomarkers: Official journal of Genetic Alliance.
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TL;DR: Although SIFT and PolyPhen may be useful in prioritizing changes that are likely to cause a loss of protein function, their low specificity means that their predictions should be interpreted with caution and further evidence to support/refute pathogenicity should be sought before reporting novel missense changes.
Abstract: Context: The interpretation of novel missense variants is a challenge with increasing numbers of such variants being identified and a responsibility to report the findings in the context of all available scientific evidence. Various in silico bioinformatic tools have been developed that predict the likely pathogenicity of missense variants; however, their utility within the diagnostic setting requires further investigation. Aim: The aim of our study was to test the predictive value of two of these tools, sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), in a set of 141 missense variants (131 pathogenic, 8 benign) identified in the ABCC8, GCK, and KCNJ11 genes. Methods: Sixty-six of the mutations caused a gain of protein function, while 67 were loss-of-function mutations. The evolutionary conservation at each residue was also investigated using multiple sequence alignments from the UCSC genome browser. Results: The sensitivity of SIFT and PolyPhen was reasonably high (69% and...
352 citations
TL;DR: An imbalance of knowledge is found between scientific and medical concepts related to genetics as well as between the medical applications and societal consequences of testing, suggesting that more effort is needed to present the benefits, risks, and limitations of genetic testing, particularly, at the social and personal levels, to ensure informed decision making.
Abstract: Background: Variable health literacy and genetic knowledge may pose significant challenges to engaging the general public in personal genomics, specifically with respect to promoting risk comprehension and healthy behaviors. Methods: We are conducting a multistage study of individual responses to genomic risk information for Type 2 diabetes mellitus. A total of 300 individuals were recruited from the general public in Durham, North Carolina: 60% self-identified as White; 70% female; and 65% have a college degree. As part of the baseline survey, we assessed genetic knowledge and attitudes toward genetic testing. Results: Scores of factual knowledge of genetics ranged from 50% to 100% (average=84%), with significant differences in relation to racial groups, the education level, and age. Scores were significantly higher on questions pertaining to the inheritance and causes of disease (mean score 90%) compared to scientific questions (mean score 77.4%). Scores on the knowledge survey were significantly higher...
187 citations
TL;DR: Overall, physicians appear underprepared, perceiving they lack sufficient knowledge and confidence to incorporate GT and PT into practice and the results underscore the importance of enhancing policies and initiatives to increase physician knowledge and comfort level.
Abstract: Purpose: Physicians will play a large role in the delivery of genomic medicine, given the limited number of trained genetics professionals. The objective of this study was to assess physician preparedness for incorporating genomic testing (GT) and pharmacogenetic testing (PT) into practice by determining knowledge, experience, comfort level, and barriers, as well as their expectations for practice and educational needs. Methods: A 30-question survey was distributed to physicians spanning all disciplines within our healthcare system. Results: Perceived knowledge was poor; 40%–72% reported “no to minimal knowledge” for all genomics topics. Recent graduates or those with no patients who had undergone GT or PT had lower comfort levels. Participating physicians anticipate usage to increase; however, most were uncertain when and how to incorporate genomics into practice. Physicians perceived lack of knowledge and time to keep updated as their greatest barriers to incorporating GT and PT into practice. Conclusio...
116 citations
TL;DR: The uptake, time course, and predictors of risk-reducing mastectomy and RRSO in BRCA carriers are determined, including age below 60 years, prior breast cancer, and utilization of another risk- reducing surgery.
Abstract: Introduction and Aims: For women who carry BRCA mutations, risk-reducing surgeries are an option to decrease breast and ovarian cancer risk. This study aims to determine the uptake, time course, and predictors of risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) in BRCA carriers. Results: In 272 female carriers, followed for a median of 3.7 years, 23% of those eligible chose RRM, and 51% percent chose RRSO. Among BRCA carriers who chose these procedures, median time to both RRM and RRSO was approximately 4 months after learning of BRCA-positive results. Predictors of RRM were as follows: age below 60 years (hazard ratio 1.8, p = 0.04), prior breast cancer (hazard ratio 2.4, p = 0.0004), and RRSO (hazard ratio 7.2, p < 0.0001). Predictors of RRSO were as follows: age below 60 years (hazard ratio 3.6, p = 0.006), prior breast cancer (hazard ratio 1.8, p = 0.002), and RRM (hazard ratio 5.4, p < 0.0001). Conclusions: Many women who undergo BRCA testing use these results to make cli...
91 citations
TL;DR: It was shown that LEP G2548A and LEPR Q223R polymorphisms and haplotype combination were associated with MetS and obesity risk in Tunisian volunteers and these significant associations disappeared after added daily energy intake in adjustment.
Abstract: Leptin is a key hormone of weight regulation that modulates food intake. Since the elaboration of the leptin action mechanism, several studies tried to establish the relationship between obesity and the common polymorphisms of leptin (LEP) and leptin receptor (LEPR) genes, but results were controversial. We studied the association of G2548A of the LEP gene and Q223R of LEPR gene polymorphisms with obesity and metabolic syndrome (MetS). We recruited 169 nonobese volunteers (body mass index [BMI] <30 kg/m2) and 160 obese ones (BMI ≥30 kg/m2). Glucose, insulin, and lipids were measured. BMI, homeostasis model assessment-insulin resistance (HOMA-IR), and daily energy intake were calculated. After adjustment to confounders parameters, 2548AA was found to increase the MetS (p=0.043) and obesity risk (p=0.019) in the studied population. After stratification according to the degree of obesity, the odds ratio [OR] of 2548AA was associated with moderate obesity (p=0.048) and morbid obesity (p=0.048). The LEPR 223RR...
87 citations