Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

Health care experiences of low-income South Indian women: using social relationships to negotiate physical, financial and informational constraints

India is a developing country that has pledged significant resources toward improving health care access for underprivileged citizens. Maternal well-being is a highlight of the government’s health care initiatives, especially in the state of Tamil Nadu where health care innovations and maternity assistance benefits for low-income women have become a model for the country. Despite improvement on key maternal health indicators over recent years, these health outcomes still lag behind those of more developed nations. In light of this maternal health outcome disparity, it is important to examine factors which may prevent low-income Indian women from accessing health care, as well as those factors which enable them to do so. Understanding such nuances in maternal health care access can impact the design of health system attributes and health initiatives which can better promote maternal well-being. This study draws from health care decision-making and health system frameworks as well as social relationship literature across disciplines to explore how low-income Indian women residing in Tamil Nadu understand and navigate their health care landscape. A convenience sample of 23 low-income women residing in Tamil Nadu, India were identified through snowball recruiting. Of these, 21 were mothers of young children or expecting mothers and two were key informants. Ages ranged from 20-35 years for current and expecting mothers. Study participants were interviewed using a semi-structured protocol. Data were analyzed using a Grounded Theory approach. Results show that these women encounter physical, financial, and informational constraints to health care decision-making and health care access. The study further finds that women utilize social relationships to assist in overcoming these constraints

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Abstract Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2

Abstract Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10−5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor–positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15–21.80] and progesterone receptor–positive (OR 5.04; 95 % CI 3.17–8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10−12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management