Whole-exome sequencing and targeted copy number analysis in primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. Clinical features may be subtle and highly variable, making the diagnosis of PCD challenging. The diagnosis can be confirmed with ciliary ultrastructure analysis and/or molecular genetic testing of 32 PCD-associated genes. However, because of this genetic heterogeneity, comprehensive molecular genetic testing is not considered the standard of care, and the most efficient molecular approach has yet to be elucidated. Here, we propose a cost-effective and time-efficient molecular genetic algorithm to solve cases of PCD. We conducted targeted copy number variation (CNV) analysis and/or whole-exome sequencing on 20 families (22 patients) from a subset of 45 families (52 patients) with a clinical diagnosis of PCD who did not have a molecular genetic diagnosis after Sanger sequencing of 12 PCD-associated genes. This combined molecular genetic approach led to the identification of 4 of 20 (20%) families with clinically significant CNVs and 7 of 20 (35%) families with biallelic pathogenic mutations in recently identified PCD genes, resulting in an increased molecular genetic diagnostic rate of 55% (11/20). In patients with a clinical diagnosis of PCD, whole-exome sequencing followed by targeted CNV analysis results in an overall molecular genetic yield of 76% (34/45)

Gaining further insight into photo-Fenton treatment of phenolic compounds commonly found in food processing industry

A mixture of eight phenolic compounds, namely 2,4-dinitrophenol, tannic, ellagic, gallic, protocatechuic, vanillic, syringic and sinapic acids, have been treated by means of a photo-Fenton process under simulated and real sunlight. An experimental design methodology, based in Doehlert matrixes, was employed to check the effect of the concentration of Fe(II) and H2O2, as well as pH. Response surfaces show that photo-Fenton can be extended to pH values clearly above 2.8, probably due to complexation of iron with the phenolic substances. Experiments performed under solar irradiation at pH = 3.9 showed that complete removal of the monitored pollutants was achieved in less than 3 min; mineralisation was also efficient, although some organics remained in the solution. Toxicity was monitored according to Pseudokirchneriella subcapitata and Daphnia magna bioassays; Recombinant Yeast Assay (RYA) was employed to assess estrogenic and dioxin-like activities. 2,4-Dinitrophenol was demonstrated to be the major concern and, in general, photo-Fenton resulted in a detoxification of the solution. Finally, excitation emission matrix (EEM) fluorimetry was employed to obtain complementary information on the behaviour of organic matter. Most peaks associated with the parent pollutants disappeared after short irradiation periods and, at 12 min of irradiation chromophores were destroyed, what can be associated with the removal of complex molecules. (C) 2015 Elsevier B.V. All rights reserved.The authors want to thank the financial support of the Spanish Ministerio de Education y Ciencia (CTQ2012-38754-C03-02) and Generalitat Valenciana (GV/2015/074). Sara Garcia-Ballesteros would like to thank Spanish Ministerio de Economia y Competitividad for her fellowship (BES-2013-066201).García Ballesteros, S.; Mora Carbonell, M.; Vicente Candela, R.; Sabater Marco, C.; Castillo López, MÁ.; Arques Sanz, A.; Amat Payá, AM. (2016). Gaining further insight into photo-Fenton treatment of phenolic compounds commonly found in food processing industry. Chemical Engineering Journal. 288:126-136. https://doi.org/10.1016/j.cej.2015.11.031S12613628

Genetic signatures of parental contribution in black and white populations in Brazil

Two hundred and three individuals classified as white were tested for 11 single nucleotide polymorphisms plus two insertion/deletions in their Y-chromosomes. A subset of these individuals (n = 172) was also screened for sequences in the first hypervariable segment of their mitochondrial DNA (mtDNA). In addition, complementary studies were done for 11 of the 13 markers indicated above in 54 of 107 black subjects previously investigated in this southern Brazilian population. The prevalence of Y-chromosome haplogroups among whites was similar to that found in the Azores (Portugal) or Spain, but not to that of other European countries. About half of the European or African mtDNA haplogroups of these individuals were related to their places of origin, but not their Amerindian counterparts. Persons classified in these two categories of skin color and related morphological traits showed distinct genomic ancestries through the country. These findings emphasize the need to consider in Brazil, despite some general trends, a notable heterogeneity in the pattern of admixture dynamics within and between populations/groups

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Peer reviewe

Whole genome analysis of a schistosomiasis-transmitting freshwater snail

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk