Early postzygotic mutations contribute to de novo variation in a healthy monozygotic twin pair

Cataloged from PDF version of article.Background: Human de novo single-nucleotide variation (SNV) rate is estimated to range between 0.82-1.70×10-8 mutations per base per generation. However, contribution of early postzygotic mutations to the overall human de novo SNV rate is unknown. Methods: We performed deep whole-genome sequencing (more than 30-fold coverage per individual) of the whole-blood-derived DNA samples of a healthy monozygotic twin pair and their parents. We examined the genotypes of each individual simultaneously for each of the SNVs and discovered de novo SNVs regarding the timing of mutagenesis. Putative de novo SNVs were validated using Sanger-based capillary sequencing. Results: We conservatively characterised 23 de novo SNVs shared by the twin pair, 8 de novo SNVs specific to twin I and 1 de novo SNV specific to twin II. Based on the number of de novo SNVs validated by Sanger sequencing and the number of callable bases of each twin, we calculated the overall de novo SNV rate of 1.31×10-8 and 1.01×10-8 for twin I and twin II, respectively. Of these, rates of the early postzygotic de novo SNVs were estimated to be 0.34×10-8 for twin I and 0.04×10-8 for twin II. Conclusions: Early postzygotic mutations constitute a substantial proportion of de novo mutations in humans. Therefore, genome mosaicism resulting from early mitotic events during embryogenesis is common and could substantially contribute to the development of diseases

Distribution of HLA antigens in breast cancer

Investigation of various tumor-specific markers has a critical role in early diagnosis and treatment of breast cancer. The aim of the this study is to investigate the Human Leukocyte Antigen (HLA) alleles, the molecules that play an important role in immunity and tumor response of the body, and its relationship with breast cancer. In this prospective clinical study, after obtaining approval from the ethics committee of Istanbul University Experimental Medical Research Institute, 22 female patients who have been hospitalized in Istanbul University Cerrahpasa Faculty of Medicine the Department of General Surgery with a diagnosis of breast cancer were selected. In the control group, there were 22 healthy women who had no relationship and were donor candidates for renal transplantation. After collecting blood in 5 ml tubes with EDTA, HLA A, B and DR groups were measured with SSP method using the GenoVision Olerup SSP (Olerup SSP, Stockholm, Sweden) kit in Istanbul University Cerrahpasa Faculty of Medicine Blood Center Tissue Type Determination Laboratory. In patient and control group, totally 53 alleles; 17 alleles of HLA-A gene, 22 alleles of B gene, 14 alleles of DR gene were detected. A statistically significant relationship was determined between HLA-B55:01 and HLA-DRb1*18:01 alleles and the development of breast cancer (p<0.05). HLA-B13:01 antigen is determined only in the control group. It was concluded that HLA-B13:01 antigen, determined only in the control group, may be protective for breast cancer and HLA-B55:01 and HLA-DRb1*18:01 antigens, determined only in the patient group, may be a risk factor for breast cancer (Tab. 5, Ref. 22). Full Text in PDF www.elis.sk

Weighing Diverse Theoretical Models on Turkish Maqam

Since the early 20th century, various theories have been advanced in order to mathematically explain and notate modes of Traditional Turkish music known as maqams. In this article, maqam scales according to various theoretical models based on different tunings are compared with pitch measurements obtained from select recordings of master Turkish performers in order to study their level of match with analysed data. Chosen recordings are subjected to a fully computerized sequence of signal processing algorithms for the automatic determination of the set of relative pitches for each maqam scale: f0 estimation, histogram computation, tonic detection + histogram alignment, and peak picking. For nine well-recognized maqams, automatically derived relative pitches are compared with scale tones defined by theoretical models using quantitative distance measures. We analyse and interpret histogram peaks based on these measures to find the theoretical models most conforming with all the recordings, and hence, with the quotidian performance trends influenced by them.TÜBİTA