The genetic structure of the Turkish population reveals high levels of variation and admixture

The construction of population-based variomes has contributed substantially to our understanding of the genetic basis of human inherited disease. Here, we investigated the genetic structure of Turkey from 3,362 unrelated subjects whose whole exomes (n = 2,589) or whole genomes (n = 773) were sequenced to generate a Turkish (TR) Variome that should serve to facilitate disease gene discovery in Turkey. Consistent with the history of present-day Turkey as a crossroads between Europe and Asia, we found extensive admixture between Balkan, Caucasus, Middle Eastern, and European populations with a closer genetic relationship of the TR population to Europeans than hitherto appreciated. We determined that 50% of TR individuals had high inbreeding coefficients (≥0.0156) with runs of homozygosity longer than 4 Mb being found exclusively in the TR population when compared to 1000 Genomes Project populations. We also found that 28% of exome and 49% of genome variants in the very rare range (allele frequency < 0.005) are unique to the modern TR population. We annotated these variants based on their functional consequences to establish a TR Variome containing alleles of potential medical relevance, a repository of homozygous loss-of-function variants and a TR reference panel for genotype imputation using high-quality haplotypes, to facilitate genome-wide association studies. In addition to providing information on the genetic structure of the modern TR population, these data provide an invaluable resource for future studies to identify variants that are associated with specific phenotypes as well as establishing the phenotypic consequences of mutations in specific genes

Endothelial progenitor cells display clonal restriction in multiple myeloma

BACKGROUND: In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. METHODS: A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V(H)). RESULTS: In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V(H )primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI. CONCLUSION: Our results suggest that EPCs in at least a substantial subpopulation of MM patients are related to the neoplastic clone and that this is an important mechanism for upregulation of tumor neovascularization in MM

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Turkish population data on the HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8, and GC loci

We have determined the allele and genotype frequencies of six PCR-based genetic markers HLA-DQ alpha, LDLR, GYPA, HBGG, D7S8 and GC in the Turkish population (n = 361 for HLA-DQ alpha, and n = 260 for PM). All loci meet Hardy-Weinberg expectations. The frequency data can be used in forensic analyses in the Turkish population

Effects of pentoxifylline in the prevention of ovarian hyperstimulation syndrome in a rabbit model

Tumor necrosis factor alpha (TNF-alpha) and other cytokines have been implicated in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-alpha synthesis. The aim of this study was to evaluate whether the use of petoxifylline would prevent the occurrence of OHSS in a rabbit mode

Ülkemizde DNA Analizi HLADQA1 LDLR GYPA HBGG ve GC Lokusları ile Değerlendirilen İlk Paternite Olguları

Moleküler genetiğin son yıllarda gösterdiği hızlı gelişim, babalık tayini davalarmda kullanılan benzemezlik testleri arasına DNA analinin de girmesine yol açmıştır. Bu test diğer benzemezlik testleri ile karşılaştırıldığında, ayrım gücü en yüksek olanıdır. Adli amaçlı DNA analizlerinin ülkemizde kullanımı için Deneysel Tıp Araştırma Enstitüsü ve Adli Tıp Kurumu 1993 yılı Mart ayından itibaren ortaklaşa bir çalışma başlatıldı. Bu çalışmanın kapsamında babalığın behrlenmesini amaçlayan benzemezlik testleri arasına DNA analizi eklendi. Söz konusu DNA analizi için Türk toplumunda allel ve genotip frekansları belirlenmiş olan altı genomik lokus seçildi. Bunlar HLADQA1, LDLR, GYPA, HBGG, D7S8 ve GC lokuslarıdır. Genotip ve fenotip incelemeleri birlikte yürütülen 96 dosyanın 26’sında baba olduğu iddia olunan davalı dışlandı. Bu 26 dosyanın 12 tanesinde babalığın reddi yalnız DNA analizi ile mümkün oldu. Fenotip incelemesi ile babalığın reddi mümkün olmayan dosyaların üç tanesinde ilgili baba adaylarının baba olma olasılıkları yalnız fenotip testleri göz önüne alındığında % 99.90, % 99.87 ve % 99.82 olarak hesaplanmış olmasına rağmen DNA analizinin kullanımı ile bu kişiler dışlandı. DNA ve fenotip analizleri ile baba adayının dışlanamadığı diğer 70 dosyanın 68’inde ise baba olma olasılığı %99.73 ve üzerinde bulundu. Bu sonuçlar babalığın belirlenmesi için kullanılan benzemezlik testleri arasında DNA analizlerinin kullanımının gerekliliğini gündeme getirdi. Anahtar kelimeler: DNA analizi, babalık tayini, PCR, HLADQA1, LDLR, GYPA, HBGG, D7S8, G