A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. Author summary The combination of various genetic and environmental risk factors makes the understanding of the molecular circuitry behind complex diseases, like cancer, a major challenge. The homogeneous nature of pedigree dog breed genomes makes these dogs ideal for the identification of both simple disease-causing genetic variants and genetic risk factors for complex diseases. Mast cell tumours are the most common type of canine skin cancer, and one of the most common cancers affecting dogs of most breeds. Several breeds, including Labrador Retrievers (which represent one of the most popular dog breeds), have an elevated risk of mast cell tumour development. Here, by using a methodological approach that combined different techniques, we identified a common inherited synonymous variant, that predisposes Labrador Retrievers to mast cell tumour development. Interestingly, we showed that this variant, despite its synonymous nature, appears to have an effect on translation dynamics as it is associated with reduced levels of DSCAM, a cell adhesion molecule. The results presented here reveal dysregulation of cell adhesion to be an important factor in mast cell tumour pathogenesis, and also highlight the important role that synonymous variants can play in complex diseases

Anadolu Neolitik insan popülasyonlarından aDNA eldesi, dizilemesi ve popülasyon genetiği analizi yoluyla Neolitik göç tarihinin anlaşılması

Antik DNA insan popülasyonlarının tarihine dair doğrudan bilgi verebilmektedir. Son yıllarda yürütülen bir dizi aDNA çalışması, Neolitik Devrim’in Orta/Kuzey Avrupa’ya nasıl taşındığı sorusuna kısmen yanıt vermiş ve tarımın en azından kısmen göçlerle varlığına işaret etmiştir. Ancak göçlerin tam olarak nereden başladığı bilinmemektedir. Bir olasılık Orta/Yakın Doğu’dan başlayan sürekli bir göç dalgası, diğer bir olasılık, önce tarımın kültürel aktarımla Akdeniz topluluklarına taşınması ve Orta/Kuzey Avrupa’ya göçün buradan başlamış olmasıdır. Bu iki olasılığı ayırd etmenin en doğrudan ve kesin yolu, Neolitik Dönem Yakın/Orta Doğu insan popülasyonlarının genetik profillerini antik DNA çalışmasıyla çıkartmaktır. Bunların bilinen Avrupa Neolitik insanlarının genetik profilleriyle karşılaştırılması, göçün Yakın/Orta Doğu’dan mı başladığı sorusunu cevaplayacaktır

Data from: A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer

Biasoli_et_al data

The compressed Biasoli_et_al data folder was created using 7-Zip 9.20. The folder contains: (1) canineHD array (Illumina) genotype data: Plink Map and Ped files for the 6 Study Sets listed in Supplementary Table S1. The individuals listed in the Ped files had a SNP call rate of >90%. (2) BAM files (and associated BAM index files) created (using BWA) by alignment of Fastq format paired-end sequence reads of a 2.9Mb region of CFA31 (CFA31:34433688-37366557), captured from 6 Labrador Retrievers affected by a mast cell tumour and 6 unaffected Labrador Retrievers, to the CanFam3.1 reference Boxer genome. (3) A text file listing the case/control status of the Labrador Retrievers whose 2.9MB CFA31 region sequences are represented in the BAM sequence alignment files

A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in labrador and golden retrievers

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breedpredisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer

A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. Author summary The combination of various genetic and environmental risk factors makes the understanding of the molecular circuitry behind complex diseases, like cancer, a major challenge. The homogeneous nature of pedigree dog breed genomes makes these dogs ideal for the identification of both simple disease-causing genetic variants and genetic risk factors for complex diseases. Mast cell tumours are the most common type of canine skin cancer, and one of the most common cancers affecting dogs of most breeds. Several breeds, including Labrador Retrievers (which represent one of the most popular dog breeds), have an elevated risk of mast cell tumour development. Here, by using a methodological approach that combined different techniques, we identified a common inherited synonymous variant, that predisposes Labrador Retrievers to mast cell tumour development. Interestingly, we showed that this variant, despite its synonymous nature, appears to have an effect on translation dynamics as it is associated with reduced levels of DSCAM, a cell adhesion molecule. The results presented here reveal dysregulation of cell adhesion to be an important factor in mast cell tumour pathogenesis, and also highlight the important role that synonymous variants can play in complex diseases

Sucul biofilm bakterilerinin arsenik, nikel ve kadmiyum dirençlerinin belirlenmesi ve moleküler karakterizasyonu

Sanayileşmedeki aşırı artış, tarımsal ve insan kaynaklı aktiviteler toprakta önemli miktarda ağır metalleride içeren toksik element birikimine sebep olmuştur. Ağır metal ve zehirli element etkisi altında kalan çeşitli mikroorganizmalardan bazıları, çevresel ortamdaki yüksek toksik konsantrasyonlara karşı direnç mekanizmaları geliştirmiştirir. Bu sebeple, bu tür mikroorganizmalar, bu tip elementler içeren toprakların bu toksik maddelerden arındırılmasında ve toprağın temizlenmesinde kullanılabilirler.Bu proje kapsamında bir sığ tatlısu gölü olan Mogan’dan elde edilen biofilm oluşturan bakterilerdeki Arsenik (As), Nikel (Ni) ve Kadmiyum (Cd) hassasiyet yada direnç seviyeleri araştırılacaktır. Seviyelerin tesbitinden sonra direnç gösteren izolatlarlarda ortaya çıkan makromoleküler adaptasyonları spektroskopik yöntemlerle belirleyecek ve adaptasyonların genetik mi epigenetik mi olduğunu moleküler biyoloji tekniklerini kullanarak araştıracağız. Insanların ve diğer canlıların sağlıklarını tehdit eden çevresel zehirli element birikimi önemli bir sorundur. Bu proje kapsamında elde edilecek sonuçlar biyoizleme ve biyoiyileştirme çalışmaları için kullanılabilecektir