A crowdsourcing database for the copy-number variation of the Spanish population

Abstract

Background Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database.

Public platform with 39,472 exome control samples enables association studies without genotype sharing

“…Alternatively, the ancestry matching is limited to the predefined major continental groups defined in gnomAD, substantially limiting the possibility of including admixed or fine-scale ancestry cohorts into the analysis (CoCoRV and Summix). Collaborative Spanish Variant Server framework offered a user with an ability to select samples that should be included in the control subset based on their phenotypes, yet this solution was limited only to copy-number variation and Spanish population, without the mechanism to perform ancestry matching 8 . GLADDB solution, proposed recently for sharing genetic data for Latin-American cohorts, potentially could be viewed as a step toward practical data sharing; however, this solution implies open individual-level data sharing, such as individual coordinates of the samples in the principal component space.…”

Rare Deletions or Large Duplications Contribute to Genetic Variation in Patients with Severe Tinnitus and Meniere Disease

“…To study the presence of SVs overlapping with the candidate variants of individuals with severe tinnitus in the reference populations, the Genome Aggregation Database (gnomAD) SVs v4.0.0 dataset was used for the global population (n = 807,162) and the Spanish Copy Number Alteration Collaborative Server (SPACNACS) database was used for the Spanish population (n = 417) [32]. In addition, constraints were evaluated for the genes covered by candidate SVs to measure their tolerance to variation.…”