Genomic and Genetic Disorders Biobank

Project description Biobanking is an important resource as support to many types of biomedical research, including research in personalized medicine. Since 2006 the Medical Genetics Unit at Casa Sollievo della Sofferenza (CSS) Hospital created a private internal repository of biological samples (mainly DNA, RNA and cell lines) from individuals affected by different genomic disorders [1–3]. The Ethics Committee of CSS approved the repository in 2006 (protocol n. 12736/06). Afterwards, in 2009, following to a peer-reviewed Italian Telethon Foundation granting call, the GGDB (http://www.operapadrepio.it/ggdbbank/) joined the Telethon Network of Genetic Biobanks (TNGB, www.biobanknetwork.org, grant #GTB12001) [4] and in 2012, became a partner of the EuroBioBank (http://www. eurobiobank.org/index), the first European Network of Biobanks of Rare Diseases [5]. Finally in 2013, the GGDB joined the Italian node of BBMRI-ERIC consortium (http:// www.bbmri.it/home). The main goals of GGDB include: i) centralizing the collection, management, and storage of biospecimens and associated clinical data of affected and healthy individuals; ii) maintaining an essential service by distributing biological samples and making them available to the scientific community; iii) implementing new and already established agreements with the Patients’ Association; iv) elucidate and study the molecular characterization of GGDB samples to improve the scientific knowledge on genomic and genetic disorders. Regarding phenotyping, importantly, the GGDB can rely on the activities of the host laboratory, which is skilled in preand post-natal diagnosis of genetic disorders. As result of the Biobank staff’s consolidated expertise on rare genetic diseases, as well as, the increased interest of the Patients’ Associations, the collection of the Biobank has been recently expanded. Indeed, an agreement has been signed between GGDB and Italian Federation of PraderWilli syndrome in 2012. To date, the GGDB has recorded and stored clinical data and biospecimens from approximately 1700 individuals (1000 affected patients and 700 healthy controls, of which 98% matched with patient) for a total of 2300 biospecimens collected so far. The great majority of healthy members are not carriers.

Regarding phenotyping, importantly, the GGDB can rely on the activities of the host laboratory, which is skilled in pre-and post-natal diagnosis of genetic disorders. As result of the Biobank staff's consolidated expertise on rare genetic diseases, as well as, the increased interest of the Patients' Associations, the collection of the Biobank has been recently expanded. Indeed, an agreement has been signed between GGDB and Italian Federation of Prader-Willi syndrome in 2012.
To date, the GGDB has recorded and stored clinical data and biospecimens from approximately 1700 individuals (1000 affected patients and 700 healthy controls, of which 98% matched with patient) for a total of 2300 biospecimens collected so far. The great majority of healthy members are not carriers.

Classification (1)
Human rare genomic and genetics diseases Species Human Classification (2) GGDB collection includes biospecimes with associated clinical, molecular, and biochemical data for genomic disorders, such as Di George syndrome, Prader Willi syndrome, Williams Beuren syndrome, WBS Duplication syndrome, and genetic diseases (including Kabuki syndrome, Supravalvar aortic stenosis, Charcot-Marie-Tooth disease

Genomic and Genetic Disorders Biobank
Carmela Fusco 1 , Lucia Micale 1 , Maria Teresa Pellico 1 , Ester Valentina D'Addetta 1 , Bartolomeo Augello 1 , Barbara Mandriani 1 , Pasquelena De Nittis 1 , Dario Cocciadiferro 1 , Natascia Malerba 1 , Michele Sacco 2 , Leopoldo Zelante 1 and Giuseppe Merla 1 The Genomic and Genetic Disorders Biobank (GGDB, formerly Genomic Disorders Biobank) was established in 2006 as an internal bioresource to the Medical Genetics Unit at Casa Sollievo della Sofferenza Hospital (Italy) to collect and store biospecimens from affected individuals with genomic-disorders (e.g. microdeletion and duplication syndromes). Since 2009 the Bioresource has joined the Telethon Network of Genetic Biobanks and has expanded the collection to also include Mendelian genetic diseases. The GGDB now gathers wholly annotated clinical and longitudinal data and biological samples from affected and healthy donors, according to standard ethical principles. Biospecimens are available to the international scientific community for research projects in the field of the pathologies collected and stored in the GGDB.

Steps
The GGDB Biobank's centralized process enables researchers to access to the service by an initial contact with the staff manager(s) of the Biobank.

Depositing samples
To deposit samples, users must fill in the Submission form available on the GGDB website providing anamnestic and clinical data of the patient/donor along with a signed copy of the Informed consent form. Signing the Submission form, the user agrees to accept the rules and policies of the Biobank, as reported in Guidelines document at http://www.biobanknetwork.org/documents/ GUIDELINES.pdf. After sample acceptance and registration, the Director of Biobank assigns an individual and unique code to each sample. Coded samples, recorded in the Bioresource database are protected by a password chosen by the Director and shared with the Biobank staff member only. The personal data related to the each sample are accessible only to personnel of the Biobank and are protected by security systems. Consistently in the sheet file, the code linked to the donor and his/her data is registered and stored separately. GGDB staff properly manages samples only.

Requesting samples
The GGDB, as member of the TNGB, manages all samples requests through a dedicate website upon users' registration. All the submitted requests are gathered in a unique Request Control Panel, a tool where each Network Partner can manage their own requests. The applicant must log in and complete the request online appropriate forms provided by GGDB Staff by declaring the reason for use, describing the research purpose and the expected results. Furthermore, as stated on the sample request form, the applicant should be in agreement with the following conditions:

Constraints
Funds to support the GGDB originate mainly from Italian Telethon Foundation, followed by peer review grants. The maintenance and development of GGDB does greatly depend on the possibility to get additional funds supporting the bioresource.

(3) Bioresource description Object name
Human Genomic and Genetic disease oriented samples and data All patients are alive at the sampling. The patient collection stands as a heterogeneous population including children.

Clinical diagnosis of patients/source
Rare genetic and genomic disorders characterized by dysmorphisms, mental retardation and intellectual disability and other anomalies affecting different tissues and organs, such as cardiovascular, gastrointestinal, muscular and skeletal anomalies.

Control samples
Healthy patients relatives and unrelated individuals.

Access criteria
Access to the database is restricted to limited number of member staff of the Biobank only. The distribution of samples stored in GGDB is reserved to donors (strictly limited to their samples) and researchers working in qualified and certified institutions engaged in health-related research or health care. The justification for use (description of the research project, grant sponsor, and expected results) should be properly declared and the project employing the samples should be in agreement with the Biobank and TNGB mission. Proper acknowledgments in the resulting scientific publication, as follows "We thank the Genomic and Genetic Disorder Biobank, member of the Telethon Network of Genetic Biobanks funded by Telethon Italy (project no. GTB12001G) for the biobanking of specimens" should be guaranteed for the Biobank. Payment for shipping cost and a cost recovery to partial coverage of the cost of some basic procedures, related to the sample preparation and distribution service, could be applied.
(4) Reuse potential GGDB samples linked data can be used for both diagnosis and research purposes in the field of the disease for which they have been stored, and never for financial gain.
In the case that a sample is requested with a purpose other than those specified above, the Biobank would contact the donor's family for a new specific consent. The GGDB Biobank preserves an adequate aliquot of the samples to the advantage of the donor and/or their relatives.