Sequencing large cohorts of ethnically homogeneous individuals yields genetic insights with implications for the entire population rather than a single individual. In order to evaluate the genetic basis of certain diseases encountered at high frequency in the Ashkenazi Jewish population (AJP), as well as to improve variant annotation among the AJP, we examined the entire exome, focusing on specific genes with known clinical implications in 128 Ashkenazi Jews and compared these data to other non-Jewish populations (European, African, South Asian and East Asian). We targeted American College of Medical Genetics incidental finding recommended genes and the Catalogue of Somatic Mutations in Cancer (COSMIC) germline cancer-related genes. We identified previously known disease-causing variants and discovered potentially deleterious variants in known disease-causing genes that are population specific or substantially more prevalent in the AJP, such as in the ATP and HGFAC genes associated with colorectal cancer and pancreatic cancer, respectively. Additionally, we tested the advantage of utilizing the database of the AJP when assigning pathogenicity to rare variants of independent whole-exome sequencing data of 49 Ashkenazi Jew early-onset breast cancer (BC) patients. Importantly, population-based filtering using our AJP database enabled a reduction in the number of potential causal variants in the BC cohort by 36%. Taken together, population-specific sequencing of the AJP offers valuable, clinically applicable information and improves AJP filter annotation.

The use of non-anonymized human genome data is becoming increasingly popular in research. Here we review the proceedings of a special meeting on this topic that took place at European Molecular Biology Organization (EMBO) in December 2014. The main points discussed centered on how to achieve ‘anonymity,’ ‘trust,’ and ‘protection of data’ in relation to new genomic technologies and research. Following our report of this meeting, we also raise three further issues for future consideration: the harmonization of international law in relation to genetic data protection; the complex issues around the ‘dividual’ nature of genetic data; and the growing commercial value of personal data. In conclusion, we stress the importance of scientists working in the area of genomic research engaging in interdisciplinary collaborations with humanities and social science scholars and addressing these complicated issues.

Next-generation sequencing (NGS; also known as deep sequencing or ultra-high throughput sequencing) has probably been the most important tool for genomic research over the past few years. NGS has led to numerous discoveries and scientific breakthroughs in the genetic field. The sequencing technology that has entered the research laboratory in the past decade is now being introduced into the clinical diagnostic laboratory. Consequently, NGS results are becoming available in the medical arena as abundance of clinically relevant variants, conferring predisposition to disease, are being discovered at a growing rate (Stanley, 2014).

Familial isolated hyperparathyroidism (FIHP) can be encountered in the context of multiple endocrine neoplasia type 1 (MEN1), hyperparathyroidism and jaw tumour syndrome (HPT–JT) and in familial hypocalciuric hypercalcaemia (FHH). In these syndromes, germline mutations in the relevant genes (MEN1, HPRT2 and CaSR, respectively) are detected. In some FIHP cases, the causative gene is still elusive. The objective of this study is to define the genetic basis of FIHP in a Georgian Jewish family with FIHP using whole exome capture and sequencing. DNA extracted from two sibs and one offspring from a single family all affected with multiglandular hyperparathyroidism was subjected to whole exome capturing and sequencing using the Roche NimbleGen V2 chip and the Illumina HiSeq2000 sequencing platform. Genetic variants were detected and annotated using a combination of the Genome Analysis Tool Kit and in-house scripts. Subsequent confirmation of the mutations and co-segregation analyses were carried out by Sanger sequencing in additional affected and unaffected family members. Whole exome capture and sequencing revealed the collection of variations common to the three-sequenced patients, including a very rare previously described missense mutation (c.T1021C: p.W341R) in the MEN1 gene. The p.W341R mutation in the MEN1 gene showed complete co-segregation in the family. Whole exome capture and sequencing led to the discovery of a missense mutation in the MEN1 gene and ruling out of the additional candidates in a single experiment. The limited expressivity of this mutation may imply a specific genotype–phenotype correlation for this mutation.

A recent E-Rare workshop reviewed the ethical aspects of whole exome and whole genome-sequencing studies (WES and WGS, respectively) in rare diseases. Leveraging new genomic technologies, which output vast amounts of known and novel genetic variants, researchers are learning more about the genetic basis and mechanisms involved in rare diseases. In some cases, these findings are translated into diagnostic tools for the benefit of rare disease patients. Among the disclosed data, which can assist in treatment management, incidental findings await, bringing with them ethical concerns for the clinicians, researchers and patients.

The publication of the human genome, more than a decade ago, alongside the development of high-throughput technologies for DNA sequencing, marked the dawn of a new era in genetics. Large genomic projects have been initiated to decipher the mysteries hidden within the human genetic code. With the rapidly ever-growing amount of genetic information, and the importance of understanding what it all means, there is a need to generate an interdisciplinary hub that will connect researchers, both experimentalists and bioinformaticians, along with physicians and community representatives in order to develop a common genomic language. This should lead to an accessible, readable and interpretive human genome with a short list of personal actionable items. We will then be able to declare that we are moving ever closer to the point at which one's own genome will affect one's personal life at a scope beyond our current comprehension.