Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Children and populations biobanks.

Access to samples and individual DNA sequence data from children included in population biobanks should, when feasible, await their consent as adults

Exome/Genome-Wide Testing in Newborn Screening: A Proportionate Path Forward

Population-based newborn screening (NBS) is among the most effective public health programs ever launched, improving health outcomes for newborns who screen positive worldwide through early detection and clinical intervention for genetic disorders discovered in the earliest hours of life. Key to the success of newborn screening programs has been near universal accessibility and participation. Interest has been building to expand newborn screening programs to also include many rare genetic diseases that can now be identified by exome or genome sequencing (ES/GS). Significant declines in sequencing costs as well as improvements to sequencing technologies have enabled researchers to elucidate novel gene-disease associations that motivate possible expansion of newborn screening programs. In this paper we consider recommendations from professional genetic societies in Europe and North America in light of scientific advances in ES/GS and our current understanding of the limitations of ES/GS approaches in the NBS context. We invoke the principle of proportionality-that benefits clearly outweigh associated risks-and the human right to benefit from science to argue that rigorous evidence is still needed for ES/GS that demonstrates clinical utility, accurate genomic variant interpretation, cost effectiveness and universal accessibility of testing and necessary follow-up care and treatment. Confirmatory or second-tier testing using ES/GS may be appropriate as an adjunct to conventional newborn screening in some circumstances. Such cases could serve as important testbeds from which to gather data on relevant programmatic barriers and facilitators to wider ES/GS implementation

Connective tissue: Cancer patients' attitudes towards medical research using excised (tumour) tissue

The objective of this article is to explore the views of Dutch cancer patients on the use of excised and stored (tumor) tissues in medical research. Excised tissues are routinely stored in hospitals for future diagnostic use. They are also important for scientific research. This article discusses and interprets concepts of ‘ownership’ in the context of the increasing scientific and commercial value of tissues. We used a mixed-methods design combining quantitative data (questionnaires) with qualitative data (interviews) and observations during an intervention study. Our analysis suggests that, for patients, the stored tissue is a hypercollective good that should remain in the public sphere in order to facilitate research. The tissue is seen as connecting the donor to relatives and other patients, the hospital, and to the larger scientific community. The respondents expressed a preference for an ongoing relationship with the tissue custodian. A substantial minority of respondents consider themselves to be owners of the tissue. Notably, tumour tissue is perceived as unique and special. Patients endorse the use of extracorporeal tissue removed during medical care in scientific research. They expect reciprocity from the tissue custodian in the form of information about findings