GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

New Records of Commercially Valuable Black Corals (Cnidaria: Antipatharia) from the Northwestern Hawaiian Islands at Mesophotic Depths.

v. ill. 23 cm.QuarterlyMesophotic coral reef ecosystems are notoriously undersurveyed worldwide and particularly in remote locations like the Northwestern Hawaiian Islands ( NWHI). A total of 37 mixed-gas technical dives were performed to depths of 80 m across the NWHI to survey for the presence of the invasive octocoral Carijoa sp., the invasive red alga Acanthophora spicifera, and conspicuous megabenthic fauna such as black corals. The two invasive species were not recorded from any of the surveys, but two commercially valuable black coral species, Antipathes griggi and Myriopathes ulex, were found, representing substantial range expansions for these species. Antipathes griggi was recorded from the islands of Necker and Laysan in 58 – 70 m, and Myriopathes ulex was recorded from Necker Island and Pearl and Hermes Atoll in 58 – 70 m. Despite over 30 yr of research in the NWHI, these black coral species had remained undetected. The new records of these conspicuous marine species highlight the utility of deepdiving technologies in surveying the largest part of the depth range of coral reef ecosystems (40 – 150 m), which remains largely unexplored

Mutations in Radial Spoke Head Protein Genes RSPH9 and RSPH4A Cause Primary Ciliary Dyskinesia with Central-Microtubular-Pair Abnormalities

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous inherited disorder arising from dysmotility of motile cilia and sperm. This is associated with a variety of ultrastructural defects of the cilia and sperm axoneme that affect movement, leading to clinical consequences on respiratory-tract mucociliary clearance and lung function, fertility, and left-right body-axis determination. We performed whole-genome SNP-based linkage analysis in seven consanguineous families with PCD and central-microtubular-pair abnormalities. This identified two loci, in two families with intermittent absence of the central-pair structure (chromosome 6p21.1, Zmax 6.7) and in five families with complete absence of the central pair (chromosome 6q22.1, Zmax 7.0). Mutations were subsequently identified in two positional candidate genes, RSPH9 on chromosome 6p21.1 and RSPH4A on chromosome 6q22.1. Haplotype analysis identified a common ancestral founder effect RSPH4A mutation present in UK-Pakistani pedigrees. Both RSPH9 and RSPH4A encode protein components of the axonemal radial spoke head. In situ hybridization of murine Rsph9 shows gene expression restricted to regions containing motile cilia. Investigation of the effect of knockdown or mutations of RSPH9 orthologs in zebrafish and Chlamydomonas indicate that radial spoke head proteins are important in maintaining normal movement in motile, “9+2”-structure cilia and flagella. This effect is rescued by reintroduction of gene expression for restoration of a normal beat pattern in zebrafish. Disturbance in function of these genes was not associated with defects in left-right axis determination in humans or zebrafish