exome sequencing

Lupski, J.R., et al. (2010). Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. New England Journal of Medicine advance online 10.1056/nejmoa0908094 Roach, J.C., & et al. (2010). Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science : 10.1126/science.1186802 Two new papers out today - the first ever studies to employ whole-genome sequencing for disease gene discovery - neatly illustrate both the promise and the challenges lying ahead both for clinical and personal genomics. The first paper presents the final - and successful -…

Personal genomics is a rapidly evolving game, with a clear end goal in sight: offering consumers an accurate, affordable and complete genome sequence, and providing them with tools to dig out the useful nuggets of information contained therein. That goal remains out of reach, and while DNA sequencing technology continues to mature companies in the personal genomics space are offering products at various points on the trade-off curve between information content and cost. At the low-information/low-cost end, companies such as 23andMe and deCODEme offer cheap (sub-$1000) genome scans looking at…

A paper just published online in Nature Genetics describes a brute force approach to finding the genes underlying serious diseases in cases where traditional methods fall flat. While somewhat successful, the study also illustrates the paradoxical challenge of working with large-scale sequencing data: there are often too many possible disease variants, and it can be extremely difficult to work out which are actually causing the disease in question. The authors looked at 208 families where multiple members suffered from mental retardation and where the family history was consistent with the…

Jones et al. (2009). Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene. Science DOI: 10.1126/science.1171202 A paper published online today in Science illustrates both the potential and the challenges of using large-scale DNA sequencing to identify rare genetic variants underlying disease risk. Traditionally, geneticists have pinned down such variants using large family studies. By using these families to track which parts of the genome tend to be co-inherited with the disease, it's possible to zoom in on the region of DNA that harbours the disease-causing mutation…

Well, it's a little late, but I finally have a list of what I see as some of the major trends that will play out in the human genomics field in 2009 - both in terms of research outcomes, and shifts in the rapidly-evolving consumer genomics industry. For genetics-savvy readers a lot of these predictions may seem, well, predictable, so I want to emphasise that my purpose here is not really to make risky forecasts; I'm more interested in laying out what I see as the major big picture trends for the year to come, with a few specific predictions about unknowns thrown in. In any case (as you will…

The promise of release of raw sequence data files from the first 10 Personal Genome Project volunteers certainly caused a media stir (see the round-up by the PGP's own Jason Bobe), but the actual released data are pretty underwhelming. So far raw sequence data files have been posted on the PGP profile sites of only four of the ten volunteers: George Church, John Halamka, Esther Dyson and James Sherley. The files are the result of targeted resequencing of a proportion (perhaps 20%) of the protein-coding regions of the genome (called exons, collectively the exome). Although a relatively small…

The first 10 participants of the ground-breaking Personal Genome Project (PGP) will be receiving a hefty chunk of data today: the sequence of the protein-coding regions from many of their genes (collectively known as the "exome"). And if all goes according to plan, they'll soon be dumping all of that data on the web for anyone to access. The PGP is an audacious endeavour led by Harvard's George Church (recently profiled in Wired). The ultimate goal of the Project is to sequence the entire genomes of 100,000 volunteers, and release both genetic and medical data from those volunteers to the…