As Daniel MacArthur notes at his blog, Genetic Future, "The latest issue of Nature contains an embarrassment of riches for those of us interested in personal genomics." First up, a news story by Kelly Rae Chi checks into how successful genome-wide association studies have been in finding common variants. Next, a review written in part by NHGRI's Teri Manolio attempts to address the unexplained heritability in complex diseases missed by GWAS; while GWAS continue to find associations, few of these confer great risk. Here, they propose new ways to find the "'dark matter' of genome-wide association."
Big news is the publication of a new map of human CNVs, appearing in the early online edition of the magazine this week. An international team led by Wellcome Trust Sanger Institute scientists used tiling oligo arrays to map almost all of the common CNVs in the genome, totaling nearly 12,000 variants. According to a story at our sister publication, GenomeWeb Daily News, the scientists concluded that common CNVs are not major contributors to complex disease trait heritability not explained by GWAS. A News and Views adds perspective.
Two opinion pieces link genetic variability to practical issues. One, written in part by J. Craig Venter, scientists found differences in results from two direct-to-consumer genetic testing companies and decide to give nine recommendations to improve predictions. Some of these include focusing on high-risk predictions and replicating associated markers in other ethnicities. A story at Technology Review details their analysis of 23andme and Navigenics, Daniel MacArthur writes about it here, and GenomeWeb Daily News explains it here.
In work from the BC Cancer Agency, scientists used Illumina machines to sequence the genomes and transcriptomes of a primary tumor and a metastatic tumor from the same breast cancer patient. They found that as the tumor progressed, it evolved and acquired more mutations – "a characteristic that underscores the importance of analyzing cancers at different stages," says a story at GenomeWeb Daily News. In finding that only 11 of the 32 mutations in the metastatic tumor were present in the original tumor, reportsThe Globe and Mail, and only five of those were present in the original cancer cells, "even in the early stages, cancer cells aren't uniform. That's significant because it proves even from the outset, cancer cells contain different mutations which change over time." A story at Tech Review and a blog post at Omics! Omics! add insight.
Finally, a genome-wide linkage and association study for autism reveals a common variant that may confer increased susceptibility to the disease. Scanning SNPs in 1,031 autism families, they found two rare variants with significant linkage on chromosomes 6q27 and 20p13 and a common association on chromosome 5p15. "The common variant the researchers implicated lies on chromosome 5 near a gene known as semaphorin 5A, which is thought to help guide the growth of neurons and their long projections called axons," says a post at Scientific Blogging. The work was led by the Gene Discovery Project of Johns Hopkins University and the Autism Consortium.