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Genomics in the Journals: Arrays 2014.07.31

NEW YORK (GenomeWeb) – In Nature Genetics, an international team led by investigators at the National Institute on Aging presented findings from a meta-analysis of Parkinson's disease genome-wide association studies.

Using directly genotyped SNPs and imputation information, the researchers considered almost 8 million SNP sites in the genomes of 13,708 individuals with Parkinson's disease and 95,282 without. A comparison of the cases and controls pointed to significant Parkinson's disease associations for SNPs at 26 loci, which they went on to test in another 5,353 individuals with Parkinson's disease and 5,551 unaffected controls using Illumina's NeuroX array.

That analysis, which also included loci implicated in past studies of the condition, verified Parkinson's disease ties at two-dozen sites in the genome. Those included 18 known Parkinson's disease risk loci and six sites in the genome not linked to Parkinson's disease in the past.

In follow-up work, the study's authors determined that a handful of the Parkinson's disease-associated SNPs were linked to methylation and gene expression profiles in post-mortem brain tissue from healthy individuals, highlighting possible functional effects for such variants.

"Unraveling the genetic underpinnings of Parkinson's is vital to understanding the multiple mechanisms involved in this complex disease, and hopefully, may one day lead to effective therapies," the study's senior author Andrew Singleton, with the National Institute on Aging, said in a statement.


Researchers from the University of Arizona at Tucson, the Helmholtz Center Munich, Dow AgroSciences, and elsewhere put together a high-quality genome assembly for the African rice Oryza glaberrima — work they described in another Nature Genetics paper.

The team used a combination of bacterial artificial clone-based physical mapping and whole-genome shotgun sequencing with Roche 454 instruments to tackle the more than 12 billion base genome of O. glaberrima, a rice species that evolved in a lineage distinct from that leading to the Asian rice O. sativa.

The researchers identified some 33,164 predicted protein-coding genes, along with hundreds of transfer RNA genes and more than 100 million bases of sequence stemming from transposable elements.

By re-sequencing the genomes of plants from 20 O. glaberrima accessions and 94 accessions of another African rice species, O. barthii, the study's authors got a look at the African plant's population history, domestication patterns, and apparent sites of related artificial selection in the African rice genomes.

Newly generated RNA sequence data from O. glaberrima, O. barthii, O. sativa, and other related species provided additional resources for their comparative genomic analysis of Oryza species.

"By understanding the entire genus at a genome level we have a whole new pool of genetic variation that can be used to combat pests and plant pathogens," co-corresponding author Rod Wing, a genomics researcher at the University of Arizona at Tucson, said in a statement.


A Nature Communications study suggests that the gut microbiomes of male and female animals may respond differently to similar diets. Researchers from the US, Sweden, and Switzerland used 16S ribosomal RNA sequencing to identify members of microbial communities in the guts of fish from a threespine stickleback population in Canada and from a Eurasian perch population in Sweden.

In these naturally occurring fish populations, they found that gut microbiomes typically varied depending on both diet and sex. Though a given diet was associated with the presence or absence of certain microbes in the fish, they explained, the precise community composition patterns present varied in male and female fish.

The group saw similar patterns in the lab, where it experimentally manipulated the diets of male and female sticklebacks. Work done with captive male and female mice indicated that the gut microbial response to a diet is sex-dependent in those animals as well, albeit to a lesser extent.

Meanwhile, a re-analysis of available data on human gut microbes in individuals with documented dietary habits hinted that the sex and diet may interact to influence gut microbial community composition in humans.

"Diet and sex do interact to influence the microbes, but we don't yet know what a desirable target for microbes is," University of Texas at Austin researcher Daniel Bolnick, the study's first author, said in a statement.

"All along we treated diet as if it works the same for men and women," he continued. "Now we'll be approaching studies of therapies in a different way."


Some types of movement by transposable elements from the long interspersed nuclear element-1 (LINE-1) retrotransposon family can contribute to the somatic mutations found in tumor genomes, according to a study by investigators at the Wellcome Trust Sanger Institute and elsewhere.

As they explained in Science, the researchers used a newly developed bioinformatics pipeline known as Transposome Finder in Cancer, or TraFiC, to scrutinize whole-genome sequence data on matched tumor and normal samples from 244 individuals with a dozen cancer types.

Their results suggest that intermittent movement of non-repetitive sequences that fall near LINE-1 elements — events known as 3' transductions — are behind a considerable subset of somatic mutations detected in tumors.

All told, they saw signs of somatic retrotranspositions in more than half of the cancer cases considered. And almost one-quarter of those stemmed from 3' transduction, a mutagenic process that scrambled bits of genes, exons, and regulatory elements around the genome.

The LINE-1 activity appeared to vary somewhat with tumor type, occurring somewhat more often in lung and colorectal cancer. There were also hints that methylation states in the genome may influence 3' transduction, with lower-than-usual methylation apparently spurring activity by the LINE-1 source elements involved.