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Genomics in the Journals : May 2, 2013

NEW YORK (GenomeWeb News) – Researchers from the UK and several other countries used sequencing and SNP analyses to characterize African and Asian populations of the malaria parasite Plasmodium falciparum — work they described in Nature Genetics.

The researchers assessed population structure in these regions using variant patterns found in the genomes of 825 P. falciparum parasites from seven countries in West Africa and Southeast Asia. Their analysis unearthed particularly pronounced P. falciparum population structure in Western Cambodia. There, the group saw three distinct artemisinin-resistant P. falciparum populations that can be traced back to a shared founder.

The populations provide a peek at the emergence of artemisinin-resistance in the region, they noted, and may serve as a more general source of information regarding parasite features associated with drug resistance.

"Whilst we have not yet identified the precise mechanism of action or resistance to artemisinin, this research represents substantial progress in that direction," co-author Nicholas White said in a statement.

"It also provides an important insight into why antimalarial drug resistance (previously to chloroquine and antifols, and now to artemisinin) arises in Western Cambodia," added White, a University of Oxford researcher and director of the Mahidol-Oxford Tropical Medicine Research Unit at Bangkok's Mahidol University.

Also in Nature Genetics, there is a paper that takes a look at genetic variants influencing amyotrophic lateral sclerosis, or ALS, risk in the Han Chinese population from an international team led by investigators in China.

Through a genome-wide association study involving 506 Han Chinese individuals with a sporadic form of ALS and nearly 1,900 unaffected individuals from the same population, the researchers narrowed in on the top 90 genetic variants suspected of having ties to the disease.

They then tested those candidate SNPs — and half a dozen implicated in past studies — in another 706 cases and 1,777 controls, uncovering significant ties between ALS risk and variants at sites on chromosomes 1 and 22.

The loci have not been implicated in ALS risk in past studies of individuals of European descent, study authors noted, hinting at population-related differences in ALS risk. "The difference in GWAS findings between the Chinese and European populations might suggest heterogeneity of ALS genetic susceptibility in the two populations," they wrote, "and the identified susceptibility loci might be population-specific genetic risk factors for ALS."

In the New England Journal of Medicine, members of the Cancer Genome Atlas Research Network reported on results from an integrated genomic and epigenetic analysis of de novo acute myeloid leukemia that included data for 200 cases.

From their collection of whole-exome sequence data from 150 tumors and matched normal samples and whole-genome sequence data on 50 tumor-normal pairs — coupled with RNA and microRNA sequence and DNA methylation profiling information — the researchers found several recurrently mutated genes in AML, despite the relatively low mutational burden in each tumor.

Consistent with past studies, investigators found frequent changes to genes such as NPM1, FLT3, DNMT3A, IDH1, and IDH2 in de novo AML. Across the suite of genes altered in AML, meanwhile, they found genes falling in nine main functional categories — from tumor suppressor and signaling genes to components of cohesin and spliceosome complexes.

Together with DNA methylation profiles, the sequence data also highlighted the importance of epigenetic alterations in de novo AML, with some 44 percent of tumors containing mutations to one or more methylation-related genes.

"We now have a genetic playbook for this type of leukemia," the study's corresponding author Timothy Ley, associated director of cancer genomics with the Genome Institute at Washington University, said in a statement.

"We don’t know all the rules yet, but we know all the major players," he added. "This information can help us begin to understand which patients need more aggressive treatment right up front and which can be treated effectively with standard chemotherapy."

A chromosome 15 variant is associated with successful weight loss following Roux-en-Y gastric bypass surgery, according to a study in the American Journal of Human Genetics. Researchers from Massachusetts General Hospital, Harvard Medical School, and elsewhere conducted a GWAS involving almost 700 individuals who had undergone the stomach-altering procedure.

By considering genotyping patterns in relationship to individuals' weight loss during the 10 months or more after gastric bypass surgery, the team tracked down a weight loss-associated variant near ST8SIA2 and SLCO3A1 — chromosome 15 genes that were subsequently found to be expressed at higher baseline levels in fat tissue from humans and/or mice that go on to lose more weight after the Roux-en-Y procedure.

Investigators verified ties between the SNP and post-surgery weight loss using data for another 327 individuals who'd had gastric bypass surgery. Results across the entire study cohort suggest that those with two favorable versions of the variant lost nearly 39 percent body weight post-surgery, on average, compared with a drop of around 34 percent or 29 percent, respectively, in those with one or no favorable versions of the variant.

"If we can identify those patients who are likely to lose more weight after surgery from those who do less well, we could help steer patients towards the therapy that best suits them," the study's senior author Lee Kaplan, with Massachusetts General Hospital and Harvard Medical School, said in a statement.

Genomics In The Journals is a weekly feature pointing readers to select, recently published articles involving genomics and related research.