In PLOS Genetics, researchers from the Sichuan Provincial People's Hospital and elsewhere attempt to tease apart genetic contributors to distinct non-syndromic orofacial cleft (NSOFC) subtypes, particularly forms of the birth defect that involve only cleft palate or only cleft lip. The team did genome-wide association and replication analyses based on array-based genotypes for almost 7,000 Han Chinese individuals with cleft lip only, cleft palate only, or cleft lip with cleft palate from southern or northern China, as well as genotypes for more than 10,100 unaffected individuals from the same populations. Along with a handful of loci linked to NSOFC in general or multiple NSOFC subtypes, the search led to nine loci associated with cleft palate specifically and another seven cleft lip-associated loci, including a dozen potential regulatory sites. "Our findings define subtypes of NSOFC using genetic factors and their functional ontologies," the authors write, "and provide a clue to improve their diagnosis and treatment in the future."
A Texas Biomedical Research Institute- and Seattle Children's Research Institute-led team describes apparent genetic contributors to Plasmodium falciparum fitness for another PLOS Genetics paper. Using an approach that relied on whole-genome amplification, pooled sequences, and parasites grown in mosquito and "humanized" mouse models, the researchers assessed allele frequency patterns over the P. falciparum life cycle, which includes asexual and sexual stages in invertebrate and vertebrate hosts. In particular, they focused on isolates with or without resistance to the antimalarial drug artemisinin from patients in Southeast Asia, tracking life cycle-related allele frequency shifts in P. falciparum parasite crosses between these isolates. "Our results provide possible insights into additional loci involved in resistance-associated malaria evolution and spread," they report, suggesting the same strategy "will accelerate genetic studies in other recombining parasites and pathogens."
Indian researchers reporting in PLOS One share findings from an epigenetic and transcriptomic analysis of pancreatic ductal adenocarcinoma (PDAC), which focused on finding drug resistance features related to the upregulation of ABC transporter genes. The team turned to RNA sequencing, chromatin immunoprecipitation sequencing, and other methods to characterize gene expression patterns and histone modification features in PDAC cell lines — analyses that helped narrow in on a potential role for the PAX2 transcription factor in drug resistance-related boosts to ABC transporter activity. Based on such findings, the authors suggested that "PAX2 significantly upregulated ABC family of genes, resulting in drugs resistance and poor survival in PDAC."