"Whole-Exome Sequencing Enables Rapid Determination of Xeroderma Pigmentosum Molecular Etiology"

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder haracterized by extreme sensitivity to actinic pigmentation changes in the skin and increased incidence of skin cancer. In some cases, patients are affected by neurological alterations. XP is caused by mutations in 8 distinct genes (XPA through XPG and XPV). The XP-V (variant) subtype of the disease results from mutations in a gene (XPV, also named POLH) which encodes for Polg, a member of the Y-DNA polymerase family. Although the presence and severity of skin and neurological dysfunctions differ between XP subtypes, there are overlapping clinical features among subtypes such that the sub-type cannot be deduced from the clinical features. In this study, in order to overcome this drawback, we undertook whole-exome sequencing in two XP sibs and their father. We identified a novel homozygous nonsense mutation (c.897T.G, p.Y299X) in POLH which causes the disease. Our results demonstrate that next generation sequencing is a powerful approach to rapid determination of XP genetic etiology.

Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies

Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations.