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Fewer than half of individuals with a suspected Mendelian or monogenic condition receive a precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in data quality and costs have heightened interest in using long-read sequencing (LRS) to streamline clinical genomic testing, but the absence of control data sets for variant filtering and prioritization has made tertiary analysis of LRS data challenging. To address this, the 1000 Genomes Project (1KGP) Oxford Nanopore Technologies Sequencing Consortium aims to generate LRS data from at least 800 of the 1KGP samples. Our goal is to use LRS to identify a broader spectrum of variation so we may improve our understanding of normal patterns of human variation. Here, we present data from analysis of the first 100 samples, representing all 5 superpopulations and 19 subpopulations. These samples, sequenced to an average depth of coverage of 37× and sequence read N50 of 54 kbp, have high concordance with previous studies for identifying single nucleotide and indel variants outside of homopolymer regions. Using multiple structural variant (SV) callers, we identify an average of 24,543 high-confidence SVs per genome, including shared and private SVs likely to disrupt gene function as well as pathogenic expansions within disease-associated repeats that were not detected using short reads. Evaluation of methylation signatures revealed expected patterns at known imprinted loci, samples with skewed X-inactivation patterns, and novel differentially methylated regions. All raw sequencing data, processed data, and summary statistics are publicly available, providing a valuable resource for the clinical genetics community to discover pathogenic SVs. 

Abstract Iridescence is widespread in the living world, occurring in organisms as diverse as bacteria, plants, and animals. Yet, compared to pigment-based forms of coloration, we know surprisingly little about the developmental and molecular bases of the structural colors that give rise to iridescence. Birds display a rich diversity of iridescent structural colors that are produced in feathers by the arrangement of melanin-containing organelles called melanosomes into nanoscale configurations, but how these often unusually shaped melanosomes form, or how they are arranged into highly organized nanostructures, remains largely unknown. Here, we use functional genomics to explore the developmental basis of iridescent plumage using superb starlings (Lamprotornis superbus), which produce both iridescent blue and non-iridescent red feathers. Through morphological and chemical analyses, we confirm that hollow, flattened melanosomes in iridescent feathers are eumelanin-based, whereas melanosomes in non-iridescent feathers are solid and amorphous, suggesting that high pheomelanin content underlies red coloration. Intriguingly, the nanoscale arrangement of melanosomes within the barbules was surprisingly similar between feather types. After creating a new genome assembly, we use transcriptomics to show that non-iridescent feather development is associated with genes related to pigmentation, metabolism, and mitochondrial function, suggesting non-iridescent feathers are more energetically expensive to produce than iridescent feathers. However, iridescent feather development is associated with genes related to structural and cellular organization, suggesting that, while nanostructures themselves may passively assemble, barbules and melanosomes may require active organization to give them their shape. Together, our analyses suggest that iridescent feathers form through a combination of passive self-assembly and active processes. 

Abstract The Hawai‘ian honeycreepers (drepanids) are a classic example of adaptive radiation: they adapted to a variety of novel dietary niches, evolving a wide range of bill morphologies. Here we investigated genomic diversity, demographic history, and genes involved in bill morphology phenotypes in 2 honeycreepers: the ‘akiapōlā‘au (Hemignathus wilsoni) and the Hawai‘i ‘amakihi (Chlorodrepanis virens). The ‘akiapōlā‘au is an endangered island endemic, filling the “woodpecker” niche by using a unique bill morphology, while the Hawai‘i ‘amakihi is a dietary generalist common on the islands of Hawai‘i and Maui. We de novo sequenced the ‘akiapōlā‘au genome and compared it to the previously sequenced ‘amakihi genome. The ‘akiapōlā‘au is far less heterozygous and has a smaller effective population size than the ‘amakihi, which matches expectations due to its smaller census population and restricted ecological niche. Our investigation revealed genomic islands of divergence, which may be involved in the honeycreeper radiation. Within these islands of divergence, we identified candidate genes (including DLK1, FOXB1, KIF6, MAML3, PHF20, RBP1, and TIMM17A) that may play a role in honeycreeper adaptations. The gene DLK1, previously shown to influence Darwin’s finch bill size, may be related to honeycreeper bill morphology evolution, while the functions of the other candidates remain unknown.