Mitogenomics supports an unexpected taxonomic relationship for the extinct diving duck Chendytes lawi and definitively places the extinct Labrador Duck

Chendytes lawi, an extinct flightless diving anseriform from coastal California, was traditionally classified as a sea duck, tribe Mergini, based on similarities in osteological characters. We recover and analyze mitochondrial genomes of C. lawi and five additional Mergini species, including the extinct Labrador Duck, Camptorhyncus labradorius. Despite its diving morphology, C. lawi is reconstructed as an ancient relictual lineage basal to the dabbling ducks (tribe Anatini), revealing an additional example of convergent evolution of characters related to feeding behavior among ducks. The Labrador Duck is sister to Steller’s Eider which may provide insights into the evolution and ecology of this poorly known extinct species. Our results demonstrate that inclusion of full length mitogenomes, from taxonomically distributed ancient and modern sources can improve phylogeny reconstruction of groups previously assessed with shorter single-gene mitochondrial sequences

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

-linked severe combined immunodeficiency (SCID-X1) is a profound deficiency of T, B, and natural killer (NK) cell immunity caused by mutations in IL2RG encoding the common chain (γc) of several interleukin receptors. Gamma-retroviral (γRV) gene therapy of SCID-X1 infants without conditioning restores T cell immunity without B or NK cell correction, but similar treatment fails in older SCID-X1 children. We used a lentiviral gene therapy approach to treat five SCID-X1 patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. Follow-up data from two older patients demonstrate that lentiviral vector γc transduced autologous HSC gene therapy after nonmyeloablative busulfan conditioning achieves selective expansion of gene-marked T, NK, and B cells, which is associated with sustained restoration of humoral responses to immunization and clinical improvement at 2 to 3 years after treatment. Similar gene marking levels have been achieved in three younger patients, albeit with only 6 to 9 months of follow-up. Lentiviral gene therapy with reduced-intensity conditioning appears safe and can restore humoral immune function to posthaploidentical transplant older patients with SCID-X1

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

An open science resource for establishing reliability and reproducibility in functional connectomics

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals’ resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

The Use of Genetics to reconstruct the biogeography of the Callitrichidae, to examine the evolution of the major histocompatibility complex DRB region in Cebus capacious imitator and to phylogenetically place two extinct duck species within Anatidae.

Genetic information is indispensable in understanding several aspects of biology. In the first chapter of this dissertation, I reconstructed a phylogenetic tree from published gene fragments for the marmosets and tamarins (Callitrichidae) that I then used to reconstruct the biogeographic history of the group. Based on the results of this and previous studies, I recommended that the genus Saguinus be formally split into two genera, Saguinus and Leontocebus. In chapter two, I used high-throughput sequencing to genotype two exons of the MHC-DRB region in the sub- species Cebus capucinus imitator from Costa Rica. As in other reports on primate taxa, I found this gene region to be highly polymorphic and there is evidence of multiple copies of the DRB gene. I also found evidence for positively selected sites in both exons. In chapter three, I use ancient DNA extraction techniques combined with high-throughput sequencing to recover complete mitochondrial genomes for two extinct species of duck and place them into a phylogeny of living Anatidae. The first species, Chendytes lawi, is found to be the sister taxon to the tribe Anatini, despite all previous studies linking it to the tribe Mergini based on morphology. The second species, Camptorhyncus labradorius, is confirmed as a member of the tribe Mergini and is further shown to be the sister taxon to Polysticta stelleri, Stellar’s Eider

Mitogenomics supports an unexpected taxonomic relationship for the extinct diving duck \u3ci\u3eChendytes lawi\u3c/i\u3e and definitively places the extinct Labrador Duck

Chendytes lawi, an extinct flightless diving anseriform from coastal California, was traditionally classified as a sea duck, tribe Mergini, based on similarities in osteological characters. We recover and analyze mitochondrial genomes of C. lawi and five additional Mergini species, including the extinct Labrador Duck, Camptorhynchus labradorius. Despite its diving morphology, C. lawi is reconstructed as an ancient relictual lineage basal to the dabbling ducks (tribe Anatini), revealing an additional example of convergent evolution of characters related to feeding behavior among ducks. The Labrador Duck is sister to Steller’s Eider which may provide insights into the evolution and ecology of this poorly known extinct species. Our results demonstrate that inclusion of full length mitogenomes, from taxonomically distributed ancient and modern sources can improve phylogeny reconstruction of groups previously assessed with shorter single-gene mitochondrial sequences