Publications

Abstract

Comparative neurobiology allows us to investigate relationships between phylogeny and the brain and understand the evolution of traits. Bats constitute an attractive group of mammalian species for comparative studies, given their large diversity in behavioural phenotypes, brain morphology, and array of specialised traits. Currently, the order Chiroptera contains over 1,450 species within 21 families and spans ca. 65 million years of evolution. To date, 194 Neotropical bat species (ca. 13% of the total number of species around the world) have been recorded in Central America. This study includes qualitative and quantitative macromorphological descriptions of the brains of 12 species from six families of Neotropical bats. These analyses, which include histological neuronal staining of two species from different families (Phyllostomus hastatus and Saccopteryx bilineata), show substantial diversity in brain macromorphology including brain shape and size, exposure of mesencephalic regions, and cortical and cerebellar fissure depth. Brain macromorphology can in part be explained by phylogeny as species within the same family are more similar to each other. However, macromorphology cannot be explained by evolutionary time alone as brain differences between some phyllostomid bats are larger than between species from the family Emballonuridae despite being of comparable diverging distances in the phylogenetic tree. This suggests that faster evolutionary changes in brain morphology occurred in phyllostomids — although a larger number of species needs to be studied to confirm this. Our results show the rich diversity in brain morphology that bats provide for comparative and evolutionary studies.

Abstract

We present a reference genome assembly from an individual male Rhynchonycteris naso (Chordata; Mammalia; Chiroptera; Emballonuridae). The genome sequence is 2.46 Gb in span. The majority of the assembly is scaffolded into 22 chromosomal pseudomolecules, with the Y sex chromosome assembled.

Abstract

We describe here the first characterization of the genome of the bat Pteronotus mexicanus, an endemic species of Mexico, as part of the Mexican Bat Genome Project which focuses on the characterization and assembly of the genomes of endemic bats in Mexico. The genome was assembled from a liver tissue sample of an adult male from Jalisco, Mexico provided by the Texas Tech University Museum tissue collection. The assembled genome size was 1.9 Gb. The assembly of the genome was fitted in a framework of 110,533 scaffolds and 1,659,535 contigs. The ecological importance of bats such as P. mexicanus, and their diverse ecological roles, underscores the value of having complete genomes in addressing information gaps and facing challenges regarding their function in ecosystems and their conservation.

Abstract

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype–phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations.

Abstract

Background Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals. Case presentation We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Homozygous family members display epilepsy, facial dysmorphisms, severe intellectual disability and impaired language. We compared these patients with previously reported individuals carrying homozygous mutations in CNTNAP2 and identified a highly recognisable phenotype. Conclusions We propose that CASPR2 loss produces a syndrome involving early-onset refractory epilepsy, intellectual disability, language impairment and autistic features that can be recognized as CASPR2 deficiency disorder. Further screening for homozygous patients meeting these criteria, together with detailed phenotypic and molecular investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development.

Abstract

Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2-7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active at a low level. Transfection of human glioma cells with the de2-7 EGFR has little effect in vitro, but when grown as tumor xenografts this mutated receptor imparts a dramatic growth advantage. We mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies specific for different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed in vitro and in vivo, including tyrosine 845, a known target in the wild-type EGFR for src kinase. There was a substantial upregulation of phosphorylation at every yrosine residue of the de2-7 EGFR when cells were grown in vivo compared to the receptor isolated from cells cultured in vitro. Upregulation of phosphorylation at tyrosine 845 could be stimulated in vitro by the addition of specific components of the ECM via an integrindependent mechanism. These observations may partially explain why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment