We describe the genome sequencing of an anonymous individual of African origin using a novel ligation-based sequencing assay that enables a unique form of error correction that improves the raw accuracy of the aligned reads to >99.9%, allowing us to accurately call SNPs with as few as two reads per allele. We collected several billion mate-paired reads yielding ;183 haploid coverage of aligned sequence and close to 3003 clone coverage. Over 98% of the reference genome is covered with at least one uniquely placed read, and 99.65% is spanned by at least one uniquely placed matepaired clone. We identify over 3.8 million SNPs, 19% of which are novel. Mate-paired data are used to physically resolve haplotype phases of nearly two-thirds of the genotypes obtained and produce phased segments of up to 215 kb. We detect 226,529 intra-read indels, 5590 indels between mate-paired reads, 91 inversions, and four gene fusions. We use a novel approach for detecting indels between mate-paired reads that are smaller than the standard deviation of the insert size of the library and discover deletions in common with those detected with our intra-read approach. Dozens of mutations previously described in OMIM and hundreds of nonsynonymous single-nucleotide and structural variants in genes previously implicated in disease are identified in this individual. There is more genetic variation in the human genome still to be uncovered, and we provide guidance for future surveys in populations and cancer biopsies.[Supplemental material is available online at

Magnetic resonance imaging (MRI) was performed on 50 dogs with intracranial neoplasia. The following tumor features were assessed: axial origin, location, shape, growth pattern, MRI signal intensity, evidence for edema, and paramagnetic contrast enhancement. Histologic diagnoses included 5 intracranially invading nasal tumors, 7 pituitary tumors, 22 meningiomas, 6 choroid plexus tumors, 7 astrocytomas, 1 ependymoma, and 2 oligodendrogliomas. Axial origin, site, shape, and growth pattern were important diagnostic characteristics for tumor type. Signal intensity Magnetic resonance imaging (MRI) is the preferred imaging method for human beings with central nervous system disease, and it has become increasingly available and affordable for use in veterinary medicine. The MRI features of canine neurologic disease have been described, but histologic diagnoses have not been available in all instance^.'.^ In this study, MRI scans of 50 histologically diagnosed canine intracranial tumors were evaluated retrospectively to identify distinguishing characteristics. Materials and Methods Selection CriteriaDogs with clinical signs of intracranial disease were referred to Washington State University Veterinary Teaching Hospital. The dogs were evaluated using a standard diagnostic protocol as part of a phase I clinical trial for boron neutron capture therapy, which was conducted with approval from the Animal Care and Use Committee.4.' Most dogs in the study had been treated with corticosteroids at the time of imaging. All patients had a complete MRI brain scan and histologic diagnosis of intracranial tumor. Patients with potential metastatic intracranial neoplasia were not included in the study. From the Magnetic Resonance Scan ProtocolDetails of the MRI protocol have been described previously.' Briefly, MRI was performed with a 1.5 T magnet (General Electric Signa, Milwaukee, WI). Under general anesthesia, dogs were placed in sternal recumbency, and a sagittal localizer series (time of relaxation or TR = 400 msec/time to echo or TE = 20 msec) was performed to delineate subsequent transverse images. Transverse proton density-weighted images (PDWI) and TZ-weighted images (TZWI) were obtained with a multiple spin echo series at TR = 2000 msec with TE = 20 to 30 and 80 to 90 msec. Transverse and sagittal precontrast and postcontrast T1-weighted images (T1 WI) were performed using TR = 800 msec and TE = 20 msec. Three to 5 mm slices with an interslice gap of 0 to 1.5 mm were obtained from the foramen magnum rostrally through the cribriform plate.

Although mothers influence the traits of their offspring in many ways beyond the transmission of genes, it remains unclear how important such ‘maternal effects’ are to phenotypic differences among individuals. Synthesizing estimates derived from detailed pedigrees, we evaluated the amount of phenotypic variation determined by maternal effects in animal populations. Maternal effects account for half as much phenotypic variation within populations as do additive genetic effects. Maternal effects most greatly affect morphology and phenology but, surprisingly, are not stronger in species with prolonged maternal care than in species without. While maternal effects influence juvenile traits more than adult traits on average, they do not decline across ontogeny for behaviour or physiology, and they do not weaken across the life cycle in species without maternal care. These findings underscore maternal effects as an important source of phenotypic variation and emphasise their potential to affect many ecological and evolutionary processes.

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