An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.

Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories.

A Rare Variant in Segregates with 7 Bipolar I Disorder Cases in a Large Pedigree.

Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a multiplex pedigree of European ancestry with 7 BPI cases. Within , a gene implicated by genome-wide association studies, a G to C nucleotide transversion at 53,835,340 base pairs (bps) was found predicting the substitution of proline for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the DNA variant was shown to co-segregate with the remaining 4 BPI cases within the pedigree.

Aristaless-Like Homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats.

Frontonasal dysplasia (FND) can have severe presentations that are medically and socially debilitating. Several genes are implicated in FND conditions, including Aristaless-Like Homeobox 1 (ALX1), which is associated with FND3. Breeds of cats are selected and bred for extremes in craniofacial morphologies.

NPAS1 represses the generation of specific subtypes of cortical interneurons.

Little is known about genetic mechanisms that regulate the ratio of cortical excitatory and inhibitory neurons. We show that NPAS1 and NPAS3 transcription factors (TFs) are expressed in progenitor domains of the mouse basal ganglia (subpallium, MGE, and CGE). NPAS1(-/-) mutants had increased proliferation, ERK signaling, and expression of Arx in the MGE and CGE.

A pilot study evaluating genetic and environmental factors for postpartum depression.

Objective: To assess the influence of genetic and environmental risk factors upon postpartum depression.

Design: Case-control, prospective study.

Setting: The University of California at San Francisco Obstetric and Gynecology Clinic.

Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.

Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans.

Array-based whole-genome survey of dog saliva DNA yields high quality SNP data.

Background: Genome-wide association scans for genetic loci underlying both Mendelian and complex traits are increasingly common in canine genetics research. However, the demand for high-quality DNA for use on such platforms creates challenges for traditional blood sample ascertainment. Though the use of saliva as a means of collecting DNA is common in human studies, alternate means of DNA collection for canine research have instead been limited to buccal swabs, from which dog DNA is of insufficient quality and yield for use on most high-throughput array-based systems.

Feline polycystic kidney disease mutation identified in PKD1.

Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder in humans that causes the formation of fluid-filled renal cysts, often leading to renal failure. PKD1 mutations cause 85% of ADPKD. Feline PKD is autosomal dominant and has clinical presentations similar to humans.