Aristaless-like homeobox protein 1 (ALX1) variant associated with craniofacial structure and frontonasal dysplasia in Burmese cats

AbstractFrontonasal 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. In particular, a lineage of Burmese cats with severe brachycephyla is extremely popular and is termed Contemporary Burmese. Genetic studies demonstrated that the brachycephyla of the Contemporary Burmese is a simple co-dominant trait, however, the homozygous cats have a severe craniofacial defect that is incompatible with life. The craniofacial defect of the Burmese was genetically analyzed over a 20 year period, using various genetic analysis techniques. Family-based linkage analysis localized the trait to cat chromosome B4. Genome-wide association studies and other genetic analyses of SNP data refined a critical region. Sequence analysis identified a 12bp in frame deletion in ALX1, c.496delCTCTCAGGACTG, which is 100% concordant with the craniofacial defect and not found in cats not related to the Contemporary Burmese

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. We thus investigated an animal-based saliva collection method for ease of use and quality of DNA obtained and tested the performance of saliva-extracted canine DNA on genome-wide genotyping arrays. Methodology/Principal Findings: Overall, we found that saliva sample collection using this method was efficient. Extractions yielded high concentrations (,125 ng/ul) of high-quality DNA that performed equally well as blood-extracted DNA on the Illumina Infinium canine genotyping platform, with average call rates.99%. Concordance rates between genotype calls of saliva- versus blood-extracted DNA samples from the same individual were also.99%. Additionally, in silico calling of copy number variants was successfully performed and verified by PCR. Conclusions/Significance: Our findings validate the use of saliva-obtained samples for genome-wide association studies i

Variation in Genes Related to Cochlear Biology Is Strongly Associated with Adult-Onset Deafness in Border Collies

WOS:000309817900003Peer reviewe

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

ObjectiveTo assess the influence of genetic and environmental risk factors upon postpartum depression.DesignCase-control, prospective study.SettingThe University of California at San Francisco Obstetric and Gynecology Clinic.ParticipantsMothers screened for postpartum depression six weeks after delivery with the Edinburgh Postnatal Depression Scale and recruited as cases and controls.MeasurementsEligible subjects completed a series of assessments and a structured clinical interview to confirm diagnosis of depression. Deoxyribonucleic acid was obtained for genotyping of 81 single nucleotide polymorphisms in 12 genes hypothesized to be postpartum depression-related.ResultsTwenty-four cases and 24 controls were eligible for analysis. Three single necleotide polymorphisms in the serotonin 2A receptor (HTR2A) gene were associated with postpartum depression. The strongest association at a functional promoter polymorphism (rs6311), a functional promoter single nucleotide polymorphisms (p=0.002, odds ratio 0.25, 95% confidence interval:0.10-0.63), was a finding robust to population stratification. Gene-wide association was significant for HTR2A (permuted p=0.008), but not when corrected for all 12 genes. Analysis of demographic and psychosocial risk factors identified distressed relationship, unplanned pregnancy, and a previous history of depression as significant predictive variables (p≤0.05).ConclusionsThis pilot data suggests deoxyribonucleic acid variations in HTR2A may be associated with postpartum depression. Psychosocial variables were also identified as risk factors. The relative influence of these variables on the manifestation of postpartum depression is yet to be determined

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. Participants: Mothers screened for postpartum depression six weeks after delivery with the Edinburgh Postnatal Depression Scale and recruited as cases and controls. Measurements: Eligible subjects completed a series of assessments and a structured clinical interview to confirm diagnosis of depression. Deoxyribonucleic acid was obtained for genotyping of 81 single nucleotide polymorphisms in 12 genes hypothesized to be postpartum depression-related. Results: Twenty-four cases and 24 controls were eligible for analysis. Three single necleotide polymorphisms in the serotonin 2A receptor (HTR2A) gene were associated with postpartum depression. The strongest association at a functional promoter polymorphism (rs6311), a functional promoter single nucleotide polymorphisms ( p =0.002, odds ratio 0.25, 95% confidence interval:0.10-0.63), was a finding robust to population stratification. Gene-wide association was significant for HTR2A (permuted p =0.008), but not when corrected for all 12 genes. Analysis of demographic and psychosocial risk factors identified distressed relationship, unplanned pregnancy, and a previous history of depression as significant predictive variables ( p ≤0.05). Conclusions: This pilot data suggests deoxyribonucleic acid variations in HTR2A may be associated with postpartum depression. Psychosocial variables were also identified as risk factors. The relative influence of these variables on the manifestation of postpartum depression is yet to be determined

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. NPAS1(-/-) mutants also had increased neocortical inhibition (sIPSC and mIPSC) and generated an excess of somatostatin(+) (SST) (MGE-derived) and vasoactive intestinal polypeptide(+) (VIP) (CGE-derived) neocortical interneurons, but had a normal density of parvalbumin(+) (PV) (MGE-derived) interneurons. In contrast, NPAS3(-/-) mutants showed decreased proliferation and ERK signaling in progenitors of the ganglionic eminences and had fewer SST(+) and VIP(+) interneurons. NPAS1 repressed activity of an Arx enhancer, and Arx overexpression resulted in increased proliferation of CGE progenitors. These results provide insights into genetic regulation of cortical interneuron numbers and cortical inhibitory tone

Manhattan plot of GWAS for adult-onset deafness.

<p>Chromosome markers are plotted on the x-axis in order and alternately shaded. The -log₁₀(p-value) is plotted on the y-axis. The red line indicates significance at the Bonferroni-corrected level for 30,000 SNPs. There is extensive regional support for an association on CFA6. The inset shows an enlargement of the 25-Mb association region, including genes of interest. The raw GWAS and permuted p-values (P_perm-gw) for the top SNP are also given.</p

Summary of association results with combined data from all stages of study.^a

a<p>SNP: marker name (location information); A1: risk allele; A2: reference allele; Fr_Case: allele frequency of A1 in cases; Fr_Cont: allele frequency of A1 in controls; P: p-values from allelic association analysis; OR: odds ratio with 95% confidence interval; Comb. P: combined p-value from meta-analysis.</p><p>The strength of association of the three variants is shown. Chr6.24500625 in <i>RBBP6</i> and Chr6.25681850 in <i>USP31</i> remain highly significant after inclusion of more cases and controls.</p