BackgroundNeurodevelopmental and neuropsychiatric disorders represent a wide spectrum of heterogeneous yet inter-related disease conditions. The overlapping clinical presentations of these diseases suggest a shared genetic etiology. We aim to identify shared structural variants spanning the spectrum of five neuropsychiatric disorders.MethodsWe investigated copy number variations (CNVs) in five cohorts, including schizophrenia (SCZ), bipolar disease (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and depression, from 7849 cases and 10,799 controls. CNVs were called based on intensity data from genome-wide SNP arrays and CNV frequency was compared between cases and controls in each disease cohort separately. Meta-analysis was performed via a gene-based approach. Quantitative PCR (qPCR) was employed to validate novel significant loci.ResultsIn our meta-analysis, two genes containing CNVs with exonic overlap reached genome-wide significance threshold of meta P value < 9.4 × 10−6 for deletions and 7.5 × 10−6 for duplications. We observed significant overlap between risk CNV loci across cohorts. In addition, we identified novel significant associations of DOCK8/KANK1 duplications (meta P value = 7.5 × 10−7) across all cohorts, and further validated the CNV region with qPCR.ConclusionsIn the first large scale meta-analysis of CNVs across multiple neurodevelopmental/psychiatric diseases, we uncovered novel significant associations of structural variants in the locus of DOCK8/KANK1 shared by five diseases, suggesting common etiology of these clinically distinct neurodevelopmental conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0494-1) contains supplementary material, which is available to authorized users.

BackgroundEhlers Danlos Syndrome is a rare form of inherited connective tissue disorder, which primarily affects skin, joints, muscle, and blood cells. The current study aimed at finding the mutation that causing EDS type VII C also known as “Dermatosparaxis” in this family.MethodsThrough systematic data querying of the electronic medical records (EMRs) of over 80,000 individuals, we recently identified an EDS family that indicate an autosomal dominant inheritance. The family was consented for genomic analysis of their de-identified data. After a negative screen for known mutations, we performed whole genome sequencing on the male proband, his affected father, and unaffected mother. We filtered the list of non-synonymous variants that are common between the affected individuals.ResultsThe analysis of non-synonymous variants lead to identifying a novel mutation in the ADAMTSL2 (p. Gly421Ser) gene in the affected individuals. Sanger sequencing confirmed the mutation.ConclusionOur work is significant not only because it sheds new light on the pathophysiology of EDS for the affected family and the field at large, but also because it demonstrates the utility of unbiased large-scale clinical recruitment in deciphering the genetic etiology of rare mendelian diseases. With unbiased large-scale clinical recruitment we strive to sequence as many rare mendelian diseases as possible, and this work in EDS serves as a successful proof of concept to that effect.

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Background: India is fortunate to have a vast livestock resource with the availability of 28 well defined goat breeds. Kerala is the home for two breeds of goats namely Malabari and Attapady Black. Due to high prolificacy and income through lower input goat rearing had attracted numerous farmers. Selection with the aid of molecular markers associated with production traits plays an essential role in goat breeding programmes. The EGR2 gene is a part of multigene family which encodes Cys2His2 type zinc-finger proteins which is responsible for DNA binding. This gene has a major role in cellular prolification, reproduction, proper growth and development ovarian follicles. Thus present study was conducted with an objective to detect single nucleotide variations of Early Growth Response 2 gene in native goat breeds of Kerala. Methods: This research was conducted in 153 Malabari goats and 129 Attappady Black goats from six centers viz., University Goat and Sheep farm Mannuthy and 5 field centers of ICAR- All India Coordinated Research Project on Goat Improvement. Genomic DNA was isolated and PCR was performed to amplify Exon 1, Exon 2 and 5 fragments of Exon 3 regions of Early Growth Response 2 gene. Single stranded conformation polymorphism (SSCP) technique was performed to detect Single Nucleotide Polymorphism (SNPs). Result: The SSCP revealed similar banding patterns and sequencing did not indicate any nucleotide variations in all the exons screened suggesting that EGR2 gene is highly conserved in native goat breeds of Kerala. This is the first study conducted to characterize EGR2 gene in goats making the current study a novel one.

Background: Healthy transition from non-lactating pregnant state to non-pregnant lactating state is an important in the profitability of dairying. Though feeding and managemental practices play an important role in the adaptation to transition, animals kept on similar feeding and management exhibit differences in adaptation indicating an underlying genetic cause. In the present study, the sequence of gene SNAI2, which is considered to have an effect on metabolic adaptability has been compared among animals with apparently varying adaptability, as indicated by their β-hydroxy butyric acid (BHBA) concentration. Methods: During the period from August 2018 to May 2019, blood was collected and serum was separated from 30 pregnant cross bred (belonging to Sunandini genetic group of cross bred cattle of Kerala) dairy cows at fortnightly intervals from four weeks before the predicted day of parturition until four weeks after parturition. Concentration of BHBA was determined. Based on BHBA concentration the animals were sorted into two groups (High BHBA and low BHBA) using cluster analysis. Blood was collected, DNA extracted and SNAI2 gene amplified using custom synthesised primers. Amplicons from representative animals of each group were sequenced. The sequences obtained were aligned and compared using clustal-ω. Result: The comparison of the sequence of SNAI2 gene amongst the animals having high BHBA and those with low BHBA revealed two variations between the groups, one at promoter region, 61 bp upstream to the gene and other was at exonic region at 1560 bp. In silico structural analysis revealed difference in protein structure. The changes observed in the gene SNAI2 between the sets of animals grouped based on BHBA has to be studied on a larger population to ascertain the suitability of them being used as markers of genetic selection for metabolic adaptability, which in turn can increase the profitability of dairying.