49 results found
Need AC, Shashi V, Schoch K, et al., 2017, The importance of dynamic re-analysis in diagnostic whole exome sequencing, JOURNAL OF MEDICAL GENETICS, Vol: 54, Pages: 155-156, ISSN: 0022-2593
Trampush JW, Yang MLZ, Yu J, et al., 2017, GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium, MOLECULAR PSYCHIATRY, Vol: 22, Pages: 336-345, ISSN: 1359-4184
Need AC, Goldstein DB, 2016, Neuropsychiatric genomics in precision medicine: diagnostics, gene discovery, and translation, DIALOGUES IN CLINICAL NEUROSCIENCE, Vol: 18, Pages: 237-252, ISSN: 1294-8322
Shashi V, Pena LDM, Kim K, et al., 2016, De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 99, Pages: 991-999, ISSN: 0002-9297
Shashi V, Xie P, Schoch K, et al., 2015, The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome, CLINICAL GENETICS, Vol: 88, Pages: 386-390, ISSN: 0009-9163
Zhu X, Petrovski S, Xie P, et al., 2015, Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios, Genetics in Medicine, Vol: 17, Pages: 774-781, ISSN: 1530-0366
Purpose:Despite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain immature. Diagnoses are based on known or presumed pathogenic variants in genes already associated with a similar phenotype. Here, we extend this paradigm by evaluating novel bioinformatics approaches to aid identification of new gene–disease associations.Methods:We analyzed 119 trios to identify both diagnostic genotypes in known genes and candidate genotypes in novel genes. We considered qualifying genotypes based on their population frequency and in silico predicted effects we also characterized the patterns of genotypes enriched among this collection of patients.Results:We obtained a genetic diagnosis for 29 (24%) of our patients. We showed that patients carried an excess of damaging de novo mutations in intolerant genes, particularly those shown to be essential in mice (P = 3.4 × 10−8). This enrichment is only partially explained by mutations found in known disease-causing genes.Conclusion:This work indicates that the application of appropriate bioinformatics analyses to clinical sequence data can also help implicate novel disease genes and suggest expanded phenotypes for known disease genes. These analyses further suggest that some cases resolved by whole-exome sequencing will have direct therapeutic implications.
Enns GM, Shashi V, Bainbridge M, et al., 2014, Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway, GENETICS IN MEDICINE, Vol: 16, Pages: 751-758, ISSN: 1098-3600
Need AC, Goldstein DB, 2014, Schizophrenia Genetics Comes of Age, NEURON, Vol: 83, Pages: 760-763, ISSN: 0896-6273
Nutt DJ, Need AC, 2014, Where now for schizophrenia research?, EUROPEAN NEUROPSYCHOPHARMACOLOGY, Vol: 24, Pages: 1181-1187, ISSN: 0924-977X
Shashi V, McConkie-Rosell A, Rosell B, et al., 2014, The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders, Genetics in Medicine, Vol: 16, Pages: 176-182, ISSN: 1098-3600
Tiwari AK, Need AC, Lohoff FW, et al., 2014, Exome sequence analysis of Finnish patients with clozapine-induced agranulocytosis, MOLECULAR PSYCHIATRY, Vol: 19, Pages: 403-405, ISSN: 1359-4184
Zhu X, Need AC, Petrovski S, et al., 2014, One gene, many neuropsychiatric disorders: lessons from Mendelian diseases, NATURE NEUROSCIENCE, Vol: 17, Pages: 773-781, ISSN: 1097-6256
Smith PJ, Need AC, Cirulli ET, et al., 2013, A comparison of the Cambridge Automated Neuropsychological Test Battery (CANTAB) with "traditional" neuropsychological testing instruments, JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY, Vol: 35, Pages: 319-328, ISSN: 1380-3395
Heinzen EL, Depondt C, Cavalleri GL, et al., 2012, Exome Sequencing Followed by Large-Scale Genotyping Fails to Identify Single Rare Variants of Large Effect in Idiopathic Generalized Epilepsy, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 91, Pages: 293-302, ISSN: 0002-9297
Need AC, McEvoy JP, Gennarelli M, et al., 2012, Exome Sequencing Followed by Large-Scale Genotyping Suggests a Limited Role for Moderately Rare Risk Factors of Strong Effect in Schizophrenia, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 91, Pages: 303-312, ISSN: 0002-9297
Need AC, Shashi V, Hitomi Y, et al., 2012, Clinical application of exome sequencing in undiagnosed genetic conditions, JOURNAL OF MEDICAL GENETICS, Vol: 49, Pages: 353-361, ISSN: 0022-2593
Zhu M, Need AC, Han Y, et al., 2012, Using ERDS to Infer Copy-Number Variants in High-Coverage Genomes, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 91, Pages: 408-421, ISSN: 0002-9297
Dennis NA, Cabeza R, Need AC, et al., 2011, Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Hippocampal Activation During Episodic Encoding and Retrieval Tasks, HIPPOCAMPUS, Vol: 21, Pages: 980-989, ISSN: 1050-9631
Ge D, Ruzzo EK, Shianna KV, et al., 2011, SVA: software for annotating and visualizing sequenced human genomes, BIOINFORMATICS, Vol: 27, Pages: 1998-2000, ISSN: 1367-4803
Pelak K, Need AC, Fellay J, et al., 2011, Copy Number Variation of KIR Genes Influences HIV-1 Control, PLOS BIOLOGY, Vol: 9, ISSN: 1544-9173
Cirulli ET, Kasperaviciute D, Attix DK, et al., 2010, Common genetic variation and performance on standardized cognitive tests, EUROPEAN JOURNAL OF HUMAN GENETICS, Vol: 18, Pages: 815-819, ISSN: 1018-4813
Cirulli ET, Kasperaviit D, Attix DK, et al., 2010, Erratum: Common genetic variation and performance on standardized cognitive tests (European Journal of Human Genetics (2010) 18 (820) DOI: 10.1038/ejhg.2010.2), European Journal of Human Genetics, Vol: 18, ISSN: 1018-4813
Dennis NA, Browndyke JN, Stokes J, et al., 2010, Temporal lobe functional activity and connectivity in young adult APOE varepsilon4 carriers., Alzheimers Dement, Vol: 6, Pages: 303-311
BACKGROUND: We sought to determine if the APOE epsilon4 allele influences both the functional activation and connectivity of the medial temporal lobes (MTLs) during successful memory encoding in young adults. METHODS: Twenty-four healthy young adults, i.e., 12 carriers and 12 noncarriers of the APOE epsilon4 allele, were scanned in a subsequent-memory paradigm, using event-related functional magnetic resonance imaging. The neuroanatomic correlates of successful encoding were measured as greater neural activity for subsequently remembered versus forgotten task items, or in short, encoding success activity (ESA). Group differences in ESA within the MTLs, as well as whole-brain functional connectivity with the MTLs, were assessed. RESULTS: In the absence of demographic or performance differences, APOE epsilon4 allele carriers exhibited greater bilateral MTL activity relative to noncarriers while accomplishing the same encoding task. Moreover, whereas epsilon4 carriers demonstrated a greater functional connectivity of ESA-related MTL activity with the posterior cingulate and other peri-limbic regions, reductions in overall connectivity were found across the anterior and posterior cortices. CONCLUSIONS: These results suggest that the APOE varepsilon4 allele may influence not only functional activations within the MTL, but functional connectivity of the MTLs to other regions implicated in memory encoding. Enhanced functional connectivity of the MTLs with the posterior cingulate in young adult epsilon4 carriers suggests that APOE may be expressed early in brain regions known to be involved in Alzheimer's disease, long before late-onset dementia is a practical risk or consideration. These functional connectivity differences may also reflect pleiotropic effects of APOE during early development.
Dennis NA, Need AC, LaBar KS, et al., 2010, COMT Val(108/158) Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals, CEREBRAL CORTEX, Vol: 20, Pages: 672-683, ISSN: 1047-3211
Heinzen EL, Need AC, Hayden KM, et al., 2010, Genome-Wide Scan of Copy Number Variation in Late-Onset Alzheimer's Disease, JOURNAL OF ALZHEIMERS DISEASE, Vol: 19, Pages: 69-77, ISSN: 1387-2877
Heinzen EL, Radtke RA, Urban TJ, et al., 2010, Rare Deletions at 16p13.11 Predispose to a Diverse Spectrum of Sporadic Epilepsy Syndromes, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 86, Pages: 707-718, ISSN: 0002-9297
Need AC, Goldstein DB, 2010, Whole genome association studies in complex diseases: where do we stand?, Dialogues Clin Neurosci, Vol: 12, Pages: 37-46, ISSN: 1294-8322
Hundreds of genome-wide association studies have been performed in recent years in order to try to identify common variants that associate with complex disease. These have met with varying success. Some of the strongest effects of common variants have been found in late-onset diseases and in drug response. The major histocompatibility complex has also shown very strong association with a variety of disorders. Although there have been some notable success stories in neuropsychiatric genetics, on the whole, common variation has explained little of the high heritability of these traits. In contrast, early studies of rare copy number variants have led rapidly to a number of genes and loci that strongly associate with neuropsychiatric disorders. It is likely that the use of whole-genome sequencing to extend the study of rare variation in neuropsychiatry will greatly advance our understanding of neuropsychiatric genetics.
Need AC, Goldstein DB, 2010, Whole genome association studies in complex diseases: Where do we stand?, Dialogues in Clinical Neuroscience, Vol: 12, Pages: 34-43, ISSN: 1294-8322
Hundreds of genome-wide association studies have been performed in recent years in order to try to identify common variants that associate with complex disease. These have met with varying success. Some of the strongest effects of common variants have been found in late-onset diseases and in drug response. The major histo-compatibility complex has also shown very strong association with a variety of disorders. Although there have been some notable success stories in neuropsychiatric genetics, on the whole, common variation has explained little of the high heritability of these traits. In contrast, early studies of rare copy number variants have led rapidly to a number of genes and loci that strongly associate with neuropsychiatric disorders. It is likely that the use of whole-genome sequencing to extend the study of rare variation in neuropsychiatry will greatly advance our understanding of neuropsychiatric genetics. © 2010, LLS SAS. All rights reserved.
Pelak K, Shianna KV, Ge D, et al., 2010, The Characterization of Twenty Sequenced Human Genomes, PLOS GENETICS, Vol: 6, ISSN: 1553-7390
Need AC, Attix DK, McEvoy JM, et al., 2009, A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB, HUMAN MOLECULAR GENETICS, Vol: 18, Pages: 4650-4661, ISSN: 0964-6906
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