The 1000 Genomes Project: deep genomic sequencing waiting for deep psychiatric phenotyping

Joober, Ridha

doi:10.1503/jpn.110026

Cited by 8 publications

(4 citation statements)

References 26 publications

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“…Deep phenotyping is increasingly recognized as critical in genetic analysis (Greenberg & Subaran, 2011; Joober, 2011) and is important to identify (see the following): (1) endophenotypes that could be used as biomarkers, (2) prognostic features (Moschetta et al., 2011), (3) and phenotypic clues to genetic heterogeneity. Subsequently, we can start to identify and control sources of genetic heterogeneity, testing the hypotheses that clinical features and family history can predict SCN1A and SLC2A1 mutations, and that cases from densely multiplex pedigrees are genetically heterogeneous from typical MAE cases.…”

Section: Genetic Strategies To Elucidate Etiologymentioning

confidence: 99%

Dissecting the genetic basis of myoclonic‐astatic epilepsy

Tang

Pal

2012

Epilepsia

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Summary Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first description. However, although the International League Against Epilepsy (ILAE) defined criteria for MAE in 1989, the diagnostic boundaries of the syndrome continue to be debated. Moreover, 40 years since Doose's first description of MAE, although a genetic predisposition is acknowledged and many studies have demonstrated familial aggregation of seizures within MAE families, the actual genetic determinants of MAE still remain unknown. Although initially thought to be within the same spectrum as severe myoclonic epilepsy of infancy, the exclusion of SCN1A mutations in non‐generalized epilepsy with febrile seizures plus (GEFS+) MAE cases has confirmed the genetic distinction of MAE. In this critical review, we shall trace the historical evolution of concepts around MAE and its distinction from Lennox‐Gastaut syndrome, review the described phenotypic features of MAE from updated studies that will allow its distinction from other overlap epilepsy syndromes, review the evidence of genetic influences and clues for genetic heterogeneity, and discuss strategies that may be helpful in elucidating the etiology of MAE in light of current genetic techniques.

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Section: Genetic Strategies To Elucidate Etiologymentioning

confidence: 99%

Dissecting the genetic basis of myoclonic‐astatic epilepsy

Tang

Pal

2012

Epilepsia

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“…Many researchers now maintain that the next step in establishing fruitful genotype-phenotype relationships between genetic mutations and diseases/disorders will be to develop more thorough descriptions of the phenotype-Next Generation Phenotyping [3] or "deep phenotyping" [6] . In a somewhat related article, Joober [7] asserts that the most important objective of the 1,000 Genomes Project is identify the greatest number of rare genetic variants as they relate to neuropsychiatric disorders. This would be achieved by selecting a large, representative sample of the general population, then partitioning the sample into two components: those with rare variants and those without.…”

Section: Ww Jacobs "The Monkey's Paw"mentioning

confidence: 99%

“…This would be achieved by selecting a large, representative sample of the general population, then partitioning the sample into two components: those with rare variants and those without. Given the presumed prevalence of rare genetic variants along with other, statistical conjectures, Joober [7] asserted that 45,000 participants randomly sampled from the population would suffice, assuming that researchers could obtain deep phenotypes of all study subjects.…”

Section: Ww Jacobs "The Monkey's Paw"mentioning

confidence: 99%

Deep Phenotyping in the -Omic Era: Methodological Issues Facing Neuropsychiatric Disorders

2018

J Psychiatry Brain Sci

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“…The exact role that these genes play and the regional effects that their variants have on the brain and secondarily on neurological and cognitive functions are mostly unknown. Strategies such as reverse phenotyping, whereby these risk alleles are associated with endopheno-types or biomarkers of disease such as neuroimaging, cerebrospinal fluid (CSF) proteomic and neuropsycho-logical measures, are becoming increasingly important in the quest to dissect the mechanisms underlying the heterogeneity of the neurodegenerations [ 16 , 17 ].…”

Section: Late-onset Versus Early-onset Dementia Syndromes: Etiologicamentioning

confidence: 99%

Early-onset dementias: diagnostic and etiological considerations

Masellis

Sherborn

Rosa‐Neto

et al. 2013

Alzheimers Res Ther

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This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect.

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The 1000 Genomes Project: deep genomic sequencing waiting for deep psychiatric phenotyping

Cited by 8 publications

References 26 publications

Dissecting the genetic basis of myoclonic‐astatic epilepsy

Dissecting the genetic basis of myoclonic‐astatic epilepsy

Deep Phenotyping in the -Omic Era: Methodological Issues Facing Neuropsychiatric Disorders

Early-onset dementias: diagnostic and etiological considerations

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