Human genetics and sleep behavior

Shi, Gongyi; Wu, David; Ptáček, Louis J.; Fu, Ying‐Hui

doi:10.1016/j.conb.2017.02.015

Cited by 26 publications

(10 citation statements)

References 47 publications

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“…However, the molecular pathways involved in regulating sleep and to what the extent they are conserved among vertebrates and invertebrates remain largely unknown. In humans, natural short sleepers exhibit a reduced amount of time in sleep without reporting daytime fatigue (reviewed in (Shi et al 2017)). In cases where the natural short sleep trait is hereditary, it is expected that the identification of the causal gene might lead to the understanding of the molecules that control sleepiness.…”

Section: Introductionmentioning

confidence: 99%

Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β

et al. 2020

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The molecular mechanism regulating sleep largely remains to be elucidated. In humans, families that carry mutations in TFAP2B, which encodes the transcription factor AP-2β, self-reported sleep abnormalities such as short-sleep and parasomnia. Notably, AP-2 transcription factors play essential roles in sleep regulation in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Thus, AP-2 transcription factors might have a conserved role in sleep regulation across the animal phyla. However, direct evidence supporting the involvement of TFAP2B in mammalian sleep was lacking. In this study, by using the CRISPR/Cas9 technology, we generated two Tfap2b mutant mouse strains, Tfap2bK144 and Tfap2bK145, each harboring a single-nucleotide mutation within the introns of Tfap2b mimicking the mutations in two human kindreds that self-reported sleep abnormalities. The effects of these mutations were compared with those of a Tfap2b knockout allele (Tfap2b-). The protein expression level of TFAP2B in the embryonic brain was reduced to about half in Tfap2b+/- mice and was further reduced in Tfap2b-/- mice. By contrast, the protein expression level was normal in Tfap2bK145/+ mice but was reduced in Tfap2bK145/K145 mice to a similar extent as Tfap2b-/- mice. Tfap2bK144/+and Tfap2bK144/K144 showed normal protein expression levels. Tfap2b+/- female mice showed increased wakefulness time and decreased non-rapid eye movement sleep (NREMS) time. By contrast, Tfap2bK145/+ female mice showed an apparently normal amount of sleep but instead exhibited fragmented NREMS, whereas Tfap2bK144/+ male mice showed reduced NREMS time specifically in the dark phase. Finally, in the adult brain, Tfap2b-LacZ expression was detected in the superior colliculus, locus coeruleus, cerebellum, and the nucleus of solitary tract. These findings provide direct evidence that TFAP2B influences NREMS amounts in mice and also show that different mutations in Tfap2b can lead to diverse effects on the sleep architecture.

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Section: Introductionmentioning

confidence: 99%

Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β

et al. 2020

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“…Sleep is governed by a host of neurophysiological networks, some of which play a key role in the physiopathology of ASD (Brown, Basheer, McKenna, Strecker, & McCarley, 2012;Shi, Wu, Ptáček, & Fu, 2017). As a matter of fact, sleep problems have been steadily reported to be found in 60%-85% of children with ASD according to parental reports, compared with 10%-30% in TD children (Richdale, 1999;Souders et al, 2017) and this has been confirmed in a meta-analysis of objective sleep measures (polysomnography and/or actigraphy), while intellectual disability and medication use was found to influence the findings (Elrod & Hood, 2015).…”

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confidence: 99%

NREM sleep EEG slow waves in autistic and typically developing children: Morphological characteristics and scalp distribution

Lehoux

Carrier

2018

Journal of Sleep Research

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Summary Autism is a developmental disorder with a neurobiological aetiology. Studies of the autistic brain identified atypical developmental trajectories that may lead to an impaired capacity to modulate electroencephalogram activity during sleep. We assessed the topography and characteristics of non‐rapid eye movement sleep electroencephalogram slow waves in 26 boys aged between 6 and 13 years old: 13 with an autism spectrum disorder and 13 typically developing. None of the participants was medicated, intellectually disabled, reported poor sleep, or suffered from medical co‐morbidities. Results are derived from a second consecutive night of polysomnography in a sleep laboratory. Slow waves (0.3–4.0 Hz; >75 µV) were automatically detected on artefact‐free sections of non‐rapid eye movement sleep along the anteroposterior axis in frontal, central, parietal and occipital derivations. Slow wave density (number per minute), amplitude (µV), slope (µV s−1) and duration (s) were computed for the first four non‐rapid eye movement periods. Slow wave characteristics comparisons between groups, derivations and non‐rapid eye movement periods were assessed with three‐way mixed ANOVAs. Slow wave density, amplitude, slope and duration were higher in anterior compared with most posterior derivations in both groups. Children with autism spectrum disorder showed lower differences in slow waves between recording sites along the anteroposterior axis than typically developing children. These group differences in the topography of slow wave characteristics were stable across the night. We propose that slow waves during non‐rapid eye movement sleep could be an electrophysiological marker of the deviant cortical maturation in autism linked to an atypical functioning of thalamo‐cortical networks.

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“…In addition, homozygous mutations often lead to lethality or severe disease, preventing examination of sleep/wake phenotype, as in the case of the Cacna1a (Drowsy) mutation (see below) (23). Indeed, genetic mutations identified in the heritable sleep disorder, such as familial advance sleep phase, show autosomaldominant inheritance (24). Several genome-wide association studies (GWAS) also show heterozygous carriers of the polymorphism having altered sleep architectures (25).…”

Section: Resultsmentioning

confidence: 99%

Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice

Miyoshi

Kim

Ezaki

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The regulatory network of genes and molecules in sleep/wakefulness remains to be elucidated. Here we describe the methodology and workflow of the dominant screening of randomly mutagenized mice and discuss theoretical basis of forward genetics research for sleep in mice. Our high-throughput screening employs electroencephalogram (EEG) and electromyogram (EMG) to stage vigilance states into a wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS). Based on their near-identical sleep/wake behavior, C57BL/6J (B6J) and C57BL/6N (B6N) are chosen as mutagenized and counter strains, respectively. The total time spent in the wake and NREMS, as well as the REMS episode duration, shows sufficient reproducibility with small coefficients of variance, indicating that these parameters are most suitable for quantitative phenotype-driven screening. Coarse linkage analysis of the quantitative trait, combined with whole-exome sequencing, can identify the gene mutation associated with sleep abnormality. Our simulations calculate the achievable LOD score as a function of the phenotype strength and the numbers of mice examined. A pedigree showing a mild decrease in total wake time resulting from a heterozygous point mutation in the Cacna1a gene is described as an example.

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Human genetics and sleep behavior

Cited by 26 publications

References 47 publications

Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β

Sleep Architecture in Mice Is Shaped by the Transcription Factor AP-2β

NREM sleep EEG slow waves in autistic and typically developing children: Morphological characteristics and scalp distribution

Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice

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