Sex-chromosome dosage effects on gene expression in humans

Raznahan, Armin; Parikshak, Neelroop N.; Chandran, V. Ravi; Blumenthal, Jonathan D.; Clasen, Liv S.; Alexander-Bloch, Aaron; Zinn, Andrew R.; Wangsa, Danny; Wise, Jasen; Murphy, Declan; Bolton, Patrick; Ried, Thomas; Ross, Judith L.; Giedd, Jay N.; Geschwind, Daniel H.

doi:10.1073/pnas.1802889115

Cited by 142 publications

(136 citation statements)

References 32 publications

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“…The presence of two X chromosomes may play a protective role and create a blueprint for slightly less variability in brain structure in females compared to males. Recent work on sex-chromosome aneuploidy has indicated a dose effect of sex-chromosomes on gene expression (48) . Additional work from the same group has found effects of sex-chromosome dosage on brain structures (49,50) .…”

Section: Discussionmentioning

confidence: 99%

Sex differences in Variability of Brain Structure Across the Lifespan

Forde

Jeyachandra

Joseph

et al. 2019

Preprint

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Several brain disorders exhibit sex differences in onset, presentation, and prevalence.Increased understanding of the neurobiology of sex-based differences across the lifespan can provide insight into potential disease risk and protective mechanisms. We focused on sex-related differences in variability, which may be indicative of both disease vulnerability and resilience. In n=3,069 participants, from 8-95 years of age, we first analyzed the variance ratio in females vs. males of cortical surface area and global and subcortical volumes for discrete brain regions, and found widespread greater variability in males. In contrast, variance in cortical thickness was similar for males and females. Multivariate analysis that accounts for structural covariance supported variance ratio findings. Findings were present from early life and stable with age. We then examined variability among brain regions by sex. We found significant age-by-sex interactions across neuroimaging metrics, whereby in very early life males had reduced among-region variability compared to females, while in very late life this was reversed. Overall, our findings of greater regional variability but less among-region variability in males in early life may aid our understanding of sex-based risk for neurodevelopmental disorders. In contrast, our findings in late life may provide a potential sex-based risk mechanism for dementia.

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Section: Discussionmentioning

confidence: 99%

Sex differences in Variability of Brain Structure Across the Lifespan

Forde

Jeyachandra

Joseph

et al. 2019

Preprint

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“…Future studies involving animal and cell lines containing allosome aneuploidy (XXX, XXY) and specific regional modifications (deletions, point mutations, etc.) are required to provide sufficient evidence regarding the role of XIST in OSCC [30].…”

Section: Discussionmentioning

confidence: 99%

Absence of Salivary lncRNA-XIST Indicates High Susceptibility to Oral Cancer

Liu¹,

Shieh²,

Wang³

et al. 2018

Preprint

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Oral cancer is one of the most common malignancies worldwide, with a two- or three-fold prevalence among men than among women. Except for lifestyle-related risk factors including smoking, drinking, and betel chewing, family history is a major determinant of risk in the absence of exposure to carcinogens. Genes predicting the susceptibility to oral cancer are associated with cell proliferation, cell invasion, angiogenesis, and DNA repair. Few studies have investigated sex-dependent X-linked gene expression in oral cancer. Hence, this study aimed to analyze salivary X-linked lncRNA-XIST, XIST anti-transcript TSIX, and X-linked tumor suppressor gene LDOC1 expression levels, their role in oral squamous cell carcinoma (OSCC) and correlations among clinicopathological data. Expression levels of these three genes were analyzed via quantitative polymerase chain reaction (qPCR) in the saliva of 59 OSCC patients and 43 healthy controls. Correlations among gene expression levels and clinicopathological characteristics were analyzed. Women lacking salivary XIST were 26-fold more susceptible (P < 0.0001) to OSCC than healthy women. TSIX and LDOC1 expression levels were positively correlated in all subjects, except for men with OSCC. LDOC1 was significantly downregulated in men with OSCC (P = 0.016) and significantly correlated with well-differentiated tumors (P = 0.001).

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“…Therefore, if one wants to find a biomarker, for instance dyslexia, one immediately carries together a group of different genetic conditions, as defined by their genotype. Because of these obstacles, an alternative approach has been proposed [109][110][111], namely trying to first understand the biology of neurodevelopmental disorders with genetically defined groups, such as those with sex chromosome aneuploidy (SCA) syndrome. This strategy can be helpful because the genetic makeups in SCA syndrome are known.…”

Section: Integrative Neuroimagingmentioning

confidence: 99%

Neuroimaging Findings for Developmental Coordination Disorder (DCD) in Adults: Critical Evaluation and Future Directions

Reid¹

2020

Neuroimaging - Neurobiology, Multimodal and Network Applications

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Approximately 75% of those diagnosed with developmental coordination disorder (DCD) exhibit motor problems in adulthood. Neuroimaging studies promise to reveal the endophenotypes of mature brain systems affected by DCD. The aim here was to review these publications. Bibliographic searches identified papers published before June 2019. Neuroimaging results revealed: functional abnormalities in the prefrontal, frontal and occipital regions, superior parietal lobe and cerebellum; structural white matter abnormalities in the corticospinal tract, internal capsule and inferior and superior longitudinal fasciculi; significantly reduced interhemispheric cortical inhibition within the primary motor cortex (hPMC); lack of increased hPMC activity during a motor imagery task and a reduced leftwards brain asymmetry for speech. These results suggest complex endophenotypes for adults with DCD (DCDAs). However, the studies have shortcomings. For instance, all relied upon small and unrepresentative samples. Gender and age were not tested systematically. The effects of many co-occurring disorders were not controlled. Most studies relied on between group comparisons, which, given the heterogeneity of DCD, may obscure the results for underrepresented cases. Overall, the young field of neuroimaging studies of DCDAs reported interesting results; however, there is an urgent need for investigations to address these shortcomings. Future research directions, including cuttingedge neuroimaging techniques and imaging genetics, are discussed. using a skill and chronological age), acquisition and execution of coordinated motor skills. Second, this motor deficit significantly interferes with the activities of everyday life, academic achievements and occupational and recreational activities. Third, DCD symptoms have their onset in early development. Fourth, deficits in motor skills are not better accounted for by intellectual or visual deficits, or neurological impairments, such as degenerative disorder, cerebral palsy, muscular dystrophy, multiple sclerosis or Parkinson's disease, which affect movement.Different prevalence rates of DCD have been reported; however, perhaps the most reliable are the results from a large UK population study of 6990 7-to 8-yearold children [2]. This study revealed a prevalence of 1.7%. An additional 3.2% of children were identified as having 'probable DCD' by using broader cut-off criteria on tests of motor coordination and activities of daily living. Males are more often affected than females, with the male to female ratio ranging from 2:1 to 7:1 [1].Until recently, motor-coordination difficulties in childhood were thought to be typically outgrown in adulthood. However, it is estimated that approximately 75% of those diagnosed with DCD will continue to exhibit motor problems into adulthood [3,4]. Indeed, studies on DCDAs [5-18] demonstrate that they perform significantly worse than control participants (CPs) on various motor tasks. If one pauses for a moment and considers that the only way humans can affect the wo...

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Sex-chromosome dosage effects on gene expression in humans

Cited by 142 publications

References 32 publications

Sex differences in Variability of Brain Structure Across the Lifespan

Sex differences in Variability of Brain Structure Across the Lifespan

Absence of Salivary lncRNA-XIST Indicates High Susceptibility to Oral Cancer

Neuroimaging Findings for Developmental Coordination Disorder (DCD) in Adults: Critical Evaluation and Future Directions

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