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- Hu, H., et al.
(författare)
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X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:1, s. 133-148
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Tidskriftsartikel (refereegranskat)abstract
- X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
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| 3. |
- Sreerekha, T.R., et al.
(författare)
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A strong ice cloud event as seen by a microwave satellite sensor : simulations and observations
- 2008
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier BV. - 0022-4073 .- 1879-1352. ; 109:9, s. 1705-1718
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Tidskriftsartikel (refereegranskat)abstract
- In this article, brightness temperatures observed by channels of the Advanced Microwave Sounding Unit-B (AMSU-B) instrument are compared to those simulated by a radiative transfer model, which can take into account the multiple scattering due to ice particles by using a discrete ordinate iterative solution method. The input fields, namely, the pressure, temperature, humidity, and cloud water content are taken from the short range forecast from the Met Office mesoscale model (UKMES). The comparison was made for a case study on the 25 January 2002 when a frontal system associated with significant cloud was present over the UK. It is demonstrated that liquid clouds have maximum impact on channel 16 of AMSU whereas ice clouds have maximum impact on channel 20. The main uncertainty for simulating microwave radiances is the assumptions about microphysical properties, such as size distribution, shape and orientation of the cloud particles, which are not known in the mesoscale model. The article examines the impact of these parameters on the cloud signal. The polarisation signal due to oriented ice particles at these frequencies is also discussed.
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