W60. ANALYSIS OF WHOLE EXOME SEQUENCING IN SEVERE MENTAL ILLNESS HINTS AT SELECTION OF BRAIN DEVELOPMENT AND IMMUNE RELATED GENES

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 75 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimers disease and cognitive abilities in genome wide association studies. We then checked whether any of these 75 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 75 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.

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Multiple Variant Calling Pipelines in Wheat Whole Exome Sequencing

International Journal of Molecular Sciences ◽

10.3390/ijms221910400 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10400

Author(s):

H. Busra Cagirici ◽

Bala Ani Akpinar ◽

Taner Z. Sen ◽

Hikmet Budak

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Variant Calling ◽

High Sensitivity ◽

Whole Exome ◽

The Impact ◽

Multiple Reference ◽

Reference Genomes ◽

Selection Of ◽

Variant Identification

The highly challenging hexaploid wheat (Triticum aestivum) genome is becoming ever more accessible due to the continued development of multiple reference genomes, a factor which aids in the plight to better understand variation in important traits. Although the process of variant calling is relatively straightforward, selection of the best combination of the computational tools for read alignment and variant calling stages of the analysis and efficient filtering of the false variant calls are not always easy tasks. Previous studies have analyzed the impact of methods on the quality metrics in diploid organisms. Given that variant identification in wheat largely relies on accurate mining of exome data, there is a critical need to better understand how different methods affect the analysis of whole exome sequencing (WES) data in polyploid species. This study aims to address this by performing whole exome sequencing of 48 wheat cultivars and assessing the performance of various variant calling pipelines at their suggested settings. The results show that all the pipelines require filtering to eliminate false-positive calls. The high consensus among the reference SNPs called by the best-performing pipelines suggests that filtering provides accurate and reproducible results. This study also provides detailed comparisons for high sensitivity and precision at individual and population levels for the raw and filtered SNP calls.

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Novel scripts for improved annotation and selection of variants from whole exome sequencing in cancer research

MethodsX ◽

10.1016/j.mex.2015.03.003 ◽

2015 ◽

Vol 2 ◽

pp. 145-153 ◽

Cited By ~ 4

Author(s):

Marcus Celik Hansen ◽

Line Nederby ◽

Anne Roug ◽

Palle Villesen ◽

Eigil Kjeldsen ◽

...

Keyword(s):

Cancer Research ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome ◽

Selection Of

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The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants

Scientific Reports ◽

10.1038/s41598-019-53500-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

J. Graham Theisen ◽

Viji Sundaram ◽

Mary S. Filchak ◽

Lynn P. Chorich ◽

Megan E. Sullivan ◽

...

Keyword(s):

Brain Development ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genetic Variants ◽

Gender Dysphoria ◽

Social Acceptance ◽

Rare Variants ◽

Estrogen Signaling ◽

Sexually Dimorphic ◽

Whole Exome

AbstractApproximately 0.5–1.4% of natal males and 0.2–0.3% of natal females meet DSM-5 criteria for gender dysphoria, with many of these individuals self-describing as transgender men or women. Despite recent improvements both in social acceptance of transgender individuals as well as access to gender affirming therapy, progress in both areas has been hampered by poor understanding of the etiology of gender dysphoria. Prior studies have suggested a genetic contribution to gender dysphoria, but previously proposed candidate genes have not yet been verified in follow-up investigation. In this study, we expand on the topic of gender identity genomics by identifying rare variants in genes associated with sexually dimorphic brain development and exploring how they could contribute to gender dysphoria. To accomplish this, we performed whole exome sequencing on the genomic DNA of 13 transgender males and 17 transgender females. Whole exome sequencing revealed 120,582 genetic variants. After filtering, 441 variants in 421 genes remained for further consideration, including 21 nonsense, 28 frameshift, 13 splice-region, and 225 missense variants. Of these, 21 variants in 19 genes were found to have associations with previously described estrogen receptor activated pathways of sexually dimorphic brain development. These variants were confirmed by Sanger Sequencing. Our findings suggest a new avenue for investigation of genes involved in estrogen signaling pathways related to sexually dimorphic brain development and their relationship to gender dysphoria.

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