Understanding the complexity of the human brain transcriptome architecture is one of the most important human genetics study areas. Previous studies have applied expression quantitative trait loci (eQTL) analysis at the genome-wide level of the brain to understand the underlying mechanisms relating to neurodegenerative diseases, primarily at the transcript level. To increase the resolution of our understanding, the current study investigates multi/single-region, transcript/exon-level and cis versus trans-acting eQTL, across 10 regions of the human brain. Some of the key findings of this study are: (i) only a relatively small proportion of eQTLs will be detected, where the sensitivity is under 5%; (ii) when an eQTL is acting in multiple regions (MR-eQTL), it tends to have very similar effects on gene expression in each of these regions, as well as being cis-acting; (iii) trans-acting eQTLs tend to have larger effects on expression compared to cis-acting eQTLs and tend to be specific to a single region (SR-eQTL) of the brain; (iv) the cerebellum has a very large number of eQTLs that function exclusively in this region, compared with other regions of the brain; (v) importantly, an interactive visualisation tool (Shiny app) was developed to visualise the MR/SR-eQTL at transcript and exon levels.
Objective
European and Australian guidelines for cystic fibrosis (CF) reproductive carrier screening recommend testing a small number of high frequency CF causing variants, rather than comprehensive CFTR sequencing. The study objective was to determine variant detection rates of commercially available targeted reproductive carrier screening tests in Australia.
Methods
Next‐generation DNA sequencing of the CFTR gene was performed on 2552 individuals from a whole population sample to identify CF causing variants. The variant detection rates of two commercially available Australian reproductive carrier screening tests, which target 50 or 175 CF causing variants, in this population were calculated. The ethnicity of individuals was determined using principal component analysis.
Results
Variant detection rates of the tests for 50 and 175 CF causing variants were 88.2% and 90.8%, respectively. No CF causing variants in individuals of East Asian ethnicity (n = 3) were detected by either test, while >86.6% (n = 69) of CF causing variants in Europeans would be identified by either test.
Conclusions
Reproductive carrier screening tests for a targeted set of high frequency CF variants are unable to detect approximately 10% of CF variants in a multiethnic Australian population, and individuals of East Asian ethnicity are disproportionally affected by this test limitation.
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