Clinical Variants in C. elegans Expressing Human STXBP1 Reveals a Novel Class of Pathogenic Variants and Classifies Variants of Uncertain Significance

Genetics in Medicine Open (2023), doi: https://doi.org/10.1016/j.gimo.2023.100823. Abstract Purpose: Modeling disease variants in animals is useful for drug discovery, understanding disease pathology, as well as classifying variants of uncertain significance (VUS) as pathogenic or benign. Methods Using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), we performed a Whole-gene Humanized Animal Model (WHAM) procedure to replace […]

The Genomic landscape of short tandem repeats across multiple ancestries

PLoS One. 2023 Jan 26;18(1):e0279430. doi: 10.1371/journal.pone.0279430. eCollection 2023. ABSTRACT Short Tandem Repeats (STRs) have been found to play a role in a myriad of complex traits and genetic diseases. We examined the variability in the lengths of over 850,000 STR loci in 996 children with suspected genetic disorders and 1,178 parents across six separate […]

Improved attention linked to sustained phenylalanine reduction in adults with early-treated phenylketonuria

Am J Med Genet A. 2021 Nov 26. doi: 10.1002/ajmg.a.62574. Online ahead of print. ABSTRACT Pegvaliase is approved to reduce phenylalanine (Phe) levels for people with phenylketonuria (PKU). PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862) data were analyzed to evaluate the relationship between Phe and inattention in adult participants with PKU. In the modified-intent-to-treat population (N = […]

Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease

Ann Clin Transl Neurol. 2021 Oct 18. doi: 10.1002/acn3.51470. Online ahead of print. ABSTRACT OBJECTIVE: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype-phenotype correlations and identify reliable prognostic disease markers. METHODS: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 […]

Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth

Sci Rep. 2021 Aug 24;11(1):17115. doi: 10.1038/s41598-021-96374-9. ABSTRACT Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has […]

Detecting methylation quantitative trait loci using a methylation random field method

Brief Bioinform. 2021 Aug 19:bbab323. doi: 10.1093/bib/bbab323. Online ahead of print. ABSTRACT DNA methylation may be regulated by genetic variants within a genomic region, referred to as methylation quantitative trait loci (mQTLs). The changes of methylation levels can further lead to alterations of gene expression, and influence the risk of various complex human diseases. Detecting […]

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