High diagnostic yield of prenatal exome sequencing in ultrasound anomalies

A study of 629 pregnancies with ultrasound-detected anomalies found that exome sequencing identified pathogenic variants in 14% of cases. The detection rate was higher in fetuses with multiple anomalies, supporting the use of prenatal ES for early diagnosis of genetic disorders. Read more about this under Article 1 below.

Article 1: The high diagnostic yield of prenatal exome sequencing followed by 3,400 gene panel analysis in 629 ongoing pregnancies with ultrasound anomalies

The diagnostic yield of routine exome sequencing (ES) in fetuses with ultrasound-detected anomalies was assessed in this study. A retrospective analysis of 629 cases from 2019 to 2022 revealed pathogenic or likely pathogenic variants in 14% of the cases. Notably, the detection rate was higher in fetuses with multiple anomalies (1 in 5) compared to those with a single major anomaly (1 in 9). These results underscore the potential of prenatal ES for identifying genetic disorders and support its implementation in selected cases with ultrasound findings. Read the full article here.

In summary: High diagnostic yield of prenatal exome sequencing

Article 2: Yield of genetic association signals from genomes, exomes and imputation in the UK Biobank

In this study, researchers compared three genetic approaches—whole-genome sequencing (WGS), whole-exome sequencing (WES), and array genotyping with imputation (IMP)—to identify complex trait associations. Utilizing data from 149,195 participants in the UK Biobank, researchers found that WES+IMP yielded the highest number of genetic signals, while WGS offered only a 1% increase in signals despite a fivefold increase in variant detection. Due to its cost-effectiveness and efficiency, WES+IMP is recommended for large-scale studies, where increasing sample sizes significantly enhances genetic discovery. Read the full article here.

In summary: WES combined with genotyping yields the best genetic signals

Article 3: Combining optical genome mapping and RNA-seq for structural variants detection and interpretation in unsolved neurodevelopmental disorders

This study evaluated the effectiveness of Optical Genome Mapping (OGM) and RNA sequencing (RNA-seq) for detecting structural variations (SVs) in patients with neurodevelopmental disorders (NDDs) who had inconclusive exome sequencing results. OGM identified four candidate SVs, and RNA-seq confirmed the pathogenicity of three. The findings emphasize the detection of SVs in non-coding regions that are often missed by ES. The integration of OGM and RNA-seq proved successful in resolving cases by providing critical insights into the genetic and transcriptional consequences of SVs in NDDs. Read the full article here.

In summary: Optical genome mapping and RNA-seq uncover structural variants

Article 4: Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height

The impact of rare non-coding genetic variants on height was investigated using whole-genome sequencing data from 333,100 individuals. Researchers identified 29 rare variants significantly associated with height, with effects ranging from -7 cm to +4.7 cm. Remarkably, variants near the HMGA1 gene were linked to an increase of 5 cm in height. This study enhances our understanding of how rare non-coding variants in regulatory regions influence complex traits and lays the groundwork for future genetic research. Read the full article here.

In summary: Rare non-coding variants significantly influence height traits

References

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