A guide for the diagnosis of rare and undiagnosed disease: beyond the exome

S Marwaha, JW Knowles, EA Ashley - Genome medicine, 2022 - Springer
Rare diseases affect 30 million people in the USA and more than 300–400 million
worldwide, often causing chronic illness, disability, and premature death. Traditional …

Strategic vision for improving human health at The Forefront of Genomics

ED Green, C Gunter, LG Biesecker, V Di Francesco… - Nature, 2020 - nature.com
Starting with the launch of the Human Genome Project three decades ago, and continuing
after its completion in 2003, genomics has progressively come to have a central and …

Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure

L Gerasimavicius, BJ Livesey, JA Marsh - Nature communications, 2022 - nature.com
Most known pathogenic mutations occur in protein-coding regions of DNA and change the
way proteins are made. Taking protein structure into account has therefore provided great …

An Atlas of Variant Effects to understand the genome at nucleotide resolution

DM Fowler, DJ Adams, AL Gloyn, WC Hahn, DS Marks… - Genome Biology, 2023 - Springer
Sequencing has revealed hundreds of millions of human genetic variants, and continued
efforts will only add to this variant avalanche. Insufficient information exists to interpret the …

CADD: predicting the deleteriousness of variants throughout the human genome

P Rentzsch, D Witten, GM Cooper… - Nucleic acids …, 2019 - academic.oup.com
Abstract Combined Annotation-Dependent Depletion (CADD) is a widely used measure of
variant deleteriousness that can effectively prioritize causal variants in genetic analyses …

Accurate classification of BRCA1 variants with saturation genome editing

GM Findlay, RM Daza, B Martin, MD Zhang, AP Leith… - Nature, 2018 - nature.com
Variants of uncertain significance fundamentally limit the clinical utility of genetic information.
The challenge they pose is epitomized by BRCA1, a tumour suppressor gene in which …

Saturation variant interpretation using CRISPR prime editing

S Erwood, TMI Bily, J Lequyer, J Yan, N Gulati… - Nature …, 2022 - nature.com
High-throughput functional characterization of genetic variants in their endogenous locus
has so far been possible only with methods that rely on homology-directed repair, which are …

[HTML][HTML] Massively parallel assessment of human variants with base editor screens

RE Hanna, M Hegde, CR Fagre, PC DeWeirdt… - Cell, 2021 - cell.com
Understanding the functional consequences of single-nucleotide variants is critical to
uncovering the genetic underpinnings of diseases, but technologies to characterize variants …

Present Status of Brugada Syndrome: JACC State-of-the-Art Review

J Brugada, O Campuzano, E Arbelo… - Journal of the American …, 2018 - jacc.org
The Brugada syndrome is an inherited disorder associated with risk of ventricular fibrillation
and sudden cardiac death in a structurally normal heart. Diagnosis is based on a …

The expanding landscape of alternative splicing variation in human populations

E Park, Z Pan, Z Zhang, L Lin, Y **ng - The American Journal of Human …, 2018 - cell.com
Alternative splicing is a tightly regulated biological process by which the number of gene
products for any given gene can be greatly expanded. Genomic variants in splicing …