A genomic mutational constraint map using variation in 76,156 human genomes

S Chen, LC Francioli, JK Goodrich, RL Collins, M Kanai… - Nature, 2024 - nature.com
The depletion of disruptive variation caused by purifying natural selection (constraint) has
been widely used to investigate protein-coding genes underlying human disorders,,–, but …

Promoting equity in polygenic risk assessment through global collaboration

IJ Kullo - Nature Genetics, 2024 - nature.com
The long delay before genomic technologies become available in low-and middle-income
countries is a concern from both scientific and ethical standpoints. Polygenic risk scores …

High-coverage nanopore sequencing of samples from the 1000 Genomes Project to build a comprehensive catalog of human genetic variation

JA Gustafson, SB Gibson, N Damaraju… - Genome …, 2024 - genome.cshlp.org
Fewer than half of individuals with a suspected Mendelian or monogenic condition receive a
precise molecular diagnosis after comprehensive clinical genetic testing. Improvements in …

Recurrent evolution and selection shape structural diversity at the amylase locus

D Bolognini, A Halgren, RN Lou, A Raveane, JL Rocha… - Nature, 2024 - nature.com
The adoption of agriculture triggered a rapid shift towards starch-rich diets in human
populations. Amylase genes facilitate starch digestion, and increased amylase copy number …

Genetic and molecular architecture of complex traits

T Lappalainen, YI Li, S Ramachandran, A Gusev - Cell, 2024 - cell.com
Human genetics has emerged as one of the most dynamic areas of biology, with a
broadening societal impact. In this review, we discuss recent achievements, ongoing efforts …

A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus

D Pellerin, GF Del Gobbo, M Couse, E Dolzhenko… - Nature …, 2024 - nature.com
The factors driving or preventing pathological expansion of tandem repeats remain largely
unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by …

Expanding the Russian allele frequency reference via cross-laboratory data integration: insights from 7452 exome samples

YA Barbitoff, DN Khmelkova… - National Science …, 2024 - academic.oup.com
Population allele frequency is crucially important for accurate interpretation of known and
novel variants in medical genetics. Recently, several large allele frequency databases, such …

Genes with differential expression across ancestries are enriched in ancestry-specific disease effects likely due to gene-by-environment interactions

J Wang, Z Zhang, Z Lu, N Mancuso, S Gazal - The American Journal of …, 2024 - cell.com
Multi-ancestry genome-wide association studies (GWASs) have highlighted the existence of
variants with ancestry-specific effect sizes. Understanding where and why these ancestry …

CHARR efficiently estimates contamination from DNA sequencing data

W Lu, LD Gauthier, T Poterba, E Giacopuzzi… - The American Journal of …, 2023 - cell.com
DNA sample contamination is a major issue in clinical and research applications of whole-
genome and-exome sequencing. Even modest levels of contamination can substantially …

The scalable variant call representation: enabling genetic analysis beyond one million genomes

T Poterba, C Vittal, D King, D Goldstein… - …, 2025 - academic.oup.com
Abstract Motivation The Variant Call Format (VCF) is widely used in genome sequencing but
scales poorly. For instance, we estimate a 150 000 genome VCF would occupy 900 TiB …