Guy Sella

Dynamics of mutators of arbitrary dominance in humans

The paper develops a population genetic model to analyze mutator alleles in humans, showing that most known mutators are consistent with purifying selection, but one variant remains unexplained.

Genetic architectures of brain-related traits are shaped by strong selective constraints

The paper compares genetic architectures of brain-related traits and finds they have weaker associations and stronger selection pressures compared to other traits.

Principled measures and estimates of trait polygenicity

The paper defines polygenicity, proposes measures, and estimates them for 36 human traits using GWAS data, finding few traits fall between Mendelian and highly polygenic categories.

Regulatory network topology and the genetic architecture of gene expression

The paper investigates how gene regulatory network topology influences the genetic architecture of gene expression, finding that local motifs and hub regulators shape heritability distribution.

Mutation-selection-drift balance models of complex diseases

The paper develops a mutation-selection-drift balance model for complex diseases, finding that directional selection has little role in common variation but may affect rare variants, and suggests heritability estimates may be biased.

Gene regulatory network structure informs the distribution of perturbation effects

The paper simulates gene regulatory networks and models perturbation effects to understand network structure and function.

When should adaptation arise from a polygenic response versus few large effect changes?

This paper investigates when adaptation arises from polygenic responses versus few large effect changes by modeling trait genetics and ecological factors.

Specificity, length, and luck: How genes are prioritized by rare and common variant association studies

This paper compares how GWAS and rare variant burden tests prioritize genes for 209 traits in the UK Biobank, showing they focus on different genes due to distinct prioritization criteria.

Disentangling sources of clock-like mutations in germline and soma

The paper develops a mathematical model to disentangle the sources of clock-like mutations in germline and soma, finding distinct origins for SBS signatures 1 and 5.

Simple scaling laws control the genetic architectures of human complex traits

The paper develops a probabilistic model to explain genetic architectures of complex traits using scaling laws, finding that traits share similar selection coefficients but differ in scaling parameters.

Measuring \"intolerance to mutation\" in human genetics

The paper explains that population genetic measures like pLI reflect selection on heterozygotes, not dominance or haploinsufficiency.

Evolutionary tradeoffs and the structure of allelic polymorphisms

The paper investigates how evolutionary tradeoffs between multiple tasks shape the genetic polymorphism structure in populations, finding that prevalent polymorphisms align with the Pareto front of phenotypic tradeoffs.