An Owner's Guide to the Human Genome:
an introduction to human population genetics, variation and disease

by Jonathan Pritchard, Stanford University

In this book I describe the forces that govern genetic variation including mutation, drift, recombination and selection, as well as what genetics teaches us about human history, and the role of genetic variation in human phenotypes and diseases. When complete, the book will combine the three pillars of human population genetics - population genetics, population history, and trait genetics - under a single umbrella, with a focus on examples and applications in human genetics. Moreover, each section emphasizes the essential interplay between theory, statistical methods, and biological applications, with a focus on building intuition while avoiding heavy technical detail where possible.

Parts 1 and 2 of the book were released in September 2023. The chapters of Part 3 were released in April and September 2024. I'll release the chapters of the final section, Part 4, as I finish them. Original material is provided under a CC-BY-4.0 Creative Commons License.

I'm very happy to hear from readers, including students at any stage, with feedback, questions, errors (or even just to say that you enjoyed it!) at pritch@stanford.edu. Include "human genetics book" in the subject line.

Download Book V 1.0 [74 MB; Parts 1 and 2 only]

Download Folder of chapters [68 MB; Parts 1 and 2 only]
All Endnotes (for side-by-side reading)

Download individual chapters

Preface

Part 1:  An Introduction to Human Genetics.
Chapter 1.1  Some Very Useful Numbers for human population genetics
Chapter 1.2  A genome owner’s starter pack
Chapter 1.3  Human genome variation and why it matters
Chapter 1.4  DNA sequencing: a fundamental tool for studying biology
Chapter 1.5  Mutation: The ultimate source of genetic variation.

Part 2:  Population genetics: the forces that shape genetic variation.
Chapter 2.1  Genetic Drift: What happens to alleles over time?
Chapter 2.2  More on genetic drift: The coalescent
Chapter 2.3  Linkage, recombination, and LD
Chapter 2.4  Genetic drift in structured populations
Chapter 2.5  Natural selection: I. Background and models
Chapter 2.6  Natural selection: II. Positive selection and adaptation
Chapter 2.7  Natural Selection III. Genome-wide extent of selection

Part 3:  Human population history and structure
Chapter 3.1  Population structure: I. Ancestry estimation [New! 4/2024]
Chapter 3.2  Population structure: II. More about admixture [New! 4/2024]
Chapter 3.3  Inferring human prehistory from genetic data [New! 9/2024]
Chapter 3.4  Ancient DNA: a genetic time capsule [New! 9/2024]

Part 4:  Genetics of phenotypic variation and disease [outline]
Chapter 4.1  A starter pack for human trait genetics
Chapter 4.2  Major effect mutations: monogenic traits
Chapter 4.3  Major effect mutations: somatic mutations and cancer
Chapter 4.4  Complex traits: I. Quantitative genetics
Chapter 4.5  Complex traits: II. The GWAS paradigm
Chapter 4.6  Complex traits: III. More about GWAS
Chapter 4.7  Complex traits: IV. Functional genomics of complex traits
Chapter 4.8  Complex traits: V. stabilizing selection, drift, and adaptation

Updates:
Chapter 3.2: Minor correction 9/24.