Human Population Genetics and Genomics

496 Pages·2019·22.071 MB·English

by  Alan R. Templeton

Human Population
Genetics and Genomics
Alan R. Templeton
Charles Rebstock Professor Emeritus
&
Department of Biology Division of Statistical Genomics
Washington University, St. Louis, MO, United States
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To Dr. Charles (Charlie) F. Sing and Dr. Edward (Ed) D. Rothman
My mentors, colleagues, and friends

Preface
Human population genetics has grown tremendously in importance and in centrality to the broader
field of human genetics, particularly since the era of genomics. The Human Genome Project began
in 1990 and was declared essentially complete in 2003. However, having a genome sequence did
notimmediatelyyieldthemedicalandresearchbenefitsthatwereusedtojustifytheproject.Itquickly
became apparent that these benefits required the study of variation: variation in the human genome,
variation in health status, variation in demographic histories, etc. As a result, additional projects
werespawnedtocreatedatabasesthatfocusedonvariation.Oncethefocuswasonvariation,human
populationgeneticsbecamecentraltothemedicalandresearchgoalsoftheseprojects.Thereasonis
simple: human population genetics is the science of human genetic variation: its past, its current
significance, and its evolutionary fate. Population genetics provides the principles and tools used by
many human geneticists in at least some aspects of their research programs. Many of these human
geneticists do not consider themselves population geneticists, but an effective and appropriate use
ofthesetoolsandprinciplesrequiressomeknowledgeofpopulationgenetics.Ihavethereforewritten
thisbooknotonlyforhumanpopulationgeneticistsandtheirstudentsbutalsoforthebroaderhuman
geneticscommunity.Moreover,becauseoftheimmenseamountofknowledgeanddataaboutourown
species, humans have become an ideal model organism for population genetic studies. Many of the
techniques,bothmolecularandanalytical,whichwerefirstdevelopedforhumanstudiesareportable
tootherspecies.Moreover,mostoftheprinciplesofhumanpopulationgeneticsareapplicabletoall
speciesandtoageneralunderstandingofevolutionwithinaspecies.Hence,thisbookisrelevanttoall
population geneticistsandnotjustthosewho focus mainly onhumans.
Besides the advances in genetics and genomics that have propelled population genetics to its
increasingly central role in human genetics, there have also been tremendous analytical advances in
statistics,bioinformatics,andcomputational biology.Advancesintheseareashavenotonlyallowed
us to handle large data sets, but also to make use of principles that have been central to population
geneticssinceitsinceptionasafielddofteninwaysunimaginabletotheoriginatorsoftheseprinci-
ples.Forexample,thepopulationgeneticprincipleofidentity-by-descenthasplayedinacriticalrole
in much population genetic theory since the 1920s, but by coupling this old principle with modern
genomic data we can apply it powerfully to identify and localize genetic diseases, map risk factors
for common systemic diseases, study inbreeding and its consequences with or without pedigrees,
and identify genomic regions under natural selection and important for human adaptationsdjust a
few of the applications of this old concept. The pace of these molecular and analytical advances is
dizzying, so I have not written a “how to” book that would become almost immediately out-of-
date,butrathera“whyandwhen”book.Computerprogramsimplementingtheseoldandestablished
principlesofpopulationsgeneticsareconstantlybeingdevelopedinnewandmorepowerfulways,but
understandingtheunderlyingpopulationgeneticprincipleswillhelpresearchersanswerthequestions
ofwhytheseprogramsdowhattheydoandwhentheyshouldbeuseddandperhapsmoreimportantly,
whentheyshouldnotbeused.Thewhyandwhendependsnotonlyonanunderstandingofpopulation
genetic principles, but also an understanding offundamental statistical principles such as maximum
likelihood (developed in the 1910s) and Bayes theorem (from the 1700s). Despite the widespread
use of maximum likelihood and Bayesian statistics in human population genetics, there is still the
xi