A landmark paper published in GENETICS founded the field of genomic prediction before the requisite technology was available.

When a new technology is developed, it can allow scientists to make great strides in addressing longstanding questions. Occasionally, however, researchers think so critically about a knowledge gap in their field that they’re able to propose a new methodology that anticipates the technology needed to make it a reality.

This is precisely what Theo Meuwissen, Ben Hayes, and Mike Goddard accomplished with their 2001 paper Prediction of Total Genetic Value Using Genome-Wide Dense Marker Maps. In it, they laid out a framework for predicting breeding values from genome-wide marker information, using simulated data to compare different approaches. The catch? There wasn’t a way to do what they were proposing—the technology didn’t exist yet.

Despite this seemingly major drawback, the authors were able to successfully use theory and simulated data to propose methods that would one day prove to revolutionize animal breeding strategies.

“In retrospect, the paper was a bit of a thought piece,” says Hayes. “Imagine if we could do this: what would it look like?”

The central goal of selective animal and plant breeding is increasing the genetic gain—that is, enhanced performance—of economically important traits. This was classically achieved by meticulously recording individuals’ phenotypic information in a population and using these records to estimate breeding values and select the best breeders for establishing the next generation. As the genomic era began to bloom toward the end of the 20th century, researchers began to incorporate genotype data into their selection strategies.

“The prevalent attitude was to try and map individual quantitative trait loci (QTLs) and then incorporate them into decisions about selection of animals,” according to Goddard.

But most of the traits in question were not associated with a small number of genes or markers, as originally anticipated. Instead, the relevant traits were likely controlled by many genes of small effects—hundreds or even thousands of genes, in fact. Existing methods were geared toward mutations of large effect, which the field was discovering weren’t likely to be found.

As the complexity of the genomic architecture underlying these traits was becoming clearer, genotyping technologies were becoming more advanced.

“It had been predicted that we would get dense marker data, but we didn’t know what to do with it. We were trying to figure out what to do if we were able to get dense marker data in a cost-efficient way,” says Meuwissen.

They explored a genome-wide approach to predict breeding values without mapping specific QTLs. They needed a high density of markers across the genome for this type of approach to work, but since that kind of real data didn’t exist yet, they simulated a genome and marker set and tested a number of statistical methods. After comparing linear regression, Best Linear Unbiased Prediction (BLUP), and multiple Bayesian methods (termed BayesA and BayesB), they concluded that “selection on genetic values predicted from markers could substantially increase the rate of genetic gain in animals and plants, especially if combined with reproductive techniques to shorten the generation interval.”

They published their work in GENETICS, noting presciently that “the advent of DNA chip technology may make genotyping of many animals for many of these markers feasible (and perhaps even cost effective).” But since SNP chips weren’t yet in the hands of researchers, the paper didn’t spark an immediate revolution in quantitative genetics or animal breeding. Meuwissen, Hayes, and Goddard had founded the field of genomic selection (also termed genome-wide prediction), but the full potential of their findings wouldn’t be realized for a number of years.
“The paper really sat in the cupboard until the technological advance came along,” says Hayes.

Thankfully, they didn’t have to wait too long: by the end of the decade, SNP chips—which allow simultaneous genotyping of thousands of markers—were available for major livestock species. And with the availability of SNP chips came an explosion of interest in the paper that founded genomic selection.

Citations to Meuwissen et al. (2001) according to PubMed and Google Scholar. From de Koning (2016).

In the nearly two decades since, the field has grown and changed in a variety of ways. For one, genotyping technology has continued to improve.

“It started off being a relatively small number of SNPs (~10,000 on the first bovine chip), and now you can get 600,000. SNP tech came onstream and rapidly advanced,” notes Goddard.

Additionally, these methodologies have also been applied more widely than livestock breeding—most notably to plant breeding and to human genetic studies of disease risk prediction. For more insight into the similarities and differences in how the methods are applied in different settings, see the new review published this month in GENETICS by Naomi Wray and colleagues.

What’s next for genomic prediction?

Researchers are still working on the best way to use whole genome sequencing (WGS) data instead of SNP chip data—though it’s now easier and cheaper than ever to sequence entire genomes, there hasn’t been much advantage to using WGS data over SNP data to date.

There are also challenges related to applying genomic prediction across breeds.

“Doing genomic prediction across breeds really doesn’t work well at the moment,” explains Hayes. “This is a problem because, in some breeds, it’s cost prohibitive to build the populations needed to drive genomic selection. There’s a lot of work going on about borrowing information across breeds.”

And as genomic prediction is being implemented widely and in many different species, it’s important for breeders to keep an eye on genomic diversity within their populations.

“We’re getting increasingly effective tools, but if we run out of diversity, we won’t be able to maintain the selection response we see today into the future,” notes Meuwissen.

Through the intervening years, the methods laid out in the 2001 paper have stood the test of time, with BayesB remaining at the forefront of genomic prediction. The field continues to grow and develop, moving into new species and honing the technologies—goals aided by the Genomic Prediction series launched in 2012 at the GSA Journals. Since then, GENETICS and G3 have collected an exciting body of work, encouraging the exploration of methods and the sharing of data to advance the field.

Genomic prediction is a striking demonstration of how science needn’t be limited by existing technology. In some cases, theoretical advances can even predict the future and help us make the most of technological advance.

CITATIONS

Prediction of Total Genetic Value Using Genome-Wide Dense Marker Maps
T. H. E. Meuwissen, B. J. Hayes and M. E. Goddard
GENETICS April 2001, 157 (4): 1819-1829.
http://www.genetics.org/content/157/4/1819

Meuwissen et al. on Genomic Selection
Dirk-Jan de Koning
GENETICS May 2016, 203(1): 5-7.
https://doi.org/10.1534/genetics.116.189795
http://www.genetics.org/content/203/1/5

, ,

Scientific Editor and Programs Manager. Genetics and Molecular Biology PhD. Follow me: @_sbay | LinkedIn

View all posts by Sarah Bay »

Read more in

  • Collage of 2021 Rosalind Franklin Award recipients

    Where are they now? Rosalind Franklin Young Investigator Award recipients share updates on their research

    Rosalind Franklin Young Investigator Award applications are open–make sure you submit your application or nomination of a colleague by September 30, 2024.

  • University of Minnesota researchers map genome of the last living wild horse species

    The study, published in G3: Genes|Genomes|Genetics, is part of larger conservation efforts to save Przewalski’s horse.

  • Congratulations to the Spring 2024 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Spring 2024! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • Carolyn Damilola headshot

    Carolyn Damilola: an NFS Rising Scientist on a lifelong quest to learn more

    Carolyn Damilola is an NFS Rising Scientist from Nigeria doing respiratory system research and paving the way for scientists from underrepresented communities through mentorship.

  • Text over a blue background image: Apply for up to $2,000 for your project from the Starter Culture Microgrant Program.

    What does a good microgrant proposal look like?

    Members of the Microgrant Review Committee share their tips for a successful proposal.

  • A blurred image of a human face is shown against a dark background.

    The first piece of the facial recognition puzzle

    New research in GENETICS gives a first peek at the molecular pathway involved in recognizing faces.

  • New Senior Editor Amy MacQueen joins GENETICS

    A new senior editor is joining GENETICS in the Genome Integrity and Transmission section. We’re excited to welcome Amy MacQueen to the editorial team.

  • Close up of an adult zebrafish with blue and white stripes in an aquarium with red lighting.

    Block party on the zebrafish sex chromosome

    Research in G3 identifies a gene regulatory block of the zebrafish genome responsible for overseeing the maternal-to-zygotic-transition.

  • Lemna Minor, the common duckweed

    Unraveling the mysteries of duckweed: epigenetic insights from Spirodela polyrhiza

    Research published in G3 offers insight into the impact of DNA methylation on clonal propagation in asexually reproducing plants.

  • Luciano Marraffini headshot

    A microbiologist’s quest to understand CRISPR in bacterial self-defense

    2024 Genetics Society of America Medal recipient Luciano Marraffini determined how CRISPR-Cas systems destroy genetic targets with precision, paving the way for gene editing technology development.

  • Elaine Ostrander headshot

    Unlocking mysteries of trait and disease heritability in dogs

    2024 Edward Novitski Prize recipient Elaine Ostrander, a pioneer of the domestic dog model, discovered numerous genes affecting dog size, morphology, behavior, and disease susceptibility—many of which have relevance in humans.

  • NSF-funded BIO-LEAPS Grant to Support Culture Change in Genetics

    GSA and collaborators Personal Genetics Education & Dialogue and Reclaiming STEM Institute launch NSF-funded BIO-LEAPS project to support culture change in genetics 

    We are thrilled to announce that the Genetics Society of America (GSA) is collaborating with the Personal Genetics Education & Dialogue (PGED) based in the Department of Genetics at Harvard Medical School, and the Reclaiming STEM Institute (RSI) on a Leading Culture Change Through Professional Societies of Biology (BIO-LEAPS) grant from the U.S. National Science…

  • Daman Saluja: Navigating Science and Policy in India

    In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the GSA Early Care­er Scientist…

  • Deborah Andrew headshot

    A fly geneticist’s journey into discovering rules of organ development

    2024 George W. Beadle Award recipient Deborah Andrew discovered new genes and pathways in Drosophila salivary gland organogenesis. Now, her work can help optimize cell secretion in therapeutic applications and fight malaria.

  • Małgorzata Gazda's headshot

    Małgorzata Gazda: How receiving the DeLill Nasser Award helped her land her dream job

    Have you ever experienced an event that changes the course of your life, or in this case, your career? Małgorzata (Gosia) Gazda is Assistant Professor at the University of Montreal and in 2022, she received the DeLill Nasser Award for Professional Development in Genetics, which she used to attend and present at the 2022 Population,…

  • Hongyu Zhao joins GENETICS as new Senior Editor

    A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team.

  • Julio Molina Pineda at TAGC 2024

    GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024 

    “At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…

  • The Fly Meeting is one-of-a-kind! Dros 2025 organizers share their excitement

    The 66th Annual Drosophila Research Conference promises to be a meeting rich with the latest in Drosophila research as well as opportunities to advance your career and connect with a global community of 1,400+ scientists. The organizers Todd Nystul, Michelle Bland, Leila Rieder, Amanda Crocker, and Justin Crocker are hard at work, planning a conference…

  • Early Career Leadership Spotlight: Olufemi Osonowo

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Olufemi Adekunle OsonowoCareer Development SubcommitteeDalhousie University Research Interest Metabolomics and genomics are two distinct but complimentary approaches that offer valuable insights into the underlying mechanisms of complex traits, such…

  • Early Career Leadership Spotlight: Hector Mendoza

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Hector MendozaCommunication and Outreach SubcommitteeUniversity of Michigan Research Interest My research goals converge around the evolution of sexual reproduction. During my doctoral program, I investigated mitochondrial inheritance, a mechanism…