An agency effort to sequence genomes: unraveling the genome of the honey bee, pig, cow, and chicken

Agricultural Research, Jan, 2005 by David Elstein, Don Comis, Jan Suszkiw, Alfredo Flores

Though mapping the human genome received a lot of same studies in other animals--with much less fanfare. Researchers from around the world are mapping, or have mapped, the genomes of several farm animals. In addition to helping with the study of agriculture, this work may help further the understanding of human health.

It's not a simple process to map and sequence the genome of an animal. It takes years to do the research. And it takes plenty of money. The National Institutes of Health's (NIH) National Human Genome Research Institute has contributed tens of millions of dollars to various sequencing centers working on other animal genomes. The U.S. Department of Agriculture's Agricultural Research Service (ARS) and Cooperative State Research, Education, and Extension Service have also contributed millions, as have universities and foreign governments.

"In the long run, it makes great business sense for all these organizations to fund genomic research," says Ronnie D. Green, ARS national program leader for Food Animal Production and leader of ARS animal genomic research.

ARS scientists are working with collaborators to map the chicken, honey bee, cow, and pig genomes to learn more about these animals and what information they can provide for the study of humans.

The "Original Chicken" Donates Blueprint to Science

The campus of Michigan State University is home to Female #256, the Red Jungle Fowl (Gallus gallus) chicken whose blood samples gave researchers the 1 billion DNA units needed to create the first high-quality draft sequence of the chicken genome. She appears no worse for wear, despite her advanced age of 7 years. Wild Red Jungle Fowl are the ancestors of today's chickens. The breed has survived at large for about 8,000 years--rare for a wild ancestor of a domesticated animal.

Chickens were chosen for mapping because they are the premier nonmammalian vertebrate model organisms. They're one of the primary models for embryology and development since they grow inside an egg rather than a mother's uterus, making for easier study. Chickens are also a major model for research on viruses and cancer.

The framework for this genome sequence came from Jerry Dodgson, a molecular biologist at Michigan State University at East Lansing, and ARS geneticist Hans H. Cheng and colleagues at the nearby ARS Avian Disease and Oncology Laboratory.

Dodgson created a physical map with Female #256's DNA. Cheng created a genetic map using DNA from progeny of Male #10394--a member of the same Red Jungle Fowl line--and a White Leghorn female from an experimental inbred line of chickens. The team used these two maps as the basis for sequencing chicken genes.

NIH funded the project, and the sequence is now online at www.ncbi.nlm.nih.gov/genome/guide/chicken.

A genetic map is a broad overview that shows the order of genes. A physical map shows the actual distance between genes. Using a driving analogy, the genetic map is like an Interstate map, and the physical map is like a local street map. Use of common genetic markers as landmarks allows for integration of the two types of maps. Aligning the genetic map with the genome sequence greatly facilitates scientific efforts to determine the function of each gene and how it influences traits.

At East Lansing, ARS maintains more than 50 inbred lines of chickens ideally suited for genetic studies. The collection--begun in the 1930s--is one of the best in the world.

Over the years, many universities have given up their living collections because maintenance costs were too high. Cheng says, "It's ironic that when the best tool for genetically analyzing these lines arrived, many universities no longer had the chickens around to analyze."

Cheng says that the new genome map to guide the search for genes makes a night-and-day difference. He went almost overnight from having 2,000 genetic markers to having potentially 3 million.

"This map makes it much easier to find genes--especially those for complex traits like disease resistance," he says. "It eliminates a lot of guesswork. It's like suddenly having the complete 'parts list' for a chicken."

Before the map, Cheng had found what he thinks are three genes that confer resistance to Marek's disease, his chief interest. "This genome sequence will be an immense help in finding the rest of the resistance genes," Cheng says. "We found the genes using a unique, integrated functional genomics approach that combines DNA, RNA, and protein methods. The genome sequence will only enhance our power and accuracy."

He expects many other payoffs, including improved vaccines for Marek's and other serious diseases. "We'll also learn how to grow a more nutritious, tastier, and healthier chicken," Cheng says. "From the ARS viewpoint, mapping and sequencing the chicken genome makes sense because poultry and egg products are a $25 billion industry and poultry is the number-one meat consumed in the United States."

Sweet Research

ARS scientists have been on the forefront of research both to breed a better honey bee and to manage the welfare and productivity of this important insect.