Perspectives Online

Zeng charts new territory in gene mapping

Dr. Zhao-Bang Zeng
Dr. Zhao-Bang Zeng has developed statistical methods and publicly available software that use molecular markers to locate genes contributing to complex traits. The methods apply to human health research and plant and animal breeding programs.
(Courtesy Pat Westphal)
Dr. Zhao-Bang Zeng, professor of statistics and genetics and member of the Bioinformatics Research Center at N.C. State, has transformed the world of gene mapping by developing statistical methods, along with publicly available software, that use molecular markers to identify locations of multiple genes that contribute to a complex trait, such as size, hardiness or shape of limbs.

Referred to as quantitative trait locus (QTL) mapping, Zeng's methods also assess how much each QTL affects the trait and how much interaction occurs among QTLs.

QTL mapping has important applications in plant and animal breeding programs, in human health research and in the study of the evolution of species.

These methods have helped Dr. Trudy Mackay, professor of genetics in the College of Agriculture and Life Sciences, to map genes that are responsible for longevity in Drosophila (flies).

Agricultural scientists, such as Dr. Charles Stuber, professor emeritus of genetics at N.C. State, have used QTL mapping to locate genes responsible for the vigor of U.S. corn hybrids. Hybrid vigor is a major contributor to the high yields of this crop in the United States.

Zeng and researchers at Texas A&M University are currently writing a National Science Foundation grant proposal to combine QTL mapping with gene expression data from microarray experiments to define genetic networks and determine how genes function together to yield hybrid vigor.

"QTL mapping is the first step in finding specific genes associated with a complex trait. When it is combined with microarray analyses and gene knockout technology, we are no longer mapping genes, we are identifying specific gene function and genetic effects networks," Zeng said.

In wood products research, Zeng and Ron Sederoff, head of N.C. State's Forest Biotechnology Group, are collaborating, using QTL mapping and whole-genome microarray gene expression data to identify the regulatory genes and genetic pathways that regulate fiber density in eucalyptus.

Zeng, whose research has been supported by a National Institute of Health program project grant since 1990, is noted for two groundbreaking advances in statistical methods of gene mapping. His "composite interval mapping" method, published in 1994, was a significant advance over previous mapping methods and quickly became the standard in the field. Still, the method could evaluate only a single QTL at a time.

In 1999, Zeng and his student Chen-Hung Kao published a "multiple interval mapping" technique that evaluates multiple loci simultaneously, including the likely magnitude of their effects and the extent of interaction among them.

QTL Cartographer, a free software package first released in 1995, has made the mapping methods accessible to other genetic researchers. Developed by Zeng and his colleagues Dr. Christopher J. Basten and Dr. Shengchu Wang at the BRC under grants from the USDA, the suite of programs is continuously updated to include advances in statistical gene mapping methods. A Windows version with built-in graphics capabilities and user manual has been available since 2001; a redesigned Windows user manual was released in 2004 (see http://statgen.ncsu.edu/qtlcart/).

"QTL Cartographer is popular, especially with the new Windows interface. We put a lot of effort into making it easy to use," said Zeng. "These methods have made a difference to the research community. That's a major achievement that my colleagues and I are proud of."

-Pat Westphal