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The rhg1-b allele of soybean is widely used for resistance against soybean cyst nematode (SCN), the most economically damaging pathogen of soybeans in the United States. Gene silencing showed that genes in a 31-kb segment at rhg1-b, encoding an amino acid transporter, an α-SNAP protein, and a WI12 (wound-inducible domain) protein, each contribute to resistance. There is one copy of the 31-kb segment per haploid genome in susceptible varieties, but 10 tandem copies in the rhg1-b haplotype. Overexpression of the individual genes in roots was ineffective, but overexpression of the genes together conferred enhanced SCN resistance. Hence Rhg1-mediated SCN resistance is conferred by copy number variation that increases the expression of a set of dissimilar genes in a repeated multi-gene segment.