Recent Patents on DNA & Gene Sequences 2007, 1, 69-76 69 1872-2156/07 $100.00+.00 © 2007 Bentham Science Publishers Ltd. Current and Future Developments in Patents for Quantitative Trait Loci in Dairy Cattle Joel I. Weller* Institute of Animal Sciences, A. R. O., The Volcani Center, P. O. Box 6, Bet Dagan 50250, Israel Received: October 5, 2006; Accepted: December 5, 2006; Revised: December 7, 2006 Abstract: Many studies have proposed that rates of genetic gain in dairy cattle can be increased by direct selection on the individual quantitative loci responsible for the genetic variation in these traits, or selection on linked genetic markers. The development of DNA-level genetic markers has made detection of QTL nearly routine in all major livestock species. The studies that attempted to detect genes affecting quantitative traits can be divided into two categories: analysis of candidate genes, and genome scans based on within-family genetic linkage. To date, 12 patent cooperative treaty (PCT) and US patents have been registered for DNA sequences claimed to be associated with effects on economic traits in dairy cattle. All claim effects on milk production, but other traits are also included in some of the claims. Most of the sequences found by the candidate gene approach are of dubious validity, and have been repeated in only very few independent studies. The two missense mutations on chromosomes 6 and 14 affecting milk concentration derived from genome scans are more solidly based, but the claims are also disputed. A few PCT in dairy cattle are commercialized as genetic tests where commercial dairy farmers are the target market. Keywords: Quantitative trait locus, Quantitative trait nucleotide, Marker-assisted selection, DNA microsatellite, Single nucleotide polymorphism, Linkage disequilibrium, Genome scan, Genetic markers, Dairy cattle. INTRODUCTION Scientific breeding programs for dairy cattle began in the 1950’s. These programs were based on phenotypic selection without regard to the individual genes responsible for the phenotypic variation. Many studies have proposed that rates of genetic gain can be increased by direct selection on the individual quantitative loci (QTL) responsible for the genetic variation in these traits, or selection on linked genetic markers termed marker-assisted selection (MAS) (reviewed by [1]). Until 1990 QTL detection was limited by the lack of suitable genetic markers in dairy cattle populations. Since then, the development of DNA-level genetic markers; specifically, DNA microsatellites and single nucleotide polymorphisms (SNP), have made detection of QTL nearly routine in all major livestock species. The studies that attempted to detect genes affecting quantitative traits via linkage to genetic markers can be divided into two categories: analysis of candidate genes, and genome scans based on within-family genetic linkage. The principles of modern breeding programs for dairy cattle will be described, and their accomplishments and limitations will be reviewed. Next the basic principles and the current state of MAS in dairy cattle will be reviewed. Detection of segregating QTL via the candidate gene approach, genetic linkage, and methods to determine the actual polymorphism responsible for the observed effect will be considered in the following sections. The specific US patents and PCT in which DNA polymorphisms are claimed to affect expression of economic traits in dairy cattle then *Address correspondence to this author at the Institute of Animal Sciences, A. R. O., The Volcani Center, P. O. Box 6, Bet Dagan 50250, Israel; Tel: 972-8-9484430; Fax: 972-9-9470587; E-mail: weller@agri.huji.ac.il will be analyzed, and in the last section an attempt will be made to predict future developments and several open questions with respect to QTL patents in dairy cattle will be addressed. TRAIT-BASED SELECTION, ACCOMPLISHMENTS AND LIMITATIONS Modern dairy cattle breeding schemes are based on the following principles: 1. Nearly all economic traits are expressed only in females. 2. Female fertility is very limited while male fertility via artificial insemination is nearly unlimited. 3. As compared to most other agricultural species, cattle breeding programs are constrained by the long generation interval and the high value of each animal. Thus unlike the situation in poultry or most plant species, dairy cattle breeding programs are based on selection within the commercial population, rather than selection within specific populations controlled by breeding enterprises. Due to the biological limitations noted above, most modern dairy cattle programs are based on the “progeny test” scheme. Most genetic gain is obtained by selection of the bulls, even though bulls do not have production records. Genetic evaluations are derived by the Individual Animal Model, including the numerator relationship matrix. Thus the genetic evaluations of animals without records are derived from the production records of all their female relatives [1]. An example of the Israeli Holstein breeding program is given in (Fig. 1). This population consists of approximately 120,000 cows of which 90% are milk recorded. Approximately 20 bulls are used for general service. Each year about 300 elite cows are selected as bull dams. These are mated to the two to four best local bulls and an equal