Searched on Dr. David R. Cox & Perlegen. Here's a few samples:
>>Science 2001 Nov 23;294(5547):1719-23
Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21.
Patil N, Berno AJ, Hinds DA, Barrett WA, Doshi JM, Hacker CR, Kautzer CR, Lee DH, Marjoribanks C, McDonough DP, Nguyen BT, Norris MC, Sheehan JB, Shen N, Stern D, Stokowski RP, Thomas DJ, Trulson MO, Vyas KR, Frazer KA, Fodor SP, Cox DR.
Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, CA 94043, USA.
Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.<<
>>Genomics 2001 Nov;78(1-2):64-72
Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21.
Olivier M, Bustos VI, Levy MR, Smick GA, Moreno I, Bushard JM, Almendras AA, Sheppard K, Zierten DL, Aggarwal A, Carlson CS, Foster BD, Vo N, Kelly L, Liu X, Cox DR.
Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, Palo Alto, California 94304, USA. molivier@mcw.edu
One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.<<
>>Genome Res 2001 Oct;11(10):1651-9
Evolutionarily conserved sequences on human chromosome 21.
Frazer KA, Sheehan JB, Stokowski RP, Chen X, Hosseini R, Cheng JF, Fodor SP, Cox DR, Patil N.
Perlegen Sciences, Santa Clara, California 95051, USA. kelly_frazer@perlegen.com
Comparison of human sequences with the DNA of other mammals is an excellent means of identifying functional elements in the human genome. Here we describe the utility of high-density oligonucleotide arrays as a rapid approach for comparing human sequences with the DNA of multiple species whose sequences are not presently available. High-density arrays representing approximately 22.5 Mb of nonrepetitive human chromosome 21 sequence were synthesized and then hybridized with mouse and dog DNA to identify sequences conserved between humans and mice (human-mouse elements) and between humans and dogs (human-dog elements). Our data show that sequence comparison of multiple species provides a powerful empiric method for identifying actively conserved elements in the human genome. A large fraction of these evolutionarily conserved elements are present in regions on chromosome 21 that do not encode known genes.<<
Cheers, Tuck |
