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.

Rice, the primary source of dietary calories for half of humanity, is the first crop plant for which a high-quality reference genome sequence from a single variety was produced. We used resequencing microarrays to interrogate 100 Mb of the unique fraction of the reference genome for 20 diverse varieties and landraces that capture the impressive genotypic and phenotypic diversity of domesticated rice. Here, we report the distribution of 160,000 nonredundant SNPs. Introgression patterns of shared SNPs revealed the breeding history and relationships among the 20 varieties; some introgressed regions are associated with agronomic traits that mark major milestones in rice improvement. These comprehensive SNP data provide a foundation for deep exploration of rice diversity and gene-trait relationships and their use for future rice improvement.introgression ͉ Oryza sativa ͉ resequencing ͉ SNP discovery T he genomes of domesticated rice, Oryza sativa, contain a wealth of information that can explain the large morphological, physiological, and ecological variation observed in the many varieties cultivated for food. To meet population demands by 2025, rice production must increase by 24% (1). The innovative use of genetic diversity will play a key role in reaching this ambitious goal.The availability of complete genome sequences provides a starting point to understanding the tremendous diversity of the rice gene pool at a fine scale. Among the organisms with a high-quality genome sequence from at least one individual or strain, such as human, mouse, and Arabidopsis, genomewide surveys of SNP variation in small or moderately sized samples have captured significant portions of within-species variation. In human and mouse, for example, a sampling of 71 and 15 individuals captured 80% and 43% of the genotypic variation, respectively (2, 3). In the model plant, Arabidopsis, 20 diverse varieties captured Ͼ90% of the common genotypic variation in the species (4).We initiated the OryzaSNP project (www.OryzaSNP.org) to discover genetic variation within 20 rice varieties and landraces. These varieties, the OryzaSNPset collection (Table S1), are genetically diverse and actively used in international breeding programs because of their wide range of agronomic attributes (5). Most varieties belong to the 2 main groups, indica and japonica, including tropical and temperate japonica, whereas others represent the aus, deep water, and aromatic rice groups. Adapting a hybridization approach previously used for human, mouse, and Arabidopsis (3, 6, 7), we determined SNP variation in 100 Mb of the rice genome, representing Ϸ80% of the nonrepetitive portion of the 390-Mb Nipponbare reference genome (8). Here, we describe the discovery of 159,478 high-quality, nonredundant SNPs distributed across the entire genomes of the OryzaSNPset. Relative to the model dicotyledenous plant Arabidopsis (4), typical haplotype blocks in indica rice varieties are longer (Ϸ200 kb). Observed patterns of shared SNPs among groups indicate introgression caused by rece...

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We have conducted a multistage genomewide association study, using 1,620,742 single-nucleotide polymorphisms to systematically investigate the genetic factors influencing intrinsic skin pigmentation in a population of South Asian descent. Polymorphisms in three genes--SLC24A5, TYR, and SLC45A2--yielded highly significant replicated associations with skin-reflectance measurements, an indirect measure of melanin content in the skin. The associations detected in these three genes, in an additive manner, collectively account for a large fraction of the natural variation of skin pigmentation in a South Asian population. Our study is the first to interrogate polymorphisms across the genome, to find genetic determinants of the natural variation of skin pigmentation within a human population.

ObjectiveTo develop a novel prenatal assay based on selective analysis of cell-free DNA in maternal blood for evaluation of fetal Trisomy 21 (T21) and Trisomy 18 (T18).MethodsTwo hundred ninety-eight pregnancies, including 39 T21 and seven T18 confirmed fetal aneuploidies, were analyzed using a novel, highly multiplexed assay, termed digital analysis of selected regions (DANSR™). Cell-free DNA from maternal blood samples was analyzed using DANSR assays for loci on chromosomes 21 and 18. Products from 96 separate patients were pooled and sequenced together. A standard Z-test of chromosomal proportions was used to distinguish aneuploid samples from average-risk pregnancy samples. DANSR aneuploidy discrimination was evaluated at various sequence depths.ResultsAt the lowest sequencing depth, corresponding to 204 000 sequencing counts per sample, average-risk cases where distinguished from T21 and T18 cases, with Z statistics for all cases exceeding 3.6. Increasing the sequencing depth to 410 000 counts per sample substantially improved separation of aneuploid and average-risk cases. A further increase to 620 000 counts per sample resulted in only marginal improvement. This depth of sequencing represents less than 5% of that required by massively parallel shotgun sequencing approaches.ConclusionDigital analysis of selected regions enables highly accurate, cost efficient, and scalable noninvasive fetal aneuploidy assessment. © 2012 John Wiley & Sons, Ltd.