A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.

functionally graded materials (FGMs) have been prepared by combined slip casting and sedimentation techniques. The final, sintered samples have a gradient in molybdenum content, with a maximum value of ϳ20 to 25 vol pct Mo. At one edge, the FGM is a good electrical conductor (for approximately one-third of the total length), while the opposite end is composed mainly of fused SiO 2 . The variation of electrical resistivity, hardness, toughness, and thermal expansion along the gradient has been analyzed. The FGMs sintered in vacuum contained a small amount of Mo oxide (ϳ2 wt pct) as a third phase. The oxide originated from the starting Mo powders and oxidation during presintering. The oxide was in the form of discrete particles and did not appreciably affect the measured properties. The Mo content had the expected effect on the FGM properties; an increase in Mo increases resistivity, thermal expansion, and toughness.

Microsatellites or short tandem repeats (STRs) are abundant in the human genome with easily assayed polymorphisms, providing powerful genetic tools for mapping both Mendelian and complex traits. Microsatellite genotyping requires detection of the products of polymerase chain reaction (PCR) amplification by electrophoresis, and analysis of the peak data for discrimination of the true allele. A high-throughput genotyping approach requires computer-based automation at both the detection and analysis phases. In order to achieve this, complicated peak patterns from individual alleles must be interpreted in order to assign alleles. Previous methods consider limited types of noise peaks and cannot provide enough accuracy. By pattern recognition of various types of noise peaks, such as stutter peaks and additional peaks, we have achieved an overall average accuracy of 94% for allele calling in our actual data. Our algorithm is crucial for a high-throughput genotyping system for microsatellite markers by reducing manual editing and human errors.

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