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The Human Genome Project, Positional Cloning of Inherited Disease Genes, and Multiple Endocrine Neoplasia Type 1

Within the coming year, 90% of the three billion nucleotide sequence of a representative human genome will be known. This is the result of the simple but ambitious Human Genome Project (HGP), a 15-year plan initiated in 1990, with its ultimate purpose to develop and make publicly available the genomic resources that will expedite research to improve the lives of people. The HGP is an international research program designed to construct detailed genetic and physical maps of the human genome, to determine the complete nucleotide sequence of human DNA, to localize the estimated 50,000-100,000 genes within the human genome, and to perform similar analyses on the genomes of several other organisms used extensively in research laboratories as model systems (http://www.nhgri.nih.gOv/HGP/#What). The evaluation of the results of the genome effort for the past eight years indicates that the interim goals have been accomplished much earlier than planned, leading to bold goals for the next 5 years The construction of physical and genetic maps of the human genome, the initial objectives, has provided maps of higher resolution than those proposed. A genetic map at 1 cM average resolution, as opposed to the proposed map of 2-5 cM resolution, was generated as early as 1994. The markers are primarily simple sequence repeats (SSR) which are highly polymorphic and allow for the efficient and high throughput PCR-based mapping efforts. A goal to generate 100,000 SNPs