RT Book, Section A1 Green, Eric D. A2 Valle, David L. A2 Antonarakis, Stylianos A2 Ballabio, Andrea A2 Beaudet, Arthur L. A2 Mitchell, Grant A. SR Print(0) ID 1181401817 T1 The Human Genome Project and Its Impact on the Study of Human Disease T2 The Online Metabolic and Molecular Bases of Inherited Disease YR 2019 FD 2019 PB McGraw-Hill Education PP New York, NY SN 9780071459969 LK ommbid.mhmedical.com/content.aspx?aid=1181401817 RD 2024/12/02 AB For many human diseases, the fundamental defect resides in a simple alteration in the genome—the master blueprint of DNA that orchestrates the basic operation of a cell and an organism. Genetic studies often provide the ability to define at a molecular level the nature of such DNA alterations (i.e., mutations). Knowledge of the normal and abnormal forms of genes is invaluable for understanding the basis of many human genetic diseases.The haploid human genome consists of ≈3 billion base pairs (bp) of DNA that are distributed among 24 distinct chromosomes (22 autosomes and 2 sex chromosomes). Within this vast array of nucleotides are encoded an estimated 50,000 to 100,000 genes and the necessary elements that control the regulation of their expression.Analyzing a genome involves the construction of various types of maps that reflect different features of the DNA, with the major classes being cytogenetic maps, genetic maps, and physical maps. The highest-resolution physical map is the DNA sequence map, which reflects the precise order of nucleotides along a chromosome. Important technological advances have produced a number of powerful methods that greatly facilitate the ability to analyze genomes.The Human Genome Project (HGP) is a large, coordinated effort to elucidate the genetic architecture of the human genome and, in parallel, that of several model organisms. The initial phase of this endeavor has mostly involved constructing relatively low-resolution genomic maps and refining the approaches for large-scale DNA sequencing. The next phase of the HGP will focus more on establishing the complete nucleotide sequence of the human and other genomes as well as beginning to decipher the encoded information systematically.The products of the HGP are providing a detailed working knowledge about the organization of human DNA and that of several model organisms as well as an infrastructure (in the form of biologic, informational, and technological tools) that is already ushering in a spectacular new era of biomedical inquiry. From a clinical viewpoint, this infrastructure is facilitating the identification and characterization of genes that directly and indirectly lead to human disease, which in turn should ultimately improve the ability to diagnose and treat affected individuals.