Appendix A: 

 Primer on Molecular 

 Genetics 



The text for this primer was adapted 

 from material and figures that were 

 supplied by Charles Cantor and 

 Sylvia Spengler of the Human 

 Genome Center, Lawrence 

 Berkeley Laboratory. 



Fig. 2. A diagram of a very short 

 section of the human genome, 

 which contains about 200 million 

 times the amount of DNA shown 

 in this section. [U.S. Congress, 

 Office of Technology Assessment. 

 Mapping Our Genes — The Genome 

 Projects: How Big, How Fast? OTA- 

 BA-373 (Washington, D.C.: U.S. 

 Government Printing Office, April 

 1988).] 



Base 



Major 

 groove 



Introduction to the Genome 



The genome is the total complement of genetic material present in a single cell. 

 This genetic material is deo.wribonucleic acid — DNA — the blueprint tor all 

 cellular activities for the lifetime of the cell or organism. Each of a person's 10 

 trillion cells contains essentially the same complement of DNA (except for mature red 

 blood cells, which contain no chromosomal DNA). 



Chromosomes 



The human genome, containing ?i billion base pairs of DNA. is divided into 23 pairs of 

 physically separate units called chromosomes. Chromosomes, which are located in 

 cellular nuclei (Fig. 1. p. 121). contain roughly equal parts of protein and DNA. Each 

 chromosome has a single DNA molecule (packaged in a complex hierarchy and whose 

 number of bases average \5i) million) that would be 2 in. long if released from the cell 

 and stretched out. DNA molecules are the largest molecules now known. 



Chromosomes can be seen under the light microscope. Cytological stains reveal a 

 pattern of light and dark bands that reflect local variations in the percentage of Adenine 

 and Thymine versus that of Guanine and Cytosine in particular regions. Differences in 

 size and banding pattern allow each of the 24 chromosomes to be distinguished from the 

 other. With microscopic examination, one can detect occasional major chromosomal 

 abnormalities that indicate differences in the genomes of some individuals. However, 

 the majority of DNA differences are more subtle and can be detected only by molecular 



analysis. These abnomialities in DNA 

 may be responsible for inherited 

 diseases or cancer. 



DNA 



The DNA structure consists of a long, 

 ribbon-like chain made of two strands 

 and divided into subunits. Each 

 position along a DNA strand can be 

 occupied by one of four nitrogenous 

 bases — adenine (A), thymine (T). 

 cytosine (C), or guanine (G) — strung 

 together along a backbone of sugars 

 and phosphates (Figs. I and 2). The 

 sequence of bases along the sugar- 

 Hvdroeen phosphate backbone encodes the 



bond 



Sugar-phosphate 

 backbone 



groove 



122 



