s is limited because YAC inserts are often not faithful representatives of the original starting DNA; many YAC clones are chimeric or have internal deletions (see 10.3.5). As a result, second generation clone contig maps have relied on bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs). Although the insert sizes of these clones (typically 70-250 kb) are much smaller than that of YACs, this disadvantage is more than outweighed by their stability, making them more faithful representatations of the original DNA. Recently the large genome centers have focused greatly on constructing large BAC contigs as a prelude to large scale DNA sequencing.As an early priority in the human genome project were the constructin of gene (transcript) maps. From the outset of the human genome project there was much debate over whether to go for an all-out assault (indiscriminate sequencing of all 3 billion bases), or whether to focus initially just on the coding DNA sequences. The average coding DNA of a human gene is about 1.7kb, but human genes occur on average, once every 40-50kb of DNA. As a result, coding DNA accounts for a mere 3% of the human genome? To obtain coding-DNA sequences, the easiest approach would be to make a range of human cDNA libraries, then sequence cDNA clones at random.The priority of coding-DNA sequencing was dependant on two arguments: firstly that coding-DNA contains the information content of the genome and so is by far the more interesting and medically relevant part and secondly, that it is such a small percentage of the genome that it can be achieved very quickly and cheaply, when compared with efforts to sequence the entire genome. Supporters of whole genome sequencing emphasized that finding all genes could be difficult (some genes may not be well represented in available cDNA libraries if they are very restricted in expression, or expressed transiently during early development). In addition, at least...
