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Home >>Molecular Maps of Animal Genome >>Top Down ( Restriction Mapping) Vs Bottom Up (Contig Mapping)
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Top Down ( Restriction Mapping) Vs Bottom Up (Contig Mapping) - One of the early goals of what is now called "Human Genome Project" is to make physical maps of each of the 22 autosomes and two sex chromosomes (X, Y) in humans. Two conceptually different types of strategies are being tried:

(i) The first strategy involves preparation of restriction maps of large DNA fragments (macro restriction analysis), generated by rare enzymes that cut the genome infrequently. It is achieved through analysis by pulse field gel electrophoresis (PFGE).

This approach is reductionist or top down approach, because we start with isolation of individual chromosomes or their large segments using hybrid cell lines of known chromosome composition.

Then from the existing genetic maps of these isolated individual chromosomes (or segments), we use probes that serve as anchor points on the physical map.

The gaps between these anchor points are then filled by extensive Southern analysis. This technique has already yielded restriction maps for yeast (Saccharomyces pombe) chromosomes.

(ii) The second strategy involves preparation of a complete ordered genomic library. This is a bottom up approach, because we start with individual clones, which are fingerprinted and through detection of overlapping of DNA segments in clones, the latter arc arranged in a large number of contiguous sets of overlapping clones (called contigs), which coalesce into a map of the whole genome.

Above two approaches are complementary, but have their limitations and benefits. For instance, the top down approach of restricition mapping of large DNA fragments, provides information about distantly spaced genomic regions.

However, it does not provide purified DNA in an immortal amplifiable form. In the second i.e., bottom up approach of ordered complete library, on the other hand, it is easy to start with individual clones, but it is difficult to complete the library, there being many gaps.

However, it provides a high resolution information and a permanent source of purified DNA. It is believed that both types of maps arc useful and should be constructed in parallel.

Utilizing the above two approaches involving restriction mapping and contig mapping, a hybrid map technology has also been suggested. In hybrid maps, we make use of restriction maps, linkage maps (RFLP maps), cytogenetics and somatic cell genetics, in order to orient and align a series of contigs.

In such a map the discontinuity of contig maps is largely overcome and clones will be available that will cover most of the mapped region.