Human Genome Project sequencing

Making maps

The approach that the worm researchers - and eventually the International Human Genome Sequencing Consortium - took to sequencing a genome is known to molecular geneticists as a 'top-down' or 'clone-by-clone' approach.

Producing a map was one of the early objectives of the Human Genome Project. As well as being invaluable in its own right, the map provided a basis for sequencing where the results are from known locations and therefore are of immediate value.

One of the earliest maps of the human genome came from studying how characteristics are passed on in families. If two (or more) characteristics tend to crop up together, we might suppose that they were coded for on the same chromosome. However, even if two characteristics are coded for on the same chromosome, occasionally they will occur separately because chromosome pairs can exchange regions of DNA when sperm or egg cells are formed (meiotic crossing over).

If two characteristics on the same chromosome are frequently separated, then we can conclude that they are far away from each other on the chromosome. If they are only rarely separated, then the two characteristics must be very close together on the chromosome. By looking at how characteristics are inherited in patterns, we can draw up a draft map of where the genes are on the chromosomes. This sort of map is called a linkage map. Genes that are on the same chromosome are said to be 'linked', and the distance between genes on the same chromosome is called a linkage distance.

The map of the human genome was considered to be a very valuable resource because it combined information about the order/pattern of inheritance of genes with the knowledge that a gene appeared because the accuracy of conventional genetic maps depends on the number of individuals who are analysed. Humans take a long time to grow up and have children, so it is only usually possible to look at three or four generations of a single family at a time. Also, there are often not enough children in each family to work out the linkage distances accurately.

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