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Science 19 June 1987:
Vol. 236. no. 4808, pp. 1567 - 1570
DOI: 10.1126/science.2884728
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Articles

Science, Vol 236, Issue 4808, 1567-1570
Copyright © 1987 by American Association for the Advancement of Science

articles

Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children

ES Lander and D Botstein

An efficient strategy for mapping human genes that cause recessive traits has been devised that uses mapped restriction fragment length polymorphisms (RFLPs) and the DNA of affected children from consanguineous marriages. The method involves detection of the disease locus by virtue of the fact that the adjacent region will preferentially be homozygous by descent in such inbred children. A single affected child of a first-cousin marriage is shown to contain the same total information about linkage as a nuclear family with three affected children. Calculations show that it should be practical to map a recessive disease gene by studying DNA from fewer than a dozen unrelated, affected inbred children, given a complete RFLP linkage map. The method should make it possible to map many recessive diseases for which it is impractical or impossible to collect adequate numbers of families with multiple affected offspring.


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