Fine-structure genetic mapping of human chromosomes using the polymerase chain reaction on single sperm: experimental design considerations |
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| Authors: | M Boehnke N Arnheim H Li F S Collins |
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| Affiliation: | Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor 48109. |
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| Abstract: | The polymerase chain reaction (PCR) makes it possible to rapidly generate a very large number of copies of a specific region of DNA. Application of PCR to individual human sperm cells permits the typing of a large number of independent male meiotic events. If the donor male is heterozygous at three loci, sperm typing using PCR will permit ordering of loci in a manner analogous to classical methods of experimental genetics. Sequential analysis of trios of loci by sperm typing will provide a very accurate means of ordering any number of tightly linked loci. Here, we describe experimental design and sample-size issues raised by the application of sperm typing by PCR for mapping human chromosomes, and we demonstrate that sperm typing will be an efficient method for generating fine-structure human genetic maps. |
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