A HIGH-RESOLUTION GENETIC-LINKAGE MAP OF THE PERICENTROMERIC REGION OF THE HUMAN X-CHROMOSOME

We generated a high-resolution genetic linkage map of the pericentrome ric region of the human X chromosome from approximately Xp11.4 to Xq22 . This map contains 41 loci defined by 50 marker systems genotyped in the CEPH families. For this study we have generated 3 new markers (DXS 1689, DXS1690, and DXS159) and 2 new primer sequences for previously d escribed markers (PGK1P1 and AR). Using two different mapping algorith ms based on genotype data alone, we developed two well-supported frame work maps containing 15 and 18 markers with average interval sizes of 2.7 and 1.7 cM. The 18 marker map is [DXS426, XS132-0.6-DXS1690-0.8-DX S453-1.4-DXS559-1.5-[PGK1, DXS1002-1.8-DXYS1X-2.0-DXS3-7.5-DXS458-2.8- DXS454, where the distance between adjacent loci is in centimorgans. A s a third approach, we used physical mapping data to define bins for m arkers; this approach permitted us to place 26 markers on our framewor k map. Finally, we constructed a map based on the physical order of 35 markers from the fifth international workshop on human X chromosome m apping. A comparison of the physical and genetic maps indicates a rela tionship of 2 cM: per megabase in this region, with two regions of red uced recombination. The first is around the centromere (DXZ1), and the second is in the region around PGK1 (DXS441 to DXS995). Our maps shou ld aid in the fine-mapping of the many disease loci that localize to t his region of the X chromosome. (C) 1995 Academic Press, Inc.