Localization of an acromesomelic dysplasia on chromosome 9 by homozygositymapping

The acromesomelic dysplasias (AMDs) are a group of genetic disorders that p rimarily affect the middle and distal segments of the extremities. A form o f AMD is present on the isolated island of St Helena in the South Atlantic, which has a population of approximately 5500 derived from a number of foun der individuals. DNA from four affected individuals and 11 first-degree rel atives in four related nuclear families segregating an AMD was collected fo r gene mapping studies. Six consecutive markers on chromosome 9, spanning a n approximately 5 cM region, showed identical homozygosity in. all affected individuals, thus identifying a region of homozygosity by descent. Multipo int analysis generated a maximum lod score of Z = 2.85. These data localize the gene for this dysplasia to the pericentromeric region of chromosome 9 where the gene for the Maroteaux form of AMD is situated. The identificatio n of the gene responsible for this disorder may shed further light on the c omplex processes involved in limb morphogenesis.