A LOCUS FOR FANCONI-ANEMIA ON 16Q DETERMINED BY HOMOZYGOSITY MAPPING

We report the results of a genomewide scan using homozygosity mapping to identify genes causing Fanconi anemia, a genetically heterogeneous recessive disorder. By studying 23 inbred families, we detected linkag e to a locus causing Fanconi anemia near marker D16S520 (16q24.3). Alt hough similar to 65% of our families displayed clear linkage to D16S52 0, we found strong evidence (P = .0013) of genetic heterogeneity. This result independently confirms the recent mapping of the FAA gene to c hromosome 16 by Pronk et al. Family ascertainment was biased against a previously identified FAC gene on chromosome 9, and no linkage was ob served to this locus. Simultaneous search analysis suggested several a dditional chromosomal regions that could account for a small fraction of Fanconi anemia in our families, but the sample size is insufficient to provide statistical significance. We also demonstrate the strong e ffect of marker allele frequencies on LOD scores obtained in homozygos ity mapping and discuss ways to avoid false positives arising from thi s effect.