A locus for Fanconi anemia on 16q determined by homozygosity mapping

Am J Hum Genet. 1996 Aug;59(2):377-84.


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 linkage to a locus causing Fanconi anemia near marker D16S520 (16q24.3). Although -65% of our families displayed clear linkage to D16S520, we found strong evidence (P = .0013) of genetic heterogeneity. This result independently confirms the recent mapping of the FAA gene to chromosome 16 by Pronk et al. Family ascertainment was biased against a previously identified FAC gene on chromosome 9, and no linkage was observed to this locus. Simultaneous search analysis suggested several additional 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 effect of marker allele frequencies on LOD scores obtained in homozygosity mapping and discuss ways to avoid false positives arising from this effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping / methods*
  • Chromosomes, Human, Pair 16*
  • Consanguinity
  • Fanconi Anemia / ethnology
  • Fanconi Anemia / etiology
  • Fanconi Anemia / genetics*
  • Gene Frequency
  • Genetic Markers
  • Genetic Testing
  • Genome, Human
  • Genotype
  • Homozygote
  • Humans
  • Lod Score
  • Pedigree


  • Genetic Markers