Alstrom syndrome: further evidence for linkage to human chromosome 2p13

Alstrom syndrome is a rare autosomal recessive disorder characterized by re tinal degeneration, sensorineural hearing loss, early-onset obesity, and no n-insulin-dependent diabetes mellitus. The gene for Alstrom syndrome (ALMS1 ) has been previously localized to human chromosome 2p13 by homozygosity ma pping in two distinct isolated populations - French Acadian and North Afric an. Pair-wise analyses resulted in maximum lod (logarithm of the odds ratio ) scores of 3.84 and 2.9, respectively. To confirm these findings, a large linkage study was performed in twelve additional families segregating for A lstrom syndrome. A maximum two-point lod score of 7.13 (theta=0.00) for mar ker D2S2110 and a maximum cumulative multipoint lod score of 9.16 for marke r D3S2110 were observed, further supporting linkage to chromosome 2p13. No evidence of genetic heterogeneity was observed in these families. Meiotic r ecombination events have localized the critical region containing ALMS1 to a 6.1-cM interval flanked by markers D2S327 and D2S286. A fine resolution r adiation hybrid map of 31 genes and markers has been constructed.