The gene for autosomal recessive forms of spinal muscular atrophy (SMA) has recently been mapped to chromosome 5q13, within a 4-cM region between the blocks D5S465/D5S125 and MAP-1B/D5S112. We identified two new highly polymorphic microsatellite DNA markers--namely, AFM265wf5 (D5S629) and AFM281yh9 (D5S637)--which are the closest markers to the SMA locus. Multilocus analysis by the location-score method was used to establish the best estimate of the SMA gene location. Our data suggest that the most likely location for SMA is between locus D5S629 and the block D5S637/D5S351/MAP-1B/D5S112/D5S357. Genetic analysis of inbred SMA families, based on homozygosity by descent and physical mapping using mega-YACs, gave additional information for the loci order as follows: cen-D5S6-D5S125/D5S465-D5S435-D5S629-SMA-+ ++D5S637-D5S351-MAP-1B/D5S112-D5S357- D5S39-tel. These data give the direction for bidirectional walking in order to clone this interval and isolate the SMA gene.

The genetic map in the region of human chromosome 5 that harbors the gene for autosomal recessive forms of spinal muscular atrophy (SMA) has been refined by a multilocus linkage study in 50 SMA-segregating families. Among six markers spanning 8 cM for combined sexes, four were shown to be tightly linked to the SMA locus. Multipoint linkage analysis was used to establish the best estimate of the SMA gene location. Our data suggest that the most likely location for the SMA locus is between blocks AFM114ye7 (D5S465)/EF5.15 (D5S125) and MAP-1B/JK53 (D5S112) at a sex-combined genetic distance of 2.4 and 1.7 cM, respectively. Thus the SMA gene lies in the 4-cM region between these two blocks. This information is of primary importance for designing strategies for isolating the SMA gene.

Journal Article Trinucleotide repeat polymorphism at the D5S556 locus Get access Philippe Burlet, Philippe Burlet Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Sonia Abdelhak, Sonia Abdelhak Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Fabrice Pascal, Fabrice Pascal Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Olivier Clermont, Olivier Clermont Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara Paul, Barbara Paul Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Arnold Munnich, Arnold Munnich Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Judith Melki Judith Melki * Unité de Recherches sur les Handicaps Genétiques de I'Enfant INSERM U-12, Hopital des Enfants-Malades, 149 rue de Sevres75743 Paris cedex 15, France *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 2, Issue 8, August 1993, Page 1328, https://doi.org/10.1093/hmg/2.8.1328 Published: 01 August 1993