title: Large linkage analysis in 100 families with autosomal recessive spinal muscular atrophy (SMA) and 11 CEPH families using 15 polymorphic loci in the region 5q11.2-q13.3.
abstract: The autosomal recessive proximal spinal muscular atrophy (SMA) gene was mapped to the region 5q11.2-q13.3 in 1990. Here, we present a large genetic linkage study of 100 SMA families and 11 CEPH families using 14 polymorphic simple sequence repeats (SSRs) and one RFLP in the region 5q11.2-q13.3. The genetic interval between the closest SMA flanking loci D5S435 and D5S557 comprises 1 cM at zmax = 27.94. Two recombinants were identified between the SMA gene and the closest telomeric marker D5S557 (theta = 0.02 at zmax = 8.63). The first places the SMA gene centromeric to this marker; the second suggests a double recombinant at D5S557, which is very unlikely. More likely explanations are discussed in the paper. No recombinant was found between D5S435 and the SMA gene (theta = 0.00 at zmax = 25.36). We localized a recently described polymorphic marker, D5S351 (Hudson et al., 1992), close to the SMA (theta = 0.00 at zmax = 19.01) and the 3'MAP1B gene (theta = 0.01 at zmax = 38.76). Due to its high PIC value of 0.70, it represents a very useful marker for prenatal diagnosis. In addition, we developed a new reverse primer for the nearest centromeric locus D5S435 (Soares et al., 1993), a useful marker for prenatal diagnosis, which has been very difficult to amplify in the past. Three of the markers presented here are newly developed polymorphic SSRs (one tetranucleotide repeat, D5S507/W15CATT, and two dinucleotide repeats, D5S544/C88.2GT and D5S682/C88.3GT). These markers are too far from the SMA gene to be relevant for cloning; nevertheless, as part of the human genome project, they are contributing to the fine genetic mapping of the region 5q11.2-q13.3. The most likely order of the loci based on two-point and multipoint linkage analyses as well as on specific recombination events and physical mapping studies is D5S76-D5S507- D5S6-D5S125-D5S680-D5S435-SMA-D5S557- D5S351-5'MAP1B-3'MAP1B-JK53CA1/2-(D5S127- D5S39)-(D5S544-D5S682). In general, the genetic distances obtained from the SMA and CEPH families are comparable.
authors.affiliation: Institute of Human Genetics, Bonn, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wirth
authors.forename: E
authors.initials: E
authors.lastname: Pick
authors.forename: A
authors.initials: A
authors.lastname: Leutner
authors.forename: A
authors.initials: A
authors.lastname: Dadze
authors.forename: B
authors.initials: B
authors.lastname: Voosen
authors.forename: M
authors.initials: M
authors.lastname: Knapp
authors.forename: B
authors.initials: B
authors.lastname: Piechaczek-Wappenschmidt
authors.forename: S
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: J
authors.initials: J
authors.lastname: Schönling
authors.forename: S
authors.initials: S
authors.lastname: Cox
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D017931:DNA Primers / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D017931:DNA Primers; D004276:DNA, Satellite; D005819:Genetic Markers