High resolution physical mapping of the spinal muscular atrophy (SMA) region utilizing YAC, PAC, and cosmid clones

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134465

Roy, N; Yaraghi, Z ^[1]; Besner, A ^[2]

---

1. Univ. of Ottawa (Canada)
2. Children`s Hospital of Eastern Ontario (Canada); and others

The childhood SMAs are a group of autosomal recessive disorders characterized by anterior horn cells degeneration resulting in muscular wasting and weakness. All three types have been mapped to a 1.4 Mb region of 5q13.1 flanked centromerically by D5S435 and telomerically by D5S557. Several groups including our own have generated YAC contigs of the region documenting deletion, duplications and repetitive sequences. We have generated a higher resolution contiguous array of cosmid clones encompassing the region containing the microsatellites (MSRs) CATT-1 and CMS-1. These MSRs exist in multiple copies, termed subloci, which are present in a variable number among chromosomes. We have mapped four of the CATT-1 subloci, two of that we have shown to be in linkage disequilibrium with SMA, to a 100 kb interval within our cosmid array. The lack of a representation of all the CMS-1 subloci in our YAC and cosmid clones, in addition to the instability of these MSRs within the YAC clones, has rendered mapping problematic. Due to the reported stability of P1 artificial chromosomes (PAC), we have also constructed a contiguous array of 11 PAC clones spanning this critical interval. The unequivocal orientation of the contig along 5q13 has been confirmed by analysis with 4 genetic markers, 4 single copy probes and 3 STSs. Preliminary analysis has shown greater retention of MSR alleles in the PACs, suggesting their greater stability when compared to YACs. Mapping of cosmid and PAC clones derived from different individuals has allowed us to map the multiple CMS-1 and CATT-1 subloci along 5q13. We have identified a recombination event indicating that the SMA gene lies telomeric to one CMS sublocus. Placement of this sublocus in our physical map has enabled further refinement of the critical SMA region from previous estimates of 700 kb to an approximate 300 kb interval flanked by the markers CMS and D5S557.

• OSTI ID: 134465
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CHROMOSOMAL ABERRATIONS
CONTIGS
DNA SEQUENCING
DNA-CLONING
GENE RECOMBINATION
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN CHROMOSOME 5
INSTABILITY
MUSCLES
PATIENTS
PROBES
RECESSIVE MUTATIONS
RESOLUTION
STRUCTURE-ACTIVITY RELATIONSHIPS
YEASTS