Genetic and physical mapping of the genomic region spanning CMT4A

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

OSTI ID:134383

Othmane, K B; Loeb, D; Roses, A D ^[1]

---

1. Duke Univ. Medical Center, Durham, NC (United States); and others

Autosomal recessive Charcot-Marie-Tooth disease (CMT4) is a severe childhood neuropathy classified into three types: A, B, and C. We previously mapped CMT4A to chromosome 8q13-q21 in four large Tunisian families. Analysis of recombination events suggested the order: cent.-D8S279-(D8S286,D8S164, CMT4A)-D8S84-tel. Families with types B and C were subsequently typed and linkage for these types was excluded for the CMT4A region and other known CMT loci. Recently, the gene for a major peripheral myelin protein (PMP2) was mapped by FISH to chromosome 8q21-q22 and therefore appeared to be a strong candidate gene for CMT4A. We used SSCP analysis, DNA sequencing, FISH and YAC mapping analysis, and demonstrated that PMP2 is not the defect in CMT4A. Using physical mapping data, we sublocalized a new genethon marker (D8S548) to the CMT4A region between D8S286 and D8S164. All affected CMT4A patients were homozygotes for this polymorphic microsatellite as expected from its physical localization. We screened the CEPH megabase YAC library using the closest markers; over 30 YACs were isolated and characterized by PFGE. FISH analysis revealed about 16% chimeras. The YACs span the 8 cM region between D8S279 and PMP2 (mapped distal to D8S84), with a current 1 cM gap between D8S164 and D8S84. We are currently using Alu-PCR and vectorette to develop end clones in order to identify new YACs in the region and further close this gap. Alu-PCR fragments have identified several new microsatellites in the region which can be used for additional mapping of the CMT4A gene.

• OSTI ID: 134383
• Report Number(s): CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1117
• Journal Information: American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
PATIENTS
HEREDITARY DISEASES
NERVOUS SYSTEM DISEASES
GENES
GENE MUTATIONS
GENETIC MAPPING
TUNISIA
HUMAN CHROMOSOME 8
MYELIN
PROTEINS
RECESSIVE MUTATIONS
DNA HYBRIDIZATION
FLUORESCENCE
YEASTS
DNA SEQUENCING
ELECTROPHORESIS
CHIMERAS
DNA-CLONING
POLYMERASE CHAIN REACTION