The CMT2D locus: Refined genetic position and construction of a bacterial clone-based physical map

Rachel E. Ellsworth, Victor Ionasescu, Charles Searby, Val C. Sheffield, Valerie V. Braden, Tamara A. Kucaba, John Douglas Mcpherson, Marco A. Marra, Eric D. Green

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Charcot-Marie-Tooth (CMT) disease is a progressive neuropathy of the peripheral nervous system, typically characterized by muscle weakness of the distal limbs. CMT is noted for its generic heterogeneity, with four distinct loci already identified for the axonal form of the disease (CMT2). In 1996, linkage analysis of a single large family revealed the presence of a CMT2 locus on chromosome 7p14 (designated CMT2D). Additional families have been linked subsequently to the same genomic region, including one with distal spinal muscular atrophy (dSMA) and one with mixed features of dSMA and CMT2; symptoms in both of these latter families closely resemble those seen in the original CMT2D family. There is thus a distinct possibility that CMT2 and dSMA encountered in these families reflect allelic heterogeneity at a single chromosome 7 locus. In the study reported here, we have performed more detailed linkage analysis of the original CMT2D family based on new knowledge of the physical locations of various genetic markers. The region containing the CMT2D gene, as defined by the original family, overlaps with those defined by at least two other families with CMT2 and/or dSMA symptoms. Both yeast artificial chromosome (YAC) and bacterial clone-based [bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC)] contig maps spanning ~ 3.4 Mb have been assembled across the combined CMT2D critical region, with the latter providing suitable clones for systematic sequencing of the interval. Preliminary analyses have already revealed at least 28 candidate genes and expressed-sequence tags (ESTs). The mapping information reported here in conjunction with the evolving sequence data should expedite the identification of the CMT2D/dSMA gene or genes.

Original languageEnglish (US)
Pages (from-to)568-574
Number of pages7
JournalGenome Research
Volume9
Issue number6
StatePublished - Jun 1999
Externally publishedYes

Fingerprint

Spinal Muscular Atrophy
Genetic Loci
Clone Cells
Genes
P1 Bacteriophage Artificial Chromosomes
Yeast Artificial Chromosomes
Charcot-Marie-Tooth Disease
Bacterial Artificial Chromosomes
Chromosomes, Human, Pair 7
Expressed Sequence Tags
Muscle Weakness
Peripheral Nervous System
Genetic Markers
Tooth
Extremities
Chromosomes

ASJC Scopus subject areas

  • Genetics

Cite this

Ellsworth, R. E., Ionasescu, V., Searby, C., Sheffield, V. C., Braden, V. V., Kucaba, T. A., ... Green, E. D. (1999). The CMT2D locus: Refined genetic position and construction of a bacterial clone-based physical map. Genome Research, 9(6), 568-574.

The CMT2D locus : Refined genetic position and construction of a bacterial clone-based physical map. / Ellsworth, Rachel E.; Ionasescu, Victor; Searby, Charles; Sheffield, Val C.; Braden, Valerie V.; Kucaba, Tamara A.; Mcpherson, John Douglas; Marra, Marco A.; Green, Eric D.

In: Genome Research, Vol. 9, No. 6, 06.1999, p. 568-574.

Research output: Contribution to journalArticle

Ellsworth, RE, Ionasescu, V, Searby, C, Sheffield, VC, Braden, VV, Kucaba, TA, Mcpherson, JD, Marra, MA & Green, ED 1999, 'The CMT2D locus: Refined genetic position and construction of a bacterial clone-based physical map', Genome Research, vol. 9, no. 6, pp. 568-574.
Ellsworth RE, Ionasescu V, Searby C, Sheffield VC, Braden VV, Kucaba TA et al. The CMT2D locus: Refined genetic position and construction of a bacterial clone-based physical map. Genome Research. 1999 Jun;9(6):568-574.
Ellsworth, Rachel E. ; Ionasescu, Victor ; Searby, Charles ; Sheffield, Val C. ; Braden, Valerie V. ; Kucaba, Tamara A. ; Mcpherson, John Douglas ; Marra, Marco A. ; Green, Eric D. / The CMT2D locus : Refined genetic position and construction of a bacterial clone-based physical map. In: Genome Research. 1999 ; Vol. 9, No. 6. pp. 568-574.
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abstract = "Charcot-Marie-Tooth (CMT) disease is a progressive neuropathy of the peripheral nervous system, typically characterized by muscle weakness of the distal limbs. CMT is noted for its generic heterogeneity, with four distinct loci already identified for the axonal form of the disease (CMT2). In 1996, linkage analysis of a single large family revealed the presence of a CMT2 locus on chromosome 7p14 (designated CMT2D). Additional families have been linked subsequently to the same genomic region, including one with distal spinal muscular atrophy (dSMA) and one with mixed features of dSMA and CMT2; symptoms in both of these latter families closely resemble those seen in the original CMT2D family. There is thus a distinct possibility that CMT2 and dSMA encountered in these families reflect allelic heterogeneity at a single chromosome 7 locus. In the study reported here, we have performed more detailed linkage analysis of the original CMT2D family based on new knowledge of the physical locations of various genetic markers. The region containing the CMT2D gene, as defined by the original family, overlaps with those defined by at least two other families with CMT2 and/or dSMA symptoms. Both yeast artificial chromosome (YAC) and bacterial clone-based [bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC)] contig maps spanning ~ 3.4 Mb have been assembled across the combined CMT2D critical region, with the latter providing suitable clones for systematic sequencing of the interval. Preliminary analyses have already revealed at least 28 candidate genes and expressed-sequence tags (ESTs). The mapping information reported here in conjunction with the evolving sequence data should expedite the identification of the CMT2D/dSMA gene or genes.",
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