A fine-structure deletion map of human chromosome 11p: Analysis of J1 series hybrids

Thomas M Glaser, David Housman, William H. Lewis, Daniela Gerhard, Carol Jones

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Deletion analysis offers a powerful alternative to linkage and karyotypic approaches for human chromosome mapping. A panel of deletion hybrids has been derived by mutagenizing J1, a hamster cell line that stably retains chromosome 11 as its only human DNA, and selecting for loss of MIC1, a surface antigen encoded by a gene in band 11p13. A unique, self-consistent map was constructed by analyzing the pattern of marker segregation in 22 derivative cells lines; these carry overlapping deletions of 11p13, but selectively retain a segment near the 11p telomere. The map orders 35 breakpoints and 36 genetic markers, including 3 antigens, 2 isozymes, 12 cloned genes, and 19 anonymous DNA probes. The deletions span the entire short arm, dividing it into more than 20 segments and define a set of reagents that can be used to rapidly locate any newly identified marker on 11p, with greatest resolution in the region surrounding MIC1. The approach we demonstrate can be applied to map any mammalian chromosome. To test the gene order, we examined somatic cell hybrids from five patients, whose reciprocal translocations bisect band 11p13; these include two translocations associated with familial aniridia and two with acute T-cell leukemia. In each patient, the markers segregate in telomeric and centromeric groups as predicted by the deletion map. These data locate the aniridia gene (AN2)and a recurrent T-cell leukemia breakpoint (TCL2)in the marker sequence, on opposite sides of MIC1. To provide additional support, we have characterized the dosage of DNA markers in a patient with Beckwith-Wiedemann syndrome and an 11p15-11pter duplication. Our findings suggest the following gene order: TEL-(HRAS1, MER2, CTSD, TH/INS/IGF2, H19, D11S32)-(RRM1, D11S1, D11S25, D11S26)-D11S12-(HBBC, D11S30)-D11S20-(PTH, CALC)-(LDHA, SAA, TRPH, D11S18, D11S21)-D11S31-D11S17-HBVS1-(FSHB, D11S16)-AN2-MIC1-TCL2-ΔJ-CAT-MIC4-D11S9-D11S14-ACP2-(D11S33, 14L)-CEN. We have used the deletion map to show the distribution on 11p of two centromeric repetitive elements and the low-order interspersed repeat A36Fc. Finally, we provide evidence for an allelic segregation event in the hamster genome that underlies the stability of chromosome 11 in J1. The deletion map provides a basis to position hereditary disease loci on 11p, to distinguish the pattern of recessive mutations in different forms of cancer and, since many of these genes have been mapped in other mammalian species, to study the evolution of a conserved syntenic group.

Original languageEnglish (US)
Pages (from-to)477-501
Number of pages25
JournalSomatic Cell and Molecular Genetics
Volume15
Issue number6
DOIs
StatePublished - Nov 1989
Externally publishedYes

Fingerprint

Human Chromosomes
Aniridia
Chromosomes, Human, Pair 11
Gene Order
Genetic Markers
Cricetinae
Genes
Mammalian Chromosomes
Beckwith-Wiedemann Syndrome
T-Cell Leukemia
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Cell Line
Inborn Genetic Diseases
Hybrid Cells
Genomic Instability
Chromosome Mapping
Telomere
DNA Probes
Surface Antigens
Isoenzymes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

A fine-structure deletion map of human chromosome 11p : Analysis of J1 series hybrids. / Glaser, Thomas M; Housman, David; Lewis, William H.; Gerhard, Daniela; Jones, Carol.

In: Somatic Cell and Molecular Genetics, Vol. 15, No. 6, 11.1989, p. 477-501.

Research output: Contribution to journalArticle

Glaser, Thomas M ; Housman, David ; Lewis, William H. ; Gerhard, Daniela ; Jones, Carol. / A fine-structure deletion map of human chromosome 11p : Analysis of J1 series hybrids. In: Somatic Cell and Molecular Genetics. 1989 ; Vol. 15, No. 6. pp. 477-501.
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N2 - Deletion analysis offers a powerful alternative to linkage and karyotypic approaches for human chromosome mapping. A panel of deletion hybrids has been derived by mutagenizing J1, a hamster cell line that stably retains chromosome 11 as its only human DNA, and selecting for loss of MIC1, a surface antigen encoded by a gene in band 11p13. A unique, self-consistent map was constructed by analyzing the pattern of marker segregation in 22 derivative cells lines; these carry overlapping deletions of 11p13, but selectively retain a segment near the 11p telomere. The map orders 35 breakpoints and 36 genetic markers, including 3 antigens, 2 isozymes, 12 cloned genes, and 19 anonymous DNA probes. The deletions span the entire short arm, dividing it into more than 20 segments and define a set of reagents that can be used to rapidly locate any newly identified marker on 11p, with greatest resolution in the region surrounding MIC1. The approach we demonstrate can be applied to map any mammalian chromosome. To test the gene order, we examined somatic cell hybrids from five patients, whose reciprocal translocations bisect band 11p13; these include two translocations associated with familial aniridia and two with acute T-cell leukemia. In each patient, the markers segregate in telomeric and centromeric groups as predicted by the deletion map. These data locate the aniridia gene (AN2)and a recurrent T-cell leukemia breakpoint (TCL2)in the marker sequence, on opposite sides of MIC1. To provide additional support, we have characterized the dosage of DNA markers in a patient with Beckwith-Wiedemann syndrome and an 11p15-11pter duplication. Our findings suggest the following gene order: TEL-(HRAS1, MER2, CTSD, TH/INS/IGF2, H19, D11S32)-(RRM1, D11S1, D11S25, D11S26)-D11S12-(HBBC, D11S30)-D11S20-(PTH, CALC)-(LDHA, SAA, TRPH, D11S18, D11S21)-D11S31-D11S17-HBVS1-(FSHB, D11S16)-AN2-MIC1-TCL2-ΔJ-CAT-MIC4-D11S9-D11S14-ACP2-(D11S33, 14L)-CEN. We have used the deletion map to show the distribution on 11p of two centromeric repetitive elements and the low-order interspersed repeat A36Fc. Finally, we provide evidence for an allelic segregation event in the hamster genome that underlies the stability of chromosome 11 in J1. The deletion map provides a basis to position hereditary disease loci on 11p, to distinguish the pattern of recessive mutations in different forms of cancer and, since many of these genes have been mapped in other mammalian species, to study the evolution of a conserved syntenic group.

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