Isolation and characterization of a novel gene deleted in digeorge syndrome

Hiroki Kurahashi, Kenzo Akagi, Johji Inazawa, Tohru Ohta, Norio Niikawa, Futoshi Kayatani, Tetsuya Sano, Shintaro Okada, Isamu Nishisho

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The region commonly deleted in DiGeorge syndrome (DGS) has been localized at 22q11.1-q11.2 with the aid of a high resolution banding technique. A 22q11 specific plasmid library was constructed with a microdissection and microcloning method. Dosage analysis proved three of 144 randomly selected microclones to detect hemizygosity in two patients with DGS. Two of the clones were found to contain independent low-copy-number repetitive sequences, all of which were included in the region deleted in the DGS patients. Screening of the cosmid library and subsequent cosmid walking allowed us to obtain two cosmid contigs corresponding to the microclones within the deletion (contig 1 and contig 2), whose order fluorescence in situ hybridization identified as centromere-contig 1 -contig 2-telomere on 22q. By direct selection strategy using one of the cosmids of contig 1, a 4.3 kb cDNA was obtained from fetal brain cDNA library. Sequence analysis of the cDNA revealed an open reading frame encoding 552 amino acids which had several characteristics of DNA-binding proteins. The gene, designated LZTR-1, which was transcribed in several essential fetal organs, proved to be hemizygously deleted in seven of eight DOS patients or its variants, but not in one DGS patient and GM00980. Although LZTR-1 does not locate in the shortest region of overlap, several of its structural characteristics identifying it as transcriptional regulator suggest that it plays a crucial role in embryogenesis and that haploinsufficiency of this gene may be partly related to the development of DGS. / 1995 Oxford University Press.

Original languageEnglish
Pages (from-to)541-549
Number of pages9
JournalHuman molecular genetics
Volume4
Issue number4
DOIs
Publication statusPublished - 01-04-1995
Externally publishedYes

Fingerprint

DiGeorge Syndrome
Cosmids
Genes
Complementary DNA
Haploinsufficiency
Microdissection
Centromere
Nucleic Acid Repetitive Sequences
Telomere
DNA-Binding Proteins
Fluorescence In Situ Hybridization
Gene Library
Open Reading Frames
Walking
Embryonic Development
Sequence Analysis
Plasmids
Clone Cells
Amino Acids
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Kurahashi, H., Akagi, K., Inazawa, J., Ohta, T., Niikawa, N., Kayatani, F., ... Nishisho, I. (1995). Isolation and characterization of a novel gene deleted in digeorge syndrome. Human molecular genetics, 4(4), 541-549. https://doi.org/10.1093/hmg/4.4.541
Kurahashi, Hiroki ; Akagi, Kenzo ; Inazawa, Johji ; Ohta, Tohru ; Niikawa, Norio ; Kayatani, Futoshi ; Sano, Tetsuya ; Okada, Shintaro ; Nishisho, Isamu. / Isolation and characterization of a novel gene deleted in digeorge syndrome. In: Human molecular genetics. 1995 ; Vol. 4, No. 4. pp. 541-549.
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Kurahashi, H, Akagi, K, Inazawa, J, Ohta, T, Niikawa, N, Kayatani, F, Sano, T, Okada, S & Nishisho, I 1995, 'Isolation and characterization of a novel gene deleted in digeorge syndrome', Human molecular genetics, vol. 4, no. 4, pp. 541-549. https://doi.org/10.1093/hmg/4.4.541

Isolation and characterization of a novel gene deleted in digeorge syndrome. / Kurahashi, Hiroki; Akagi, Kenzo; Inazawa, Johji; Ohta, Tohru; Niikawa, Norio; Kayatani, Futoshi; Sano, Tetsuya; Okada, Shintaro; Nishisho, Isamu.

In: Human molecular genetics, Vol. 4, No. 4, 01.04.1995, p. 541-549.

Research output: Contribution to journalArticle

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AU - Kurahashi, Hiroki

AU - Akagi, Kenzo

AU - Inazawa, Johji

AU - Ohta, Tohru

AU - Niikawa, Norio

AU - Kayatani, Futoshi

AU - Sano, Tetsuya

AU - Okada, Shintaro

AU - Nishisho, Isamu

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N2 - The region commonly deleted in DiGeorge syndrome (DGS) has been localized at 22q11.1-q11.2 with the aid of a high resolution banding technique. A 22q11 specific plasmid library was constructed with a microdissection and microcloning method. Dosage analysis proved three of 144 randomly selected microclones to detect hemizygosity in two patients with DGS. Two of the clones were found to contain independent low-copy-number repetitive sequences, all of which were included in the region deleted in the DGS patients. Screening of the cosmid library and subsequent cosmid walking allowed us to obtain two cosmid contigs corresponding to the microclones within the deletion (contig 1 and contig 2), whose order fluorescence in situ hybridization identified as centromere-contig 1 -contig 2-telomere on 22q. By direct selection strategy using one of the cosmids of contig 1, a 4.3 kb cDNA was obtained from fetal brain cDNA library. Sequence analysis of the cDNA revealed an open reading frame encoding 552 amino acids which had several characteristics of DNA-binding proteins. The gene, designated LZTR-1, which was transcribed in several essential fetal organs, proved to be hemizygously deleted in seven of eight DOS patients or its variants, but not in one DGS patient and GM00980. Although LZTR-1 does not locate in the shortest region of overlap, several of its structural characteristics identifying it as transcriptional regulator suggest that it plays a crucial role in embryogenesis and that haploinsufficiency of this gene may be partly related to the development of DGS. / 1995 Oxford University Press.

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