Integration of Transcript and Genetic Maps of Chromosome 16 at Near-1-Mb Resolution: Demonstration of a “Hot Spot” for Recombination at 16p12

Callen, David F.; Sa, Lane; Kozman, H.; Kremmidiotis, Gabriel; Sa, Whitmore; M, Lowenstein; Doggett, Na; Kenmochi, Naoya; Dc, Page; Dr, Maglott

doi:10.1006/geno.1995.9005

Cited by 38 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[9][10][11][12][13][14][15][16][17] Primer sequences, expected PCR product sizes and PCR conditions to amplify parts of these sequences were obtained from these web sites. The ESTs and STSs were PCR amplified from genomic DNA isolated from somatic human-mouse hybrid cell lines that contain a single human chromosome 16 fragment 18 and electrophoresed on sequencing gels. ESTs and STSs located on 16q24.1 were PCR amplified from the YAC contig described in this study, and the products analysed on 2% agarose gels.…”

Section: Isolation and Analysis Of Yacs And Bacsmentioning

confidence: 99%

Giant axonal neuropathy locus refinement to a < 590 kb critical interval

Cavalier

Benhamida²,

Amouri³

et al. 2000

Eur J Hum Genet

View full text Add to dashboard Cite

Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder, characterisedclinically by the development of chronic distal polyneuropathy during childhood, mental retardation, kinky or curly hair, skeletal abnormalities and, ultrastructurally, by axons in the central and peripheral nervous systems distended by masses of tightly woven neurofilaments. We recently localised the GAN locus in 16q24.1 to a 5-cM interval between the D16S507 and D16S511 markers by homozygosity mapping in three consanguineous Tunisian families. We have now established a contig-based physical map of the region comprising YACs and BACs where we have placed four genes, ten ESTs, three STSs and two additional microsatellite markers, and where we have identified six new SSCP polymorphisms and six new microsatellite markers. Using these markers, we have refined the position of our previous flanking recombinants. We also identified a shared haplotype between two Tunisian families and a small region of homozygosity in a Turkish family with distant consanguinity, both suggesting the occurrence of historic recombinations and supporting the conclusions based on the phase-known recombinations. Taken together, these results allow us to establish a transcription map of the region, and to narrow down the GAN position to a < 590 kb critical interval, an important step toward the identification of the defective gene.

show abstract

Section: Isolation and Analysis Of Yacs And Bacsmentioning

confidence: 99%

Giant axonal neuropathy locus refinement to a < 590 kb critical interval

Cavalier

Benhamida²,

Amouri³

et al. 2000

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…These data suggest that mutations of A2BP1 are unlikely to contribute significantly to the etiology of sporadic mental retardation or epilepsy. It should be noted that heterozygous deletions of entire exons would not be detected by the procedures used.A total of six de novo translocations were represented in the total of 60 balanced chromosome 16 translocations that had breakpoints mapped on the somatic cell hybrid panel (Callen et al 1995). Of the six, in two cases, the subjects of this report were the only patients with known abnormalities.…”

mentioning

confidence: 99%

“…A total of six de novo translocations were represented in the total of 60 balanced chromosome 16 translocations that had breakpoints mapped on the somatic cell hybrid panel (Callen et al 1995). Of the six, in two cases, the subjects of this report were the only patients with known abnormalities.…”

mentioning

confidence: 99%

“…The mouse/human somaticcell hybrid CY196 retained the der(16)t(1;16), and the hybrid CY182 retained the der(16)t(14;16). These two hybrids enabled rapid positioning of the breakpoints at 16p13.3 within the established physical map of chromosome 16 that was based on an extensive somatic hybrid mouse/human hybrid panel (Callen et al 1995). The available gene and DNA markers that were mapped to this panel could not separate the chromosome 16 breakpoints of the two hybrids, and therefore, more detailed mapping was undertaken.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene

et al. 2004

View full text Add to dashboard Cite

The 16p13.3 breakpoints of two de novo translocations of chromosome 16, t(1;16) and t(14;16), were shown by initial mapping studies to have physically adjacent breakpoints. The translocations were ascertained in patients with abnormal phenotypes characterized by predominant epilepsy in one patient and mental retardation in the other. Distamycin/DAPI banding showed that the chromosome 1 breakpoint of the t(1;16) was in the pericentric heterochromatin therefore restricting potential gene disruption to the 16p13.3 breakpoint. The breakpoints of the two translocations were localized to a region of 3.5 and 115 kb respectively and were approximately 900 kb apart. The mapping was confirmed by fluorescence in situ hybridization (FISH) of clones that spanned the breakpoints to metaphase spreads derived from the patients. The mapping data showed both translocations disrupted the ataxin-2-binding protein 1 (A2BP1) gene that encompasses a large genomic region of 1.7 Mb. A2BP1 encodes a protein that is known to interact with the spinocerebellar ataxia type 2 (SCA2) protein. It is proposed that disruption of the A2BP1 gene is a cause of the abnormal phenotype of the two patients. Ninety-six patients with sporadic epilepsy and 96 female patients with mental retardation were screened by SSCP for potential mutations of A2BP1. No mutations were found, suggesting that disruption of the A2BP1 gene is not a common cause of sporadic epilepsy or mental retardation.Keywords A2BP1 AE Chromosome 16 AE Spinocerebellar ataxia binding protein AE De novo translocation De novo chromosome rearrangements are associated with an increased risk of congenital malformations (Warburton 1991). Disruption of a critical gene at the translocation breakpoint is thought to be the basis for this increased risk. We report the finding of two patients with de novo translocations that involve a breakpoint at 16p13.3, show that there is disruption of the ataxin-2-binding protein 1 (A2BP1) gene by these 16p13.3 breakpoints, and propose that the disruption of A2BP1 is the basis for the patients' clinical phenotypes.The first of the de novo translocations was ascertained in a boy with severe intellectual and developmental retardation (developmental skills at 2-2.5 years when examined at 4 years 11 months) but with no dysmorphic features other than strabismus and down-turned angles of the mouth. There was a single recorded episode of fitting at 5 days old. Chromosome analysis showed at(1;16)(q12;p13.3). Parental karyotypes were normal. Both parents were considered to have mild intellectual disability. Distamycin A/DAPI, which stains the pericentromeric heterochromatin of chromosomes 1 and 16, was used to stain the chromosomes (Fig. 1a). The der(1)t(1;16) showed a single band; the der(16) had two bands, one representing the 16 heterochromatin and the other at the 16p13.3 breakpoint derived from chromosome 1 heterochromatin (Fig. 1a). This observation is consistent with the location of the chromosome 1 breakpoint within the 1q12 heterochromatin. If the boy'...

show abstract

“…However, de novo translocations are associated with an increased risk of clinical abnormalities (Warburton 1991), which can arise from the disruption of genes at the translocation breakpoints. An extensive somatic cell mouse/human hybrid panel has been constructed (Callen et al 1995). Included in this panel is the hybrid CY196, which is derived from a de novo translocation ascertained in a patient with epilepsy and mental retardation.…”

Section: Introductionmentioning

confidence: 99%

C16orf5, a novel proline-rich gene at 16p13.3, is highly expressed in the brain

et al. 1999

View full text Add to dashboard Cite

A novel gene has been characterized, designated C16orf5, with an unusually high content of proline residues (40% over 104 residues) at the N-terminus of the protein.The C-terminus of the protein is also cysteine rich with 14 cysteine residues present. Analysis using Northern and dot blots showed that the highest expression of this gene is in the brain. The gene was located on chromosome 16 at band p13.3 by FISH to metaphase chromosomes. Southern blot analysis with a human-rodent somatic cell hybrid panel showed a location between the somatic hybrid breakpoints 23HA and CY196. This gene comprises at least four exons and an open reading frame of 786 bp encoding a predicted protein of 261 amino acids. Analysis of this protein using PSORTII predicted a nuclear localization.

show abstract

Integration of Transcript and Genetic Maps of Chromosome 16 at Near-1-Mb Resolution: Demonstration of a “Hot Spot” for Recombination at 16p12

Cited by 38 publications

References 0 publications

Giant axonal neuropathy locus refinement to a < 590 kb critical interval

Giant axonal neuropathy locus refinement to a < 590 kb critical interval

The de novo chromosome 16 translocations of two patients with abnormal phenotypes (mental retardation and epilepsy) disrupt the A2BP1 gene

C16orf5, a novel proline-rich gene at 16p13.3, is highly expressed in the brain

Contact Info

Product

Resources

About