The 32·6 kb Indian δβ‐thalassaemia deletion ends in a 3·4 kb L1 element downstream of the β‐globin gene

Gilman, J. G.; Brinson, Eleanor; Mishima, Nozomu

doi:10.1111/j.1365-2141.1992.tb06439.x

Cited by 14 publications

(9 citation statements)

References 26 publications

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“…The 3' regions of two clones (T12 and C8) were not Mouse sequenced. One gene (T12) coded for only nine amino acids and may Chicken be a nonfunctional sequence identity over 208 bp with the human Alu-lA sequence (Gilman et al 1992), 65% identity over 52 bp for the mouse B 1 repetitive element (Shehee et al, 1989), 62% over 110 bp for a rabbit delta-globin pseudogene direct repeat (Margot et al 1989), and 59% identity over 105 bp with the rat B2 repetitive sequence (Matsunaga et al 1990). Two constant region genes coding for 177 amino acids were identified (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Characterization of horse (Equus caballus) T-cell receptor beta chain genes

1994

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Genes encoding the horse (Equus caballus) T-cell receptor beta chain (TCRB) were cloned and characterized. Of 33 cDNA clones isolated from the mesenteric lymph node, 30 had functionally rearranged gene segments, and three contained germline sequences. Sixteen unique variable segments (TCRBV), 14 joining genes (TCRBJ), and two constant region genes (TCRBC) were identified. Horse TCRBV were grouped into nine families based on similarity to human sequences. TCRBV2 and TCRBV12 were the most commonly represented horse families. Analysis of predicted protein structure revealed the presence of conserved regions similar to those seen in TCRB of other species. A decanucleotide promoter sequence homologous to those found in humans and mice was located in the 5' untranslated region of one horse gene. Germline sequences included the 5' region of the TCRBD2 gene with flanking heptamer/nonamer recombination signals and portions of the TCRBJ2-C2 intron. Southern blot hybridizations demonstrated restriction fragment length polymorphisms at the TCRBC locus among different horse breeds.

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Section: Resultsmentioning

confidence: 99%

“…7A, B Nucleotide sequences of portions of horse TCRBJ2-C2 intron. A 238 bp of 5' region of intron with closest similarity to human (Gilman et al 1992) and mouse (Shehee et al 1989) repetitive sequences. B 360 bp of 3' region of TCRBJ2-C2 intron including splice acceptor site (underlined) and beginning of TCRBC2 exon 1 (arrow).…”

Section: Resultsmentioning

confidence: 99%

Characterization of horse (Equus caballus) T-cell receptor beta chain genes

1994

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“…L1 elements have repeatedly been implicated in various disease-associated deletions in humans [Henthorn et al, 1990;Gilman et al, 1992;Drechsler and Royer-Pokora, 1996;Segal et al, 1999] although Alu elements seemed to be more frequently found to be involved in non-homologous recombination events than L1 elements. Burwinkel and Kilimann [1998] compiled the breakpoints of 10 non-homologous recombinations involving L1 elements unilaterally and showed that all occurred at different sites of the L1 element.…”

Section: Discussionmentioning

confidence: 98%

Characterization of breakpoint sequences of five rearrangements inL1CAM andABCD1 (ALD) genes

et al. 2002

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Mutations in L1CAM are responsible for X-linked hydrocephalus, whereas those in the ALD gene (ABCD1) cause adrenoleukodystrophy. In both genes, most of the mutations reported so far are short-length mutations and only a few patients with larger rearrangements have been documented. We have characterized three intragenic deletions of the ALD gene at the molecular level and describe here the first two L1CAM rearrangements resulting in deletion of several exons in one case and about 50 kb, including the entire gene, in the second case. At both breakpoints of an ALD deletion, Alu repeats have been found and, additionally, a short Alu region of approximately 130 bp was inserted, suggesting that this rearrangement is the result of a more complex non-allelic homologous recombination event. Only one Alu element was present at the breakpoint of the second ALD rearrangement, including a 26-bp Alu core sequence that was suggested to be a recombinogenic hot spot. These data suggest the involvement of an Alu core sequence-stimulated non-homologous recombination as a possible cause for this rearrangement. Short direct repeats were identified at all putative mispaired sequences in the L1CAM breakpoints and at both breakpoints of the third ALD deletion characterized, suggesting non-homologous (illegitimate) recombination as the molecular mechanism by which these latter deletions occurred. In conclusion, our results indicate that highly repetitive elements as well as short direct repeats are frequently involved in the formation of ALD and L1CAM gene rearrangements.

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“…Many of these deletions represent nonhomologous recombination events that have 5′ breakpoints within the transcriptional units and 3′ breakpoints within or near L1 family repeats. They can be assigned to discrete categories by size, and members of the same category have close breakpoints (Henthorn et al 1986(Henthorn et al , 1990Zhang et al 1988;Feingold and Forget 1989;Gilman et al 1992;Kulozik et al 1992;Motum et al 1992). These structural analyses suggested that the occurrence of the majority of deletions within the β-globin locus was probably related to chromatin configuration (Taramelli et al 1986;Gilman et al 1992), and also revealed a propensity to nonhomologous events mediated by L1 repetitive elements.…”

Section: Introductionmentioning

confidence: 91%

The 3? breakpoint of the Yunnanese ( A ???) 0 -thalassemia deletion lies in an L1 family sequence: implications for the mechanism of deletion and the reactivation of the G ?-globin gene

Zhang

1998

Human Genetics

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We have cloned the junction region of the previously characterized Yunnanese (Agammadeltabeta)0-thalassemia deletion and the normal DNA region surrounding its 3' breakpoint. The sequence of 1138 bp of the 3'-flanking region and 555 bp of the normal region surrounding the 3' breakpoint was determined. The 5' breakpoint of the deletion is positioned between 116 and 117 bp upstream of the Agamma-globin gene, and the 3' breakpoint at 34 bp downstream of the BglII site that lies approximately 12.7 kb upstream of the 3' deletion breakpoint of Chinese (Agammadeltabeta)0-thalassemia. There is no significant homology between the normal DNAs flanking the 5' and 3' breakpoints, except 2-bp (TG) identity and two pairs of short direct repeats at the deletion junction. The 3' breakpoint is within an L1 family sequence that normally occurs about 66 kb downstream of the beta-globin gene in 11p15. This L1 element is partially in reversed orientation at the 5' side and is therefore, presumably, an inactive element. This type of junction indicates illegitimate DNA breakage and end-joining involving the L1 sequence. Similar to many other deletions in the beta-globin locus, the Yunnanese (Agammadeltabeta)0-thalassemia deletion lacks a sequence characteristic of defined recombination factors near the deletion junction, suggesting that chromatin configuration and other locus-specific features are important. Computer-aided analysis revealed that several transcriptional factors could bind to putative motifs present in the 3'-flanking sequence. It is possible that binding features of the distal L1 element are required to generate a suitable chromatin configuration for the recombination event in Yunnanese (Agammadeltabeta)0-thalassemia. This may also be related to the reactivation of the Ggamma-globin gene in adults with the Yunnanese (Agammadeltabeta)0-thalassemia mutation.

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The 32·6 kb Indian δβ‐thalassaemia deletion ends in a 3·4 kb L1 element downstream of the β‐globin gene

Cited by 14 publications

References 26 publications

Characterization of horse (Equus caballus) T-cell receptor beta chain genes

Characterization of horse (Equus caballus) T-cell receptor beta chain genes

Characterization of breakpoint sequences of five rearrangements inL1CAM andABCD1 (ALD) genes

The 3? breakpoint of the Yunnanese ( A ???) 0 -thalassemia deletion lies in an L1 family sequence: implications for the mechanism of deletion and the reactivation of the G ?-globin gene

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