Genomic Mapping of Chromosomal Region 2p15–p21 (D2S378–D2S391): Integration of Genemap'98 within a Framework of Yeast and Bacterial Artificial Chromosomes

Kirschner, Lawrence S.; Taymans, Susan E.; Pack, Svetlana D.; Pak, Evgenia; Pike, Brian L.; Chandrasekharappa, Settara C.; Zhuang, Zhengping; Stratakis, Constantine A.

doi:10.1006/geno.1999.5957

Cited by 27 publications

(28 citation statements)

References 47 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA was collected by tail snips from mice and analyzed by PCR using standardized conditions (Kirschner et al, 1999). Polymorphic mouse genomic primers used in the analysis were obtained from the Mouse Genome Informatics website (http://www.informatics.jax.org/).…”

Section: Pcr and Rt-pcrmentioning

confidence: 99%

Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region

Pavel¹,

Zhao²,

Powell³

et al. 2007

Int. J. Dev. Biol.

Self Cite

View full text Add to dashboard Cite

The mouse limb deformity (ld) phenotype is characterized by developmental failure of distal limb structures often associated with renal anomalies. It is caused by loss of the BMPantagonist Gremlin in the limb buds, either through mutation of Grem1, or by loss of a transcriptional global control region (GCR) located in the neighboring Fmn1 gene. In this report, we describe a new allele of ld due to complete deletion of Fmn1, including its GCR. Unlike many other ld strains, these mice are viable and fertile as homozygotes. As expected, this genomic deletion causes loss of Gremlin in the developing limb buds, but effects in other tissues are variable. Specifically, Grem1 expression is retained in the developing lung and kidney, whereas expression is lost from the corresponding adult tissues. In contrast, expression in the brain appears to be unaffected by loss of the GCR. To provide information about long-range transcriptional effects of this region, effects of the deletion on the transcription of neighboring genes were also investigated. This analysis revealed that alterations in neighboring genes do occur, but only in a limited fashion. These data indicate that the predominant effect of the Ld GCR is to activate the expression of Grem1 in the developing limb buds, although it may serve a minor role in longrange transcriptional effects that extend beyond Fmn1 and Grem1.

show abstract

Section: Pcr and Rt-pcrmentioning

confidence: 99%

Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region

Pavel¹,

Zhao²,

Powell³

et al. 2007

Int. J. Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…7 To characterise this region and isolate candidate genes, the 2p15-21 area was cloned and a yeast artificial chromosome (YAC)-bacterial artificial chromosome (BAC) map covering approximately 10 Mb of physical distance between markers D2S378 and D2S391 on the centromeric and the telomeric sides, respectively, was generated. 8 A number of candidate expressed sequences from the region have been identified and excluded 6 9-11 (Kirschner and Stratakis, unpublished data). Following the identification of the gene responsible for CNC in 17q mapping families, 5 all of the available CNC kindreds, including those linked to 2p16, 3 were screened for PRKAR1A mutations.…”

mentioning

confidence: 99%

Chromosome 2 (2p16) abnormalities in Carney complex tumours

Matyakhina

Pack²,

Kirschner³

et al. 2003

Journal of Medical Genetics

117

View full text Add to dashboard Cite

Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia and lentiginosis syndrome characterised by spotty skin pigmentation, cardiac, skin, and breast myxomas, and a variety of endocrine and other tumours. The disease is genetically heterogeneous; two loci have been mapped to chromosomes 17q22-24 (the CNC1 locus) and 2p16 (CNC2). Mutations in the PRKAR1A tumour suppressor gene were recently found in CNC1 mapping kindreds, while the CNC2 and perhaps other genes remain unidentified. Analysis of tumour chromosome rearrangements is a useful tool for uncovering genes with a role in tumorigenesis and/or tumour progression. CGH analysis showed a low level 2p amplification recurrently in four of eight CNC tumours; one tumour showed specific amplification of the 2p16-p23 region only. To define more precisely the 2p amplicon in these and other tumours, we completed the genomic mapping of the CNC2 region, and analysed 46 tumour samples from CNC patients with and without PRKAR1A mutations by fluorescence in situ hybridisation (FISH) using bacterial artificial chromosomes (BACs). Consistent cytogenetic changes of the region were detected in 40 (87%) of the samples analysed. Twenty-four samples (60%) showed amplification of the region represented as homogeneously stained regions (HSRs). The size of the amplicon varied from case to case, and frequently from cell to cell in the same tumour. Three tumours (8%) showed both amplification and deletion of the region in their cells. Thirteen tumours (32%) showed deletions only. These molecular cytogenetic changes included the region that is covered by BACs 400-P-14 and 514-O-11 and, in the genetic map, corresponds to an area flanked by polymorphic markers D2S2251 and D2S2292; other BACs on the centromeric and telomeric end of this region were included in varying degrees. We conclude that cytogenetic changes of the 2p16 chromosomal region that harbours the CNC2 locus are frequently observed in tumours from CNC patients, including those with germline, inactivating PRKAR1A mutations. These changes are mostly amplifications of the 2p16 region, that overlap with a previously identified amplicon in sporadic thyroid cancer, and an area often deleted in sporadic adrenal tumours. Both thyroid and adrenal tumours constitute part of CNC indicating that the responsible gene(s) in this area may indeed be involved in both inherited and sporadic endocrine tumour pathogenesis and/or progression.

show abstract

“…Of these the more centromeric is spanned by YAC 888g9. BAC R-436K12 (not shown) is linked to the contig published by Kirchener et al, 31 and links our YAC contig at the centromeric end. …”

Section: Construction Of a Yac Contigmentioning

confidence: 68%

“…31 Thus combined with this published YAC contig, this provides a continuous map that spans chromosome 2p15-2p21 (D2S1364 ± D2S1754, *14 Mb) and contains several human disease loci. 31 Sixty-seven new STSs were identified by inter-Alu PCR and YAC/BAC end sequencing. The high-resolution physical map generated in this study spans *2 Mb with complete coverage of the minimal region of sitosterolemia.…”

Section: Bac Map Of Chromosome 2p21mentioning

confidence: 99%

“…Therefore, the accuracy of GeneMap'99 for the D2S119-D2S2291 interval is only 25%, which is similar to the 30% reported by Kirschener et al for the D2S123-D2S2251 interval, but much lower than 75% in the D2S2291-D2S123 interval reported by the same authors. 31 In summary, we have developed 67 new STSs, constructed an integrated YAC and BAC contigs for sitosterolaemia region and mapped eight known genes and 48 ESTs to the contig. These results will facilitate the identification of the sitosterolaemia gene and other disease genes located in this region.…”

Section: Bac Map Of Chromosome 2p21mentioning

confidence: 99%

See 1 more Smart Citation

High-resolution physical and transcript map of human chromosome 2p21 containing the sitosterolaemia locus

Lee

Carpten

et al. 2001

Eur J Hum Genet

View full text Add to dashboard Cite

Sitosterolaemia (phytosterolaemia) is an autosomal recessive disorder characterised by the presence of tendon xanthomas in the face of normal or mildly elevated plasma cholesterol levels, premature atherosclerotic disease and has diagnostically elevated plasma and tissue plant sterol concentrations. Affected individuals show an increased absorption of both cholesterol and sitosterol from the diet, decreased bile clearance of these sterols and their metabolites resulting in markedly expanded whole body cholesterol and sitosterol pools. The defective gene is therefore hypothesised to play a crucial role in regulating dietary cholesterol absorption, and its elucidation may shed light on these molecular processes. We have previously localised the defective gene to human chromosome 2p21, between microsatellite markers D2S1788 and D2S1352, a distance of approximately 15 cM. Recently, the disease locus interval has been narrowed to lie between D2S2294 and D2S2291/D2S2174. We have constructed a high-resolution YAC and BAC contigs by using known STSs and generating novel STSs from the minimal interval. Eight previously identified genes and 60 ESTs were mapped to these contigs. The BAC contig contains 60 BAC clones and 108 STSs and encompasses a physical distance of approximately 2.0 cM between microsatellite markers D2S2294 and D2S2291. These results will not only facilitate cloning of the sitosterolaemia gene, but also other disease genes located in this region, and accelerate sequencing of the corresponding genomic clones.

show abstract

Genomic Mapping of Chromosomal Region 2p15–p21 (D2S378–D2S391): Integration of Genemap'98 within a Framework of Yeast and Bacterial Artificial Chromosomes

Cited by 27 publications

References 47 publications

Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region

Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region

Chromosome 2 (2p16) abnormalities in Carney complex tumours

High-resolution physical and transcript map of human chromosome 2p21 containing the sitosterolaemia locus

Contact Info

Product

Resources

About