10 Search Results

We study the population of Herbig-Haro (HH) flows and jets in an area of Cygnus OB7 designated the Braid Nebula star formation region. This complex forms part of the L 1003 dark cloud, and hosts two FU Orionis (FUor)-like objects as well as several other active young stars. To trace outflow activity and to relate both known and newly discovered flows to young star hosts we intercompare new, deep, narrowband H{alpha} and [S II] optical images taken on the Subaru 8 m Telescope on Mauna Kea, Hawaii. Our images show that there is considerable outflow and jet activity in thismore » region suggesting the presence of an extensive young star population. We confirm that both of the FUor-like objects drive extensive HH flows and document further members of the flows in both objects. The L 1003 star formation complex is a highly kinematically active region with young stars in several different stages of evolution. We trace collimated outflows from numerous young stars although the origin of some HH objects remains elusive.« less

We recently cloned a cDNA for CLN3, the gene for juvenile-onset neuronal ceroid lipofuscinosis or Batten disease. To resolve the genomic organization we used a cosmid clone containing CLN3 to sequence the entire gene in addition to 1.1 kb 5{prime} of the start of the published CLN3 cDNA and 0.3 kb 3{prime} to the polyadenylation site. CLN3 is organized into at least 15 exons spanning 15 kb and ranging from 47 to 356 bp. The 14 introns vary from 80 to 4227 bp, and all exon/intron junction sequences conform to the GTAG rule. Numerous repetitive Alu elements are present withinmore » the introns and 5{prime}- and 3{prime}-untranslated regions. The 5{prime} region of the CLN3 gene contains several potential transcription regulatory elements but no consensus TATA-1 box was identified. CLN3 is homologous to 27 deposited human ESTs, and sequence comparisons suggest alternative splicing of the gene and the existence of transcribed sequences upstream to the start of the published CLN3 cDNA. 19 refs., 2 figs., 1 tab.« less

We have sequenced a large proportion of the open reading frames (ORFs) of two phenol sulphotransferase gene transcripts (STP and STM) from three patients with Batten disease. This was done using reverse transcription and PCR amplification of total RNA followed by direct sequencing of the PCR products. No mutations or changes have been observed in either gene after sequencing 93% of the STP ORF and 72% of the STM ORF. Work is in the progress to finish sequencing both genes which will allow the confirmation or exclusion of these phenol sulphotransferases having a role in the development of Batten disease.more » 11 refs., 1 fig.« less

A yeast artificial chromosome (YAC) contig has been constructed in 16p12.1-p11.2 that encompasses three loci (D16S288, D16S299, and D16S298) closely linked to the gene causing Batten disease or juvenile-onset neuronal ceroid lipofuscinosis (CLN3). The physical map has been ordered using 42 sequence tagged sites. Four genes, interleukin-4 receptor (ILA4R), phenol-preferring phenol sulfotransferase (STP), monoamine preferring phenol sulfotransferase (STM), and sialophorin (SPN), have been mapped to the YAC contig. A partial genomic restriction map has been constructed to confirm the order and distances between D16S288 and STM. This part of the YAC contig is represented in eight cosmid contigs. One ofmore » these contains D16S298, predicted to be the locus closest to CLN3. The overlapping genomic clones are a valuable resource for cloning the Batten gene (CLN3) and other genes in the region. 45 refs., 2 figs., 5 tabs.« less

Haplotype analysis in a collaborative collection of 143 families with juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten (Spielmeyer-Vogt-Sjoegren) disease has permitted refined localization of the disease gene, CLN3, which was assigned to chromosome 16 in 1989. Recombination events in four maternal meioses delimit new flanking genetic markers for CLN3 which localize the gene to the chromosome interval 16p12.1-11.2 between microsatellite markers D16S288 and D16S383. This narrows the position of CLN3 to a region of 2.1 cM, a significant reduction from the previous best interval. Using haplotypes, analysis of the strong linkage disequilibrium that exists between genetic markers within the D16S288-D16S383more » interval and CLN3 shows that CLN3 is in closest proximity to loci D16S299 and D16S298. Analysis of markers across the D16S288-D16S383 region in four families with a variant form of JNCL characterized histologically by cytosomal granular osmiophilic deposits (GROD) has excluded linkage of the gene locus to the CLN3 region of chromosome 16, suggesting that JNCL with GROD is not an allelic form of JNCL. 8 refs., 2 figs., 2 tabs.« less

CLN3 has been mapped genetically to 16p12, to the interval between D16S288 and D16S383, a sex-averaged genetic distance of 2.1 cM. Analysis of disease haplotypes from 134 families and four microsatellite markers in this interval, D16S288, D16S299, D16S298 and SPN, revealed significant allelic association between one allele at each of these loci and CLN3. All four of the associated markers have been used as nucleation sites in the isolation of genomic clones (YACs). A contig of approximately 860 Kb was assembled which contained three of the four associated markers and which confirmed the relative order of these markers. The distancemore » between D16S288 and D16S299 is 430 Kb; that between D16S299 and D16S298 is less than 200 Kb. Marker D16S272 has been located on the physical map between D16S288 and D16S299. The YAC contig has now been extended towards the fourth associated marker. A detailed restriction map has revealed the location of possible CpG islands. Four cosmid contigs have been localized onto the physical map. Two genes, STP and STPM, have been mapped on the YAC contig proximal to D16S298 and are therefore candidates for CLN3. Sequence analysis of the coding region of these genes so far reveals no mutations.« less

The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while themore » gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.« less

CLN3, the gene for juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten disease, has been localized by genetic linkage analysis to chromosome 16p between loci D16S297 and D16S57. The authors have now further refined the localization of CLN3 by haplotype analysis using two new microsatellite markers from loci D16S383 and SPN in the D16S297-D16S57 interval on a larger collaborative family resource consisting of 142 JNCL pedigrees. Crossover events in 3 maternal meioses define new flanking markers for CLN3 and localize the gene to the interval at 16p12.1-11.2 between D16S288 and D16S383, which corresponds to a genetic distance of 2.1 cM. Withinmore » this interval 4 microsatellite loci are in strong linkage disequilibrium with CLN3, and extended haplotype analysis of the associated alleles indicates that CLN3 is in closest proximity to loci D16S299 and D16S298. 6 refs., 1 fig., 2 tabs.« less

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: Infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjoegren-Vogt, or Batten disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). Themore » three childhood subtypes of NCL therefore arise from mutations at distinct loci. 17 refs., 2 figs., 3 tabs.« less

Batten disease, juvenile onset neuronal ceroid lipofuscinosis, is an autosomal recessive neurodegenerative disorder characterized by accumulation of autofluorescent lipopigment in neurons and other cell types. The disease locus (CLN3) has previously been assigned to chromosome 16p. The genetic localization of CLN3 has been refined by analyzing 70 families using a high-resolution map of 15 marker loci encompassing the CLN3 region on 16p. Crossovers in three maternal meioses allowed localization of CLN3 to the interval between D16S297 and D16S57. Within that interval alleles at three highly polymorphic dinucleotide repeat loci (D16S288, D16S298, D16S299) were found to be in strong linkage disequilibriummore » with CLN3. Analysis of haplotypes suggests that a majority of CLN3 chromosomes have arisen from a single founder mutation. 15 refs., 2 figs., 5 tabs.« less