| 1. |
|
|
| 2. |
|
|
| 3. |
- Weston, M. D., et al.
(author)
-
Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa (USH2A)
- 2000
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 66:4, s. 199-210
-
Journal article (peer-reviewed)abstract
- Usher syndrome type IIa (USHIIa) is an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa. This disorder maps to human chromosome 1q41. Recently, mutations in USHIIa patients were identified in a novel gene isolated from this chromosomal region. The USH2A gene encodes a protein with a predicted molecular weight of 171.5 kD and possesses laminin epidermal growth factor as well as fibronectin type III domains. These domains are observed in other protein components of the basal lamina and extracellular matrixes; they may also be observed in cell-adhesion molecules. The intron/exon organization of the gene whose protein we name "Usherin" was determined by direct sequencing of PCR products and cloned genomic DNA with cDNA-specific primers. The gene is encoded by 21 exons and spans a minimum of 105 kb. A mutation search of 57 independent USHIIa probands was performed with a combination of direct sequencing and heteroduplex analysis of PCR-amplified exons. Fifteen new mutations were found. Of 114 independent USH2A alleles, 58 harbored probable pathologic mutations. Ten cases of USHIIa were true homozygotes and 10 were compound heterozygotes; 18 heterozygotes with only one identifiable mutation were observed. Sixty-five percent (38/58) of cases had at least one mutation, and 51% (58/114) of the total number of possible mutations were identified. The allele 2299delG (previously reported as 2314delG) was the most frequent mutant allele observed (16%; 31/192). Three new missense mutations (C319Y, N346H, and C419F) were discovered; all were restricted to the previously unreported laminin domain VI region of Usherin. The possible significance of this domain, known to be necessary for laminin network assembly, is discussed in the context of domain VI mutations from other proteins.
|
|
| 4. |
- Kimberling, William J., et al.
(author)
-
Gene mapping of Usher syndrome type IIa : localization of the gene to a 2.1-cM segment on chromosome 1q41
- 1995
-
In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 56:1, s. 216-223
-
Journal article (peer-reviewed)abstract
- Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor β2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.
|
|
| 5. |
- Weston, M. D., et al.
(author)
-
Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients
- 1996
-
In: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 59:5, s. 1074-1083
-
Journal article (peer-reviewed)abstract
- Usher syndrome type 1b (USH1B) is an autosomal recessive disorder characterized by congenital profound hearing loss, vestibular abnormalities, and retinitis pigmentosa. The disorder has recently been shown to be caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14. In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal coding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons. Twenty-three mutations were found segregating with the disease in 20 families. Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greatest percentage of observed mutant alleles (8/23, 31%). Six of the 13 mutations caused premature stop codons, 6 caused changes in the amino acid sequence of the myosin VIIa protein, and 1 resulted in a splicing defect. Three patients were homozygotes or compound heterozygotes for mutant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His-Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is presumed that the mutation on the other allele is present in the unscreened regions of the gene. None of the mutations reported here were observed in 96 unrelated control samples, although several polymorphisms were detected. These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16.
|
|
| 6. |
- Eudy, James D., et al.
(author)
-
Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa
- 1998
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 280:5370, s. 1753-1757
-
Journal article (peer-reviewed)abstract
- Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Axelson, H, et al.
(author)
-
A new variant 15; 16 translocation in mouse plasmacytoma leads to the juxtaposition of c-myc and immunoglobulin lambda
- 1991
-
In: Oncogene. - 0950-9232. ; 6:12, s. 70-2263
-
Journal article (peer-reviewed)abstract
- Mouse plasmacytomas (MPCs) induced by pristane oil, or by a combination of pristane oil and Abelson virus, carry one of two chromosomal translocations. The typical 12; 15 translocation leads to the juxtaposition of c-myc and immunoglobulin heavy-chain sequences, whereas the 6; 15 translocation links the kappa light-chain locus with the pvt-1 (plasmacytoma variant translocation) locus, located at least 75kb 3' of c-myc [Cory, S., Graham, M., Webb, E., Corcoran, L. & Adams, J. (1985). EMBO J., 4, 675-681]. Unlike the human Burkitt's lymphoma-associated translocation, the lambda/myc juxtaposed variant translocation has not been found previously in MPCs. Using unconventional MPC induction systems in which the tumor precursor cell was induced to proliferate in a secondary host, we have recently identified a 15; 16 translocation in six of the derived MPCs [Wiener, F., Silva, S., Sugiyama, H., Babonits, M. & Klein, G. (1990). Genes Chromosomes Cancer, 2, 36-43]. Chromosome 16 harbors the lambda light-chain gene. To explore whether the 15; 16 translocation represents the lambda/myc juxtaposition, we have mapped the breakpoints on chromosomes 15 and 16 by pulsed-field gel electrophoresis (PFGE). The pvt-1 region was mapped to approximately 220 kb 3' of c-myc. The breakpoint on chromosome 15 in ABPC-Ch-163-10, one of the six 15; 16 translocation-carrying MPCs, was situated approximately 80 kb 3' of c-myc and 140 kb 5' of pvt-1b, the major breakpoint cluster region of the previously analysed 6; 15 variant MPCs. The breakpoint on chromosome 16 was found to cut between the V1 and C3 regions of the lambda locus. Co-migration experiments showed that the C3 and the myc gene were juxtaposed head to tail on the 15; 16 translocation chromosome. On the reciprocal product V1 was juxtaposed to pvt-1.
|
|
| 12. |
- Fields, Randall R., et al.
(author)
-
Usher syndrome type III : revised genomic structure of the USH3 gene and identification of novel mutations
- 2002
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:3, s. 607-617
-
Journal article (peer-reviewed)abstract
- Usher syndrome type III is an autosomal recessive disorder characterized by progressive sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa. The disease gene was localized to 3q25 and recently was identified by positional cloning. In the present study, we have revised the structure of the USH3 gene, including a new translation start site, 5′ untranslated region, and a transcript encoding a 232–amino acid protein. The mature form of the protein is predicted to contain three transmembrane domains and 204 residues. We have found four new disease-causing mutations, including one that appears to be relatively common in the Ashkenazi Jewish population. We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10.
|
|
| 13. |
|
|
| 14. |
- Markovic, S.B., et al.
(author)
-
The Crvenka loess-paleosol sequence : A record of continuous grassland domination in the southern Carpathian Basin during the Late Pleistocene
- 2018
-
In: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182 .- 1872-616X. ; 509, s. 33-46
-
Journal article (peer-reviewed)abstract
- In this study, we compare two independent paleoenvironmental proxies for a loess sequence in northern Serbia, in the southern Carpathian Basin: novel n-alkane biomarkers and traditional land snail assemblages. Both are associated with other, more widely used proxy data for loess sections, such as environmental magnetism, grain size, and geochemical indices. Together, these paleoenvironmental proxy records provide evidence for the continued dominance of grasslands during the Late Pleistocene in the Southern Carpathian Basin. It is contrary to other European loess provinces, which are characterized by high diversity of Late Pleistocene environments (ranging from tundra-like to deciduous forest habitats). These findings highlight the southeastern part of Carpathian Basin as an important, but still insufficiently investigated, biogeographical refugium, and biodivarsity preservation zone. The reason for this is a mostly stable paleoclimate for much of the Late Pleistocene.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Sümegi, Pál, et al.
(author)
-
Comparison of High-Resolution 14C and Luminescence-Based Chronologies of the MIS 2 Madaras Loess/Paleosol Sequence, Hungary : Implications for Chronological Studies
- 2022
-
In: Quaternary. - : MDPI. - 2571-550X. ; 5:4
-
Journal article (peer-reviewed)abstract
- Numerous loess/paleosol sequences (LPS) in the Carpathian Basin span the period of Marine Isotope Stage (MIS) 2 and the last glacial maximum (LGM). Nevertheless, only two known records-Madaras and Dunaszekcso-preserve highly resolved records with absolute chronologies with minimal uncertainties, which enable the meaningful assessment of feedbacks and short-term climatic fluctuations over this period. The Madaras profile is located at the northern margin fringe of the Bacska loess plateau; Dunaszekcso, located on the Danube to its west, yields a chronology built on over 100 C-14 dates yet spans only part of MIS 2, missing half of the LGM including its peak. Here, we add to the previously published C-14 chronology for Madaras (15 dates) with an additional 17 C-14 and luminescence ages. Resulting age models built solely on quartz OSL and feldspar pIRIRSL data underestimate the C-14 based chronology, which is likely based on inaccuracies related to luminescence signal behavior; we observe age underestimations associated with unusual quartz behavior and significant signal loss, a phenomenon also observed in Serbian and Romanian loess, which may relate to non-sensitized grains from proximal sources. Our new chronology provides higher resolution than hitherto possible, yielding consistent 2 sigma uncertainties of similar to 150-200 years throughout the entire sequence. Our study indicates that the addition of further dates may not increase the chronological precision significantly. Additionally, the new age model is suitable for tackling centennial-scale changes. The mean sedimentation rate based on our new age-depth model (10.78 +/- 2.34 years/cm) is the highest yet recorded in the Carpathian Basin for MIS 2. The resolution of our age model is higher than that for the Greenland NGRIP ice core record. The referred horizons in our profile are all characterized by a drop in accumulation and a higher sand input, the latter most likely deriving from nearby re-exposed sand dunes.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
