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| 2. |
- Arnell, Henrik, et al.
(författare)
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Progressive familial intrahepatic cholestasis (PFIC) : evidence for genetic heterogeneity by exclusion of linkage to chromosome 18q21-q22
- 1997
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 100:3-4, s. 378-381
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Tidskriftsartikel (refereegranskat)abstract
- Progressive familial intrahepatic cholestasis (PFIC) is the second most common form of familial intrahepatic cholestasis. The genes for PFIC and for a milder form of the disease, benign recurrent intrahepatic cholestasis (BRIC), were recently mapped to a 19-cM region on chromosome 18q21-q22. The results suggest that PFIC and BRIC are allelic diseases. We have studied 11 Swedish patients from eight families with clinical and biochemical features consistent with PFIC. The families were genotyped for markers D18S69, D18S64, D18S55 and D18S68, spanning the PFIC candidate region. Unexpectedly, the segregation of haplotypes excluded the entire region in three families, and no indications for shared haplotypes were found in the patients of the six remaining families. A four-point linkage analysis of all families excluded linkage from D18S69 to D18S55 (Zmax < -5). Thus, our data strongly suggest the presence of a second, yet unknown, locus for PFIC. The results indicate that great care should be taken when using 18q markers for prenatal diagnosis and genetic counseling for the disease.
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| 3. |
- Balciuniene, Jorune, et al.
(författare)
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Alpha-tectorin involvement in hearing disabilities : One gene-two phenotypes
- 1999
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 105:3, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- The human alpha-tectorin (TECTA) gene has recently been cloned and proposed to be involved in autosomal dominant non-syndromic hearing impairment (NSHI) in two families linked to the DFNA12 locus. We have studied a Swedish pedigree with autosomal dominant NSHI with possible digenic inheritance of the disease, involving locus DFNA12 in chromosome 11 and locus DFNA2 in chromosome 1. Mutation analysis of the TECTA gene in this family has identified eight nucleotide substitutions indicating that TECTA is highly polymorphic. One of the changes results in a cysteine to serine (C 1057 S) mutation, in the zonadhesin domain of TECTA; this segregates with the disease haplotype on chromosome 11 and is not present in a control population. The mutation results in the replacement of a cysteine in one of the repeats of the zonadhesin/Von Willebrand domain of the protein and might cause a change in the crosslinking of the polypeptide. These findings add support to the involvement of TECTA in hearing disabilities. However, the three families carrying different TECTA mutations also show phenotypic differences: the hearing loss ranges from prelingual to progressive with late onset. The explanation for the different phenotypes and some clues regarding the functions of TECTA may lie in the localization of the mutations in the different modules of the protein. Another possibility is that the phenotype in the Swedish family is the result of two defective genes.
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| 5. |
- Broberg, K, et al.
(författare)
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Clonal chromosome aberrations are present in vivo in synovia and osteophytes from patients with osteoarthritis
- 1997
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 101:3, s. 8-295
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported recurrent clonal chromosomal aberrations in synovia, osteophytes and articular cartilage from patients with osteoarthritis (OA). In particular, gain of chromosomes 5 and 7 was found to be strongly associated with OA. In order to exclude the possibility of in vitro artefacts, we studied three to four parallel, independent cultures from ten samples of synovia and three samples of osteophytes from ten women with primary OA. In all, 40 cultures were cytogenetically analysed, 39 of which had clonal chromosomal aberrations. The most common aberrations were +7 and +5 which were found in 38 and 12 cultures, respectively. There were striking karyotype similarities among the parallel cultures from each case. Out of a total of 83 clones, only 11 were unique for one culture, 7 from synovia and 4 from osteophytes. The genetic homogeneity among different cultures from the same patients excludes the possibility of in vitro artefacts and indicates a widespread distribution of the cytogenetically aberrant clones in vivo.
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| 10. |
- Gisselsson Nord, David, et al.
(författare)
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The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells
- 1999
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 1432-1203 .- 0340-6717. ; 104:4, s. 315-325
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Tidskriftsartikel (refereegranskat)abstract
- Acquired ring chromosomes have been found in most types of human neoplasia, with a frequency approaching 10% in malignant mesenchymal tumours. In this study, the composition and dynamics of ring chromosomes were analysed in eight cases of acute myelogenous leukaemia, 17 solid tumours, and five cases with constitutional rings. Chromosomal banding and fluorescence in situ hybridisation were performed to determine the content and the structural heterogeneity of the rings. Telomeric repeats were detected using peptide nucleic acid probes or primed in situ labelling, whereas centromeric activity was evaluated by detection of kinetochore proteins. Mitotic instability was assessed by the frequency of anaphase bridges. The results suggest that human ring chromosomes can be structurally and functionally divided into two categories. In the first of these, size variation is minimal and rearrangement at cell division is uncommon. The majority of such rings contain subtelomeric sequences. Constitutional ring chromosomes and most rings in leukaemias belong to this group, whereas only a few mesenchymal tumours exhibit rings of this type. The second category consists of rings with amplified sequences, primarily from chromosome 12, characteristically occurring in atypical lipomatous tumours and other subtypes of low or borderline malignant mesenchymal neoplasms. Variation in size and number is extensive, and breakage-fusion-bridge events occur at a high frequency. Abnormalities in pericentromeric sequences are common and, in some cases, kinetochores assemble in the absence of alphoid DNA. We conclude that it is not only the ring structure per se or the neoplastic nature of the host cell that determines ring instability, but probably also the functional role of the genes carried in the ring.
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