| 1. |
- Dahlman, A., et al.
(författare)
-
Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3
- 2010
-
Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 13:4, s. 369-375
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.
|
|
| 2. |
|
|
| 3. |
- Halldén, Christer, 1957-, et al.
(författare)
-
Investigation of disease-associated factors in haemophilia A patients without detectable mutations
- 2012
-
Ingår i: Haemophilia. - : Blackwell. - 1351-8216 .- 1365-2516. ; 18:3, s. e132-e137
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.
|
|
| 4. |
- Johansson, Anna M., et al.
(författare)
-
Detecting deletions in families affected by a dominant disease by use of marker data
- 2005
-
Ingår i: Human Heredity. - : Karger. - 0001-5652 .- 1423-0062. ; 60:1, s. 26-35
-
Tidskriftsartikel (refereegranskat)abstract
- A method of testing for whether inherited deletions are a cause of a single-locus dominant disease was derived, involving analysis of the marker segregation within the pedigree of a single family that segregates for the disease. It is shown that markers can be used to test deductively for the presence of an inherited deletion. The probabilities of confirming or rejecting the presence of a deletion in an arbitrary pedigree without inbreeding are then derived. The power of the test is shown to be limited in single trios but to increase rapidly as the size of the pedigree increases. For larger pedigrees, the probabilities of confirming or rejecting a deletion are higher than 0.9 for SNPs having a minor allele frequency greater than 0.4. The probabilities are higher using multiallelic markers such as microsatellites, reaching levels as high as 0.9 in even rather small pedigrees. In certain cases the test outcome is not deductive, a deletion being neither confirmed nor rejected. It is shown to still be possible then to employ a statistical test for the presence of a deletion by use of an a priori probability for a deletion.
|
|
| 5. |
- Johansson, Anna M., et al.
(författare)
-
Large deletions of the PROS1 gene in a large fraction of mutation-negative patients with protein S deficiency
- 2005
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 94:5, s. 951-957
-
Tidskriftsartikel (refereegranskat)abstract
- Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS1 gene. Conventional mutation detection techniques fail to detect a pathogenic PROS1 mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS1 are found in families where mutations in the PROS1 gene have not been found despite sequencing. For this purpose,a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions encompassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS1 are relatively common in protein S deficiency patients and screening for large deletions in PROS1 mutation-negative individuals are therefore warranted.
|
|
| 6. |
|
|
| 7. |
- Kraft, T., et al.
(författare)
-
Estimating genetic variation in sugar beets and wild beets using pools of individuals
- 1997
-
Ingår i: Genome. - 0831-2796 .- 1480-3321. ; 40:4, s. 527-533
-
Tidskriftsartikel (refereegranskat)abstract
- The study describes the genetic structure in sugar beets and in wild beets (Beta vulgaris) using 30 RFLP markers. Samples consisting of pooled plant material of 100 individuals from each line and population were used to analyse 120 sugar beet breeding lines and 91 wild beet populations. Greater variation was found among the wild populations than among the breeding lines. Although the two major groups of breeding lines, monogerm and multigerm, had approximately equal amounts of genetic variation, in the monogerm group more of this variation was partitioned among the lines than within the lines. Furthermore, despite most of the variation being shared by the two groups, the two groups were found to be separated along the first two components in a principal component analysis. Computer simulations were carried out to evaluate the usefulness of the pooled-sample strategy employed in the investigation. These simulations showed the use of pooled samples to be a better alternative than that of analysing a few plants individually.
|
|
| 8. |
- Kraft, T., et al.
(författare)
-
Positive correlation between recombination rates and levels of genetic variation in natural populations of sea beet (Beta vulgaris subsp. maritima)
- 1998
-
Ingår i: Genetics. - 0016-6731 .- 1943-2631. ; 150:3, s. 1239-1244
-
Tidskriftsartikel (refereegranskat)abstract
- The relation between the level of genetic variation and the rate of recombination per physical unit was investigated in sea beet (Beta vulgaris subsp. maritima). The rate of recombination per physical unit was estimated indirectly through marker density in an RFLP linkage map of sugar beet. From this map, we also selected RFLP markers covering two of the nine chromosomes in Beta. The markers were used to estimate the level of genetic variation in three populations of sea beet, two from Italy and one from England. Two estimates of genetic variation were employed, one based on the number of alleles in the sample and the other on heterozygosity. A statistically significant positive correlation was found between recombination rate and genetic variation. Several theoretical explanations for this are discussed, background selection being one. A correlation similar to this has been observed previously in Drosophila, one that was higher than what we obtained for Beta. This is consistent with various biological differences between the two species.
|
|
| 9. |
- Lanke, E., et al.
(författare)
-
Co-segregation of the PROS1 locus and protein S deficiency in families having no detectable mutations in PROS1
- 2004
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Wiley-Blackwell. - 1538-7933 .- 1538-7836. ; 2:11, s. 1918-1923
-
Tidskriftsartikel (refereegranskat)abstract
- Inherited deficiency of protein S constitutes an important risk factor of venous thrombosis. Many reports have demonstrated that causative mutations in the protein S gene are found only in approximately 50% of the cases with protein S deficiency. It is uncertain whether the protein S gene is causative in all cases of protein S deficiency or if other genes are involved in cases where no mutation is identified. The aim of the current study was to determine whether haplotypes of the protein S gene cosegregate with the disease phenotype in cases where no mutations have been found. Eight protein S-deficient families comprising 115 individuals where previous DNA sequencing had failed to detect any causative mutations were analyzed using four microsatellite markers in the protein S gene region. Co-segregation between microsatellite haplotypes and protein S deficiency was found in seven of the investigated families, one family being uninformative. This suggests that the causative genetic defects are located in or close to the protein S gene in a majority of such cases where no mutations have been found.
|
|
| 10. |
- Lanke, E., et al.
(författare)
-
Genetic analysis of 31 Swedish type 1 von Willebrand disease families reveals incomplete linkage to the von Willebrand factor gene and a high frequency of a certain disease haplotype
- 2005
-
Ingår i: Journal of Thrombosis and Haemostasis. - : Wiley-Blackwell. - 1538-7933 .- 1538-7836. ; 3:12, s. 2656-2663
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The most common type of von Willebrand disease (VWD), type 1, has in only a few cases been explained by an identified causative mutation in the von Willebrand factor (VWF) gene. The ABO blood group and other modifier loci outside the VWF gene may contribute to the development of type 1 VWD. OBJECTIVES AND METHODS: Our aim was to determine whether there was genetic linkage to the VWF gene in 31 Swedish type 1 VWD families. Stringent diagnostic criteria in accordance with ISTH guidelines were used. Genetic linkage was investigated by using two highly informative dinucleotide microsatellite markers, which we have recently identified, located in introns six and 15 of the VWF gene. We also investigated the existence of common disease haplotypes and the relation between type 1 VWD and ABO blood group. RESULTS: We found genetic linkage to the VWF gene in 27 (87%) of the families. However, in four (13%) of the families, there was clearly no genetic linkage. We found the 4751A>G (Tyr1584Cys) sequence variation in exon 28, which is a common mutation in the Canadian VWD population (14.3%), in only one of the 31 families (3.2%). A possible common mutation was identified in six of the 27 (22%) families with genetic linkage. Blood group O was over-represented among type 1 VWD patients. CONCLUSION: We conclude that there is linkage between the VWF gene and hereditary type 1 VWD in a majority of families.
|
|
