Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was performed in Norwegian subjects heterozygous for familial hypercholesterolemia (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and cytoplasmatic domains of the receptor had been deleted. A polymerase chain reaction (PCR) method was developed to identify this deletion among other Norwegian FH subjects. As a result of this screening one additional subject was found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated Norwegian FH subject possessed this deletion. The deletion was found on the same haplotype in the three unrelated subjects, suggesting a common mutagenic event. The deletion is identical to a deletion (FH-Helsinki) that is very common among Finnish FH subjects. However, it is not yet known whether the mutations evolved separately in the two countries.
A gene (DYT1) for early onset idiopathic torsion dystonia was mapped to chromosome 9q34 in non-Jewish and Jewish families. The DYT1 gene region has been excluded in other families with adult onset and cervical or cranial onset idiopathic torsion dystonia from the United States, Great Britain, and France. The role of DYT1 in a Swedish family with adult onset idiopathic torsion dystonia in four generations was examined. The disease seems to be inherited in an autosomal dominant mode with reduced penetrance in this family. There were 10 affected family members, with a mean age of onset of 27 (range 18 to 50) years. The disease showed variable expression, with focal, multifocal, and generalised forms of dystonia in different family members. Genetic analysis excluded the chromosomal region containing the DYT1 locus as being responsible for dystonia in this family.
Cites: Am J Hum Genet. 1984 Mar;36(2):460-56585139
Cites: Mov Disord. 1994 Nov;9(6):626-327845403
Cites: Ann Neurol. 1989 Nov;26(5):612-202817837
Cites: Neuron. 1989 May;2(5):1427-342576373
Cites: Ann Neurol. 1990 Feb;27(2):114-202317008
Cites: Neurology. 1990 Jul;40(7):1107-102356013
Cites: Am J Hum Genet. 1991 Aug;49(2):366-711867195
Cites: Am J Hum Genet. 1992 Mar;50(3):619-281347197
Cites: Brain. 1993 Jun;116 ( Pt 3):739-448513401
Cites: Genomics. 1993 Sep;17(3):587-918244374
Cites: Nat Genet. 1993 Dec;5(4):386-918298648
Cites: Neurology. 1994 Feb;44(2):283-78309575
Cites: Clin Genet. 1994 Feb;45(2):88-928004804
Cites: Am J Hum Genet. 1994 Sep;55(3):468-758079990
BACKGROUND: Macrophages are involved in asthma, but their pulmonary turnover is unknown. We compared the ability of bronchoalveolar lavage (BAL) and bronchial macrophages to proliferate in normal subjects and patients with asthma. METHODS: BAL cells from eight patients with asthma and eight normal volunteers were separated with a discontinuous Percoll gradient (Pharmacia Fine Chemicals, Uppsala, Sweden). In a first experiment, nuclei of each alveolar macrophage (AM) fraction, stained with propidium iodide, were analyzed for DNA content with a flow cytometer, and the proportions of cells in the G0/G1, S, and G2 + M phases were determined. In a second experiment, expression of Ki-67-related antigen was sought on AMs by immunocytochemistry. Macrophages from 10 patients with asthma and 10 normal volunteers were studied in biopsy specimens by means of immunohistochemistry with a panmacrophage monoclonal antibody (HAM-56) and a monoclonal antibody against proliferating cell nuclear antigen. RESULTS: The proportions of BAL AMs in the different phases of the cell cycle were similar in normal subjects and patients with asthma for all fractions, and the percentage of cells in S and G2 +/- M phases ranged from 7.3% to 11.3%. Under 1% of BAL AMs expressed Ki-67-related antigen. None of the macrophages present in the biopsy specimens expressed proliferating cell nuclear antigen. CONCLUSIONS: This study does not indicate that an important source of airway macrophages is local proliferation.
The authors discuss the problem of selective derivation of the genetic material of spermatozoa for molecular genetic identification from mixed biological traces containing sperm on material evidence. Possible methods of improving the efficacy of differential lysis of cells present in mixed traces are analyzed. Effects of some routinely used extractants on biological substrata, most often contaminating the sperm in expert material, have been studied, and conditions for their most complete elimination from objects of investigation optimized.
Amplification of HER-2(erbB-2/neu) oncogene was detected in 36 of 142 (25%) breast carcinomas (BC) RNA expression was examined in 42 carcinomas, in 10 of them overexpression was revealed. Amplification was matched by overexpression. No association was found between the increased number of HER-2(erbB-2/neu) copies and tumor size, lymph node involvement, stage of disease, age of onset, and estrogen and progesterone receptor level. HER-2(erbB-2/neu) amplification was shown to be of independent prognostic significance in the group of 32 BC patients with sufficient follow-up (more than 40 months). Six of 7 HER-2(erbB-2/neu) amplification-positive patients and only 2 of 25 HER-2(erbB-2/neu) amplification-negative ones relapsed (p
The frequency distributions of the length of restriction fragments (HinfI) revealed by RFLP-analysis (restriction fragment length polymorphism) of blood samples from 482 Danish Caucasians using the single locus VNTR (variable number of tandem repeats) probes MS1, MS31, MS43a and YNH24 are reported. From two blood samples three fragments were obtained with MS1. The consistency of the characteristic allele frequency distribution for each probe is exemplified by comparing the accumulated frequency curves obtained with MS43a in samples consisting of 50 and 920 bands, respectively. The distribution of the differences in migration distance for the two fragments of a bandpair was investigated. The results suggest that the high frequency of apparent homozygotes observed is due mainly to coalescence of close heterozygotes. The distribution of frequencies of 437 DNA-profiles is reported.
Short tandem repeat (STR) loci represent a rich source of highly polymorphic markers in the human genome which are useful for the purposes of forensic identification and determination of biological relatedness of individuals. Here, as a part of an ongoing extensive study, we report the analysis of a multilocus genotype survey of 642 to 870 chromosomes in the French Canadian Caucasian population of Québec at six STR loci. The loci HUMCSF1PO, HUMTPOX, HUMTH01, HUMF13A01, HUMFESFPS, and HUMvWA were typed using two multiplex polymerase chain reactions (PCR). Amplified DNA samples were subsequently analyzed by polyacrylamide gel electrophoresis followed by silver staining. The heterozygote frequencies of the loci range from 0.614 to 0.820 (0.661 to 0.818 expected) and the number of alleles from 7 to 12 per locus. Although statistically significant deviation from Hardy-Weinberg expectations of genotype frequencies was noted at some loci by one or more tests, in general, the genotype frequencies are well estimated from the product of allele frequencies at all loci. The most frequent six-locus genotype is expected to occur in the French Canadian population with a frequency of 3.50 by 10(-5) and together, these six loci have an average probability of discrimination of 0.9999985. The study presented here indicates that these six STR loci are informative genetic markers for identity testing purposes in the French Canadian Caucasian population of Québec.
The genetic structure of the Gidra-speaking population inhabiting 13 villages in Papua New Guinea was investigated, based on the analysis of HLA-DRB1 polymorphism. Nei's fixation indices (F(IS), F(IT), and F(ST)) showed that the Gidra villages were genetically differentiated. The genetic distances significantly correlated with the geographic distances among the 13 villages. Thus, it is likely that a low intervillage migration rate has been maintained since the Gidra community was established. Correspondence analysis revealed that the Gidra, who belong to non-Austronesian-speaking groups, are genetically located at the intermediate point between the Aboriginal Australian groups and the Austronesian-speaking groups. Moreover, the HLA-DRB1*0802 allele, which has been observed in only two Polynesian groups (Austronesian-speaking groups) of Oceanian populations, was also found in the Gidra. These results suggest that the admixture of Austronesian and indigenous non-Austronesian groups beyond the linguistic boundary occurred partly in Papua New Guinea before Austronesian groups spread to the Pacific.
DNA from the locus D1S80 was amplified by polymerase chain reaction (PCR) and analyzed by electrophoresis in vertical polyacrylamide gels followed by silverstaining. DNA samples from 119 unrelated Danes and 97 mother/child pairs were examined. The amplified fragment length polymorphism (AMP-FLP) analysis of the D1S80 locus demonstrated 21 alleles and a heterozygosity of 77%. Of the 231 possible phenotypes, 57 were observed. All mother/child pairs shared at least one D1S80 allele. The D1S80 typing results in 70 Danes were compared to the results obtained on the same samples in another laboratory and the results were concordant in all cases.
BACKGROUND: The macrophage scavenger receptor 1 (MSR1) gene on chromosome 8p22 was recently reported as a candidate gene for hereditary prostate cancer (HPC). Here, we further elucidate the role of MSR1 in both Swedish families with HPC and in a cohort of unselected prostate cancer. METHODS: DNA samples from 83 Swedish HPC families and 215 unselected population based cases of prostate cancer as well as 425 age-matched controls were genotyped. RESULTS: A total of 18 variants were identified, including 2 exonic, 7 intronic changes, and 9 changes in the 5'- or 3'-uncoding region. Of the two exonic changes, one previously reported truncation mutation was identified, a R293X nonsense mutation. This mutation was found in 2 of the 83 (2.4%) HPC families. The R293X mutation was found more frequently in men with PC (4.9%) than in unaffected men (2.7%), consistent with previous published results, however our results were not significant (P = 0.16). To additionally test for potential association of common sequence variants and increased risk for the disease, five common polymorphisms (PRO3, INDEL1, IVS5-57, P275A, INDEL7) were genotyped in the group of 215 prostate cancer cases and 425 age-matched controls. No association between any of the five common sequence variants and prostate cancer were found. CONCLUSION: Our results suggest that mutations in MSR1 gene might play a role in prostate cancer susceptibility, particularly the R293X mutation. This study warrants further investigations of the role of MSR1 in prostate cancer etiology.