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E Lundqvist

Publications and source records attributed to E Lundqvist.

11 recordsLinked to original sources
PubMed2001

Genetic diversity in populations of plants with different breeding and dispersal strategies in a free-flowing boreal river system.

We have studied the genetic diversity of three plant species: Angelica archangelica (Apiacieae), Bistorta vivipara (Polygonaceae) and Viscaria alpina (Caryophyllaceae) along the free-flowing Vindel River in northern Sweden. The plants differ in reproductive strategy. A archangelica and V. alpina are insect pollinated outbreeders while B. vivipara reproduces with apomixis through bulbils. The seeds of A. archangelica may float for over a year, while the propagules (seeds and bulbils, respectively) of V. alpina and B. vivipara float for less than two days. Genetic diversity was assessed using starch gel electrophoresis. The clonal diversity of B. vivipara measured by Simpson's index (D) ranged between 0.78 and 0.99. Only a few clones were shared between localities. The average percentages polymorphic loci and mean He based on polymorphic loci for V. alpina over all localities were 23.1 and 0.15, respectively. Wright's F-statistics showed a significant overall deficit of heterozygotes. The diversity of A. archangelica was found to increase downstream. Genetic diversity of each species is sufficiently high to be used in studies on hydrochory. Dispersal appears to be related to the floating ability of progagules.

Genes, Plant↗
PubMed1999

Genetic mechanisms for duplication and multiduplication of the human CYP2D6 gene and methods for detection of duplicated CYP2D6 genes.

The polymorphic CYP2D6 gene determines the rates at which several different classes of clinically important drugs are metabolized in vivo. A specific phenotype whereby a subject metabolizes drugs very rapidly (ultrarapid metabolizer, UM) has been shown to be caused by the presence of multiple active CYP2D6 genes on one allele. Hitherto, individuals with 1, 2, 3, 4, 5, or 13 CYP2D6 genes in tandem have been described for various ethnic groups. In the present investigation, we present results from restriction mapping of the CYP2D loci of individuals with two or more consecutive CYP2D6 genes, along with sequence analysis of this gene (CYP2D6*2). Our results indicate that alleles with duplicated or multiduplicated genes have occurred through unequal crossover at a specific breakpoint in the 3'-flanking region of the CYP2D6*2B allele with a specific repetitive sequence. In contrast, alleles with 13 copies of the gene are proposed to have been formed by unequal segregation and extrachromosomal replication of the acentric DNA. We present a rapid and efficient PCR-based allele-specific method for the detection of duplicated, multiduplicated, or amplified CYP2D6 genes.

Alleles↗
PubMed1997

Screening of germline mutations in the CDKN2A and CDKN2B genes in Swedish families with hereditary cutaneous melanoma.

BACKGROUND: Approximately 10% of human cutaneous melanomas occur in families in which several members are affected. The familial predisposition to this disease is often associated with dysplastic nevus syndrome, a condition in which afflicted family members have multiple dysplastic nevi (atypical moles). The chromosome region 9p21 and markers on chromosomes 1p and 6p have been linked to melanoma susceptibility. The tumor suppressor genes CDKN2A and CDKN2B have been mapped to the 9p21 region, and genetic analyses have revealed the presence of germline CDKN2A alterations in melanoma families. The reported frequencies of such alterations, however, vary among these families. PURPOSE: The present investigation was carried out to determine the frequencies of CDKN2A and CDKN2B germline gene mutations among members in a population-based cohort of Swedish melanoma families (i.e., melanoma kindreds). METHODS: DNA was prepared from blood samples obtained from 181 individuals belonging to 100 melanoma kindreds. The polymerase chain reaction (PCR) technique, followed by single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses, were used to identify the types and frequencies of mutations in exons 1, 1beta, 2, and 3 of the CDKN2A gene and in exons 1 and 2 of the CDKN2B gene. RESULTS: CDKN2A gene aberrations were independently identified by both SSCP and nucleotide-sequence analyses. Nucleotide-sequence analysis identified a single point mutation leading to a substitution of leucine for proline in codon 48 of exon 1 in a family with a history of melanoma and several other cancers. A second abnormality, leading to an insertion of an extra arginine residue at codon number 113 of exon 2, was seen in four separate families. The CDKN2A exon-3 coding region had the wild-type sequence in all samples. No germline mutations were found in the alternative exon 1beta of the CDKN2A gene or in exons 1 and 2 of the CDKN2B gene. CONCLUSIONS: The present investigation demonstrates that CDKN2A germline gene mutations were observed in 7.8% of the 64 Swedish melanoma kindreds that each included at least two first-degree relatives with melanoma and dysplastic nevus syndrome. No CDKN2A exon 1beta or CDKN2B mutations were identified. The critical genes responsible for the inheritance of a susceptibility to develop melanoma among family members in this population have yet to be identified.

Carrier Proteins↗
PubMed1996

Mutational analysis of the CDKN2 gene in metastases from patients with cutaneous malignant melanoma.

We analysed 26 metastases from 25 patients with sporadic cutaneous malignant melanoma for alterations in the CDKN2 gene by a combined polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP)/nucleotide sequencing approach. Eleven alterations (one in exon 1, five in exon 2 and five in the 3' non-coding sequence of the exon 3 region) were concordantly and independently detected by both SSCP and nucleotide sequence analysis. Two of the exon 2 changes and the five changes in the non-coding exon 3 region are likely to represent natural polymorphism. Four (15%) of 26 metastases thus had CDKN2 mutations and belonged to 3 (12%) of 25 patients. Semi-quantitative PCR furthermore revealed no sign of homozygous deletions of the CDKN2 exon 2 region. The results support an involvement of the CDKN2 product in the development of a subgroup of sporadic melanomas and encourage the search for alterations in additional genes of the 9p21 region.

Alleles↗
PubMed1996

PCR-based genotyping for duplicated and deleted CYP2D6 genes.

The debrisoquine hydroxylase (CYP2D6), which metabolizes more than 30 different drugs, is highly polymorphic. In subjects having either very low or very high enzyme activity, drug therapy at recommended doses using CYP2D6 substrates may lead to either increased risk of side effects or therapeutic failure. We here describe PCR-based methods for detection of alleles having either duplicated, multiduplicated or deleted active CYP2D6 genes. As a control reaction, the entire coding region of the CYP2D6 gene is amplified. In conjunction with analysis of common mutations using this product as a template, the methods described can be used for genotyping of individuals being either poor, intermediate rapid, normal or ultrarapid metabolizers and provides an efficient tool for individualization of drug therapy.

Cytochrome P-450 CYP2D6↗
PubMed1993

Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine.

Deficient hydroxylation of debrisoquine is an autosomal recessive trait that affects approximately 7% of the Caucasian population. These individuals (poor metabolizers) carry deficient CYP2D6 gene variants and have an impaired metabolism of severely commonly used drugs. The opposite phenomenon also exists, and certain individuals metabolize the drugs very rapidly, resulting in subtherapeutic plasma concentrations at normal doses. In the present study, we have investigated the molecular genetic basis for ultrarapid metabolism of debrisoquine. Restriction fragment length polymorphism analysis of the CYP2D locus in two families with very rapid metabolism of debrisoquine [metabolic ratio (MR) for debrisoquine = 0.01-0.1] revealed the variant CYP2D6 gene CYP2D6L. Eco RI RFLP and Xba I pulsed-field gel electrophoresis analyses showed that this gene had been amplified 12-fold in three members (father and his two children) of one of the families, and two copies were present among members of the other family. The CYP2D6L gene had an open reading frame and carried two mutations causing amino acid substitutions: one in exon 6, yielding an Arg-296-->Cys exchange and one in exon 9 causing Ser-486-->Thr. The MR of subjects carrying one copy of the CYP2D6L gene did not significantly differ from that of those with the wild-type gene, indicating that the structural alterations were not of importance of the catalytic properties of the gene product. Examination of the MR among subjects carrying wild-type CYP2D6, CYP2D6L, or deficient alleles revealed a relationship between the number of active genes and MR. The data show the principle of inherited amplification of an active gene. Furthermore, the finding of a specific haplotype with two or more active CYP2D6 genes allows genotyping for ultrarapid drug metabolizers. This genotyping could be of predictive value for individualized and more efficient drug therapy.

Alleles↗
PubMed1991

Seasonal variation in ethylene concentration in the wood of Pinus sylvestris L.

Ethylene concentrations were determined in gas samples extracted from sealed holes made in the sapwood and heartwood of stems of 70-100-year-old Scots pine (Pinus sylvestris L). Gas could be collected from the heartwood holes by lowering the pressure by means of a large syringe. However, attempts to extract gas from air spaces in the sapwood with the same technique failed, presumably because of lack of an interconnected system of gas-filled canals. High ethylene concentrations, usually in excess of 1 ppm, accumulated in the sapwood holes within one day after sealing. Ethylene concentrations in the sapwood rose to 3-7 ppm during the growing season, and decreased to 0.1-0.3 ppm during the winter. In response to extreme drought, sapwood ethylene concentration increased to 30 ppm, followed by a rapid decrease after the onset of rain. Ethylene concentrations in gas samples from the heartwood were consistently lower than 1 ppm. The lowest values, about 0.1 ppm, were found during the autumn and early winter, whereas values around 0.5 ppm were typical from February to August.

Journal Article↗