Biomedical subjects

Ulf Gyllensten

Publications and source records attributed to Ulf Gyllensten.

11 recordsLinked to original sources

PubMed2006

A recent genetic link between Sami and the Volga-Ural region of Russia.

The genetic origin of the Sami is enigmatic and contributions from Continental Europe, Eastern Europe and Asia have been proposed. To address the evolutionary history of northern and southern Swedish Sami, we have studied their mtDNA haplogroup frequencies and complete mtDNA genome sequences. While the majority of mtDNA diversity in the northern Swedish, Norwegian and Finnish Sami is accounted for by haplogroups V and U5b1b1, the southern Swedish Sami have other haplogroups and a frequency distribution similar to that of the Continental European population. Stratification of the southern Sami on the basis of occupation indicates that this is the result of recent admixture with the Swedish population. The divergence time for the Sami haplogroup V sequences is 7600 YBP (years before present), and for U5b1b1, 5500 YBP amongst Sami and 6600 YBP amongst Sami and Finns. This suggests an arrival in the region soon after the retreat of the glacial ice, either by way of Continental Europe and/or the Volga-Ural region. Haplogroup Z is found at low frequency in the Sami and Northern Asian populations but is virtually absent in Europe. Several conserved substitutions group the Sami Z lineages strongly with those from Finland and the Volga-Ural region of Russia, but distinguish them from Northeast Asian representatives. This suggests that some Sami lineages shared a common ancestor with lineages from the Volga-Ural region as recently as 2700 years ago, indicative of a more recent contribution of people from the Volga-Ural region to the Sami population.

Asian People↗

PubMed2006

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study.

BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. METHODS: We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma.

Aged↗

PubMed2006

mtDB: Human Mitochondrial Genome Database, a resource for population genetics and medical sciences.

The mitochondrial genome, contained in the subcellular mitochondrial network, encodes a small number of peptides pivotal for cellular energy production. Mitochondrial genes are highly polymorphic and cataloguing existing variation is of interest for medical scientists involved in the identification of mutations causing mitochondrial dysfunction, as well as for population genetics studies. Human Mitochondrial Genome Database (mtDB) (http://www.genpat.uu.se/mtDB) has provided a comprehensive database of complete human mitochondrial genomes since early 2000. At this time, owing to an increase in the number of published complete human mitochondrial genome sequences, it became necessary to provide a web-based database of human whole genome and complete coding region sequences. As of August 2005 this database contains 2104 sequences (1544 complete genome and 560 coding region) available to download or search for specific polymorphisms. Of special interest to medical researchers and population geneticists evaluating specific positions is a complete list of (currently 3311) mitochondrial polymorphisms among these sequences. Recent expansions in the capabilities of mtDB include a haplotype search function and the ability to identify and download sequences carrying particular variants.

Databases, Nucleic Acid↗

PubMed2006

Lifestyle, genetics, and disease in Sami.

AIM: To present a summary of the lifestyle, genetic origin, diet, and disease in the population of Sami, indigenous people of northern Fennoscandia. METHOD: A survey of the available scientific literature and preliminary results from our own study of the Swedish Sami population. RESULTS: The Sami probably have a heterogeneous genetic origin, with a major contribution of continental or Eastern European tribes and a smaller contribution from Asia. The traditional Sami diet, high in animal products, persists in Sami groups still involved with reindeer herding, but others have adopted a diet typical of Western cultures. Early reports indicated a lower prevalence of heart disease and most cancers, except stomach cancer. Recent studies have not found a lower risk of heart disease, but have consistently shown an overall reduced cancer risk. Sami have been reported to share some specific health-related genetic polymorphisms with other European populations, but none that would explain the observed differences in disease risk. CONCLUSION: The genetic structure of the Sami population makes it suitable for studies of the genetic and environmental factors influencing the development of common diseases. The difference in incidence of heart disease between studies may reflect the ongoing transition from a traditional to a more Westernized lifestyle. The ability to compare population segments with different lifestyles, combined with the genetic structure of the population, creates unusual possibilities for studies of the genetic and environmental factors involved in the development of common disease.

Cardiovascular Diseases↗

PubMed2004

Type-specific associations of human papillomavirus load with risk of developing cervical carcinoma in situ.

We have previously shown that high human papillomavirus (HPV) 16 load in Papanicolaou smears negative for dysplasia is strongly associated with risk for carcinoma in situ (CIS) of the cervix. Here we study the amount of HPV DNA for some of the most frequent high-risk HPV types as determinants of progression to cervical CIS. Real-time PCR is used to estimate the normalized viral load of HPV 16, 18, 31, 33, 35, 39, 45, 52, 58 and 67 in 457 cases of cervical CIS and 552 matched population controls. A total of 2,747 archival Pap smears from gynecologic health examinations, collected over a period of up to 26 years, were analyzed to assess viral load during the infection history. Cervical smear samples differ widely in amount of DNA, underscoring the need for normalization of HPV load to number of cells in the sample. The risk of developing cervical CIS increases with higher viral load for most of the HPV types studied. The range of copy numbers per cell does not differ between HPV types but the odds ratio for CIS in the percentile with highest viral load is substantially higher for HPV 16 (OR = 36.9; 95% CI = 8.9-153.2) than for HPV 31 (OR = 3.2; 95% CI = 1.1-9.1) or HPV 18/45 (OR = 2.6; 95% CI = 1.0-6.4). Therefore, HPV viral load may be predictive of future risk of cervical CIS at a stage when smears are negative for squamous abnormalities, but differences between HPV types need closer attention.

Adult↗

PubMed2004

Linkage disequilibrium between microsatellite markers in the Swedish Sami relative to a worldwide selection of populations.

The pattern of linkage disequilibrium (LD) is affected by a number of factors, including population demography. High LD is seen in populations with a relatively limited and constant size, presumably because of genetic drift. We have examined the extent of LD among over 300 genome-wide pattern microsatellite loci in 29 populations from around the world. The pattern of LD varied between populations, with a larger extent of LD in populations with limited size relative to larger populations. In addition, the LD between 88 less well-spaced microsatellite markers from 10 different genomic regions was examined in the Sami compared with the general Swedish population. For these markers, increased LD extending up to 5 Mb was detected in the Sami. The amount of LD also differed between the chromosomal regions. The amount of LD in the Sami makes this population suitable for the mapping of complex genetic traits.

Genetic Markers↗

PubMed2004

Affected sib-pair analysis of the contribution of HLA class I and class II loci to development of cervical cancer.

Cervical cancer is a multifactorial disease and infection by oncogenic human papilloma viruses represents the main environmental risk factor. Only a subset of infections becomes persistent and develops into cancer, implying that genetic susceptibility factors are needed for malignant progression. Here, we use a population-based cohort of affected sib-pairs (ASPs) to examine the role of the human leukocyte antigen (HLA) class I and class II loci in cervical cancer susceptibility. Analysis of 278 ASPs revealed significant excess genetic sharing for all three HLA class II loci studied, DPB1, DQB1 and DRB1, with the strongest evidence for DQB1 and DRB1. No evidence of excess sharing was observed for the HLA class I HLA-B and HLA-A loci. When the material was stratified on the basis of the DQB1*0602/DRB1*1501 susceptibility haplotype, carriers showed significant sharing for all loci, whereas non-carriers showed no evidence of excess genetic sharing at any of the loci. However, for the DPB1 locus there was no difference in allele frequency between carriers and non-carriers indicating that the effect seen in DPB1 is not simply due to linkage disequilibrium. Our results show that the HLA class II represents a major genetic susceptibility locus to cervical cancer in contrary to the class I that do not appear to have a significant impact on predisposition to the disease. The strongest class II effects are coming from the DQB1 and DRB1 loci, but the DPB1 locus also contributes to the susceptibility to cervical cancer.

Cohort Studies↗

PubMed2003

A novel method for automatic genotyping of microsatellite markers based on parametric pattern recognition.

Genetic mapping of loci affecting complex phenotypes in human and other organisms is presently being conducted on a very large scale, using either microsatellite or single nucleotide polymorphism (SNP) markers and by partly automated methods. A critical step in this process is the conversion of the instrument output into genotypes, both a time-consuming and error prone procedure. Errors made during this calling of genotypes will dramatically reduce the ability to map the location of loci underlying a phenotype. Accurate methods for automatic genotype calling are therefore important. Here, we describe novel algorithms for automatic calling of microsatellite genotypes using parametric pattern recognition. The analysis of microsatellite data is complicated both by the occurrence of stutter bands, which arise from Taq polymerase misreading the number of repeats, and additional bands derived form the non-template dependent addition of a nucleotide to the 3' end of the PCR products. These problems, together with the fact that the lengths of two alleles in a heterozygous individual may differ by only two nucleotides, complicate the development of an automated process. The novel algorithms markedly reduce the need for manual editing and the frequency of miscalls, and compares very favourably with commercially available software for automatic microsatellite genotyping.

Algorithms↗

PubMed2003

Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines.

To study the evolutionary history of the Australian and New Guinean indigenous peoples, we analyzed 101 complete mitochondrial genomes including populations from Australia and New Guinea as well as from Africa, India, Europe, Asia, Melanesia, and Polynesia. The genetic diversity of the Australian mitochondrial sequences is remarkably high and is similar to that found across Asia. This is in contrast to the pattern seen in previously described Y-chromosome data where an Australia-specific haplotype was found at high frequency. The mitochondrial genome data indicate that Australia was colonized between 40 and 70 thousand years ago, either by a single migration from a heterogeneous source population or by multiple movements of smaller groups occurring over a period of time. Some Australian and New Guinea sequences form clades, suggesting the possibility of a joint colonization and/or admixture between the two regions.

Africa↗

PubMed2003

Real-time PCR-based system for simultaneous quantification of human papillomavirus types associated with high risk of cervical cancer.

We have previously shown that women with a high titer of human papillomavirus type 16 (HPV16) in cervical epithelial cells have an increased risk of developing cervical carcinoma in situ. In order to study the relationship between viral DNA amount and risk of cervical carcinoma for the HPV types most commonly found in cervical tumors, we developed a real-time PCR assay for the detection and quantification of HPV16, -18, -31, -33, -35, -39, -45, -52, -58, and -67. These HPV types are analyzed in two reaction tubes, allowing for independent quantification of three viral types, or groups of viral types, in each reaction. A separate reaction is used for estimating the number of a nuclear single-copy gene and is used to calculate the HPV copy number per genomic DNA equivalent in the sample. The system has a dynamic range from 10(2) to 10(7) HPV copies per assay and is applicable to both fresh clinical samples and DNA extracted from archival samples. Reconstitution experiments, made to mimic infections with several HPV types, shows that individual HPV types can be detected in a mixture as long as they represent 1 to 10% of the main type. The system was evaluated with respect to technical specificity and sensitivity, reproducibility, reagent stability, and sample preparation protocol and then used to analyze clinical samples. This homogeneous assay provides a fast and sensitive way for estimating the viral load of a series of the most frequent oncogenic HPV types in biopsies, as well as cervical smear samples.

Cervix Uteri↗

PubMed2002

Real-time DNA quantification of nuclear and mitochondrial DNA in forensic analysis.

The rapid development of molecular genetic analysis tools has made it possible to analyze most biological materialfound at the scene of a crime. Evidence materials containing DNA quantities too low to be analyzed using nuclear markers can be analyzed using the highly abundant mtDNA. However, there is a shortage of sensitive nDNA and mtDNA quantification assays. In this study, an assay for the quantification of very small amounts of DNA, based on the real-time Taq-Man assay, has been developed. This analysis will provide an estimate of the total number of nDNA copies and the total number of mtDNA molecules in a particular evidence material. The quantification is easy to perform, fast, and requires a minimum of the valuable DNA extracted from the evidence materiaL The results will aid in the evaluation of whether the specific sample is suitable for nDNA or mtDNA analysis. Furthermore, the optimal amount of DNA to be used in further analysis can be estimated ensuring that the analysis is successful and that the DNA is retained for future independent analysis. This assay has significant advantages over existing techniques because of its high sensitivity, accuracy, and the combined analysis of nDNA and mtDNA. Moreover, it has the potential to provide additional information about the presence of inhibitors in forensic samples. Subsequent mitochondrial and nuclear analysis of quantified samples illustrated the potential to predict the number of DNA copies required for a successful analysis in a certain typing assay.

Cell Nucleus↗