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S Nørby

Publications and source records attributed to S Nørby.

At least 19 recordsLinked to original sources
PubMed2000

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Africa, Northern↗
PubMed2000

Tracing European founder lineages in the Near Eastern mtDNA pool.

Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2, 804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.

DNA, Mitochondrial↗
PubMed2000

[Genetic mapping].

Explore the source record for details and available documents.

Chromosome Mapping↗
PubMed2000

mtDNA variation among Greenland Eskimos: the edge of the Beringian expansion.

The Eskimo-Aleut language phylum is distributed from coastal Siberia across Alaska and Canada to Greenland and is well distinguished from the neighboring Na Dene languages. Genetically, however, the distinction between Na Dene and Eskimo-Aleut speakers is less clear. In order to improve the genetic characterization of Eskimos in general and Greenlanders in particular, we have sequenced hypervariable segment I (HVS-I) of the mitochondrial DNA (mtDNA) control region and typed relevant RFLP sites in the mtDNA of 82 Eskimos from Greenland. A comparison of our data with published sequences demonstrates major mtDNA types shared between Na Dene and Eskimo, indicating a common Beringian history within the Holocene. We further confirm the presence of an Eskimo-specific mtDNA subgroup characterized by nucleotide position 16265G within mtDNA group A2. This subgroup is found in all Eskimo groups analyzed so far and is estimated to have originated <3,000 years ago. A founder analysis of all Eskimo and Chukchi A2 types indicates that the Siberian and Greenland ancestral mtDNA pools separated around the time when the Neo-Eskimo culture emerged. The Greenland mtDNA types are a subset of the Alaskan mtDNA variation: they lack the groups D2 and D3 found in Siberia and Alaska and are exclusively A2 but at the same time lack the A2 root type. The data are in agreement with the view that the present Greenland Eskimos essentially descend from Alaskan Neo-Eskimos. European mtDNA types are absent in our Eskimo sample.

Alaska↗
PubMed1998

A new mitochondrial tRNA(Met) gene mutation in a patient with dystrophic muscle and exercise intolerance.

A 30-year-old woman with a novel heteroplasmic U4409C mtDNA mutation in the tRNA(Met) gene presented with growth retardation, muscle weakness, severe exercise intolerance, and lactic acidosis. Muscle biopsy showed unusually severe dystrophic features. The mutation was not present in maternal relatives or 25 healthy subjects. Single-fiber PCR-RFLP analysis of mtDNA showed higher proportion of the mutation in COX-negative than in COX-positive muscle fibers.

Adult↗
PubMed1997

A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2).

Recently the second gene for autosomal dominant polycystic kidney disease (ADPKD), located on chromosome 4q21-q22, has been cloned and characterized. The gene encodes an integral membrane protein, polycystin-2, that shows amino acid similarity to the PKD1 gene product and to the family of voltage-activated calcium (and sodium) channels. We have systematically screened the gene for mutations by single-strand conformation-polymorphism analysis in 35 families with the second type of ADPKD and have identified 20 mutations. So far, most mutations found seem to be unique and occur throughout the gene, without any evidence of clustering. In addition to small deletions, insertions, and substitutions leading to premature translation stops, one amino acid substitution and five possible splice-site mutations have been found. These findings suggest that the first step toward cyst formation in PKD2 patients is the loss of one functional copy of polycystin-2.

Adult↗
PubMed1997

Quantification, by solid-phase minisequencing, of the telomeric and centromeric copies of the survival motor neuron gene in families with spinal muscular atrophy.

In an analysis of 30 families affected by spinal muscular atrophy (SMA) we have used the solid-phase minisequencing method to determine the ratio between the number of telomeric and centromeric copies of the survival motor neuron gene (SMN and cBCD541 respectively) on normal and SMA chromosomes. This has enabled us to establish haplotypes with regard to SMN and cBCD541, and estimate their frequencies, on both types of chromosomes. Six predominant haplotypes were identified, three for normal chromosomes and three for SMA chromosomes, characterized by having 0, 1, or 2 copies, respectively, of cBCD541. We found evidence for the presence of patients homozygous for a deletion of SMN and with only one copy of cBCD541, but found none deleted for all copies of this gene. Several asymptomatic carriers of SMA with only a single copy of SMN and no copy of cBCD541 were identified. We could not confirm the hypothesis that the presence of more copies of cBCD541 is correlated to a less severe course of the disease. The frequencies of haplotypes characterized by having 0, 1, or 2 copies, respectively, of cBCD541 were found to differ significantly between normal and SMA chromosomes. This distribution can be explained by an underrepresentation of the haplotype completely lacking SMN genes, which is expected to cause early embryonic death in homozygotes. This first report of a direct haplotype analysis of SMN and cBCD541 should help clarify the role of cBCD541 in the pathogenesis of SMA.

Centromere↗
PubMed1997

Genetic heterogeneity of migraine with and without aura in Danes cannot be explained by mutation in mtDNA nucleotide pair 11084.

INTRODUCTION: Migraine is a genetic heterogeneous disorder. The 11084 A to G base substitution is in the gene for the ND4 subunit of the respiratory complex I, and leads to a Thr to Ala amino acid replacement. This mutation had been found in 25% of Japanese migraineurs, while tension-type headache sufferers and non-migraineurs did not have it. MATERIAL AND METHODS: We investigated the importance of this mutation in Danish migraineurs without aura, migraineurs with aura and non-migraineurs from the general population. RESULTS: We did not detect this mutation in Danes. CONCLUSION: Our result excludes a significant role of this mutation in the etiology of migraine in Denmark, and its absence in non-migraineurs supports that this mutation is rare in non-Japanese populations.

Adult↗
PubMed1996

Ocular myopathy and mitochondrial DNA deletion. A presentation of seven identified Danish patients.

This paper summarizes the data on Danish patients with ocular myopathy and mitochondrial DNA deletion (delta mtDNA). To date, a single Danish patient harbouring delta mtDNA has been reported. In the present study we have identified seven additional ones and characterized the nature of their deletion, both qualitatively and quantitatively. All patients are sporadic cases each with a single deletion in the range of 2.3-78 kb, the delta mtDNA accounting for 10-75% of the total mtDNA in the biopsy analyzed. The clinical severity correlates with the percentage of deletion molecules, and not with the size of the deletion.

Adult↗