Biomedical subjects

P Lahermo

Publications and source records attributed to P Lahermo.

10 recordsLinked to original sources

PubMed2003

A genome scan for developmental dyslexia confirms linkage to chromosome 2p11 and suggests a new locus on 7q32.

Developmental dyslexia is a distinct learning disability with unexpected difficulty in learning to read despite adequate intelligence, education, and environment, and normal senses. The genetic aetiology of dyslexia is heterogeneous and loci on chromosomes 2, 3, 6, 15, and 18 have been repeatedly linked to it. We have conducted a genome scan with 376 markers in 11 families with 38 dyslexic subjects ascertained in Finland. Linkage of dyslexia to the vicinity of DYX3 on 2p was confirmed with a non-parametric linkage (NPL) score of 2.55 and a lod score of 3.01 for a dominant model, and a novel locus on 7q32 close to the SPCH1 locus was suggested with an NPL score of 2.77. The SPCH1 locus has previously been linked with a severe speech and language disorder and autism, and a mutation in exon 14 of the FOXP2 gene on 7q32 has been identified in one large pedigree. Because the language disorder associated with the SPCH1 locus has some overlap with the language deficits observed in dyslexia, we sequenced the coding region of FOXP2 as a candidate gene for our observed linkage in six dyslexic subjects. No mutations were identified. We conclude that DYX3 appears to be important for dyslexia susceptibility in many Finnish families, and a suggested linkage of dyslexia to chromosome 7q32 will need verification in other data sets.

Chromosome Mapping↗

PubMed2001

Detecting errors in mtDNA data by phylogenetic analysis.

Sequencing and documenting a sample of homologous DNA stretches is prone to copying errors in a way rather analogous to the biological replication process. Previous attempts at obtaining representative mtDNA sequences, typically of the control region, for evolutionary studies or forensic purposes have yielded rather unsatisfactory results in many cases. The key ingredient in pinpointing problems with given data is the phylogenetic analysis of closely related mtDNAs within the framework of an established worldwide phylogeny that is supported by coding region information. We develop some general rules by which likely errors in data tables can readily be detected without rereading whole sequences repeatedly. Following these guidelines, one can expect to lower the error rate by at least an order of magnitude, although it will still be hard to beat the mitochondrial gamma polymerase in precision.

DNA, Mitochondrial↗

PubMed2001

Mapping of the second locus for the Van der Woude syndrome to chromosome 1p34.

The Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, cleft lip and/or cleft palate. It is the most common cleft syndrome. VWS has shown remarkable genetic homogeneity in all populations, and so far, all families reported have been linked to 1q32-q41. A large Finnish pedigree with VWS was recently found to be unlinked to 1q32-q41. In order to map the disease locus in this family, a genome wide linkage scan was performed. A maximum lod score of 3.18 was obtained with the marker D1S2797, thus assigning the disease locus to chromosomal region 1p34. By analyses of meiotic recombinants an approximately 30 cM region of shared haplotypes was identified. The results confirm the heterogeneity of the VWS syndrome, and they place the second disease locus in 1p34. This finding has a special interest because the phenotype in VWS closely resembles the phenotype in non-syndromic forms of cleft lip and palate.

Abnormalities, Multiple↗

PubMed2000

MtDNA polymorphism in the Hungarians: comparison to three other Finno-Ugric-speaking populations.

Mitochondrial DNA sequence variation as well as restriction site polymorphisms were examined in 437 individuals from four Finno-Ugric-speaking populations. These included the Hungarians (Budapest region and the Csángós from Hungary and Romania), the Finns and two Saami groups from northeastern Finland (Inari Saami and Skolt Saami), and the Erzas from central Russia. The mtDNA data obtained in this study were combined with our previous data on Y chromosomal variation for eight different loci in these populations. The genetic variation observed among the Hungarians resembled closely that found in other European populations. The Hungarians could not be distinguished from the neighboring populations (e.g., the Austrians) any more than from their Finno-Ugric linguistic relatives.

DNA, Mitochondrial↗

PubMed1998

mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe.

mtDNA sequence variation was studied in 419 individuals from nine Eurasian populations, by high-resolution RFLP analysis, and it was followed by sequencing of the control region of a subset of these mtDNAs and a detailed survey of previously published data from numerous other European populations. This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an autochthonous European haplogroup, which most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas. Its sister haplogroup, H, which is distributed throughout the entire range of Caucasoid populations and which originated in the Near East approximately 25,000-30,000 years ago, also took part in this expansion, thus rendering it by far the most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and northern Europe. This scenario, already implied by archaeological records, is given overwhelming support from both the distribution of the autochthonous European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic maps of nuclear data.

DNA, Mitochondrial↗

PubMed1998

Selenium and arsenic in the environment in Finland.

A characteristic feature of glaciated Precambrian environments is their low selenium content, as a chalcophile element, Se, replaces sulfur in many of the sulfide minerals, for example, pyrite, chalcopyrite, pyrrhotite, and pentlandite. The average Se concentration in rocks and related till deposits in Finland is in the range of 0.01 to 0.2 mg/kg. Due to geological conditions, Se concentrations in surface and ground water are low in Finland compared with other countries. In a nationwide study dealing with the hydrogeochemistry of headwater streams, the median Se concentration in streams during August to September 1990 was 30 to 180 microg/L. For comparison, Se concentrations in shallow well waters are generally in the range of 50 to 1000 microg/L. The Se concentrations in stream sediments varied from 0.03 to 3.94 mg/kg. There was a highly significant correlation between the Se concentrations in stream water and in stream sediment. The streams with Se concentrations exceeding the general level in both water and sediment were most common in southern Finland. A speciation study on Finnish stream waters revealed that there were equal proportions of Se complexed with humic substances (36%) and Se as a selenate species (36%), whereas selenite accounted for less than 10% of total Se. About 8% of the Se in stream water occurred in particulate form. In an effort to enhance the Se intake of Finns through diet, Se-supplemented fertilizers have been used nationwide since 1985. While greatly improving Se levels in the population, the measure has raised concerns about undesirable environmental effects. Therefore, the amount of Se added to fertilizers has been reduced since 1991. Differing in behavior from Se, arsenic is considered one of the most toxic metals derived from the natural environment. Alarm has been triggered in Finland by the recent lowering from 50 microg/L to 10 microg/L of the upper level of As permissible in potable water, the recent information of high As concentrations in water from drilled bedrock wells, and the findings of international medical studies suggesting that As is a carcinogen. The most important source of As is arsenopyrite (FeAsS). Hence, high As concentrations most frequently occur in areas of sulfide mineralization, often in connection with occurrences of mafic rocks such as gabbros, amphibolites, and peridotites. The As concentrations in till fines, the most common glaciogenic soil type in Finland, reflect those in bedrock. The concentrations in groundwater are controlled by the chemical composition of the bedrock and the soil and prevailing hydrogeochemical conditions, for example, pH and Eh levels. Arsenic concentrations are lowest in surface water and swiftly flowing shallow ground water discharged by springs and are somewhat higher in shallow wells dug into overburden. By far, the highest As concentrations are to be found in wells drilled into bedrock (maximum 1 to 2 mg/L), although the concentrations vary by several orders of magnitude from well to well. The highest probability of encountering deleteriously arsenious well water is in areas with characteristic As anomalies in the till and bedrock. Hence, it is important to understand local geological conditions, particularly in the case of wells drilled into bedrock. The risk of deleteriously high As concentrations occurring in captured springs and shallow wells is slight.

Animals↗

PubMed1996

The genetic relationship between the Finns and the Finnish Saami (Lapps): analysis of nuclear DNA and mtDNA.

The genetic relationships between two Finno-Ugric-speaking populations, the Finns and the Finnish Saami (Lapps), were studied by using PCR for six nuclear-DNA marker loci, mitochondrial restriction-site polymorphism, and sequence variation of a 360-bp segment of the mitochondrial control region. The allele frequencies of each of the nuclear-DNA marker loci and the frequencies of mtDNA restriction haplotypes were significantly different between the populations. The Saami showed exceptionally low variation in their mtDNA restriction sites. The 9-bp deletion common in East Asian populations was not observed, nor did the haplotype data fit into the haplogroup categorization of Torroni et al. The average number of nucleotide substitutions from the mtDNA haplotype data indicated that the Finnish Saami may be closer to the Finns than to the other reference populations, whereas nuclear DNA suggested that the Finns are more closely related to the European reference populations than to the Finnish Saami. The similarity of the Finns to the other Europeans was even more pronounced according to the sequence data. We were unable to distinguish between the Finns and either the Swiss or Sardinian reference populations, whereas the Finnish Saami clearly stood apart. The Finnish Saami are distinct from other Circumarctic populations, although two of the lineages found among the Saami showed closer relationship to the Circumarctic than to the European lineages. The sequence data indicated an exceptionally high divergence for the Saami mtDNA control lineages. The distribution of the pairwise nucleotide differences in the Saami suggested that this population has not experienced an expansion similar to what was indicated for the Finns and the reference populations.

Base Sequence↗

PubMed1995

Genes and languages in Europe: an analysis of mitochondrial lineages.

When mitochondrial DNA sequence variation is analyzed from a sample of 637 individuals in 14 European populations, most populations show little differentiation with respect to each other. However, the Saami distinguish themselves by a comparatively large amount of sequence difference when compared with the other populations, by a different distribution of sequence diversity within the population, and by the occurrence of particular sequence motifs. Thus, the Saami seem to have a long history distinct from other European populations. Linguistic affiliations are not reflected in the patterns of relationships of mitochondrial lineages in European populations, whereas prior studies of nuclear gene frequencies have shown a correlation between genetic and linguistic evolution. It is argued that this apparent contradiction is attributable to the fact that genetic lineages and gene frequencies reflect different time perspectives on population history, the latter being more in concordance with linguistic evolution.

Base Sequence↗

PubMedDate not supplied

Y chromosomal polymorphisms reveal founding lineages in the Finns and the Saami.

Y chromosomal polymorphisms were studied in 502 males from 16 Eurasian ethnic groups including the Finns, Saami (Inari Lake area and Skolt Saami), Karelians, Mari, Mokshas, Erzas, Hungarians (Budapest area and Csángós), Khanty, Mansi, Yakuts, Koryaks, Nivkhs, Mongolians, and Latvians. The samples were analysed for polymorphisms in the Y chromosome specific Alu insertion (YAP) and six microsatellites (DYS19, DYS389-I and II, DYS390, DYS392, DYS393). The populations were also screened for the recently described Tat polymorphism. The incidence of YAP+ type was highest in the Csángós and in other Hungarians (37.5% and 17.5%, respectively). In the Karelians and the Latvians it was present at approximately the same level as commonly found in other European populations, whilst absent in our further samples of Eurasian populations, including the Finns and the Saami. Aside from the Hungarians, the C allele of the Tat polymorphism was common in all the Finno-Ugric speaking populations (from 8.2% to 63.2%), with highest incidence in the Ob-Ugrian Khanty. The C allele was also found in the Latvians (29.4%). The haplotypes found associated with the Tat C allele showed consistently lower density than those associated with the T allele, indicating that the T allele is the original form. The computation of the age of the Tat C suggested that the mutation might be a relatively recent event giving a maximum likelihood estimate of 4440 years (95% confidence interval about 3140-6200 years). The distribution patterns of the 222 haplotypes found varied considerably among the populations. In the Finns a majority of the haplotypes could be assigned to two distinct groups, one of which harboured the C allele of the Tat polymorphism, indicating dichotomous primary source of genetic variation among Finnish males. The presence of a bottleneck or founding effect in the male lineages of some of the populations, namely in the Finns and the Saami, would appear to be one likely interpretation for these findings.

Alu Elements↗

PubMedDate not supplied

mtDNA haplotype analysis in Finnish families with leber hereditary optic neuroretinopathy.

The mitochondrial DNA (mtDNA) sequence variation of 24 Finnish Leber hereditary optic neuroretinopathy (LHON) probands was characterized by sequencing and restriction endonuclease analyses. All LHON-associated substitutions and Caucasoid haplogroup-specific mutations were screened in the families. Analysis of the mtDNAs revealed that the Finnish LHON families have two unique features: an absence of the ND6/14484 mutation and a high number of families (10/24) without the primary mutations ND1/3460 and ND4/11778. Furthermore, the LHON families showed considerable mtDNA heterogeneity: among 24 families 22 haplotypes were detected. Overall, the haplogrouping of LHON families was similar to other European populations. However, the frequency of ND4/11778-positive families in haplogroup J was high, which may indicate that background mutations in this haplogroup together with the ND4/11778 primary mutation promote the penetrance of LHON.

Adolescent↗