Original Paper

Evidence for mtDNA Admixture between the Finns and the Saami
Maria Meinilä, Saara Finnilä, Kari Majamaa

Departments of Neurology and Medical Biochemistry, and Biocenter, University of Oulu, Oulu, Finland

Address of Corresponding Author

Hum Hered 2001;52:160-170 (DOI: 10.1159/000053372)

 Outline

• Key Words
• Abstract
• Introduction
• Subjects and Methods
• Subjects and Samples
• Analysis of mtDNA Haplogroups and Haplotypes
• Summary Statistics and Interpopulation Analysis
• Results
• Frequencies of mtDNA Haplogroups in Four Regions in Finland
• Sequence Variation in the HVS-I in Northern and Central Finland
• Admixture between the Saami and Finnish Populations in Northern Finland
• Discussion
• Acknowledgements
• Appendix
• References

• Author Contacts
• Article Information
• Publication Details
• Drug Dosage / Copyright

  Key Words

• Population genetics
• mtDNA haplotypes
• Admixture

  Abstract

Objectives: The Finns, and to a more extreme extent the Saami, are genetic outliers in Europe. Despite the close geographical contact between these populations, no major contribution of Saami mtDNA haplotypes to the Finnish population has been detected. Methods: To examine the extent of maternal gene flow from the Saami into Finnish populations, we determined the mtDNA variation in 403 persons living in four provinces in central and northern Finland. For all of these samples, we assessed the frequencies of mtDNA haplogroups and examined sequence variation in the hypervariable segment I (HVS-I). The resulting data were compared with published information for Saami populations. Results: The frequencies of the mtDNA haplogroups differed between the populations of the four provinces, suggesting a distinction between northern and central Finland. Analysis of molecular variance suggested that the Saami deviated less from the population of northern Finland than from that of central Finland. Five HVS-I haplotypes, including that harboring the Saami motif and the Asian-specific haplogroup Z, were shared between the Finns and the Saami and allowed comparisons between the populations. Their frequency was highest in the Saami and decreased towards central Finland. Conclusions: The high frequency of certain mtDNA haplotypes considered to be Saami specific in the Finnish population suggests a genetic admixture, which appears to be more pronounced in northern Finland. Furthermore, the presence of haplogroup Z in the Finns and the Saami indicates that traces of Asian mtDNA genotypes have survived in the contemporary populations.

Copyright © 2001 S. Karger AG, Basel

 introduction

The oldest archeological evidence of settlement in Finland dates back approximately 9,000 years. The origin of these people is unknown, but they could have been ancestors of the Saami [1]. They subsisted on hunting, fishing and gathering, and probably came from the area of the Ural Mountains. The second wave of settlers arrived in the southern parts of Finland around 5,500 years before present. Permanent settlement extended across southern Finland and the coast and riversides of Ostrobothnia in the 16th century, but the forest areas of northern and eastern Finland still had no resident population [2]. Thereafter a major colonization of these areas began, with people mainly from southern Savo being directed to them by the Crown authorities.

The Finns are considered to be one of the outliers on the genetic map of Europe [3]. Geographic and cultural isolation has greatly shaped the Finnish gene pool. For example, certain recessive diseases are prevalent there even if they are infrequent elsewhere [2]. Furthermore, previous studies on the sequence variation in the Y chromosome and mitochondrial DNA (mtDNA) have shown high homogeneity in the Finnish population [4, 5, 6, 7, 8]. An Asian-specific polymorphism is quite frequent in the Finnish Y chromosome pool [8], whereas a clear West Eurasian pattern of polymorphisms has been detected in mtDNA [4, 5, 6, 7]. About 40% of the Finns belong to mtDNA haplogroup H, which is also common among other Europeans [7, 9]. Other common haplogroups among the Finns include haplogroup U, with a frequency of 16%, haplogroup J, with a frequency of 14%, and haplogroup T, with a frequency of 6%. The remaining haplogroups (I, K, M, V, W, X) are less common, each with a frequency below 4% [7].

The Saami are a small ethnic group living in the northern parts of Finland, Sweden, Norway and northwestern Russia. Genetically they are the most unique population in Europe and are sharply differentiated from an otherwise homogeneous set of Eruopean populations [3, 10, 11, 12, 13]. In particular, Saami mtDNA show restricted sequence variation, with many of them being characterized by a motif defined by the nucleotide variants 16144TC, 16189TC and 16270CT that belong to subcluster U5 [10, 14]. Because of the high frequency of these U5 mtDNA in Saami populations (32-52%) and their near absence in other European populations [10], it is thought that they originated in the Saami, with the series of mutations defining U5 being called the 'Saami motif'. The majority of the remaining Saami mtDNAs exhibited a high frequency of the 16298TC nucleotide variant.

Previous studies have failed to demonstrate any major contribution of the Saami mtDNA haplotypes to the Finnish population, although the settlers and the original population probably lived in close contact during the colonization of Finland and members of the original population probably acculturated with the settlers [1]. Signs of such contacts would be most probable in regions that have been colonized by the Finns during recorded history. To identify the maternal genetic contribution of the Saami to the Finnish population, we collected samples from four neighboring provinces in central and northern Finland, areas that differ in their population history but are currently devoid of a Saami population. For all of these samples, we assessed the frequencies of mtDNA haplogroups and examined sequence variation in the hypervariable segment I (HVS-I). The resulting data were compared with published information for Saami populations.

 subjects and methods

 subjects and samples

A total of 403 samples from healthy blood donors (242 men, 161 women) were obtained at the Finnish Red Cross offices in the capitals of the provinces of Northern Ostrobothnia, Kainuu, Northern Savo and Central Ostrobothnia (fig. 1). Because the population of Finland is concentrated in the southern part of the country, the provinces of Northern Ostrobothnia and Kainuu will represent northern Finland, while the provinces of Northern Savo and Central Ostrobothnia will represent the central part. The province of Lapland, lying north of Northern Ostrobothnia (fig. 1), was not used as a source of samples because it was not possible to exclude blood donors who might have immediate maternal ancestors in the Saami population.

Fig. 1. Map of Finland showing the provinces of Northern Ostrobothnia (PO), Kainuu (PK), Northern Savo (PS) and Central Ostrobothnia (PL).

The mean age of the donors was 41 ± 12 years (range 18-64 years). The donors and their mothers were required to be free of the common manifestations of mitochondrial diseases, such as diabetes mellitus, hearing impairment and neurological ailments. In addition, it was required that the donors and their mothers had been born in the same province. After obtaining this information, the samples were anonymized. The generation time in the population of the provinces of Northern Ostrobothnia and Kainuu has recently been calculated to be 28.4 years [15], suggesting that the mothers of the blood donors had been born between the years 1906 and 1952. The research protocol was approved by the Ethics Committee of the Medical Faculty, University of Oulu, and the Ethics Committee of the Finnish Red Cross.

Previously published Saami sequences were obtained from the EMBL data library under accession numbers X90001-X90115 [10].

 analysis of mtdna haplogroups and haplotypes

Total DNA was isolated from blood cells using the QIAamp Blood Kit (Qiagen, Hilden, Germany), and mtDNA haplogroups were determined by restriction fragment analysis to identify the most informative polymorphic sites [7], except that 12308AG was detected by Dde I digestion of a fragment amplified in the presence of a mismatched (underlined nucleotide) forward primer 12279-12307 (5'-AAC AGC TAT CCA TTG GTC TTA GGC CC AA-3'). The cleavage was observed when 12308AG was present. The mtDNA haplogroups (H, I, J, K, M, T, U, V, W, X) and clusters of related haplogroups (HV, TJ, UK, WIX) were defined according to the published criteria [7, 9].

The polymorphism 9477GA, determining haplogroup U5 [14], was detected by conformation-sensitive gel electrophoresis (CSGE). The DNA fragment spanning between nts 9211 and 9595 was first amplified and a portion of the PCR product was then taken for heteroduplex formation, where an unknown fragment was mixed with the corresponding fragment harboring the polymorphic variant 9477A. Mixtures of the amplified fragments were denatured at 95°C for 5 min and the heteroduplexes subsequently allowed to anneal at 68°C for 30 min. CSGE was carried out as described earlier [14].

The mtDNA sequence between nts 16024 and 16400 in HVS-I was determined by automated sequencing (ABI PRISM^TM 377 Sequencer using the Dye Terminator Cycle Sequencing Ready Kit, Perkin Elmer, Foster City, Calif., USA) after treatment with exonuclease I and shrimp alkaline phosphatase [16]. Each unique mtDNA sequence was defined as a haplotype.

 summary statistics and interpopulation analysis

Differences in mtDNA haplogroup frequencies between the populations were evaluated using the exact test of population differentiation [17] as implemented in ARLEQUIN 2.0 [18] or, if applicable, by the ² test or Fischer's exact test. Sequence data on the mtDNA HVS-I were used to calculate molecular diversity indices within populations by means of the ARLEQUIN 2.0 software package [18]. Analysis of molecular variance (AMOVA) was used to detect variance among and within populations. The HVS-I sequence spanning the nts 16024-16400 was used for the Finnish populations, whereas comparisons between the Finns and Saami were based on the nts 16024-16383 sequence.

 results

 frequencies of mtdna haplogroups in four regions in finland

Determination of the frequencies of mtDNA haplogroups in individuals from central and northern Finland showed haplogroups H and U to be the most common mtDNA genotypes, with frequencies of 40 and 28%, respectively (table 1). Haplogroup W was the third most common, while the remaining ones were considered rare, being present in less than 6%. In addition, macrohaplogroup M was present in 2.5% of the Finnish populations, based on the presence of the Dde I site at nt 10934 and Alu I site at nt 10397. The haplogroup of one sample could not be determined.

Table 1. Mitochondrial DNA haplogroup frequencies in the four populations

The frequencies of the haplogroups differed from those reported previously for the Finns (p = 0.04; exact test of population differentiation) [7], as also did the frequencies of the five mtDNA haplogroup clusters HV, UK, TJ, WIX and M (² test, p = 0.006). Analysis at the province level (table 2) showed that the samples from the two provinces in northern Finland did not differ from each other, nor did those from the two provinces in central Finland. However, significant differences in haplogroup frequencies were observed between all pairs of one northern and one central province. Haplogroups that were more frequent in the northern provinces included U, V, T and M, while haplogroups H, J and I were more frequent in the central provinces (table 1).

Table 2. Exact test of population differentiation

 sequence variation in the hvs-i in northern and central finland

Sequencing of the HVS-I in the mtDNA of the 403 samples revealed 103 haplotypes characterized by 82 polymorphic sites and including 77 transitions, 8 transversions and 2 single base deletions (see Appendix). The standard indices of genetic heterogeneity (table 3) were quite similar to those previously reported for the Finns [19]. The distribution of pairwise differences in the samples from the four provinces was unimodal, with a mode value between 3 and 5 and with raggedness values between 0.0122 and 0.0157. AMOVA in the HVS-I segment suggested differences between the populations of the two northern provinces and those of the two central provinces (table 4).

Table 3. mtDNA HVS-I sequence diversity in central and northern Finland

Table 4. AMOVA results for the populations of the four provinces in central and northern Finland

Three HVS-I haplotypes were the most common among Finnish populations. These included haplotype H/ht1 (10%), which is identical to the Cambridge reference sequence (CRS) [22], haplotype W/ht1 (8.9%), and haplotype U/ht1 (7.4%), which contains the Saami motif (see Appendix). Haplotypes U/ht6 and U/ht7 also harbored the Saami motif, making its frequency 8.7%, the highest observed outside the Saami population. However, the frequency of the Saami motif differed between northern (12.3%) and central (5.0%) Finland (p = 0.01, Fischer's exact test). In addition, the partial Saami motif 16189TC and 16270CT was found at a frequency of 7.4% (8.4% in the northern provinces and 6.5% in the central provinces). Altogether, 16270CT was found in 82% of the samples belonging to haplogroup U. This substitution has been used to define subcluster U5, but we found that an additional 11 samples belonged to this subcluster when the 9477GA polymorphism was used as well (see Appendix) [14]. Thus subcluster U5 was found at a frequency of 26% in the Finnish population.

Another interesting feature of the Finnish mtDNA haplotypes was the findings that 9 out of the 10 samples that had been tentatively assigned to macrohaplogroup M exhibited a motif characterized by 16129GA, 16185CT, 16223CT, 16224TC, 16260CT and 16298TC. The same motif has been observed in mtDNAs from populations inhabiting northeastern Asia and has been taken to define haplogroup Z [23]. The presence of 16298TC was intriguing, because this polymorphism is commonly used as evidence of haplogroup V. However, we found that 31% of the Finnish samples harboring 16298TC in fact belonged to haplogroup Z.

 admixture between the saami and finnish populations in northern finland

HVS-I sequences from 403 Finns were compared to those from 115 Saami [10]. The Saami HVS-I sequences contained 26 haplotypes, of which 10 were common to both the Saami and Finnish populations (table 5). However, 5 of these were rare in the Saami, whereas haplotypes V/ht1, V/ht3, U/ht1, U/ht12 and M/ht1 were more prevalent (see Appendix). Interestingly, the frequencies of these haplotypes differed between the Saami and the Finns in a manner that suggested a geographical gradient (table 5). Their combined frequencies were 68% in the Saami, 20% in northern Finland and 6.0% in central Finland (p < 0.001 for the difference, ² test).

Table 5. Frequencies of mtDNA haplotypes that are common to the Finnish and Saami populations

These five haplotypes harbored sequence signatures that are common among the Saami but less frequent or absent elsewhere in Europe [9, 10]. Haplotype U/ht1 was characterized by the Saami motif, while haplotype U/ht12 harbored a partial motif lacking 16144TC. The 16298TC polymorphism has been reported to occur at a high frequency in the Saami, and haplotypes V/ht1 and V/ht3 appeared to contribute to this. Interestingly, haplotype M/ht1, which is known to represent haplogroup Z, was found in 5 Saami mtDNAs, and a nearly identical HVS-I was found in 1 sample.

AMOVA suggested that whereas variance due to variation among samples was low in northern and central Finland, a remarkably high variance was observed between the Saami and Finnish samples (table 6). Interestingly, the variance due to variation among populations was slightly lower between the northern Finland material and the Saami than between central Finland and the Saami (table 6).

Table 6. AMOVA results for the populations of central and northern Finland and the Saami

 discussion

The frequencies of the mtDNA haplogroups were found to differ significantly from those reported earlier for the Finns [7, 10], the most conspicuous difference being the high frequency of haplogroup U. The finding may be due to a true difference in haplogroup frequencies between southern and northern Finland. The majority of the Finns live in the southern part of the country, suggesting that, in the case of random ascertainment, the samples in the two previous studies [7, 10] represent southern Finland. Indeed, the analysis of haplogroup frequencies between the populations of four neighbouring provinces in this study and the results of AMOVA suggested differences in the genetic structure of the populations of northern and central Finland. The subjects had been enrolled on the basis of their province of residence, but it was also required that their mothers should have been born in the same province, to ensure that the samples represented the ancestral population of the respective provinces. We estimated that the mothers of the subjects had been born between the years 1906 and 1952. The majority of the population was rural and the average migration rate had been low during the period concerned [24]. In fact, 96% of the Finns in 1880 were living in the same province where they had been born, and the corresponding percentage in 1920 was 95% in the provinces of Northern Ostrobothnia and Kainuu and slightly lower in Central Ostrobothnia and Northern Savo [1].

The population of northern Finland differed markedly from other European populations in the freqeuncy of haplogroup U. In fact, in this population, subcluster U5 comprised 92% of mtDNAs from this haplogroup (see Appendix). By contrast, subcluster U5 appears at much lower frequencies in Europe as a whole, varying in frequency from 0% in Western European countries to 53% in the Saami [12]. On average, the frequency of this subcluster is twice as high in Finland as in Europe as a whole [12], but it appears to be even higher in northern Finland. However, this comparison of frequencies is subject to an unknown error due to the fact that U5 was previously defined by the presence of 16270CT [see 12]. Further examination of these HVS-I sequences indicates that a certain portion of subcluster U5 has experienced a back mutation at this site [14], resulting in approximately 10% of the Finnish haplotypes lacking the 16270CT polymorphism.

The results of AMOVA suggested that variance due to variation among populations was slightly lower between the northern Finland population and the Saami than between that of central Finland and the Saami. Ten out of the 103 Finnish and 26 Saami haplotypes were shared, giving a similar estimate for the frequency of shared haplotypes as has been reported previously [11]. Five of the 10 haplotypes occurred at a frequency >1% in the Saami and, interestingly, each of them was more frequent in northern Finland than in central Finland. One of these harbored the Saami motif [10]. Haplotypes with this motif have been thought to be restricted to the Saami and have been observed at a frequency of 58% in the Norwegian Saami [25] and 34% in the Finnish and Swedish Saami [10], but the motif is rare elsewhere in northern Europe and absent in other parts of Europe [9, 10]. We found the frequency of this motif to be 12.3% in the samples from northern Finland and 5% in the samples from central Finland (see Appendix), and it has been reported in 1 out of 32 samples (3%) representing the entire Finnish population [11]. The Saami motif has been found at a frequency of 1.0% among Russians [26] and 2.3% among Norwegians [27], but it was not detected in a small sample of Swedes [7], although 3197TC, a polymorphism suggestive of subcluster U5 [14], has been found at a frequency of 11% [28].

The Saami are considered genetic outliers in Europe [3, 29], and therefore the high frequency of the Saami motif in northern Finland is interesting, as it suggests admixture between the Saami and Finnish settlers during the colonization of Finland. On the basis of the differences in haplotype frequencies between northern and central Finland and on the assumption that the acculturation of Saami women to an agricultural lifestyle was more probable than that of Finnish women to a nomadic lifestyle, it may be said that the flow of mtDNA has been from the Saami to the Finns. However, gene flow has probably been reciprocal, and an opposite flow may be suggested by the observation of three closely related European-specific haplotypes H/ht1, H/ht12 and H/ht19 in the Saami and by the presence of haplotype V/ht3 that is widely distributed in European populations [21].

In addition to the Saami motif, we found haplotypes V/ht1, V/ht3 and M/ht1 to occur at a higher rate in northern Finland than in central Finland. The 16298CT polymorphism has been used to define haplogroup V in European populations [7, 9, 12], but we found that it was also present in samples belonging to macrohaplogroup M. In fact, this macrohaplogroup accounted for 9.4% of the Saami samples harboring 16298TC and 31% of the Finnish samples harboring 16298CT (see Appendix). Both haplogroup V and macrohaplogroup M showed a geographical variation in frequency similar to that observed for the Saami motif. Interestingly, 9 out of the 10 Finnish samples and 5 out of the 6 Saami samples belonging to macrohaplogroup M exhibited the HVS-I motif of haplogroup Z. Haplogroup Z mtDNAs have recently been identified in two Kamchatka populations, with a frequency of 6.5% in the Itel'men and 5.4% in the Koryaks [23]. It has also been found with a frequency of 26% in the Evens population of northeastern Asia [30] and with a frequency of 1.9% in Mongolians [31], but it is absent in many other east Asian populations [23]. Interestingly, it is present in 4.3% of the Saami [10, 11] and 3.9% of the population of northern Finland, and it has also been detected in one sample representing the Norwegians [25].

The European pattern of mtDNA haplotypes is evident in the Finns, whereas the Saami are quite distinct from all other European populations [10, 12]. Certain haplotypes considered to be Saami-specific had high frequencies in the Finns, suggesting a genetic admixture. This maternal genetic contribution appeared to have been more pronounced in northern Finland. Previous data have shown a high frequency of Asian Y chromosome haplotypes in the Finns and Saami [8], whereas the mtDNA haplotypes in the Finns have been considered distinctively European. The presence of haplogroup Z in the Finns and Saami evidently indicates that traces of Asian mtDNA genotypes have survived in the contemporary populations, but the discrepancy between the high frequency of Asian-specific haplotypes of the Y chromosome and the rarity of Asian-specific mtDNA haplotypes may suggest that the Y chromosome and mtDNA are subject to differential drifting that has led to an almost complete loss of Asian-specific mtDNA haplotypes.

 acknowledgements

The expert technical assistance of Ms. Irma Vuoti, Ms. Kaisu Korhonen and Ms. Anja Heikkinen is acknowledged. This work was supported in part by grants from the Medical Research Council of the Academy of Finland, the Sigrid Juselius Foundation, the Neurology Foundation, the Maire Taponen Foundation and the Finnish Medical Foundation.

 appendix

This appendix shows the HVS-I lineages in the various mtDNA haplogroups. It is organized into four parts. The left-hand columns show the haplotype definitions and the right-hand columns the population frequencies of the haplotypes. The status at nucleotide position 9744 is also shown in haplogroup UK. CRS = Cambridge reference sequence; PO = population of Northern Ostrobothnia; PK = population of Kainuu; PS = population of Northern Savo; PL = population of Central Ostrobothnia; d = deletion.

Haplogroups H and V

Haplogroups U and K

Haplogroups T and J

Haplogroups W, I, X, and M (one sample without a haplogroup definition is also listed here)

  References

1.

Pitkänen K: Suomen väestön historialliset kehityslinjat; in Koskinen S, Martelin T, Notkola IL, Notkola V, Pitkänen K (eds): Suomen Väestö. Hämeenlinna, Gaudeamus, 1994, pp 19-63.

2.

Norio R, Nevanlinna HR, Perheentupa J: Hereditary diseases in Finland; rare flora in rare soil. Ann Clin Res 1973;5:109-141.

3.

Cavalli-Sforza LL, Piazza A: Human genomic diversity in Europe: A summary of recent research and prospects for the future. Eur J Hum Genet 1993;1:3-18.

4.

Vilkki J, Savontaus ML, Nikoskelainen EK: Human mitochondrial DNA types in Finland. Hum Genet 1988;80:317-321.

5.

Pult I, Sajantila A, Simanainen J, Georgiev O, Schaffner W, Pääbo S: Mitochondrial DNA sequences from Switzerland reveal striking homogeneity of European populations. Biol Chem Hoppe Seyler 1994;375:837-840.

6.

Sajantila A, Salem AH, Savolainen P, Bauer K, Gierig C, Pääbo S: Paternal and maternal DNA lineages reveal a bottleneck in the founding of the Finnish population. Proc Natl Acad Sci USA 1996;93:12035-12039.

7.

Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, Scozzari R, Obinu D, Savontaus ML, Wallace DC: Classification of European mtDNAs from an analysis of three European populations. Genetics 1996;144:1835-1850.

8.

Zerjal T, Dashnyam B, Pandya A, Kayser M, Roewer L, Santos FR, Schiefenhovel W, Fretwell N, Jobling MA, Harihara S, Shimizu K, Semjidmaa D, Sajantila A, Salo P, Crawford MH, Ginter EK, Evgrafov OV, Tyler-Smith C: Genetic relationships of Asians and Northern Europeans, revealed by Y-chromosomal DNA analysis. Am J Hum Genet 1997;60:1174-1183.

9.

Richards MB, Macaulay VA, Bandelt HJ, Sykes BC: Phylogeography of mitochondrial DNA in western Europe. Ann Hum Genet 1998;62:241-260.

10.

Sajantila A, Lahermo P, Anttinen T, Lukka M, Sistonen P, Savontaus ML, Aula P, Beckman L, Tranebjaerg L, Gedde-Dahl T, Issel-Tarver L, DiRienzo A, Pääbo S: Genes and languages in Europe: An analysis of mitochondrial lineages. Genome Res 1995;5:42-52.

11.

Lahermo P, Sajantila A, Sistonen P, Lukka M, Aula P, Peltonen L, Savontaus ML: The genetic relationship between the Finns and the Finnish Saami (Lapps): Analysis of nuclear DNA and mtDNA. Am J Hum Genet 1996;58:1309-1322.

12.

Simoni L, Calafell F, Pettener D, Bertranpetit J, Barbujani G: Geographic patterns of mtDNA diversity in Europe. Am J Hum Genet 2000;66:262-278.

13.

Sajantila A, Pääbo S: Language replacement in Scandinavia. Nat Genet 1995;11:359-360.

14.

Finnilä S, Hassinen IE, Ala-Kokko L, Majamaa K: Phylogenetic network of the mtDNA haplogbroup U in Northern Finland based on sequence analysis of the complete coding region by conformation-sensitive gel electrophoresis. Am J Hum Genet 2000;66:1017-1026.

15.

Moilanen JS, Majamaa K: Relative fitness of carriers of the mitochondrial DNA mutation 3243AG. Eur J Hum Genet 2001;9:59-62.

16.

Werle E, Schneider C, Renner M, Volker M, Fiehn W: Convenient single-step, one tube purification of PCR products for direct sequencing. Nucleic Acids Res 1994;22:4354-4355.

17.

Rousset F, Raymond M: Testing heterozygote excess and deficiency. Genetics 1995;140:1413-1419.

18.

Schneider S, Roessli D, Excoffier L: Arlequin ver. 2.000: A software for population genetics data analysis. Genetics and Biometry Laboratory, University of Geneva, 2000.

19.

Helgason A, Sigurdardottir S, Gulcher JR, Ward R, Stefansson K: mtDNA and the origin of the Icelanders: Deciphering signals of recent population history. Am J Hum Genet 2000;66:999-1016.

20.

Richards M, Côrte-Real H, Forster P, Macaulay V, Wilkinson-Herbots H, Demaine A, Papiha S, Hedges R, Bandelt HJ, Sykes B: Paleolithic and neolithic lineages in the European mitochondrial gene pool. Am J Hum Genet 1996;59:185-203.

21.

Kittles RA, Bergen AW, Urbanek M, Virkkunen M, Linnoila M, Goldman D, Long JC: Autosomal, mitochondrial, and Y chromosome DNA variation in Finland: Evidence for a male-specific bottleneck. Am J Phys Anthropol 1999;108:381-399.

22.

Anderson S, Bankier AT, Barrell BG, deBruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG: Sequence and organization of the human mitochondrial genome. Nature 1981;290:457-465.

23.

Schurr TG, Sukernik RI, Starikovskaya YB, Wallace DC: Mitochondrial DNA variation in Koryaks and Itel'men: Population replacement in the Okhotsk Sea-Bering Sea region during the Neolithic. Am J Phys Anthropol 1999;108:1-39.

24.

Koskinen S, Martelin T, Notkola IL, Notkola V, Pitkänen K: Suomen Väestö. Hämeenlinna, Gaudeamus, 1994.

25.

Dupuy BM, Olaisen B: mtDNA sequences in the Norwegian Saami and main populations; in Carracedo A, Brinkmann B, Bär W (eds): Advances in forensic haemogenetics 6. Berlin, Springer, 1996, pp 23-25.

26.

Orekhov V, Poltoraus A, Zhivotovsky LA, Spitsyn V, Ivanov P, Yankovsky N: Mitochondrial DNA sequence diversity in Russians. FEBS Lett 1999;445:197-201.

27.

Opdal SH, Rognum TO, Vege A, Stave AK, Dupuy BM, Egeland T: Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome. Acta Paediatr 1998;1039:1044.

28.

Lindholm E, Cavelier L, Howell WM, Eriksson I, Jalonen P, Adolfsson R, Blackwood DH, Muir WJ, Brookes AJ, Gyllensten U, Jazin EE: Mitochondrial sequence variants in patients with schizophrenia. Eur J Hum Genet 1997;5:406-412.

29.

Guglielmino CR, Piazza A, Menozzi P, Cavalli-Sforza LL: Uralic genes in Europe. Am J Phys Anthropol 1990;83:57-68.

30.

Derenko MV, Shields GF: Diversity of mitochondrial DNA nucleotide sequences in three groups of aboriginal inhabitants of Northern Asia. Mol Biol (Mosk) 1997;31:784-789.

31.

Kolman CJ, Sambuughin N, Bermingham E: Mitochondrial DNA analysis of Mongolian populations and implications for the origin of New World founders. Genetics 1996;142:1321-1334.

  Author Contacts

Dr. Kari Majamaa, MD
University of Oulu, Department of Neurology
PO Box 5000
FIN-90014 University of Oulu (Finland)
Tel. +358 8 315 4526, Fax +358 8 315 4544, E-Mail kari.majamaa@oulu.fi

  Article Information

Received: Received: December 4, 2000
Accepted: January 23, 2001
Revision received: January 3, 2001
Number of Print Pages : 11
Number of Figures : 1, Number of Tables : 6, Number of References : 31

  Publication Details

Human Heredity (International Journal of Human and Medical Genetics)
Founded 1950 as Acta Genetica et Statistica Medica by Gunnar Dahlberg; Continued by M. Hauge (1965-1983)

Vol. 52, No. 3, Year 2001 (Cover Date: Released September 2001)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001-5652 (print), 1423-0062 (Online)

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