3000 years of solitude: extreme differentiation in the island isolates of Dalmatia, Croatia

Vitart, Véronique; Biloglav, Zrinka; Hayward, Caroline; Janičijević, Branka; Smolej-Narančić, Nina; Barać, Lovorka; Peričić, Marijana; Klarić, Irena Martinović; Škarić‐Jurić, Tatjana; Barbalić, Maja; Polašek, Ozren; Kolčić, Ivana; Carothers, Andrew D.; Rudan, Pavao; Hastie, Nick; Wright, Alan F.; Campbell, Harry; Rudan, Igor

doi:10.1038/sj.ejhg.5201589

Cited by 56 publications

(77 citation statements)

References 34 publications

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“…8 -13 Such populations were often distributed worldwide, 14 -16 but sometimes geographically close and isolated. 17 Nonetheless, all populations investigated so far were well differentiated; values of Wright's genetic variance between sub-populations, F st , were always 40.01. It is unknown whether and to what extent these methods can efficiently describe the structure of scantydifferentiated populations, such as those inhabiting small geographical regions.…”

Section: Introductionmentioning

confidence: 99%

Comparing population structure as inferred from genealogical versus genetic information

et al. 2009

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Algorithms for inferring population structure from genetic data (ie, population assignment methods) have shown to effectively recognize genetic clusters in human populations. However, their performance in identifying groups of genealogically related individuals, especially in scanty-differentiated populations, has not been tested empirically thus far. For this study, we had access to both genealogical and genetic data from two closely related, isolated villages in southern Italy. We found that nearly all living individuals were included in a single pedigree, with multiple inbreeding loops. Despite F st between villages being a low 0.008, genetic clustering analysis identified two clusters roughly corresponding to the two villages. Average kinship between individuals (estimated from genealogies) increased at increasing values of group membership (estimated from the genetic data), showing that the observed genetic clusters represent individuals who are more closely related to each other than to random members of the population. Further, average kinship within clusters and F st between clusters increases with increasingly stringent membership threshold requirements. We conclude that a limited number of genetic markers is sufficient to detect structuring, and that the results of genetic analyses faithfully mirror the structuring inferred from detailed analyses of population genealogies, even when F st values are low, as in the case of the two villages. We then estimate the impact of observed levels of population structure on association studies using simulated data.

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Section: Introductionmentioning

confidence: 99%

Comparing population structure as inferred from genealogical versus genetic information

et al. 2009

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“…We performed preliminary population genetic analyses of these populations (eg, differentiation between villages based on Wright's fixation index and linkage disequilibrium) using 26 STR markers genotyped in all those individuals (Figure 1). 15 The results of a model-based clustering algorithm, implemented in STRUCTURE (http://pritch.bsd.uchicago.edu/software.html), defined six clusters with very distinct genetic signatures, four of which corresponded to single villagesSusak (red), Lopar (blue) Mljet (yellow) and Barbat (green) (Figure 1).…”

Section: Population Samplementioning

confidence: 99%

“…3,15 Measurements A total of 1184 STR markers were genotyped at the Marshfield genotyping facility in Wisconsin, USA. They were all assessed for Hardy -Weinberg equilibrium with 198 showing some evidence of departure from Hardy -Weinberg equilibrium (at Po0.05 level).…”

Section: Population Samplementioning

confidence: 99%

“…First, we have characterised, in detail, a metapopulation of nine Croatian villages from five Dalmatian islands that may be reasonably representative of historic rural European populations in population genetic terms. 15 Second, we used a small subset of individuals from this sample (with varying degrees of consanguinity determined from genealogical records) to define statistical methods that could be used to determine each individual's h-values using both STR and SNP-based genome-wide scans with reasonable precision. 16 Third, we applied this approach to investigate the effects of h on a range of biomedically relevant human quantitative traits with two main conclusions: (i) our estimated h-values showed a very high correlation with genealogical expectations; and (ii) we showed statistically significant associations between h and blood pressure and cholesterol levels.…”

Section: Introductionmentioning

confidence: 99%

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Quantifying the increase in average human heterozygosity due to urbanisation

et al. 2008

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The human population is undergoing a major transition from a historical metapopulation structure of relatively isolated small communities to an outbred structure. This process is predicted to increase average individual genome-wide heterozygosity (h) and could have effects on health. We attempted to quantify this increase in mean h. We initially sampled 1001 examinees from a metapopulation of nine isolated villages on five Dalmatian islands (Croatia). Village populations had high levels of genetic differentiation, endogamy and consanguinity. We then selected 166 individuals with highly specific personal genetic histories to form six subsamples, which could be ranked a priori by their predicted level of outbreeding. The measure h was then estimated in the 166 examinees by genotyping 1184 STR/indel markers and using two different computation methods. Compared to the value of mean h in the least outbred sample, values of h in the remaining samples increased successively with predicted outbreeding by 0.023, 0.038, 0.058, 0.067 and 0.079 (Po0.0001), where these values are measured on the same scale as the inbreeding coefficient (but opposite sign). We have shown that urbanisation was associated with an average increase in h of up to 0.08-0.10 in this Croatian metapopulation, regardless of the method used. Similar levels of differentiation have been described in many populations. Therefore, changes in the level of heterozygosity across the genome of this magnitude may be common during isolate break-up in humans and could have significant health effects through the established genetic mechanism of hybrid vigour/heterosis.

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“…The CROATIA-VIS study is a family-based, cross-sectional study in the villages of Komiza and Vis on the isolated island of Vis, which included 1056 examinees aged 18-93 years. 16 The CROATIA-VIS study genotyping used the Illumina Hap300v1 SNP chip (San Diego, CA, USA). The CROATIA-KORCULA study is a family-based, cross-sectional study in the villages of Lumbarda, Zrnovo and Racisce on the isolated island of Korcula in Croatia.…”

Section: Cohorts Under Studymentioning

confidence: 99%

Inference of identity by descent in population isolates and optimal sequencing studies

Glodzik

Navarro²,

Vitart³

et al. 2013

Eur J Hum Genet

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In an isolated population, individuals are likely to share large genetic regions inherited from common ancestors. Identity by descent (IBD) can be inferred from SNP genotypes, which is useful in a number of applications, including identifying genetic variants influencing complex disease risk, and planning efficient cohort-sequencing strategies. We present ANCHAP -a method for detecting IBD in isolated populations. We compare accuracy of the method against other long-range and local phasing methods, using parent-offspring trios. In our experiments, we show that ANCHAP performs similarly as the other longrange method, but requires an order-of-magnitude less computational resources. A local phasing model is able to achieve similar sensitivity, but only at the cost of higher false discovery rates. In some regions of the genome, the studied individuals share haplotypes particularly often, which hints at the history of the populations studied. We demonstrate the method using SNP genotypes from three isolated island populations, as well as in a cohort of unrelated individuals. In samples from three isolated populations of around 1000 individual each, an average individual shares a haplotype at a genetic locus with 9-12 other individuals, compared with only 1 individual within the non-isolated population. We describe an application of ANCHAP to optimally choose samples in resequencing studies. We find that with sample sizes of 1000 individuals from an isolated population genotyped using a dense SNP array, and with 20% of these individuals sequenced, 65% of sequences of the unsequenced subjects can be partially inferred. INTRODUCTIONIn isolated populations, most individuals share relatively recent common ancestors. If more than one individual inherited the same ancient haplotype in a region, we call them haplotype sharers. Segments of their chromosomes are identical by descent -their haplotypes 'descend from a common ancestor without either of them experiencing a recombination' . 1 Although SNP arrays and nextgeneration sequencing do not reveal gametic phase, haplotype sharers can be identified using computational methods. The applications of inferred regions of identity by descent (IBD) include optimization of resequencing studies and mapping genetic effects on complex traits. 2,3 In the first application, when the SNP genotypes are available and next-generation sequencing is planned, haplotype sharing between the individuals can save resources. With sharing inferred from SNP genotypes, it is possible to choose a minimally redundant subset of individuals to be sequenced, and then to impute sequence data into other subjects with SNP genotype data. Imputations that rely on IBD are now recognized to increase the power of sequencing studies in population isolates. 4 In the second application, shared haplotypes may make it possible to detect the effects of genes in which functional variants that are rare in the general population have drifted to high frequency in the

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3000 years of solitude: extreme differentiation in the island isolates of Dalmatia, Croatia

Cited by 56 publications

References 34 publications

Comparing population structure as inferred from genealogical versus genetic information

Comparing population structure as inferred from genealogical versus genetic information

Quantifying the increase in average human heterozygosity due to urbanisation

Inference of identity by descent in population isolates and optimal sequencing studies

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