Ancestral kinship and cancer in Lastovo Island, Croatia.

The aim of this study was to compute the average kinship coefficient of cancer cases in an extreme isolate (Lastovo Island, Croatia) and to compare it to the corresponding value for the island's unaffected population. Kinship estimates were obtained by Wright's path method (phi) based on pedigree reconstruction and Lasker's coefficient of relationship by isonymy (Ri) based on surname distribution. A total of 76 cancer cases were recorded on the island between 1971 and 1995. The unaffected control population of 1144 persons was obtained from the population census in 1971. The data on five ancestral generations were collected from parish registries preserved in the local church, and included 5484 persons born on the island between 1750 and 1970. Both Wright's path method and Lasker's isonymy method indicated significantly greater kinship of female cancer cases than of the unaffected population. Cancer cases with increased values of Ri among them and Ri among their ancestors included cancers of the ovary, colon, brain, breast, and prostate and leukemias. This study confirms the role of heredity and common ancestry in the development of cancer, providing a rough insight into their relative importance for specific cancer sites.     

On the genealogy of a population of biparental individuals

If one goes backward in time, the number of ancestors of an individual doubles at each generation. This exponential growth very quickly exceeds the population size, when this size is finite. As a consequence, the ancestors of a given individual cannot be all different and most remote ancestors are repeated many times in any genealogical tree. The statistical properties of these repetitions in genealogical trees of individuals for a panmictic closed population of constant size N can be calculated. We show that the distribution of the repetitions of ancestors reaches a stationary shape after a small number G(c) approximately log N of generations in the past, that only about 80% of the ancestral population belongs to the tree (due to coalescence of branches), and that two trees for individuals in the same population become identical after G(c)generations have elapsed. Our analysis is easy to extend to the case of exponentially growing population.     

Class endogamy, inbreeding and migration during the Argentinean colonial period: analysis based on individuals of European ancestry

During the Spanish colonial period, Córdoba was an important town due to its location suitable for controlling communication throughout a wide region of Argentina. As a typical colonial society, where individuals belonged to a well established social class, marriages among Whites were the result of strict norms and prejudices founded on nets of kinship, friendship and neighbouring. The objective of this paper is to determine, whether the elevated class endogamy among Whites during the colonial period resulted in high consanguinity and whether a process of selection of surnames was present in 1813. In both cases the interaction with the migratory flow was taken into account. It is concluded that (a) Although an endogamy of "class" existed among Whites, there is no evidence of the consequences on the biological structure of the population through preferential mating between relatives, as deduced from the low level of inbreeding from isonymy. (b) There was no differential reproduction reflecting the selection of families carrying certain surnames; therefore surnames followed a "neutral" model. (c) The diversity of surnames and the gene flow deduced from them were of a magnitude similar to present populations; this fact could have balanced the effect of the "class" endogamy. (d) Finally, the congruence between information derived from the population age distribution and historic data and the quantification of migration from surnames allowed the detection of mistakes in the census data file regarding the number of foreigners, thus validating the use of surnames as biological markers of the population structure.     

Genetic steady-state under BLUP selection for an infinite and homogeneous population with discrete generations

A matrix derivation is proposed to analytically calculate the asymptotic genetic variance-covariance matrix under BLUP selection according to the initial genetic parameters in a large population with discrete generations. The asymptotic genetic evolution of a homogeneous population with discrete generations is calculated for a selection operating on an index including all information (pedigree and records) from a non-inbred and unselected base population (BLUP selection) or on an index restricted to records of a few ancestral generations. Under the first hypothesis, the prediction error variance of the selection index is independent of selection and is calculated from the genetic parameters of the base population. Under the second hypothesis, the prediction error variance depends on selection. Furthermore, records of several generations of ancestors of the candidates for selection must be used to maintain a constant prediction error variance over time. The number of ancestral generations needed depends on the population structure and on the occurrence of fixed effects. Without fixed effects to estimate, accounting for two generations of ancestors is sufficient to estimate the asymptotic prediction error variance. The amassing of information from an unselected base population proves to be important in order not to overestimate the asymptotic genetic gains and not to underestimate the asymptotic genetic variances.     

Trends of consanguineous marriages in a Sunni Muslim population of West Bengal, India

The Muslim population of the Chaltaberia village in the district of South 24 Parganas in West Bengal is divided into several wards (paras) inhabited by people of specific surnames. The frequency of endogamous marriages within surnames is greater than randomly expected ones. An incomplete reproductive isolation is observed among the five dominant surnames. Consanguineous marriages occur more often outside the village than inside. Leaving out marriages between long distances, a small median distance of 6.36 km is recorded. The neighborhood area works up to be 552.2 km2, which is rather small. There is an underlying process of breeding isolation by distance. A generation length of 21 years has been used for examining the temporal change in consanguineous marriages and inbreeding, which generally appears to increase. There is a general trend of decline in consanguineous marriages towards the southern part of West Bengal and eastern part of Assam among the Bengalee Muslims. The frequency of consanguineous marriages is 7.3% out of all marriages (N=1153) that have taken place in six generations in the population. The first cousin marriage is nearly 50% of all marriages. Patrilineal marriages are common in marriages between second and third cousins. An increase of consanguineous marriages in the younger generation was observed, but the total frequency agrees with a general trend of a decline in the frequency of consanguineous marriages among the Muslims in this part of India.     

Ancestral state reconstruction of body size in the Caniformia (Carnivora, Mammalia): the effects of incorporating data from the fossil record

A recent molecular phylogeny of the mammalian order Carnivora implied large body size as the ancestral condition for the caniform subclade Arctoidea using the distribution of species mean body sizes among living taxa. "Extant taxa-only" approaches such as these discount character state observations for fossil members of living clades and completely ignore data from extinct lineages. To more rigorously reconstruct body sizes of ancestral forms within the Caniformia, body size and first appearance data were collected for 149 extant and 367 extinct taxa. Body sizes were reconstructed for four ancestral nodes using weighted squared-change parsimony on log-transformed body mass data. Reconstructions based on extant taxa alone favored large body sizes (on the order of 10 to 50 kg) for the last common ancestors of both the Caniformia and Arctoidea. In contrast, reconstructions incorporating fossil data support small body sizes (< 5 kg) for the ancestors of those clades. When the temporal information associated with fossil data was discarded, body size reconstructions became ambiguous, demonstrating that incorporating both character state and temporal information from fossil taxa unambiguously supports a small ancestral body size, thereby falsifying hypotheses derived from extant taxa alone. Body size reconstructions for Caniformia, Arctoidea, and Musteloidea were not sensitive to potential errors introduced by uncertainty in the position of extinct lineages relative to the molecular topology, or to missing body size data for extinct members of an entire major clade (the aquatic Pinnipedia). Incorporating character state observations and temporal information from the fossil record into hypothesis testing has a significant impact on the ability to reconstruct ancestral characters and constrains the range of potential hypotheses of character evolution. Fossil data here provide the evidence to reliably document trends of both increasing and decreasing body size in several caniform clades. More generally, including fossils in such analyses incorporates evidence of directional trends, thereby yielding more reliable ancestral character state reconstructions.     

The French Canadian Tay-Sachs disease deletion mutation: identification of probable founders

Summary Tay-Sachs disease (TSD) is an inherited neurodegenerative ganglioside storage disorder caused by deficiency of the hexosaminidase A enzyme. A deletion allele (FCD) at the HEXA locus has attained high frequency in the French Canadian population. The distribution of affected probands shows a likely center of diffusion for this mutation located in the Bas-St.-Laurent and Gaspésie regions of the province of Quebec. We have reconstructed the genealogies of 15 obligate carriers of the FCD allele to an average depth of 12 generations identifying 60 ancestors and 80 European founders common to all of them. The ancestral origins of the European founders show a significantly greater number of individuals born in the French provinces of Normandy and Perche than expected based on information regarding the origins of the 8,500 immigrants who settled the colony of New France during the French regime. We have identified common ancestors among the 10 who were born in Quebec who appear to be likely candidates for the origin of the FCD mutation. One such couple had 11 children, 5 of whom settled in regions of Quebec or New Brunswick that today have elevated heterozygote frequencies for the FCD. The five offspring are ancestors of all known carriers. By contrast, the absence of FCD alleles among TSD probands in France suggests that the mutation did not occur in a European founder.     

Isonymic relationships in ethno-social categories (Argentinian colonial period) including illegitimate reproduction

Surnames provide a useful method to study the structure of human populations for which biological data are not available. The isonymic method has had multiple applications, but difficulties emerge when dealing with groups where extramarital reproduction is common and the sample size is small, and even more so when only paternal surnames are taken into account.Therefore, it could be of interest to retain female surnames, including those of unmarried mothers. This study was carried out using all birth records froman Argentinian population in the colonial period, which was characterized by the presence of different ethno-social groups (Spanish, Indian and 'Mestizo'or mixed Spanish-Indian) and various reproductive patterns regarding legitimacy. Coefficient of relationship by isonymy (Ri) kinship matrices between geographical populations were obtained, and the results derived from sets of surnames (paternal, maternal of legitimate and illegitimate children,and all surnames in the registers) compared. The results show similar surname distribution regardless of the set of surnames and group considered.Kinship Ri matrices using paternal surnames, maternal surnames of legitimate children, maternal surnames of illegitimate children, and the set of whole surnames showed the same relationships among populations, indicating a similar pattern for Spanish, Indian and Mixed ethno-social groups. Mantel test correlation between all pairs of matrices was significant in all different ethno-social groups. The results suggest that in populations with high illegitimacy, such as that studied here, it is possible to include maternal surnames, even corresponding to single mothers, in order to consider total reproduction and therefore maximize sample size.     

Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago

The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 − 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies.     

Indian Siddis: African descendants with Indian admixture

The Siddis (Afro-Indians) are a tribal population whose members live in coastal Karnataka, Gujarat, and in some parts of Andhra Pradesh. Historical records indicate that the Portuguese brought the Siddis to India from Africa about 300-500 years ago; however, there is little information about their more precise ancestral origins. Here, we perform a genome-wide survey to understand the population history of the Siddis. Using hundreds of thousands of autosomal markers, we show that they have inherited ancestry from Africans, Indians, and possibly Europeans (Portuguese). Additionally, analyses of the uniparental (Y-chromosomal and mitochondrial DNA) markers indicate that the Siddis trace their ancestry to Bantu speakers from sub-Saharan Africa. We estimate that the admixture between the African ancestors of the Siddis and neighboring South Asian groups probably occurred in the past eight generations (～200 years ago), consistent with historical records.     

On recombination-induced multiple and simultaneous coalescent events

Coalescent theory deals with the dynamics of how sampled genetic material has spread through a population from a single ancestor over many generations and is ubiquitous in contemporary molecular population genetics. Inherent in most applications is a continuous-time approximation that is derived under the assumption that sample size is small relative to the actual population size. In effect, this precludes multiple and simultaneous coalescent events that take place in the history of large samples. If sequences do not recombine, the number of sequences ancestral to a large sample is reduced sufficiently after relatively few generations such that use of the continuous-time approximation is justified. However, in tracing the history of large chromosomal segments, a large recombination rate per generation will consistently maintain a large number of ancestors. This can create a major disparity between discrete-time and continuous-time models and we analyze its importance, illustrated with model parameters typical of the human genome. The presence of gene conversion exacerbates the disparity and could seriously undermine applications of coalescent theory to complete genomes. However, we show that multiple and simultaneous coalescent events influence global quantities, such as total number of ancestors, but have negligible effect on local quantities, such as linkage disequilibrium. Reassuringly, most applications of the coalescent model with recombination (including association mapping) focus on local quantities.     

The incidental response to uniform natural selection

When populations are exposed to novel conditions of growth, they often become adapted to a similar extent, and at the same time, evolve some degree of impairment in their original environment. They may also come to vary widely with respect to characters which are uncorrelated with fitness, as the result of chance genetic associations among the founders, when these are a small sample from a large and variable ancestral population. I report an experiment in which 240 replicate lines of the unicellular chlorophyte Chlamydomonas were derived from primarily photoautotrophic ancestors and cultured as heterotrophs in the dark. All adapted to the dark and were impaired in the light after several hundred generations of culture. They also displayed a wide range of colony morphologies that were uncorrelated with fitness. This incidental response to selection probably arose through random variation in the initial composition of the lines. The differences between closely related species or varieties may likewise arise, in similar circumstances, by sampling error rather than natural selection.     

The Surname Space of the Czech Republic: Examining Population Structure by Network Analysis of Spatial Co-Occurrence of Surnames

In the majority of countries, surnames represent a ubiquitous cultural attribute inherited from an individual''s ancestors and predominantly only altered through marriage. This paper utilises an innovative method, taken from economics, to offer unprecedented insights into the “surname space” of the Czech Republic. We construct this space as a network based on the pairwise probabilities of co-occurrence of surnames and find that the network representation has clear parallels with various ethno-cultural boundaries in the country. Our inductive approach therefore formalizes a simple assumption that the more frequently the bearers of two surnames concentrate in the same locations the higher the probability that these two surnames can be related (considering ethno-cultural relatedness, common co-ancestry or genetic relatedness, or some other type of relatedness). Using the Czech Republic as a case study this paper offers a fresh perspective on surnames as a quantitative data source and provides a methodology that can be easily incorporated within wider cultural, ethnic, geographic and population genetics studies already utilizing surnames.     

Genetic aspects of genealogy

The supplementary historical discipline genealogy is also a supplementary genetic discipline. In its formation, genetics borrowed from genealogy some methods of pedigree analysis. In the 21th century, it started receiving contribution from computer-aided genealogy and genetic (molecular) genealogy. The former provides novel tools for genetics, while the latter, which employing genetic methods, enriches genetics with new evidence. Genealogists formulated three main laws ofgenealogy: the law of three generations, the law of doubling the ancestry number, and the law of declining ancestry. The significance and meaning of these laws can be fully understood only in light of genetics. For instance, a controversy between the exponential growth of the number of ancestors of an individual, i.e., the law of doubling the ancestry number, and the limited number of the humankind is explained by the presence of weak inbreeding because of sibs' interference; the latter causes the pedigrees' collapse, i.e., explains also the law of diminishing ancestry number. Mathematic modeling of pedigrees' collapse presented in a number of studies showed that the number of ancestors of each individual attains maximum in a particular generation termed ancestry saturated generation. All representatives of this and preceding generation that left progeny are common ancestors of all current members of the population. In subdivided populations, these generations are more ancient than in panmictic ones, whereas in small isolates and social strata with limited numbers of partners, they are younger. The genealogical law of three generations, according to which each hundred years contain on average three generation intervals, holds for generation lengths for Y-chromosomal DNA, typically equal to 31-32 years; for autosomal and mtDNA, this time is somewhat shorter. Moving along ascending lineas, the number of genetically effective ancestors transmitting their DNA fragment to descendants increases far slower than the number of common ancestors, because the time to the nearest common ancestor is proportional to log2N, and the time to genetically effective ancestor, to N, where N is the population size. In relatively young populations, the number of genetically effective ancestors does not exceed the number of recombination hot spots, which is equal to 25000-50000. In ancient African populations with weaker linkage disequilibrium, their number may be higher. In genealogy, the degree of kinship is measured by the number of births separating the individuals under comparison, and in genetics, by Wright's coefficients of relationship (R). Genetic frames of a "large family" are limited by the average genomic differences among the members of the human population, which constitute approximately 0.1%. Conventionally it can be assumed that it is limited by relatives, associated with the members of the given nuclear family by the 7th degree of relatedness (R approximately 0.78%). However, in the course of the HapMap project it was established that 10-30% of pairs of individuals from the same population have at least one common genome region, which they inherited from a recent common ancestor. A nuclear family, if it is not consanguinous, unites two lineages, and indirectly, a multitude of them, constituting a "suprafamily" equivalent to a population. Some problems ofgenealogy and related historical issues can be resolved only with the help of genetics. These problems include identification of "true" and "false" Rurikids and the problem of continuity of the Y-chromosomal lineage of the Romanov dynasty. On the other hand, computer-aided genealogy and molecular genealogy seem to be promising in resolving genetic problems connected to recombination and coalescence ofgenomic regions.     

Genomic contributions in livestock gene introgression programmes

The composition of the genome after introgression of a marker gene from a donor to a recipient breed was studied using analytical and simulation methods. Theoretical predictions of proportional genomic contributions, including donor linkage drag, from ancestors used at each generation of crossing after an introgression programme agreed closely with simulated results. The obligate drag, the donor genome surrounding the target locus that cannot be removed by subsequent selection, was also studied. It was shown that the number of backcross generations and the length of the chromosome affected proportional genomic contributions to the carrier chromosomes. Population structure had no significant effect on ancestral contributions and linkage drag but it did have an effect on the obligate drag whereby larger offspring groups resulted in smaller obligate drag. The implications for an introgression programme of the number of backcross generations, the population structure and the carrier chromosome length are discussed. The equations derived describing contributions to the genome from individuals from a given generation provide a framework to predict the genomic composition of a population after the introgression of a favourable donor allele. These ancestral contributions can be assigned a value and therefore allow the prediction of genetic lag.     

Purging of inbreeding depression within the Irish Holstein-Friesian population

The objective of this study was to investigate whether inbreeding depression in milk production or fertility performance has been partially purged due to selection within the Irish Holstein-Friesian population. Classical, ancestral (i.e., the inbreeding of an individual''s ancestors according to two different formulae) and new inbreeding coefficients (i.e., part of the classical inbreeding coefficient that is not accounted for by ancestral inbreeding) were computed for all animals. The effect of each coefficient on 305-day milk, fat and protein yield as well as calving interval, age at first calving and survival to second lactation was investigated. Ancestral inbreeding accounting for all common ancestors in the pedigree had a positive effect on 305-day milk and protein yield, increasing yields by 4.85 kg and 0.12 kg, respectively. However, ancestral inbreeding accounting only for those common ancestors, which contribute to the classical inbreeding coefficient had a negative effect on all milk production traits decreasing 305-day milk, fat and protein yields by -8.85 kg, -0.53 kg and -0.33 kg, respectively. Classical, ancestral and new inbreeding generally had a detrimental effect on fertility and survival traits. From this study, it appears that Irish Holstein-Friesians have purged some of their genetic load for milk production through many years of selection based on production alone, while fertility, which has been less intensely selected for in the population demonstrates no evidence of purging.     

Estimation of inbreeding,kinship and genetic distances from surnames--coastal population of middle Dalmatia,Croatia

This work was dedicated to the investigation of the population structure of the middle Dalmatia settlements: Jesenice, Mimice, Zivogos?e and Zaostrog by surname distribution study and applying the isonymous method. The surnames of males and females in marital pairs were analyzed as well as of their first and second-generation ancestors on the sample of a total of 3,024 examinees. The analyses of surnames pointed to the rates of inbreeding, kinship and genetic distances of the populations. Although the values of the inbreeding coefficient are high in all the four settlements, the inbreeding coefficient is exceptionally high in Mimice. A total kinship coefficient for the four settlements speaks also in favor of the high rate of kinship in the examined settlements, i.e. of the high rate of the reproductive isolation of the whole region during the analyzed period. The reasons for such high coefficients are natural features of the examined region (the mountains of Mosor, Biokovo and Rili?), poor traffic connection of this region in the past, the patrilineal mode of inheritance and the demographic specifics of the population. The matrix of genetic distances between examined settlement pairs reveals that Mimice, a settlement with the highest share of isonymous marriages, shows the greatest distances in comparison to the other settlements. On the other hand, Jesenice, Zivogos?e and Zaostrog are characterized by small genetic distances, which is the fact that speaks in favor of their genetic homogenization and "openness" toward interpopulational migrations, i.e. the gene flow.     

Quantification of inbreeding due to distant ancestors and its detection using dense single nucleotide polymorphism data

Inbreeding depression, which refers to reduced fitness among offspring of related parents, has traditionally been studied using pedigrees. In practice, pedigree information is difficult to obtain, potentially unreliable, and rarely assessed for inbreeding arising from common ancestors who lived more than a few generations ago. Recently, there has been excitement about using SNP data to estimate inbreeding (F) arising from distant common ancestors in apparently "outbred" populations. Statistical power to detect inbreeding depression using SNP data depends on the actual variation in inbreeding in a population, the accuracy of detecting that with marker data, the effect size, and the sample size. No one has yet investigated what variation in F is expected in SNP data as a function of population size, and it is unclear which estimate of F is optimal for detecting inbreeding depression. In the present study, we use theory, simulated genetic data, and real genetic data to find the optimal estimate of F, to quantify the likely variation in F in populations of various sizes, and to estimate the power to detect inbreeding depression. We find that F estimated from runs of homozygosity (Froh), which reflects shared ancestry of genetic haplotypes, retains variation in even large populations (e.g., SD=0.5% when Ne=10,000) and is likely to be the most powerful method of detecting inbreeding effects from among several alternative estimates of F. However, large samples (e.g., 12,000-65,000) will be required to detect inbreeding depression for likely effect sizes, and so studies using Froh to date have probably been underpowered.     

Mating pattern and population structure in Escazú, Costa Rica: a study using marriage records

A primary focus of historical demographic research is to understand how a population's mating pattern can affect its genetic structure. By using surnames, researchers can reconstruct gene flow into a population as well as within it: the population structure. Indeed, Lasker (1988a) noted that the distribution of surnames reflects the effect of mate choice on a population's genetic structure. Here, we study the mating pattern of a small, clearly established breeding population in Costa Rica (Escazú) during 1800-1839 and 1850-1899. We found that a large proportion of marriages involved individuals who were members of long-standing or core families. Indeed, 27 families provided 56% of all consorts throughout the period under study. When new surnames appeared in the records (presumably as a result of immigration), they were introduced more frequently by males, indicating that more males than females migrated into the community. The core families did not mate preferentially among themselves but appear to have readily accepted the migrants. Indeed,the greatest preponderance of repeated-surname marriages was that expected by chance. However, nonrandom surname repetition is evident when marriages between nonillegitimate consorts are analyzed. That is, the frequency of repeated-pair surname marriages is statistically significant in marriages involving brides and grooms who carried 2 surnames. Interestingly, significant departures from random repetition of surnames occurred during the decade in which the great cholera epidemic affected Costa Rica and during the decade following it. This departure from panmixia supports the notion that mating patterns were altered as a result of the epidemic, a suggestion we made previously when we reported that inbreeding increased in these same decades (Madrigal and Ware 1997).