High-resolution inference of genetic relationships among Jewish populations.

Recent studies have used genome-wide single-nucleotide polymorphisms (SNPs) to investigate relationships among various Jewish populations and their non-Jewish historical neighbors, often focusing on small subsets of populations from a limited geographic range or relatively small samples within populations. Here, building on the significant progress that has emerged from genomic SNP studies in the placement of Jewish populations in relation to non-Jewish populations, we focus on population structure among Jewish populations. In particular, we examine Jewish population-genetic structure in samples that span much of the historical range of Jewish populations in Europe, the Middle East, North Africa, and South Asia. Combining 429 newly genotyped samples from 29 Jewish and 3 non-Jewish populations with previously reported genotypes on Jewish and non-Jewish populations, we investigate variation in 2789 individuals from 114 populations at 486,592 genome-wide autosomal SNPs. Using multidimensional scaling analysis, unsupervised model-based clustering, and population trees, we find that, genetically, most Jewish samples fall into four major clusters that largely represent four culturally defined groupings, namely the Ashkenazi, Mizrahi, North African, and Sephardi subdivisions of the Jewish population. We detect high-resolution population structure, including separation of the Ashkenazi and Sephardi groups and distinctions among populations within the Mizrahi and North African groups. Our results refine knowledge of Jewish population-genetic structure and contribute to a growing understanding of the distinctive genetic ancestry evident in closely related but historically separate Jewish communities.

Genetics and the history of the Samaritans: Y-chromosomal microsatellites and genetic affinity between Samaritans and Cohanim.

The Samaritans are a group of some 750 indigenous Middle Eastern people, about half of whom live in Holon, a suburb of Tel Aviv, and the other half near Nablus. The Samaritan population is believed to have numbered more than a million in late Roman times but less than 150 in 1917. The ancestry of the Samaritans has been subject to controversy from late Biblical times to the present. In this study, liquid chromatography/electrospray ionization/quadrupole ion trap mass spectrometry was used to allelotype 13 Y-chromosomal and 15 autosomal microsatellites in a sample of 12 Samaritans chosen to have as low a level of relationship as possible, and 461 Jews and non-Jews. Estimation of genetic distances between the Samaritans and seven Jewish and three non-Jewish populations from Israel, as well as populations from Africa, Pakistan, Turkey, and Europe, revealed that the Samaritans were closely related to Cohanim. This result supports the position of the Samaritans that they are descendants from the tribes of Israel dating to before the Assyrian exile in 722-720 BCE. In concordance with previously published single-nucleotide polymorphism haplotypes, each Samaritan family, with the exception of the Samaritan Cohen lineage, was observed to carry a distinctive Y-chromosome short tandem repeat haplotype that was not more than one mutation removed from the six-marker Cohen modal haplotype.

Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens.

BACKGROUND: Scaleless (sc/sc) chickens carry a single recessive mutation that causes a lack of almost all body feathers, as well as foot scales and spurs, due to a failure of skin patterning during embryogenesis. This spontaneous mutant line, first described in the 1950s, has been used extensively to explore the tissue interactions involved in ectodermal appendage formation in embryonic skin. Moreover, the trait is potentially useful in tropical agriculture due to the ability of featherless chickens to tolerate heat, which is at present a major constraint to efficient poultry meat production in hot climates. In the interests of enhancing our understanding of feather placode development, and to provide the poultry industry with a strategy to breed heat-tolerant meat-type chickens (broilers), we mapped and identified the sc mutation. RESULTS: Through a cost-effective and labour-efficient SNP array mapping approach using DNA from sc/sc and sc/+ blood sample pools, we map the sc trait to chromosome 4 and show that a nonsense mutation in FGF20 is completely associated with the sc/sc phenotype. This mutation, common to all sc/sc individuals and absent from wild type, is predicted to lead to loss of a highly conserved region of the FGF20 protein important for FGF signalling. In situ hybridisation and quantitative RT-PCR studies reveal that FGF20 is epidermally expressed during the early stages of feather placode patterning. In addition, we describe a dCAPS genotyping assay based on the mutation, developed to facilitate discrimination between wild type and sc alleles. CONCLUSIONS: This work represents the first loss of function genetic evidence supporting a role for FGF ligand signalling in feather development, and suggests FGF20 as a novel central player in the development of vertebrate skin appendages, including hair follicles and exocrine glands. In addition, this is to our knowledge the first report describing the use of the chicken SNP array to map genes based on genotyping of DNA samples from pooled whole blood. The identification of the sc mutation has important implications for the future breeding of this potentially useful trait for the poultry industry, and our genotyping assay can facilitate its rapid introgression into production lines.

Genomic microsatellites identify shared Jewish ancestry intermediate between Middle Eastern and European populations.

BACKGROUND: Genetic studies have often produced conflicting results on the question of whether distant Jewish populations in different geographic locations share greater genetic similarity to each other or instead, to nearby non-Jewish populations. We perform a genome-wide population-genetic study of Jewish populations, analyzing 678 autosomal microsatellite loci in 78 individuals from four Jewish groups together with similar data on 321 individuals from 12 non-Jewish Middle Eastern and European populations. RESULTS: We find that the Jewish populations show a high level of genetic similarity to each other, clustering together in several types of analysis of population structure. Further, Bayesian clustering, neighbor-joining trees, and multidimensional scaling place the Jewish populations as intermediate between the non-Jewish Middle Eastern and European populations. CONCLUSION: These results support the view that the Jewish populations largely share a common Middle Eastern ancestry and that over their history they have undergone varying degrees of admixture with non-Jewish populations of European descent.

[Application of single nucleotide polymorphisms (SNPs) for the detection of genes involved in the control of complex diseases].

The advances in the Human Genome Project (HGP), which have created a huge database, may contribute to our understanding of the etiopathology of complex diseases. These diseases are characterized by a high prevalence within families and by the influence of genetic factors as well as environmental conditions on its natural history (multifactorial diseases). Researchers nowadays focus on the genetic diversity between people by learning the biological significance of a certain DNA marker--the single nucleotide polymorphism (SNP). The universal technology of miniaturization of biological and electronic devices is producing an important infrastructure. Among these tools of infrastructure is the high--throughput genotyping system which enables researchers to perform whole genome screening for hundreds of thousands of SNPs in a relatively short period of time. The evolving data is accumulating rapidly and is pushing the field of bioinformatics into the forefront. The more association studies there are on block-like structure of haplotypes of SNPs in complex diseases the more our ability to identify persons in presymptomatic states will improve. The end product of the above-mentioned developments is expected to contribute to better ways of treatment (pharmacogenomics).

QTLs detected in a multigenerational resource chicken population.

The genetic structure of resource populations affects the power of tests to detect associations between DNA markers and complex traits. Following a chicken interline cross (White Plymouth Rock background), we produced a multigenerational resource population based on 4 pedigreed generations. In this large sibship, 265 parents have been genotyped, and their 3317 progenies have been phenotyped for BW21, BW42, breast meat weight, fat pad weight, and egg production. We developed an approach to increase test power by imposing several ways of validation including the minimization of false-positive associations. Some of our detected associations were in agreement with QTLs previously reported in the literature. A large fraction of the 81 screened markers was found to be associated with quantitative traits. We examined 729 associations, of which 150 (21%) were significant, and of these, 54 are supported by the literature. These 54 associations were identified by 42 markers (some of which are linked to each other). This finding not only supports the results obtained in our resource population but may also give some indication about their general properties.

Genetic diversity and population structure inferred from the partially duplicated genome of domesticated carp, Cyprinus carpio L.

Genetic relationships among eight populations of domesticated carp (Cyprinus carpio L.), a species with a partially duplicated genome, were studied using 12 microsatellites and 505 AFLP bands. The populations included three aquacultured carp strains and five ornamental carp (koi) variants. Grass carp (Ctenopharyngodon idella) was used as an outgroup. AFLP-based gene diversity varied from 5% (grass carp) to 32% (koi) and reflected the reasonably well understood histories and breeding practices of the populations. A large fraction of the molecular variance was due to differences between aquacultured and ornamental carps. Further analyses based on microsatellite data, including cluster analysis and neighbor-joining trees, supported the genetic distinctiveness of aquacultured and ornamental carps, despite the recent divergence of the two groups. In contrast to what was observed for AFLP-based diversity, the frequency of heterozygotes based on microsatellites was comparable among all populations. This discrepancy can potentially be explained by duplication of some loci in Cyprinus carpio L., and a model that shows how duplication can increase heterozygosity estimates for microsatellites but not for AFLP loci is discussed. Our analyses in carp can help in understanding the consequences of genotyping duplicated loci and in interpreting discrepancies between dominant and co-dominant markers in species with recent genome duplication.

Female-specific DNA sequences in the chicken genome.

Eight in silico W-specific sequences from the WASHUC1 chicken genome assembly gave female-specific PCR products using chicken DNA. Some of these fragments gave female-specific products with turkey and peacock DNA. Sequence analysis of these 8 fragments (3077 bp total) failed to detect any polymorphisms among 10 divergent chickens. In contrast, comparison of the DNA sequences of chicken with those of turkey and peacock revealed a nucleotide difference every 25 and 28 bp, respectively. Radiation hybrid mapping verified that these amplicons exist only on chromosome W. The homology of 6 W-specific fragments with chromo-helicase-DNA-binding gene and expressed sequenced tags from chicken and other species indicate that these fragments may have or have had a biological function. These fragments may be used for early sexing in commercial chicken and turkey flocks.

Four linked genes participate in controlling sporulation efficiency in budding yeast.

Quantitative traits are conditioned by several genetic determinants. Since such genes influence many important complex traits in various organisms, the identification of quantitative trait loci (QTLs) is of major interest, but still encounters serious difficulties. We detected four linked genes within one QTL, which participate in controlling sporulation efficiency in Saccharomyces cerevisiae. Following the identification of single nucleotide polymorphisms by comparing the sequences of 145 genes between the parental strains SK1 and S288c, we analyzed the segregating progeny of the cross between them. Through reciprocal hemizygosity analysis, four genes, RAS2, PMS1, SWS2, and FKH2, located in a region of 60 kilobases on Chromosome 14, were found to be associated with sporulation efficiency. Three of the four "high" sporulation alleles are derived from the "low" sporulating strain. Two of these sporulation-related genes were verified through allele replacements. For RAS2, the causative variation was suggested to be a single nucleotide difference in the upstream region of the gene. This quantitative trait nucleotide accounts for sporulation variability among a set of ten closely related winery yeast strains. Our results provide a detailed view of genetic complexity in one "QTL region" that controls a quantitative trait and reports a single nucleotide polymorphism-trait association in wild strains. Moreover, these findings have implications on QTL identification in higher eukaryotes.

Reconstruction of patrilineages and matrilineages of Samaritans and other Israeli populations from Y-chromosome and mitochondrial DNA sequence variation.

The Samaritan community, which numbered more than a million in late Roman times and only 146 in 1917, numbers today about 640 people representing four large families. They are culturally different from both Jewish and non-Jewish populations in the Middle East and their origin remains a question of great interest. Genetic differences between the Samaritans and neighboring Jewish and non-Jewish populations are corroborated in the present study of 7,280 bp of nonrecombining Y-chromosome and 5,622 bp of coding and hypervariable segment I (HVS-I) mitochondrial DNA (mtDNA) sequences. Comparative sequence analysis was carried out on 12 Samaritan Y-chromosome, and mtDNA samples from nine male and seven female Samaritans separated by at least two generations. In addition, 18-20 male individuals were analyzed, each representing Ethiopian, Ashkenazi, Iraqi, Libyan, Moroccan, and Yemenite Jews, as well as Druze and Palestinians, all currently living in Israel. The four Samaritan families clustered to four distinct Y-chromosome haplogroups according to their patrilineal identity. Of the 16 Samaritan mtDNA samples, 14 carry either of two mitochondrial haplotypes that are rare or absent among other worldwide ethnic groups. Principal component analysis suggests a common ancestry of Samaritan and Jewish patrilineages. Most of the former may be traced back to a common ancestor in the paternally-inherited Jewish high priesthood (Cohanim) at the time of the Assyrian conquest of the kingdom of Israel.

Biodiversity of 52 chicken populations assessed by microsatellite typing of DNA pools.

In a project on the biodiversity of chickens funded by the European Commission (EC), eight laboratories collaborated to assess the genetic variation within and between 52 populations from a wide range of chicken types. Twenty-two di-nucleotide microsatellite markers were used to genotype DNA pools of 50 birds from each population. The polymorphism measures for the average, the least polymorphic population (inbred C line) and the most polymorphic population (Gallus gallus spadiceus) were, respectively, as follows: number of alleles per locus, per population: 3.5, 1.3 and 5.2; average gene diversity across markers: 0.47, 0.05 and 0.64; and proportion of polymorphic markers: 0.91, 0.25 and 1.0. These were in good agreement with the breeding history of the populations. For instance, unselected populations were found to be more polymorphic than selected breeds such as layers. Thus DNA pools are effective in the preliminary assessment of genetic variation of populations and markers. Mean genetic distance indicates the extent to which a given population shares its genetic diversity with that of the whole tested gene pool and is a useful criterion for conservation of diversity. The distribution of population-specific (private) alleles and the amount of genetic variation shared among populations supports the hypothesis that the red jungle fowl is the main progenitor of the domesticated chicken.

Recent duplication of the common carp (Cyprinus carpio L.) genome as revealed by analyses of microsatellite loci.

Genome duplications may have played a role in the early stages of vertebrate evolution, near the time of divergence of the lamprey lineage. Additional genome duplication, specifically in ray-finned fish, may have occurred before the divergence of the teleosts. The common carp (Cyprinus carpio) has been considered tetraploid because of its chromosome number (2n = 100) and its high DNA content. We studied variation using 59 microsatellite primer pairs to better understand the ploidy level of the common carp. Based on the number of PCR amplicons per individual, about 60% of these primer pairs are estimated to amplify duplicates. Segregation patterns in families suggested a partially duplicated genome structure and disomic inheritance. This could suggest that the common carp is tetraploid and that polyploidy occurred by hybridization (allotetraploidy). From sequences of microsatellite flanking regions, we estimated the difference per base between pairs of alleles and between pairs of paralogs. The distribution of differences between paralogs had two distinct modes suggesting one whole-genome duplication and a more recent wave of segmental duplications. The genome duplication was estimated to have occurred about 12 MYA, with the segmental duplications occurring between 2.3 and 6.8 MYA. At 12 MYA, this would be one of the most recent genome duplications among vertebrates. Phylogenetic analysis of several cyprinid species suggests an evolutionary model for this tetraploidization, with a role for polyploidization in speciation and diversification.

Generation and mapping of AFLP, SSRs and SNPs in Lycopersicon esculentum.

Amplified Fragment Length Polymorphism (AFLP), Simple Sequence Repeat (SSR) and Single Nucleotide Polymorphism (SNP), were applied to the tomato genome for assessment of polymorphism and for mapping. The polymorphism of AFLP was studied in twenty-one commercial tomato (L. esculentum) varieties. Four AFLP primer combinations produced 298 clear bands; an average of 75 bands per combination. SSR markers were generated from two sources: (1) size-selected genomic libraries screened with (AT)n, (CT)n, (GT)n, (ATT)n and (CTT)n probes. (2) GeneBank database. Primers were designed for 114 loci and used for genotyping 13 tomato varieties and three Lycopersicon species. Eighteen markers were used to evaluate the polymorphism among the commercial cultivars and were found to be a useful tool for cultivar identification. In-silico comparison of DNA sequences (ESTs and genes) of L. pennellii and L. esculentum, yielded 312 SNPs. Ten L. pennelli genomic fragments were sequenced and the comparison with L. esculentum yielded 22 SNPs. Another 19 SNPs were discovered by sequencing and comparing L. pennellii genomic DNA to L. esculentum DNA fragments containing SSRs. The average SNP frequency was found to be one in a few tens of base pairs. A total of 52 microsatellites, 159 polymorphic AFLP markers and six SNPs were mapped using the Introgression Lines generated by [1]. Map location and markers' distribution are presented.

Microsatellite marker analysis of an anther-derived potato family: skewed segregation and gene-centromere mapping.

Segregation patterns of polymorphic simple sequence repeat (SSR) primer pairs were investigated in monoploid potato families derived from anther culture. A total of 14 primers developed from the sequences in the database, as well as from a genomic library of potato, was used. Distorted segregation was observed for seven (50%) polymorphic loci among monoploids derived from an interspecific hybrid. Similar distortion was observed for only one of five loci that could be contrasted between the two monoploid families. Segregation distortion was less common in the sexually derived backcross population between the interspecific hybrid and either of its parents. One locus could be putatively linked to a lethal allele because it showed distorted segregation in both monoploid families, a group of 70 heterozygous diploids derived from unreduced gametes through anther culture, and a backcross population. These diploids were used to map the polymorphic SSR markers with respect to the centromeres using half-tetrad analysis. The majority of the SSR loci mapped more than 33 cM from the centromere, suggesting the occurrence of a single crossover per chromosome arm.

Evaluation of the genetic diversity among maize lines (Zea mays L.) by DNA fingerprinting analysis / Avaliação de diversidade genética entre linhagens de milho (Zea mays L.) por analisis de "DNA fingerprinting

Informativo DNA fingerprint profiles of eight homozygotic maize lines were obtained by the electrophoretic separation of DNA restriction fragments and the ir hybridization with the minisatellite probe R18.1. The analysis of the bandsharing frequencies allowed to identify all the lines and to estimate the genetic distances between them. The relationship obtained by DNA fingerprinting analysis of the eight inbreed lines was highly consistem with the ir genetical origin.

Perfis altamente informativos de oito linhagens homozigotas de milho foram obtidos através de análise de DNA fingerprinting, hibridizando-se os fragmentos de restrição com a sonda minisatélite R18,1. A análise de bandas coincidentes permitiu identificar todas as linhagens e estimar as distâncias genéticas entre elas. A relação entre as linhagens obtidas por esta análise é consistente com a origem genética das mesmas.

Minisatellite probes in yeast DNA fingerprinting

As sequências 33.6, 33.15, M13 e R18.1 foram utilizadas como sondas para a análise do parentesco de linhagens de leveduras. A sonda R18.1 originária de um banco genômico bovino mostrou intensa hidridizaçäo, produzindo perfis com alto grau de polimorfismo do DNA em Saccharomyces cerevisae e Kluyveromyces marxianus. Nas comparaçöes intra e interespecíficas, os perfis polimórficos permitiram identificaçäo de todas as linhagens, mesmo aquelas altamente relacionadas