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PubMed2002

Construction of a combined sorghum linkage map from two recombinant inbred populations using AFLP, SSR, RFLP, and RAPD markers, and comparison with other sorghum maps.

Sorghum [ Sorghum bicolor (L.) Moench] is an important crop in the semi-arid tropics that also receives growing attention in genetic research. A comprehensive reference map of the sorghum genome would be an essential research tool. Here, a combined sorghum linkage map from two recombinant inbred populations was constructed using AFLP, SSR, RFLP and RAPD markers. The map was aligned with other published sorghum maps which are briefly reviewed. The two recombinant inbred populations (RIPs) analyzed in this study consisted of 225 (RIP 1) and 226 (RIP 2) F(3:5) lines, developed from the crosses IS 9830 x E 36-1 (RIP 1) and N 13 x E 36-1 (RIP 2), respectively. The genetic map of RIP 1 had a total length of 1,265 cM (Haldane), with 187 markers (125 AFLPs, 45 SSRs, 14 RFLPs, 3 RAPDs) distributed over ten linkage groups. The map of RIP 2 spanned 1,410 cM and contained 228 markers (158 AFLPs, 54 SSRs, 16 RFLPs) in 12 linkage groups. The combined map of the two RIPs contained 339 markers (249 AFLPs, 63 SSRs, 24 RFLPs, 3 RAPDs) on 11 linkage groups and had a length of 1,424 cM. It was in good agreement with other sorghum linkage maps, from which it deviated by a few apparent inversions, deletions, and additional distal regions.

Journal Article↗
PubMed1991

The genetic structure of natural populations of Drosophila melanogaster. XXII. Comparative study of DNA polymorphisms in northern and southern natural populations.

Restriction map variation in four gene regions (Adh, Amy, Pu and Gpdh) was surveyed for 86 second chromosomes from northern (Aomori) and southern (Ogasawara) Japanese populations of Drosophila melanogaster (43 chromosomes from each population). The regions examined cover a total of 62 kilobases. Estimates of nucleotide diversity (pi) were approximately constant across the gene regions and populations examined. The distribution of restriction site polymorphisms was compatible with the expectation from the neutral mutation-random genetic drift hypothesis, but insertion/deletion polymorphisms were not consistent with it. While the two populations shared a majority of restriction site polymorphisms, frequencies of individual restriction site variants were significantly different between the two populations at 7 out of 35 segregating sites. In addition, an insertion in the Amy region was found in 15 chromosomes from the Ogasawara sample but absent in the Aomori sample. A considerable difference was observed in the number of rare insertions and deletions between the two populations. The numbers of aberrations uniquely represented were 16 in the Ogasawara sample and only 3 in the Aomori sample. These findings suggest that the two populations were differentiated from each other to some degree by means of random genetic drift and/or other factors.

Alcohol Dehydrogenase↗
PubMed1999

Biomarker responses in human populations: towards a worldwide map.

The discipline of epidemiology studies the determinants of diseases in human populations, identifies causes, determines outcomes and develops prevention strategies. Traditional epidemiology is most useful for studies of acute, relatively common diseases with short incubation periods but less so for studies of chronic low incidence diseases with long incubation periods. Molecular epidemiology, which employs biological responses or biomarkers as surrogates of exposures or effects, can help with the latter. For this reason, there is a great interest in developing and validating biomarkers. DNA damage underlies an important group of chronic diseases with long incubation periods, i.e., cancer. Biomarkers may measure the exposures that induce the DNA damage, the damage itself, or individual susceptibility to damage. Before they can be used for human population research, however, these measures must be validated. Biomarker validation critically depends on field studies. This is accomplished through transitional epidemiological studies that 'bridge the gap' between laboratory and field. Transitional epidemiological studies are of three varieties: (i) Developmental, (ii) Characterization, and (iii) Applied. Biomarkers are the dependent variables in transitional studies. An international network of laboratories for human population monitoring requires yet another dimension for validation, i.e., the comparability of results among laboratories must be determined. This will be achieved by sample sharing projects, with workshops to compare results. Only then can results in one population be compared with results in another. Interlaboratory standardization of assays for biomarkers validated by transitional studies will have far-reaching benefits. It will allow development of worldwide databases of background values for the various biomarkers-or biomarker maps. This, in turn, will facilitate problem identification and eventually constitute the baselines for area-specific population monitoring. Biomarker databases so developed can be compared with worldwide databases for cancer and heritable diseases, validating the former as statistical surrogates of the latter.

Biomarkers↗
PubMed1989

Computer-aided mapping of specific neuronal populations in the human brain.

Antibody-staining methods and computer-aided microscopic systems have been used to generate high-resolution panoramic maps of specific neuronal populations in the human brain (4,6,11). This report focuses on the problems inherent in attempting high-resolution mapping of large brain sections, and describes how they are solved by computer-aided mapping. Further applications of computers to the study of brain structure are considered.

Brain↗
PubMed2003

[Construction of a microsatellite linkage map in a DH population].

A doubled haploid population (DH) consisting of 86 lines derived by anther culture of Peiai64s/E32, a two-line hybrid rice variety with high heterosis, was used to construct a microsatellite or SSLP linkage map of rice chromosomes. A total of 302 PCR primers for SSLP analysis on these chromosomes were chosen from a map published by Cornell University (designated CUMAP) and 127 (42.05%) of them were found polymorphic between the two parents. Those polymorphic PCR primers were used for population genotyping. The map (designated PEMAP) comprises 122 microsatellite maker loci,covering a total length of 1213.4 cM. The PEMAP is highly comparable with the CUMAP. Most of the markers were mapped onto the same chromosomes and aligned in the same order. Serious segregation distortion was observed in this DH population,with 34 (27.8%) markers showing significant deviation. It is noted that all markers on chromosomes 1,3,10 and 11 were biased to Peiai64s, while those on chromosomes 4,6,7,8 and 9 were opposite.

English Abstract↗
PubMed1986

Beta-globin gene polymorphism in the Saudi Arab population.

DNA mapping with the restriction endonucleases, Hpa I and Mst II, has been used to investigate beta-globin gene polymorphism in the Saudi Arab population. Using Hpa I digestion, 13.0 kb and 7.6 kb fragments were found in association with the beta A and beta S genes. The frequency of the polymorphic forms in two regions investigated vary significantly. In Al-Hafouf and the surrounding villages, situated in the Eastern Province of Saudi Arabia, the frequencies of association of the beta A gene with the Hpa I 7.6 kb, 7.0 kb, and 13.0 kb fragments were 0.866, 0.043, and 0.071, respectively. The frequency of association of beta S with the 7.6 kb and 13.0 kb fragments resulting from the Hpa I digestion were 0.875 and 0.125. In Khaiber, Tehamat-Aseer, and surrounding villages, in the Western Province, the frequency of association of beta A with 7.6 kb, 7.0 kb, and 13.0 kb fragments were 0.836, 0.027, and 0.0136, respectively, while that of beta S was 0.250 and 0.750 with 7.0 kb and 13.0 kb Hpa I fragments, respectively. Using Mst II digestion, beta A was found to be linked to a 1.15 kb fragment, while beta S was linked to a 1.35 kb fragment. The normal (Hb AA), heterozygotes (Hb AS), and homozygotes (Hb SS) gave 1.15, 1.15/1.35, and 1.35 kb fragments, respectively. The results of this study show extensive polymorphism at the Hpa I restriction site of the beta A and beta S globin genes with the different polymorphic forms existing at a variable frequency in different regions of Saudi Arabia.

Anemia, Sickle Cell↗
PubMedDate not supplied

Linkage disequilibrium in admixed populations: applications in gene mapping.

A method to detect linkage of genetic traits to polymorphic DNA markers in outbred populations when pedigree analysis is not feasible is presented. The procedure takes advantage of increased linkage disequilibrium that occurs when isolated races or subspecies mate and interbreed. By selecting restriction fragment length polymorphism (RFLP) or microsatellite marker loci that have different allele frequencies in admixed populations, genetic associations produced de novo by hybridization will persist as a function of theta (map distance) for 10-20 generations after initial interbreeding. By careful selection of loci and study populations, the procedure detects linkage of traits otherwise refractory to linkage analysis.

Alleles↗
PubMed1997

Assessment of genetic diversity in space by superimposition of a distorted geographic map with a spatial population clustering. Application to GM haplotypes of native Amerindian tribes.

The GM immunoglobulin (Ig) allotype distributions of 49 native Amerindian populations from North to South America were analysed by a new technique called 'Mobile Sites Method' (MSM). This allows the global interpretation of genetic diversity in space by means of a distorted geographic map called a 'genetic similarity map'. This approach has been improved by superimposing in the distorted geographic map both the haplotype set (represented by hypothetical populations having a 100% frequency of the haplotype considered) and the 'geography-genetics discontinuities' (i.e. the zones between homogeneous population clusters). This bidimensional representation completes the interpretation of the genetic distances between populations in terms of local genetic diversity and possible migrations. Our results concerning the spatial distribution of the Amerindian populations show: (i) a great interdependence of the geographic locations and the GM haplotype distributions (the importance of the geographic factor was checked with the usual technique of 'random sampling' and the percentage of explained distance variability decreases from 78% with the observed data to a level less than 67% with the random data); (ii) a parallelism between genetics and linguistics groups as indicated by the population clusters in the similarity map, and (iii) a complex distorted map revealing the presence of multiple population migrations and admixtures in the course of time. A particular distortion of South America suggests possible migrations by sea along the western and eastern coasts of Central America, or multiple migration waves without population admixture across Central America.

Cluster Analysis↗
PubMed1992

The alcohol dehydrogenase polymorphism in natural populations of Drosophila melanogaster: restriction map variation in the region of the Adh locus in populations from two hemispheres.

Restriction endonuclease variation in the 12 kb region surrounding the Adh locus was measured in seven Australian and six Chinese populations of Drosophila melanogaster. There is a higher level of nucleotide-substitution variation in the Australian populations than in the Chinese, which is possibly a reflection of their origins. None of the restriction site polymorphisms, nor any of the insertions, showed a significant association with latitude. A 0.2 kb deletion varied with latitude in the Chinese populations. In accordance with previous studies, a majority of the insertions were located in a region 1.5-3.5 kb 3' from the Adh coding region, and a majority of the deletions were at a site 3 kb 5' to the Adh coding region. Two of the insertions shared homologies with known mobile elements. Overall, the data suggest that restriction endonuclease variation in the Adh region is not related to the cline in Adhs frequencies.

Alcohol Dehydrogenase↗
PubMed1997

Evidence from Polygene Mapping for a Causal Relationship between Potato Tuber Dormancy and Abscisic Acid Content.

In previous studies polygene mapping of a backcross population derived from haploid potato (Solanum tuberosum) and a diploid wild species (Solanum berthaultii) showed at least eight quantitative trait loci (QTLs) associated with tuber dormancy. The same population was mapped for abscisic acid (ABA) content in tubers so that any QTLs identified could be compared with those detected previously. At least three distinct loci on three chromosomes (2, 4, and 7) were associated with variation in ABA content. One of the QTLs was detected only as a main (single locus) effect, and two QTLs were found through two-locus interaction analysis (epistasis). Interaction between QTLs at markers TG234 (chromosome 2) and TG155 (chromosome 4) explained 20% of total phenotypic variance for this trait. The interaction closely resembled one previously detected for dormancy, suggesting an association between high ABA content and long tuber dormancy. Although relationships between ABA level and dormancy could be demonstrated through polygene mapping, there was no indication of a relationship between these traits when they were subjected to a conventional correlation test. This illustrates the usefulness of polygene mapping as a tool to identify possible associations between hormone levels and plant development.

Journal Article↗
PubMed2005

Comparative microsatellite linkage analysis and genetic structure of two populations of F6 lines derived from Lycopersicon pimpinellifolium and L. cheesmanii.

A population of recombinant inbred lines (RILs) has several advantages over its F2 population counterpart with respect to quantitative trait loci (QTLs) and genomic studies. The objective of the investigation reported here was the comparative characterization by simple sequence repeat (SSR) and sequence characterized amplified region (SCAR) markers of two populations of F6 lines derived from Lycopersicon pimpinellifolium (P population, consisting of 142 lines) and L. cheesmanii (C population, consisting of 115 lines) and sharing the female parent, L. esculentum var. cerasiforme. Almost the same percentage of polymorphic markers was found for each population although a different set of markers was involved. The proportion of SSR primer pairs (93 in total) that resulted in polymorphism for the main band was larger (55-56%) than for SCAR ones (13-16%). The C population showed the largest proportion of markers with zygotic and gametic segregation distortion, which is in agreement with the larger genetic distance reported between L. esculentum and L. cheesmanii than with the former and L. pimpinellifolium. Zygotic distortion corresponded primarily to an excess of heterozygotes in both populations, suggesting that the increment of homozygosity was the main factor limiting viability/self-fertility of the lines. Despite both populations sharing the female parent, P alleles were slightly favored in the P population while E alleles were the most frequently fixed in the C population. A linkage map for each population was obtained, with the average distances between consecutive markers being 3.8 cM or 3.4 cM depending on the population. Discrepancy between the maps for the location of only four markers on chromosomes 3, 6 and 10 was observed. Two possible causes of this discrepancy were investigated and can not be discarded: (1) the presence of duplicated markers and (2) segregation distortion caused by the selective advantage of gametes carrying one of the two alleles. This marker characterization of both populations will continue and will enable the comparative QTLs and candidate gene analysis of complex traits towards a more efficient utilization of genetic resources and breeding strategies.

Chromosome Mapping↗
PubMed2000

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping.

HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbrück equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.

Alleles↗
PubMed1987

Alpha-thalassemia haplotypes in the Algerian population.

DNA mapping was performed in seven unrelated Hb H patients and nine carriers for alpha-thalassemia trait originating from Algeria. This study has allowed us to identify four alpha-thalassemia haplotypes: the (-alpha 3.7) haplotype, which is the most frequent (18 of 23 alpha-thalassemic chromosomes), the (-(alpha)20.5) haplotype, a (--) haplotype, and an (alpha alpha)T haplotype. Our results also show that the (-alpha 3.7) haplotypes encountered in the Algerian population are heterogeneous and differ by the site of the unequal crossover responsible for the 3.7-kb deletion and the size of the interzeta fragment. In addition, during this survey we observed that normal chromosomes bearing a polymorphic BglII site are associated with different interzeta fragments.

Algeria↗
PubMed1987

MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations.

With the advent of RFLPs, genetic linkage maps are now being assembled for a number of organisms including both inbred experimental populations such as maize and outbred natural populations such as humans. Accurate construction of such genetic maps requires multipoint linkage analysis of particular types of pedigrees. We describe here a computer package, called MAPMAKER, designed specifically for this purpose. The program uses an efficient algorithm that allows simultaneous multipoint analysis of any number of loci. MAPMAKER also includes an interactive command language that makes it easy for a geneticist to explore linkage data. MAPMAKER has been applied to the construction of linkage maps in a number of organisms, including the human and several plants, and we outline the mapping strategies that have been used.

Chromosome Mapping↗
PubMed1995

Batten disease gene, CLN3: linkage disequilibrium mapping in the Finnish population, and analysis of European haplotypes.

The gene for Batten disease (juvenile-onset neuronal ceroid lipofuscinosis, or Spielmeyer-Sjögren disease), CLN3, maps to 16p11.2-12.1. Four microsatellite markers--D16S288, D16S299, D16S298, and SPN--are in strong linkage disequilibrium with CLN3 in 142 families from 16 different countries. These markers span a candidate region of approximately 2.1 cM. CLN3 is most prevalent in northern European populations and is especially enriched in the isolated Finnish population, with an incidence of 1:21,000. Linkage disequilibrium mapping was applied to further refine the localization of CLN3 in 27 Finnish families by using linkage disequilibrium data and information about the population history of Finland to estimate the distance of the closest markers from CLN3. CLN3 is predicted to lie 8.8 kb (range 6.3-13.8 kb) from D16S298 and 165.4 kb (132.4-218.1 kb) from D16S299. Enrichment of allele "6" at D16S298 (on 96% of Finnish and 92% of European CLN3 chromosomes) provides strong evidence that the same major mutation is responsible for Batten disease in Finland as in most other European countries and that it is therefore not a Finnish mutation. Genealogical studies show that Batten disease is widespread throughout the densely populated regions of Finland. The ancestors of two Finnish patients carrying rare alleles "3" and "5" at D16S298 in heterozygous form originate from the southwestern coast of Finland, and these probably represent other foreign mutations. Analysis of the number and distribution of CLN3 haplotypes from 12 European countries provides evidence that more than one mutation has arisen in Europe.

Chromosome Mapping↗
PubMed2006

Improving QTL mapping resolution based on genotypic sampling--a case using a RIL population.

The QTL mapping results were compared with the genotypically selected and random samples of the same size on the base of a RIL population. The results demonstrated that there were no obvious differences in the trait distribution and marker segregation distortion between the genotypically selected and random samples with the same population size. However, a significant increase in QTL detection power, sensitivity, specificity, and QTL resolution in the genotypically selected samples were observed. Moreover, the highly significant effect was detected in small size of genotypically selected samples. In QTL mapping, phenotyping is a more sensitive limiting factor than genotyping so that the selection of samples could be an attractive strategy for increasing genome-wide QTL mapping resolution. The efficient selection of samples should be more helpful for QTL maker assistant selection, fine mapping, and QTL cloning.

Chromosome Mapping↗
PubMedDate not supplied

Mapping and estimating the population at risk from lymphatic filariasis in Africa.

Lymphatic filariasis remains a major public health problem in Africa and is 1 of the World Health Organization's 6 diseases targeted for global eradication. However, no detailed maps of the geographical distribution of this disease exist, making it difficult to target control activities and quantify the population at risk. We hypothesized that the distribution lymphatic filariasis is governed by climate. The climate at sites in Africa where surveys for lymphatic filariasis had taken place was characterized using computerized climate surfaces. Logistic regression analysis of the climate variables predicted with 76% accuracy whether sites had microfilaraemic patients or not. We used the logistic equation in a geographical information system to map risk of lymphatic filariasis infection across Africa, which compared favourably with expert opinion. Further validation with a quasi-independent data set showed that the model predicted correctly 88% of infected sites. A similar procedure was used to map risk of microfilaraemia in Egypt, where the dominant vector species differs from those in sub-Saharan Africa. By overlaying risk maps on a 1990 population grid, and adjusting for recent population increases, we estimate that around 420 million people will be exposed to this infection in Africa in the year 2000. This approach could be used to produce a sampling frame, based on estimated risk of microfilaraemia, for conducting filariasis surveys in countries that lack accurate distribution maps and thus save on costs.

Africa↗