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Results for “Haplotype structures”

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PubMed1989

The N haplotype of the murine beta-glucuronidase gene is altered in both its systemic regulation and its response to androgen induction.

A new haplotype of the beta-glucuronidase gene complex, [Gus]N, has been characterized following its transfer from the PAC/Cr strain to the standard strain C57BL/6J. The N haplotype contains a novel structural gene allele which encodes an allozyme differing from all previously characterized allozymes in both size and charge. Altered systemic regulation is exhibited by the [Gus]N haplotype. Multiple tissues contain levels of GUS protein that are 60 +/- 15% those found in the standard B haplotype. The regulatory mechanism for reduction is complex, involving tissue-specific changes in both enzyme synthesis and enzyme turnover. The changes in GUS protein synthesis do not result from changes in GUS mRNA levels. Instead, the amount of mature enzyme formed per mRNA molecule, or translational yield, is altered. These regulatory changes parallel those seen in other systemic regulatory variants of GUS which are also altered in translational yield. A commonality of mechanism among systemic regulatory variants of this gene is suggested. The N haplotype is also exceptional in the nature of its response to androgenic induction in kidney proximal tubule epithelial cells. The time course for GUS induction consists of a lag period followed by a progressive increase in mRNA, rate of enzyme synthesis, and enzyme activity. For the [Gus]N haplotype the lag is of an exceptionally short duration and the plateau is of a greater magnitude than for any haplotype previously described.

Animals↗

PubMed1998

A PCR method for molecular epidemiology of Plasmodium falciparum Msp-1.

Merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a strong malaria vaccine candidate. However, MSP-1 exhibits extensive antigenic polymorphism, an issue which may compromise the development of effective vaccine based on this molecule. Since polymorphic nature of MSP-1 has not been fully understood in endemic areas of malaria, variation of the MSP-1 gene (Msp-1) must be studied in detail in natural parasite populations. Here, a PCR-based method for determination of P. falciparum Msp-1 haplotype is described, which can detect up to 24 different haplotypes per infected person. The method can be applied to various purposes of molecular epidemiology of not only Msp-1 haplotype but the genetic structure of P. falciparum populations.

Animals↗

PubMed2001

Genetic trends in a population evolving antibiotic resistance.

The evolution of antibiotic resistance provides a well-documented, rapid, and recent example of a selection driven process that has occurred in many bacterial species. An exhaustive collection of Moraxella catarrhalis that spans a transition to chromosomally encoded penicillin resistance was used to analyze genetic changes accompanying the transition. The population was characterized by high haplotypic diversity with 148 distinct haplotypes among 372 isolates tested at three genomic regions. The power of a temporally stratified sample from a single population was highlighted by the finding of high genetic diversity throughout the transition to resistance, population numbers that remained high over time, and no evidence of departures from neutrality in the allele frequency spectra throughout the transition. The direct temporal analysis documented the persistence, antibiotic status, and haplotypic identity of strains undergoing apparent clonal expansions. Several haplotypes that were beta-lactamase nonproducers in early samples converted to producers in later years. Maintenance of genetic diversity and haplotype conversions from sensitive to resistant supported the hypothesis that penicillin resistance determinants spread to a diverse array of strains via horizontal exchange. Genetic differentiation between sample years, estimated by F(ST), was increasing at a rate that could cause complete haplotype turnover in less than 150 years. Widespread linkage disequilibrium among sites within one locus (copB) suggested recent mutation followed by clonal expansion. Nonrandom associations between haplotypes and resistance phenotypes provided further evidence of clonal expansion for some haplotypes. Nevertheless, the population structure was far from clonal as evidenced by a relatively low frequency of disequilibria both within sites at a second locus (M46) as well as between loci. The haplotype-antibiotic resistance association that was accompanied by gradual haplotype turnover is consistent with a hypothesis of genetic drift at marker loci with directional selection at the resistance locus.

Analysis of Variance↗

PubMed2005

Origin and diversification of Hibiscus glaber, species endemic to the oceanic Bonin Islands, revealed by chloroplast DNA polymorphism.

Abstract Two woody Hibiscus species co-occur in the Bonin Islands of the northwestern Pacific Ocean: Hibiscus glaber Matsum. is endemic to the islands, and its putative ancestral species, Hibiscus tiliaceus L., is widely distributed in coastal areas of the tropics and subtropics. To infer isolating mechanisms that led to speciation of H. glaber and the processes that resulted in co-occurrence of the two closely related species on the Bonin Islands, we conducted molecular phylogenetic analyses on chloroplast DNA (cpDNA) sequences. Materials collected from a wide area of the Pacific and Indian Oceans were used, and two closely related species, Hibiscus hamabo Siebold Zucc. and Hibiscus macrophyllus Roxb., were also included in the analyses. The constructed tree suggested that H. glaber has been derived from H. tiliaceus, and that most of the modern Bonin populations of H. tiliaceus did not share most recent ancestry with H. glaber. Geographic isolation appears to be the most important mechanism in the speciation of H. glaber. The co-occurrence of the two species can be attributed to multiple migrations of different lineages into the islands. While a wide and overlapping geographical distribution of haplotypes was found in H. tiliaceus, localized geographical distribution of haplotypes was detected in H. glaber. It is hypothesized that a shift to inland habitats may have affected the mode of seed dispersal from ocean currents to gravity and hence resulted in geographical structuring of H. glaber haplotypes.

Base Sequence↗

PubMed2002

Extending STR markers in Y chromosome haplotypes.

Two multiplex reactions were developed to amplify 16 Y-STRs (DYS19, DYS385, DYS389 I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, GATA A7.1, GATA A7.2, GATA A10, GATA C4, GATA H4). Here we extend previous population studies done in a sample from northern Portugal for the GATA A7.1, GATA A7.2, GATA C4 and GATA H4 loci. A total of 199 different haplotypes identified by the 16 Y-STR markers were observed in a sample of 208 male individuals, of which 190 were unique and 9 were found twice. The overall haplotype diversity was 0.9996. The haplotype diversity of the Y-STR set composed of the 8 new markers is higher than the Y-STR core set included in the Y-STR haplotype reference database. Sequence structure of new alleles for GATA C4 and GATA H4 is reported. The usefulness of the inclusion of this new set of Y-STRs in forensic casework was also assessed. The increase in haplotype diversity with the addition of any new Y-STR marker to the 8 Y-STR core set is dependent not only on the gene diversity (positively) but also (negatively) on the degree of gametic association between the markers and the haplotypes previously defined. For instance, in our sample the addition of the DYS437, DYS438 and GATA A7.2 to a 13-locus set increased haplotype diversity only by 0.0001.

Base Sequence↗

PubMed2003

Dynamics in the evolution of sexual traits: losses and gains, radiation and convergence in yellow wagtails (Motacilla flava).

We analyse patterns of genetic diversity and song complexity in the Palaearctic yellow wagtail (Motacilla flava), a highly polytypic species complex. Mitochondrial and nuclear DNA show that the complex is polyphyletic, despite parallel plumage variation in western and eastern clades. In the western clade there is genetic structure among southern subspecies, haplotype diversity decreases with latitude, and northern subspecies show evidence of bottlenecking and rapid expansions, as expected from isolation in glacial refugia followed by postglacial colonization. However, northern subspecies, which have more divergent male plumages, lack genetic structure and sing simpler songs. Loss of song complexity and evolution of plumage in founder populations are consistent with the Kaneshiro model, which posits that variation among species is a consequence of founder-induced shifts in female preference leading to loss of ancestral male sexual traits. Our results suggest possible postglacial founder-effect mechanisms for the morhological diversification of the yellow wagtail complex.

Animals↗

PubMed1990

Genetic and molecular analysis of the proximal region of the mouse t-complex using new molecular probes and partial t-haplotypes.

The t-complex is located on the proximal third of chromosome 17 in the house mouse. Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development. Partial t-haplotypes derived through rare recombination between t-haplotypes and wild-type homologs have been critical in the analysis of these properties. Utilizing two new DNA probes. Au3 and Au9, and several previously described probes, we have analyzed the genetic structure of several partial t-haplotypes that have arisen in our laboratory, as well as several wild-type chromosomes deleted for loci in this region. With this approach we have been able to further our understanding of the structural and dynamic characteristics of the proximal region of the t-complex. Specifically, we have localized the D17Tul locus as most proximal known in t-haplotypes, achieved a better structural analysis of the partial t-haplotype t6, and defined the structure and lethal gene content of partial t-haplotypes derived from the lethal tw73 haplotype.

Animals↗

PubMed2002

Population genetic structure and male-biased dispersal in the queenless ant Diacamma cyaneiventre.

In this study we investigated the population genetic structure of the queenless ant Diacamma cyaneiventre. This species, lacking winged queens, is likely to have a restricted female dispersal. We used both mitochondrial and microsatellite markers to assess the consequence of such restricted female dispersal at three geographical scales: within a given locality (< 1 km), between localities within a given region (< 10 km) and between regions (> 36 km). Within a locality, a strong population structure was observed for mitochondrial DNA (mtDNA) whereas weak or nonexistent population genetic structure was observed for the microsatellites (around 5% of the value for mtDNA). Male gene flow was estimated to be about 20-30 times higher than female gene flow at this scale. At a larger spatial scale, very strong genetic differentiation for both markers was observed between localities - even within a single region. Female dispersal is nonexistent at these scales and male dispersal is very restricted, especially between regions. The phylogeographical structure of the mtDNA haplotypes as well as the very low genetic diversity of mtDNA within localities indicate that new sites are colonized by a single migration event from adjacent localities, followed by successive colony fissions. These patterns of genetic variability and differentiation agree with what is theoretically expected when colonization events are kin-structured and when, following colonization, dispersion is mainly performed by males.

Animals↗

PubMed1988

Structural organization of the beta-globin locus of B-haplotype sheep.

Goats and some sheep synthesize a juvenile hemoglobin, Hb C (alpha 2 beta C2), at birth and produce this hemoglobin exclusively during severe anemia. Sheep that synthesize this juvenile hemoglobin are of the A haplotype. Other sheep, belonging to a separate group, the B haplotype, do not synthesize hemoglobin C and during anemia continue to produce their adult hemoglobin. To understand the basis for this difference we have determined the structural organization of the beta-globin locus of B-type sheep by constructing and isolating overlapping genomic clones. These clones have allowed us to establish the linkage map 5' epsilon I-epsilon II-psi beta I-beta B-epsilon III-epsilon IV-psi beta II-beta F3' in this haplotype. Thus, B sheep lack four genes, including the BC gene, and have only eight genes, compared with the 12 found in the goat globin locus. The goat beta-globin locus is as follows: 5' epsilon I-epsilon II-psi beta X-beta C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta Y-beta F3'. Southern blot analysis of A-type sheep reveals that these animals have a beta-globin locus similar to that of goat, i.e., 12 globin genes. Thus, the beta-globin locus of B-haplotype sheep resembles that of cows and may have retained the duplicated locus of the ancestor of cows and sheep. Alternatively, the B-sheep locus arrangement may be the result of a deletion of a four-gene set from the triplicated locus.

Amino Acid Sequence↗

PubMed2000

Linkage disequilibrium mapping in populations of variable size using the decay of haplotype sharing and a stepwise-mutation model.

Linkage-disequilibrium (LD) mapping is a powerful tool for fine-mapping disease genes. Recently, McPeek and Strahs [(1999) Am J Hum Genet 65:858-875] proposed a multilocus model for LD mapping based on the decay of haplotype sharing. Here we extend their approach in two ways. First, instead of assuming each marker allele has an equal chance to mutate to one of the other marker alleles, we use the stepwise-mutation model to describe the mutation process for microsatellite markers. Second, in addition to the independence model and the constant population size model they considered, we model the dependence among observed haplotypes due to population structure by using a general conditional-coalescent model with variable population size. Through simulation studies, we study the effects of the stepwise-mutation model and variable population size on the estimates of disease gene location, mutation rate, and time to the most recent common ancestor of the sampled haplotypes. We then use this method to analyze progressive myoclonus epilepsy data.

Chromosome Mapping↗

PubMed2025

Polyploidy-mediated variations in glutamate receptor proteins linked to Fusarium wilt resistance in upland cotton.

Cotton production in the US faces a serious threat from Fusarium oxysporum f. sp. vasinfectum race 4 (FOV4), a soil-borne fungus causing Fusarium wilt by infecting the roots and vascular system of susceptible cotton, leading to rapid wilting and death. Here, we investigate genetic mechanisms of resistance to FOV4 in the highly resistant upland cotton genotype "U1" using an early-generation segregating biparental population ("U1" × "CSX8308") with comprehensive genomic resources. Reference-grade genomic assemblies of the parents revealed minor structural variations between "U1" haplotypes, a high degree of collinearity at chromosome synteny and micro-synteny levels, and significant divergence from "CSX8308" with 8.9 million SNPs. QTL analysis identified significant markers on chromosomes D03 and A02 linked to reduced Fusarium wilt severity. Within these regions, two glutamate-receptor-like (GLR) genes showed structural variation and overlapped between translocated segments on A02 and D03, suggesting a rare but important reinforcing effect of parallel evolution between susceptible and resistant genotypes. Transcriptome profiles of "U1" under FOV4 infection reveal activation of calcium-binding proteins and transcription factors regulating plant hormones (ethylene, abscisic acid, jasmonic acid, and salicylic acid), along with enzymes involved in cell wall remodeling and phytoalexin production. Advancing cotton improvement depends on incorporating durable genetic disease resistance into high-yielding, high-quality cultivars.

Fusarium↗

PubMed2006

Comparison of the genome structure of the self-incompatibility (S) locus in interspecific pairs of S haplotypes.

The determinants of recognition specificity of self-incompatibility in Brassica are SRK in the stigma and SP11/SCR in the pollen, both of which are encoded in the S locus. The nucleotide sequence analyses of many SRK and SP11/SCR alleles have identified several interspecific pairs of S haplotypes having highly similar sequences between B. oleracea and B. rapa. These interspecific pairs of S haplotypes are considered to be derived from common ancestors and to have maintained the same recognition specificity after speciation. In this study, the genome structures of three interspecific pairs of S haplotypes were compared by sequencing SRK, SP11/SCR, and their flanking regions. Regions between SRK and SP11/SCR in B. oleracea were demonstrated to be much longer than those of B. rapa and several retrotransposon-like sequences were identified in the S locus in B. oleracea. Among the seven retrotransposon-like sequences, six sequences were found to belong to the ty3 gypsy group. The gag sequences of the retrotransposon-like sequences were phylogenetically different from each other. In Southern blot analysis using retrotransposon-like sequences as probes, the B. oleracea genome showed more signals than the B. rapa genome did. These findings suggest a role for the S locus and genome evolution in self-incompatible plant species.

Brassica↗

PubMed2000

Recent common ancestry of human Y chromosomes: evidence from DNA sequence data.

We consider a data set of DNA sequence variation at three Y chromosome genes (SMCY, DBY, and DFFRY) in a worldwide sample of human Y chromosomes. Between 53 and 70 chromosomes were fully screened for sequence variation at each locus by using the method of denaturing high-performance liquid chromatography. The sum of the lengths of the three genes is 64,120 bp. We have used these data to study the ancestral genealogy of human Y chromosomes. In particular, we focused on estimating the expected time to the most recent common ancestor and the expected ages of certain mutations with interesting geographic distributions. Although the geographic structure of the inferred haplotype tree is reminiscent of that obtained for other loci (the root is in Africa, and most of the oldest non-African lineages are Asian), the expected time to the most recent common ancestor is remarkably short, on the order of 50,000 years. Thus, although previous studies have noted that Y chromosome variation shows extreme geographic structure, we estimate that the spread of Y chromosomes out of Africa is much more recent than previously was thought. We also show that our data indicate substantial population growth in the effective number of human Y chromosomes.

Biological Evolution↗

PubMed1996

Geographic clustering of human Y-chromosome haplotypes.

Five polymorphic markers on the Y-chromosome (mostly microsatellites) were typed in 121 individuals from 13 populations around the world. With these markers 78 different haplotypes were detected. Haplotypes present more than once tend to be shared by individuals from the same population or continent. A reconstruction of haplotype phylogeny also indicates significant geographic structure in the data. Based on the similarity of the haplotypes, population relationships were examined and found to be largely concordant with those obtained with other markers. Even though the sample size and the number of markers are small, there is very signficant clustering of the haplotypes by continent of origin.

Alleles↗

PubMed2006

High-resolution characterization of linkage disequilibrium structure and selection of tagging single nucleotide polymorphisms: application to the cholesteryl ester transfer protein gene.

Full characterization of intragenic variation may improve candidate gene associations. This study selected tagging (t) single nucleotide polymorphisms (SNPs) to comprehensively represent genetic variability in the cholesteryl ester transfer protein (CETP) gene. Nineteen SNPs were identified in 50 unrelated individuals in the SNP discovery phase, and 13 intronic SNPs were added from the literature. These 32 SNPs were genotyped in 339 apparently healthy individuals and 190 coronary artery disease (CAD) patients. Using phased haplotypes, linkage disequilibrium (LD) structure was characterized and tSNPs selected using a principal component analysis (PCA) method. In healthy individuals, seven LD groups were identified that accounted for 93.4% of the observed genetic variation. These LD groups highlighted a complex LD structure for CETP, including both recombination and mutation, and eleven tSNPs were selected. Among CAD patients the results were essentially the same. Results from PCA using diploid genotype data were reasonably comparable. Finally, the selected tSNPs successfully represented the association evidence discovered for all of the other SNPs studied. This study provides an optimal set of tSNPs for association analyses of CETP. The observed complexity of LD structure highlights the importance of using methods, such as PCA, that allow for multiple dynamics in intragenic LD structure.

Aged↗

PubMed2006

Structural variation on the short arm of the human Y chromosome: recurrent multigene deletions encompassing Amelogenin Y.

Structural polymorphism is increasingly recognized as a major form of human genome variation, and is particularly prevalent on the Y chromosome. Assay of the Amelogenin Y gene (AMELY) on Yp is widely used in DNA-based sex testing, and sometimes reveals males who have interstitial deletions. In a collection of 45 deletion males from 12 populations, we used a combination of sequence-tagged site mapping, and binary-marker and Y-short tandem repeat haplotyping to understand the structural basis of this variation. Of the 45 deletion males, 41 carry indistinguishable deletions, 3.0-3.8 Mb in size. Breakpoint mapping strongly implicates a mechanism of non-allelic homologous recombination between the proximal major array of TSPY gene-containing repeats, and a single distal copy of TSPY; this is supported by the estimation of TSPY copy number in deleted and non-deleted males. The remaining four males carry three distinct non-recurrent deletions (2.5-4.0 Mb), which may be due to non-homologous mechanisms. Haplotyping shows that TSPY-mediated deletions have arisen seven times independently in the sample. One instance, represented by 30 chromosomes mostly of Indian origin within haplogroup J2e1*/M241, has a time-to-most-recent-common-ancestor of approximately 7700+/-1300 years. In addition to AMELY, deletion males all lack the genes PRKY and TBL1Y, and the rarer deletion classes also lack PCDH11Y. The persistence and expansion of deletion lineages, together with direct phenotypic evidence, suggests that absence of these genes has no major deleterious effects.

Amelogenin↗

PubMedDate not supplied

Widespread heteroplasmy in schistosomes makes an mtVNTR marker "nearsighted".

Mitochondrial markers are often hailed as the preferred DNA elements for analyses of population subdivision. To this end we have employed a mitochondrial repeat element to examine the population structure in Schistosoma mansoni (human blood flukes). Schistosome isolates were collected from each of 21 different patients representing seven different areas of a Brazilian village. These parasite isolates demonstrate substantial genetic polymorphism, with an average of 10 genotypes infecting each patient, which is more readily detected because of high levels of heteroplasmy (i.e., 72.5% of the individual worms exhibit multiple versions of this repeat region with different numbers of repeats). Due to the high number of common haplotypes in the population, this repeat element from S. mansoni has a large proportion (47%) of its genetic variation described by differences among mitochondrial genomes within individual worms. However, when only rare haplotypes are considered, population structure can be detected. It seems that heteroplasmy in the schistosome population of Melquiades is both the source of plentiful genetic variation and a confounding factor in the analysis of that variation. Thus the schistosome population in Melquiades may actually be more strongly subdivided than we are able to detect using this mitochondrial marker.

Animals↗

PubMed1995

[Genetic and molecular analysis of new recombinant t-haplotypes t(M8) and t(M9)].

The results of genetic and molecular analysis of new recombinant mouse haplotypes tM8 and tM9, derived from tw12 and t12, are described. Data on viability and fertility of tM/tM homozygotes are presented, as well as that on t-chromosome transmission ratio distortion (TRD) in the progeny of heterozygous males. Blot-hybridization analysis was performed using four t-specific probes: Tu48, Tu66, Tu119, and Tu122. Comparison of data obtained in the study with that on the structure of the initial haplotypes suggests that both recombinant haplotypes resulted from unequal crossing-over. In the case of tM9 haplotype, the crossing-over site was probably located in the region of distal t complex inversion, and tM8 haplotype resulted from two crossing-over events in the medial part of t complex.

Animals↗