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Results for “Haplotype structures”

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PubMed2004

[Analysis of genetic structure in population of Larix kaempferi by chloroplast SSR markers].

Genetic structure of seven populations in Larix kaempferi in Japan was studied by use of cpSSR markers. Ten different length fragments in and ten different kinds of haplotypes were reduced in 197 samples based on 3 pairs of polymorphic primers screened from 11 pairs of primers. There were significant variant haplotypes among the populations. The genetic variation in the populations of Larix kaempferi was detected by using cpSSR with the number of average loci A=3.33, the number of average efficient loci NE=1.20, gene diversity HE=0.17 and 5.37% variation from different populations. The genetic variation was mainly from individuals in population.

Chloroplasts↗

PubMedDate not supplied

[AFBN1 gene in patients with Marfan syndrome].

30 exons have been analyzed using SSCP in patients with MFS or related phenotypes. We report 2 missense mutations occur in calcium-binding Epidermal Growth Factor-like (EGFcb) domains and 9 polymorphisms located both in coding and noncoding regions of FBN1 gene. Three intragenic microsatellite polymorphic markers MTS-1, MTS-2 and MTS-4 have been analyzed in patients with MFS and unrelated unaffected control individuals. We found significant differences in allele frequency distribution of MTS-2 and MTS-4 loci between MFS patients and unaffected individuals. Haplotype frequency distribution on normal and mutant chromosomes were significantly different. The most common haplotype was 2-11-8 which was predominant on normal chromosomes of affected individuals. Haplotype 2-2-8 was observed in 18% of cases on mutant chromosomes and in 4% of cases on normal chromosomes. These data demonstrate possibility and application of haplotype-segregation analysis with use of these intragenic markers for diagnostic purposes in affected families by Marfan's syndrome.

Calcium↗

PubMed1992

Broad cross-reactivity with marked fine specificity in the cytotoxic T cell response to flaviviruses.

Cytotoxic T (Tc) cells were generated in mice of five H-2 haplotypes against the flaviviruses Kunjin and West Nile (WNV). A panel of recombinant vaccinia viruses which between them expressed cDNA of the entire Kunjin virus genome were used to infect targets. Anti-Kunjin virus responses to determinants derived from non-structural proteins, especially NS3, NS4A and NS4B, were dominant in most mouse strains; usually only one class I major histocompatibility complex (MHC) restriction element was involved. WNV-immune Tc cells showed similar but not identical patterns of antigen recognition to Kunjin virus-immune Tc cells. The extent to which WNV-immune Tc cells recognized Kunjin virus-encoded determinants varied considerably between mice of different MHC haplotypes.

Animals↗

PubMed2003

The R2-haplotype associated Asp2194Gly mutation in the light chain of human factor V results in lower expression levels of FV, but has no influence on the glycosylation of Asn2181.

The R2 haplotype of the FV gene spans from exon 8 through 25 and comprises several strongly linked polymorphisms in the FV gene, including some missense mutations. Carriership of the R2-FV allele has been associated with reduced plasma FV levels, increased FV1/FV2 ratios and mild APC resistance. Some studies have reported that carriership of the R2-FV allele is associated with an increased risk of venous thombosis. At this moment, the individual contribution to the R2-associated phenotypes of the different mutations linked to the R2 haplotype of FV is unclear. The main objective of our study was to obtain insight in the influence of the R2-related Asp2194Gly mutation on FV expression, FV structure and FV function using Bdomainless rFV mutants. Replacing Asp at position 2194 by Gly resulted in a more than threefold reduction of rFV expression compared to rFV wild-type. Therefore, we propose that the R2-linked Asp2194Gly mutation is an important determinant of the association of the R2-FV allele with lower FV levels. Furthermore, the light chains from Asp2194Gly containing rFV mutants showed similar molecular weights as the light chains of the non-glycosylated rFVwt or the plasma FV2 isoform, indicating that glycosylation at Asn2181 is not stimulated by the presence of a glycine in position 2194. Finally, the apparent K(d) for dissociation of the FXaVa complex (K(1/2Xa)) was not higher in rFV mutants with the Asp2194Gly mutation than for rFVwt, suggesting that also the affinity for negatively charged phospholipids is not affected by substitution of Asp into Gly at position at 2194.

Alleles↗

PubMed1999

ORFless, intronless, and mutant transcription units in the mouse t complex responder (Tcr) locus.

Mouse t haplotypes exhibit transmission ratio distortion (TRD), whereby heterozygous males (+/t) transmit the t chromosome to nearly all offspring. TRD is mediated by the t complex responder locus (Tcr), whose transmission is elevated above Mendelian levels by additive contribution of several t haplotype-encoded quantitative trait loci (QTLs) called t complex distorters (Tcd1-Tcd5). The entire genetically defined Tcr interval has been cloned and consists of under 200 kb. This interval is one of three large duplication units in t haplotypes that retain high levels of similarity. The cis-active nature of Tcr raises the possibility that it is not a protein-encoding gene, but another anomaly such as a structural anomaly of chromatin. To further investigate the Tcr-critical interval, a 30-kb region upstream of the Tcp10b(t) gene (a testis-expressed former candidate for Tcr) was sequenced, along with the duplicated paralogous region associated with Tcp10c(t), which lies immediately adjacent but outside the Tcr interval. Several genes or transcriptional units were identified, including the 3' end of ribosomal s6 kinase (Rsk3); two apparently intronless and ORF-less genes; and Gpr31, an intronless, putative G-protein coupled receptor. While the 30-kb regions were 98% identical, the Gpr31 paralog from the Tcr-critical region (Gpr31b(t)) contained an in-frame 210-bp deletion that disrupted two of the seven predicted transmembrane domains. Furthermore, an intronless and ORFless gene from this interval, Trex1b(t), contained a 4-bp deletion that distinguished it from all other homologs in t haplotypes and wild-type chromosomes. Although it is unknown whether any of these genes are involved in TRD, their discovery raises new possibilities regarding the nature of Tcr, including a model whereby it might function as an RNA rather than a protein or chromatin anomaly.

Amino Acid Sequence↗

PubMed2001

Hierarchical patterns of global human Y-chromosome diversity.

We examined 43 biallelic polymorphisms on the nonrecombining portion of the Y chromosome (NRY) in 50 human populations encompassing a total of 2,858 males to study the geographic structure of Y-chromosome variation. Patterns of NRY diversity varied according to geographic region and method/level of comparison. For example, populations from Central Asia had the highest levels of heterozygosity, while African populations exhibited a higher level of mean pairwise differences among haplotypes. At the global level, 36% of the total variance of NRY haplotypes was attributable to differences among populations (i.e., Phi(ST) = 0.36). When a series of AMOVA analyses was performed on different groupings of the 50 populations, high levels of among-groups variance (Phi(CT)) were found between Africans, Native Americans, and a single group containing all 36 remaining populations. The same three population groupings formed distinct clusters in multidimensional scaling plots. A nested cladistic analysis (NCA) demonstrated that both population structure processes (recurrent gene flow restricted by isolation by distance and long-distance dispersals) and population history events (contiguous range expansions and long-distance colonizations) were instrumental in explaining this tripartite division of global NRY diversity. As in our previous analyses of smaller NRY data sets, the NCA detected a global contiguous range expansion out of Africa at the level of the total cladogram. Our new results support a general scenario in which, after an early out-of-Africa range expansion, global-scale patterns of NRY variation were mainly influenced by migrations out of Asia. Two other notable findings of the NCA were (1) Europe as a "receiver" of intercontinental signals primarily from Asia, and (2) the large number of intracontinental signals within Africa. Our AMOVA analyses also supported the hypothesis that patrilocality effects are evident at local and regional scales, rather than at intercontinental and global levels. Finally, our results underscore the importance of subdivision of the human paternal gene pool and imply that caution should be exercised when using models and experimental strategies based on the assumption of panmixia.

Africa South of the Sahara↗

PubMed2025

Recent Adaptation in a Threatened Salmonid Revealed by Museum Genomics.

Steelhead/rainbow trout (Oncorhynchus mykiss) is an imperilled salmonid with two main life history strategies: migrate to the ocean or remain in freshwater. Domesticated hatchery forms of this species have been stocked into almost all California waterways, possibly resulting in introgression into natural populations and altered population structure. We compared whole-genome sequence data from contemporary populations against a set of museum population samples of steelhead from the same locations that were collected prior to most hatchery stocking. We observed minimal introgression and few steelhead-hatchery trout hybrids despite a century of extensive stocking. Our historical data show signals of introgression with a sister species and indications of an early hatchery facility. Finally, we found that migration-associated haplotypes have become less frequent over time, a likely adaptation to decreased opportunities for migration. Since contemporary migration-associated haplotype frequencies have been used to guide species management, we consider this to be a rare example of shifting baseline syndrome that has been validated with historical data. We suggest cautious optimism that a century of hatchery stocking has had minimal impact on California steelhead population genetic structure, but we note that continued shifts in life history may lead to further declines in the ocean-going form of the species.

Animals↗

PubMed2000

Glacial vicariance and historical biogeography of rock ptarmigan (Lagopus mutus) in the Bering region.

In this paper, we address alternative hypotheses for the evolution of subspecies of rock ptarmigan (Lagopus mutus) endemic to the Aleutian Archipelago. To do this we examined patterns of genetic differentiation among populations of rock ptarmigan in the Aleutian Islands and parts of both Alaska and Siberia. Variation in mitochondrial control region sequences of 105 rock ptarmigan from 10 subspecies within the Bering region revealed three major phylogenetic lineages, two of which are endemic to the Aleutian Islands. Accordingly, haplotype and nucleotide diversities of rock ptarmigan within the archipelago are much higher than within mainland Alaska or Siberia. For Aleutian rock ptarmigan, analyses of molecular variance indicated significant genetic structuring and low estimates of gene flow among populations, despite small interisland distances within the archipelago. However, isolation by distance did not describe the pattern of gene flow or differentiation at this scale. Our estimates of divergence times of lineages suggest that Aleutian rock ptarmigan became isolated prior to the most recent Pleistocene glaciation event (late Wisconsin Stade) and that current patterns of genetic variation reflect the postglacial redistribution of divergent lineages and subsequent limited gene flow. In addition, genetic divergence among lineages was concordant with the distribution of plumage types among subspecies. The patterns of genetic variation described here for rock ptarmigan provide evidence for the role of glacial vicariance in contributing to genetic diversity within this and other Bering region species.

Alaska↗

PubMed2001

Characterization and structural impact of five novel PROS1 mutations in eleven protein S-deficient families.

Heterozygozity for four novel missense mutations (W108C, W342R. E349K and L485S) and one novel 4 bp deletion (ACdelAAAG affecting codons 632-633) was identified in PROS1 of unrelated thrombosis prone Danish families with protein S type I or III deficiency. The 4 bp deletion results in a frameshift leading to replacement of the coding sequence for the 3 C-terminal amino acids by an abnormal extended sequence that codes for 9 amino acids. The E349K substitution was found in 7 families. Haplotype analysis using 7 microsatellite markers flanking PROS1 was consistent with a common founder for this mutation. The mutations reported here are most likely the cause of the protein S deficiency. Firstly, the four missense mutations cosegregate with the abnormal plasma protein S phenotype and lead to the loss of highly conserved amino acids. Secondly, computer analysis of structural models of protein S predicts that the substitutions could affect proper protein folding and/or stability. Analysis of platelet mRNA from subjects with the W108C, E349K, L485S mutation or the 4 bp deletion showed that mutated mRNA was expressed in significant amounts suggesting that mutated molecules are synthesized. Our results are compatible with defective protein folding/unstable molecules, impaired secretion and intracellular degradation of mutated protein, which appear to be the major molecular disease mechanisms for missense mutations and certain other mutations found in genetic disorders.

Adolescent↗

PubMed2005

Development of microsatellite markers for Japanese scallop (Mizuhopecten yessoensis) and their application to a population genetic study.

The Japanese scallop (Mizuhopecten yessoensis) is one of the main fishery products in Japan, but with the expansion of culture operations of the Japanese scallop, various problems have been encountered including high mortality, poor growth, poor seed production, and so on. Moreover, there is concern that many years of cultivation may have affected the genetic structure of the scallop population. To approach these problems and concerns, we developed microsatellite markers as a molecular tool for population genetic studies. By using 4 microsatellite markers as well as a mitochondrial marker, we investigated the genetic structure of samples from the islands of Hokkaido (14 populations) and Honshu (Tohoku, 3 populations) in Japan, and south Primorye (4 populations) in Russia. All the populations sampled had high genetic diversity (average expected heterozygosity, 0.7011 to 0.7622; haplotype diversity, 0.6090 to 0.8848), and almost all showed a tendency of homozygote excess, which was significant in 2 populations. Hierarchical analysis of molecular variance tests based on the microsatellite and mitochondrial markers indicated that the 3 geographic regions were genetically divergent from one another, with little evidence of divergence within regions. Homogeneity in allele frequency distributions between natural and cultured scallops and allele frequency stability over a period of 2 decades indicated that the culturing operations have probably not had a substantial effect on the genetic structure of the populations.

Animals↗

PubMed2005

Phylogeographic structure and postglacial evolutionary history of water voles (Arvicola terrestris) in the United Kingdom.

The phylogeographic pattern of mitochondrial DNA variation in water voles (Arvicola terrestris) from 57 localities across the United Kingdom and representative samples from Spain, France, Switzerland and Finland was determined from sequence variation in the central portion of the control region. Twenty-seven different haplotypes were resolved which formed two distinct phylogenetic clades. This major division separated haplotypes found in Scotland from those found in England and Wales. Nested clade analysis of haplotypes indicated that such a division was a consequence of allopatric fragmentation. The haplotypes found in Switzerland, France and Spain clustered with Scottish haplotypes, whereas the haplotype from Finland clustered with the English/Welsh haplotypes. These patterns indicate that contemporary Scottish populations are derived from an Iberian glacial refugium, whereas English and Welsh populations are derived from an eastern European refugium. As such, the postglacial recolonization of the United Kingdom must have involved two colonization events, either in different localities with no subsequent contact, or as two waves separated over time, with the second wave of colonizers displacing the first. An analysis of molecular variance (AMOVA) identified significant population genetic divergence within both the major clades, indicative of restricted gene flow and regional population isolation. The implications of both phylogeographical and population genetic structure are discussed in context with the conservation of water voles in Britain.

Analysis of Variance↗

PubMed2001

Linkage disequilibrium and haplotype analysis among ten single-nucleotide polymorphisms of interleukin 11 identified by sequencing of the gene.

Interleukin (IL11) is a member of the interleukin 6 (IL6)-related cytokine subfamily, which stimulates T cell-dependent development of immunoglobulin-producing B cells. IL11 is also an important paracrine regulator of bone metabolism that induces formation of osteoclasts. In the work reported here, we sequenced the entire IL11 structural gene of 48 alleles in a Japanese test population. These experiments identified ten single-nucleotide polymorphisms (SNPs) and determined their allelic frequencies. One polymorphism was identified upstream of exon 1, one in exon 3, four in intron 4 and four in the 3' untranslated region (3'UTR) of exon 5. Based on the genotype data, we constructed six haplotypes in the tested population. Two-way comparisons of SNPs revealed two combinations in complete linkage disequilibrium, one with SNPs at nucleotide positions 2753, 3644, 5154, and 5568, and another with SNPs at positions 3686, 5141, and 5734. These results will be useful in disease-association studies where a contribution of the human IL11 gene has been suspected, especially in disorders affecting immune response and bone metabolism.

3' Untranslated Regions↗

PubMed1986

Analysis of somatic cell H-2 variants to define the structural requirements for class I antigen expression.

We have taken the approach of producing somatic cell variants with altered H-2 products to study the structural requirements for cell surface expression of class I histocompatibility molecules. H-2 antigen variants generated by chemical mutagenesis of a cell line expressing the H-2b haplotype were first selected with alloantisera for their loss of H-2Kb expression, and then were analyzed by radioimmunoassay for the appearance of intracellular Kb antigen. For one such variant (69.9.15), whereas the H-2Kb antigen was absent from the cell surface as assayed by antibody-mediated complement-dependent cytotoxicity, an H-2Kb molecule was detected within the cell lysate as confirmed by direct immune precipitation with Kb-specific monoclonal antibodies. The product had an altered antigenic phenotype, since it reacted with only two anti-Kb monoclonal antibodies (Y-3 and EH-144) and not with a third (5F1.2). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified the beta 2 microglobulin-associated, intracellular H-2Kb heavy chain to be slightly smaller in Mr than the H-2Kb of the parental cell line. Hybridization analysis revealed the Kb gene from the variant to be without gross alterations, and furthermore, identified a Kb mRNA species that was identical in size to wild-type Kb mRNA. Because complementation was not observed after somatic cell fusion of variant cells with BALB/c splenocytes, it appeared that the alteration in Kb expression was due to a cis-acting defect. In addition, DNA-mediated gene transfer of the wild-type Kb gene into the variant cell line resulted in expression of the Kb antigen on the cell surface, thus confirming that the defect in expression of the mutant Kb product was not due to other factors in the 69.9.15 cell line. Such findings are consistent with the conclusion that stable H-2Kb surface-negative somatic variants can arise due to limited alterations in the Kb gene, resulting in the synthesis of a class I molecule that is expressed only as an intracellular product.

Animals↗

PubMed1991

Murine T cell-stimulatory peptides from the 19-kDa antigen of Mycobacterium tuberculosis. Epitope-restricted homology with the 28-kDa protein of Mycobacterium leprae.

Fifteen overlapping synthetic peptides, spanning the entire amino acid sequence of the Mycobacterium tuberculosis 19-kDa protein, were used to identify epitopes recognized by murine T cells. Five of the 15 peptides tested were able to elicit in vitro lymph node T cell proliferative responses in C57BL/10 mice primed by footpad inoculation with homologous peptide. Analysis in congenic strains of mice revealed H-2 restriction in the response to four peptides. However, one peptide, 19.7 (residues 61 to 80), induced T cell responses in all four haplotypes tested. This peptide was also unique in being able to stimulate lymph node cells from C57BL/10 mice immunized with recombinant 19-kDa protein, killed M. tuberculosis, or live bacillus Calmette Guerin infection. T cell lines specific for peptide 19.7 were of the CD4 phenotype. Significantly, sequence analysis revealed that residues 61 to 80 of the 19-kDa protein exhibited considerable homology with a single 20-amino acid sequence (residues 120 to 140), but not with any other region of the 28-kDa protein expressed in Mycobacterium leprae. This finding is the first evidence of epitope-restricted homology between otherwise structurally unrelated microbial Ag.

Amino Acid Sequence↗

PubMed1995

Nucleotide sequence and structural analysis of the rat RT1.Eu and RT1.Aw3l genes, and of genes related to RT1.O and RT1.C.

A cDNA library was constructed using mRNA isolated from the R21 strain of rats which have the major histocompatibility complex (MHC) haplotype RT1.AlBlDlEu and the growth and reproduction complex (grc) genotype grc+. The cDNA clones that hybridized with the class I probes pAG64c and pARI.5 and were 1.3-1.7 kilobases were selected. Full-length clones were identified by sequencing partially the 5' and 3' ends of each clone, by the presence of a start codon at the 5' end, and by a polyadenylation sequence at the 3' end. The full-length cDNA clones were examined for in vitro transcription by transfection into human CIR cells using electroporation, and expression was detected by flow cytometry using monoclonal antibodies specific to the heavy chains and polyclonal antibody to beta 2-microglobulin. The RT1.Eu gene was transcribed and expressed optimally, and its nucleotide and deduced amino acid sequences differed significantly from the RT1.Aa, RT1.A(l), RT.Au, LW2, and 11/3R genes but only slightly from the RT1.K gene. The high level of sequence similarity between RT1.Eu and RT1.K suggests that the two genes may have originated from a common ancestral gene. In addition, three new genes (RT1.Aw3l, RT1.C-type, and RT1.O-type) were identified. The RT1.Aw3l gene is almost identical to RT1.A(l) with the exception of an in frame deletion of 21 nucleotides in exon 2 leading to a 7 amino acid deletion in the alpha 1 domain of the deduced amino acid sequence and 11 nucleotide substitutions and insertions in the rest of the sequence. It transcribed optimally, but no significant expression was detected. The RT1.C-type gene 119 is very similar (97%) to the LW2 gene in the 3' untranslated region, which suggests that it is in the RT1.C region. It transcribed optimally, but no significant expression was detected. The RT1.O-type gene 149 has all the features of a class Ib gene, but a premature stop codon in the alpha 1 domain causes incomplete translation. Its in vitro transcription was very low, and no expression was detected. These studies, combined with previous work, indicate that in the MHC of the R21 strain three class Ia genes (Eu, A(l), Aw3l) and three class Ib genes (C-type, O-type, N) are transcribed but only two class Ia genes (Eu, A(l)) are expressed.

Amino Acid Sequence↗

PubMed2004

Genetic diversity and phylogeny of Japanese sake-brewing rice as revealed by AFLP and nuclear and chloroplast SSR markers.

Japanese rice ( Oryza sativa L.) cultivars that are strictly used for the brewing of sake (Japanese rice wine) represent a unique and traditional group. These cultivars are characterized by common traits such as large grain size with low protein content and a large, central white-core structure. To understand the genetic diversity and phylogenetic characteristics of sake-brewing rice, we performed amplified fragment length polymorphism and simple sequence repeat analyses, using 95 cultivars of local and modern sake-brewing rice together with 76 cultivars of local and modern cooking rice. Our analysis of both nuclear and chloroplast genome polymorphisms showed that the genetic diversity in sake-brewing rice cultivars was much smaller than the diversity found in cooking rice cultivars. Interestingly, the genetic diversity within the modern sake-brewing cultivars was about twofold higher than the diversity within the local sake-brewing cultivars, which was in contrast to the cooking cultivars. This is most likely due to introgression of the modern cooking cultivars into the modern sake-brewing cultivars through breeding practices. Cluster analysis and chloroplast haplotype analysis suggested that the local sake-brewing cultivars originated monophyletically in the western regions of Japan. Analysis of variance tests showed that several markers were significantly associated with sake-brewing traits, particularly with the large white-core structure.

Analysis of Variance↗

PubMed2001

Population structure and genetic diversity of the amphiatlantic haploid peatmoss Sphagnum affine (Sphagnopsida).

Nineteen populations of Sphagnum affine were included in a study of genetic diversity and structure in fragmented and less fragmented landscapes, and differentiation at intercontinental and three regional levels. Isozyme electrophoresis of eight enzyme systems revealed 12 variable loci, which could be used for haplotype identification. A hierachical analysis of variance (AMOVA) revealed no significant intercontinental differentiation, and very limited differentiation among European regions. A trend of decreasing diversity with increasing latitude was apparent. Gametic phase disequilibria was high, suggesting nonrandom mating and regionally high incidences of inbreeding. The partitioning of genetic variation within and among populations in each region varied among regions, the northernmost populations having 86% of the total variation among populations, the southernmost in Scandinavia having 25% of the variation among populations, whereas the American populations displayed 89% of the variation within populations. Fifteen alleles at eight loci occurred in the U.S.A. which were not encountered in Europe, whereas only three European alleles at one locus in three populations were not encountered in U.S.A. The differences in diversity between North America and Europe may result from loss of genetic diversity caused by founder effects during postglacial recolonization of northern Europe. In Europe, the main mountain ranges extend E-W, posing severe barriers to northwards migration of lowland species, compared to the N-S trend of mountain ranges in North America. The decline in genetic diversity and increase in population differentiation and gametic phase disequilibria towards the north in Scandinavia may be caused by a series of founder effects during postglacial migration. These may have corresponded to minor climatic oscillations that influenced the migration front/leading edge in the suboceanic lowlands of Norway. According to this model random genetic drift will be an increasingly important structuring factor with latitude.

Analysis of Variance↗

PubMed1999

Detection of additional structural variation at the FES/FPS system and population data from S. Tomé e Príncipe and North Portugal.

Comparative analysis of heteroduplex patterns on the STR FES/FPS system led to the detection of a new non-consensus allele 10 in the African population of São Tomé e Príncipe. Automated sequencing confirmed a T-->C substitution at position 177 (1stT of the 6th repeat) which was exclusively found in haplotypic combination with base A in the previously described polymorphic position 34. The new substitution was not detected in a sample from North Portugal. Sequence analysis revealed a triplet of inverted bases, from positions 101 to 103, relative to the sequence described in the GeneBank (Accession No. X06292). This work confirms the capacity of heteroduplex analysis in the detection of DNA structural microvariation and emphasises the complementary utility of manual system analysis and semi-automated techniques for a full characterisation of the genetic variability of STRs.

Adult↗