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Results for “Haplotype structures”

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PubMed2007

Phylogeography of the green turtle, Chelonia mydas, in the Southwest Indian Ocean.

Patterns of mitochondrial DNA (mtDNA) variation were used to analyse the population genetic structure of southwestern Indian Ocean green turtle (Chelonia mydas) populations. Analysis of sequence variation over 396 bp of the mtDNA control region revealed seven haplotypes among 288 individuals from 10 nesting sites in the Southwest Indian Ocean. This is the first time that Atlantic Ocean haplotypes have been recorded among any Indo-Pacific nesting populations. Previous studies indicated that the Cape of Good Hope was a major biogeographical barrier between the Atlantic and Indian Oceans because evidence for gene flow in the last 1.5 million years has yet to emerge. This study, by sampling localities adjacent to this barrier, demonstrates that recent gene flow has occurred from the Atlantic Ocean into the Indian Ocean via the Cape of Good Hope. We also found compelling genetic evidence that green turtles nesting at the rookeries of the South Mozambique Channel (SMC) and those nesting in the North Mozambique Channel (NMC) belong to separate genetic stocks. Furthermore, the SMC could be subdivided in two different genetic stocks, one in Europa and the other one in Juan de Nova. We suggest that this particular genetic pattern along the Mozambique Channel is attributable to a recent colonization from the Atlantic Ocean and is maintained by oceanic conditions in the northern and southern Mozambique Channel that influence early stages in the green turtle life cycle.

Acanthaceae↗

PubMed1993

Fine analysis of recognition sites of monoclonal antibodies, 1B7 and 1E4, using L cell transfectants of recombinant mouse MHC class II genes.

Recognition sites of two monoclonal antibodies (mAbs), 1B7 and 1E4, specific for murine MHC class II were determined, using eleven L cell transfectants which express recombinant class II (I-A) molecules. 1B7 positive cells possessed a haplotype k in the alpha-helix of the beta-chain, whereas 1E4 positive cells had haplotype b at the alpha-helix of the beta-chain. The alpha-helix of the beta-chains is regarded as an important site for antigen binding. Thus, the 1B7 and 1E4 mAbs may be useful for analysis of functional sites on class II molecules involved in antigen recognition.

Animals↗

PubMed2003

Impairment by mucosal adjuvants and cross-reactivity with variant peptides of the mucosal immunity induced by injection of the fusion peptide PADRE-ELDKWA.

Secretory immunity protects against mucosal transmission of viruses, as demonstrated with the oral poliovirus vaccine. In a previous study we showed that this immunity could be induced in mice by injection of a fusion peptide consisting of an unnatural peptide-like sequence (PADRE) and a viral epitope (ELDKWASLW). PADRE is a T-helper-cell epitope able to bind most major histocompatibility complex class II molecules of different haplotypes in mice and humans and to increase antibody responses. ELDKWA is a well-known consensual sequence of gp41 involved in a key structure of human immunodeficiency virus (HIV) type 1. Here, the antibody response to the native form of ELDKWA was mainly of the immunoglobulin A isotype and selectively occurred in mucosa. Adjuvants, such as cholera toxin and cytosine polyguanine, were useless and even competed with PADRE for the response. Interestingly, these antibodies were cross-reactive with the three major variants of the epitope, as shown both by direct enzyme-linked immunosorbent assay and by inhibition. This unconventional route of mucosal immunization allows control of the administered dose. The lack of adjuvant and the cross-reactivity of the antibodies increase the safety and the spectrum of the candidate vaccine, respectively. The drug-like nature of the construct suggests further improvements by synthesis of more antigenic sequences. The reasonable cost of short peptides at the industrial level and their purity make this approach of interest for future vaccines against mucosal transmission of HIV or other pathogens.

Adjuvants, Immunologic↗

PubMed2004

Population genetics, history, and health patterns in native americans.

Over the past two decades, detailed studies of mitochondrial DNA and the Y chromosome have increased our understanding of the history and population genetics of Native American populations. Variation in autosomal DNA has also been investigated, but to a more limited extent. A low level of genetic diversity in Native American populations is a robust finding from all lines of evidence. In contrast to the previous multiple migration scenarios for the Pleistocene peopling of the Americas, it now seems that a single migration satisfactorily explains the genetic data. Native Americans show greater genetic similarity to populations in east central Asia than they do to the current easternmost Siberian populations. Recent studies on the Y chromosome indicate a date of entry (about 17,000 years ago) into the Americas roughly consistent with the archaeological record. Native Americans experienced two episodes of reduced population size: one with the peopling of the Americas and the other with European contact. The former is the more important determinant for the number of gene lineages and founding haplotypes seen in populations. It may also be an important determinant of the genetic variation underlying common complex diseases, and especially diabetes. The tribal structure of contemporary Native American populations is relevant to the distribution of rare Mendelian disorders because most tribes constitute relatively small, semi-independent gene pools. This leads us to expect that the allelic spectrum for Mendelian diseases will be simple within individual tribes but complex for Native Americans as a whole.

Genetics, Population↗

PubMed2004

Association of polymorphisms and haplotypes in the elastin gene in Dutch patients with sporadic aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: A locus containing the elastin gene has been linked to familial intracranial aneurysms in 2 distinct populations. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes of SNPs in the elastin gene with the occurrence of subarachnoid hemorrhage (SAH) from sporadic aneurysms in the Netherlands. METHODS: We genotyped 167 SAH patients and 167 matching controls for 18 exonic and intronic SNPs in the elastin gene. A Bonferroni correction was applied for multiple comparisons with all novel associations, with a correction factor derived from the number of SNPs tested (P value after Bonferroni correction [P(corr)]). RESULTS: SAH was statistically significant associated with an SNP in exon 22 of the elastin gene (minor allele frequency was 0.000 in patients and 0.028 in controls; odds ratio [OR], 0.0; 95% CI, 0.0 to 0.7; P=0.004; P(corr)=0.05) and possibly with an SNP in intron 5 (minor allele frequency was 0.062 in patients and 0.128 in controls; OR, 0.5; 95% CI, 0.2 to 0.8; P=0.007; P(corr)=0.08). Haplotypes of intron 5/exon 22 (P(corr)=0.002), intron 4/exon 22 (P(corr)=0.02), and intron 4/intron 5/exon 22 (P=9.0x10(-9)) were also associated with aneurysmal SAH. CONCLUSIONS: Variants and haplotypes within the elastin gene are associated with the risk of sporadic SAH in Dutch patients. Gradual increase of statistical power with the inclusion of 2 or 3 SNPs in the studied haplotypes supports the validity of our conclusion that the elastin gene is a susceptibility locus for SAH.

Alleles↗

PubMed2006

A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin.

PURPOSE: To identify the genetic defect in an autosomal dominant congenital cataract family, having 15 members in three generations, affected with bilateral cataract that gave the appearance of "full moon" with Y-sutural opacities. METHODS: A detailed family history and clinical data were recorded. A genome-wide scan by two point linkage analysis using nearly 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bidirectional sequencing of amplified products. RESULTS: A maximum two point lod score of 5.45 at theta=0.00 was obtained with marker D1S534. Haplotype analysis placed the cataract locus to a 14.1 cM region between D1S221 and D1S498, in close proximity to the gene for the gap junction channel protein connexin 50 (GJA8) at 1q21. Mutation screening in GJA8 identified a novel G>C transversion at nucleotide position c.235. This nucleotide change resulted in the substitution of highly conserved valine by leucine at codon 79 (V79L). This nucleotide substitution was neither seen in any unaffected member of the family nor in 180 unrelated control subjects (360 chromosomes) from same ethnic background tested by sequence analysis of GJA8. CONCLUSIONS: The present study describes the mapping of a locus for congenital cataract that appeared like "full moon" with Y-sutural opacities at 1q21 and identifies a previously unreported mutation in GJA8. These findings thus expand the mutation spectrum of GJA8.

Asian People↗

PubMed1980

Studies on the C2-deficiency gene in man.

A one-step haemolytic assay using cellular intermediates was used to determine C2 levels in 50 HLA-A25 and B18 positive blood donors and four families suspected to have the C2-deficiency gene. The method clearly discriminated between homozygous normals and heterozygous deficient individuals, and it was found that approx. 50% of individuals with the haplotype HLA-A25, B18 had low levels of functional C2. In the four families studied, the close linkage of the C2-deficiency gene and the haplotype HLA-A25, B18 was confirmed. Furthermore, the C2-deficiency gene was shown to be a silent or null allele at the structural locus.

Child↗

PubMed2005

Genetic variation of the Y chromosome in Chibcha-speaking Amerindians of Costa Rica and Panama.

Genetic variation of the Y chromosome in five Chibchan tribes (Bribri, Cabecar, Guaymi, Huetar, and Teribe) of Costa Rica and Panama was analyzed using six microsatellite loci (DYS19, DYS389A, DYS389B, DYS390, DYS391, and DYS393), the Y-chromosome-specific alphoid system (alphah), the Y-chromosome Alu polymorphism (YAP), and a specific pre-Columbian transition (C-->T) (M3 marker) in the DYS 199 locus that defines the Q-M3 haplogroup. Thirty-nine haplotypes were found, resulting in a haplotype diversity of 0.937. The Huetar were the most diverse tribe, probably because of their high levels of interethnic admixture. A candidate founder Y-chromosome haplotype was identified (15.1% of Chibchan chromosomes), with the following constitution: YAP-, DYS199*T, alphah-II, DYS19*13, DYS389A*17, DYS389B*10, DYS390*24, DYS391*10, and DYS393*13. This haplotype is the same as the one described previously as one of the most frequent founder paternal lineages in native American populations. Analysis of molecular variance indicated that the between-population variation was smaller than the within-population variation, and the comparison with mtDNA restriction data showed no evidence of differential structuring between maternally and paternally inherited genes in the Chibchan populations. The mismatch-distribution approach indicated estimated coalescence times of the Y chromosomes of the Q-M3 haplogroup of 3,113 and 13,243 years before present; for the mtDNA-restriction haplotypes the estimated coalescence time was between 7,452 and 9,834 years before present. These results are compatible with the suggested time for the origin of the Chibchan group based on archeological, linguistic, and genetic evidence.

Analysis of Variance↗

PubMed2000

Triosephosphate isomerase deficiency: historical perspectives and molecular aspects.

In this chapter, the original descriptions and pre-molecular studies of triosephosphate isomerase (TPI) deficiency are summarized, and the molecular aspects of the disease presented. The gene is well characterized, and several mutations have been described. Structure-function studies have led to an increased understanding of impaired catalysis. All kindreds that have been studied with the predominant Glu104Asp mutation are linked by a common haplotype, indicating descent from a common ancestor. Variant upstream substitutions occur in high frequency in persons of African and East Asian lineage and in lower frequency in other groups, but the possible role, if any, of these variants in clinical TPI deficiency requires further investigation. The possible contribution of deviant lipid metabolism to the pathogenesis of the disorder has been extensively investigated, and an intriguing new area of inquiry is the apparent cell-to-cell transfer of enzyme in cell culture systems, raising the question of the feasibility of enzyme or gene replacement therapy.

Anemia, Hemolytic, Congenital Nonspherocytic↗

PubMed2005

The effects of habitat fragmentation via forestry plantation establishment on spatial genotypic structure in the small marsupial carnivore, Antechinus agilis.

Dispersal is an important influence on species' distributions, patch colonization and population persistence in fragmented habitat. We studied the impacts of habitat fragmentation resulting from establishment of an exotic pine plantation on dispersal of the marsupial carnivore, Antechinus agilis. We applied spatial analyses of individual multilocus microsatellite genotypes and mitochondrial haplotypes to study patterns of gene flow in fragmented habitat and natural habitat 'control' areas, and how this is affected by the spatial dispersion of habitat patches, the presence of corridors and a 'mainland' source of migrants. Spatial analysis of molecular variance and partial Mantel tests confirmed the absence of cryptic barriers to gene flow in continuous habitat, which if present would confound the comparison of genetic structures in fragmented vs. unfragmented habitats. Spatial genotypic structure suggested that although dispersal was male-biased in both habitat types, fragmentation restricted dispersal of males more than that of females and the degree of restriction of male dispersal was dependent on the geographical isolation of the patch. The scale of positive genotypic structure in fragmented habitat was restricted to the two closest patches for females and the three closest patches for males. Our results provide evidence for significantly increased gene flow through habitat corridors relative to that across the matrix and for significantly lower gene flow between 'mainland' unfragmented habitat and habitat patches relative to that within either habitat type, suggesting a behavioural barrier to crossing habitat interfaces.

Animals↗

PubMed2005

An efficient algorithm for Perfect Phylogeny Haplotyping.

The Perfect Phylogeny Haplotyping (PPH) problem is one of the many computational approaches to the Haplotype Inference (HI) problem. Though there are many O(nm(2)) solutions to the PPH problem, the complexity of the PPH problem itself has remained an open question. In this paper, We introduce the FlexTree data structure that represents all the solutions for a PPH instance. We also introduce row-ordering that arranges the genotypes in a more manageable fashion. The column ordering, the FlexTree data structure and the row ordering together make the O(nm) OPPH algorithm possible. We also present some results on simulated data which demonstrate that the OPPH algorithm performs quiet impressively when compared to the earlier O(nm(2)) algorithms.

Algorithms↗

PubMed2004

Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus.

Susceptibility to autoimmunity in B6.Sle1b mice is associated with extensive polymorphisms between two divergent haplotypes of the SLAM/CD2 family of genes. The B6.Sle1b-derived SLAM/CD2 family haplotype is found in many other laboratory mouse strains but only causes autoimmunity in the context of the C57Bl/6 (B6) genome. Phenotypic analyses have revealed variations in the structure and expression of several members of the SLAM/CD2 family in T and B lymphocytes from B6.Sle1b mice. T lymphocytes from B6.Sle1b mice have modified signaling responses to stimulation at 4-6 weeks of age. While autoimmunity may be mediated by a combination of genes in the SLAM/CD2 family cluster, the strongest candidate is Ly108, a specific isoform of which is constitutively upregulated in B6.Sle1b lymphocytes.

Alleles↗

PubMed2004

Genetic structure and variation in the relict populations of Alsophila spinulosa from southern China based on RAPD markers and cpDNA atpB-rbcL sequence data.

RAPD markers and sequences of chloroplast DNA (cpDNA) atpB-rbcL intergenic spacers were used to characterize the pattern of genetic variation and the phylogenetic relationships of the relict populations of Alsophila spinulosa located in Jian Feng Ling (JFL) and Diao Luo Shan (DLS), Hainan, and Tang Lang Shan (TLS), Ding Hu Shan (DHS), and Da Xi Shan (DXS), Guangdong, of southern China. 28 random primers generated 118 bands, out of which 26 (22.03%) were polymorphic loci, distinguishing 17 different RAPD phenotypes. Percentage of polymorphic loci, Shannon phenotypic diversity and Nei's gene diversity comprehensively indicated that JFL possessed the highest diversity, TLS and DHS in intermediate and DLS or DXS the least; the corresponding values of the population appeared correlated with the population size. Differentiation was detected among populations of A. spinulosa (1-Hpop/Hsp=0.7453, GST=0.7763, and phist=0.8145). AMOVA showed that 47.44% of the variance was partitioned among regions (Hainan and Guangdong), 34.01% attributed among populations within regions, whereas only 18.55% occurring within populations. Low level of intra-specific diversity was maintained in A. spinulosa with Shannon diversity and gene diversity merely 0.0560 and 0.0590, repectively. Sequence length of atpB-rbcL intergenic spacer varied from 724 bp to 730 bp. Base composition was with A+T content between 63.17% and 63.70%. 13 haplotypes of atpB-rbcL noncoding spacers were identified. UPGMA dendrogram of RAPD phenotypes, principal components analysis based on RAPD patterns, minimum spanning network and neighbour-joining (NJ) tree established on atpB-rbcL haplotypes consistently suggested the geographical subdivision of populations of A. spinulosa between Hainan and Guangdong. Breeding system and conservation strategy of A. spinulosa was discussed based on the information of population genetic structure and variation.

Base Composition↗

PubMed2006

'Ovar-Mhc' - ovine major histocompatibility complex: structure and gene polymorphisms.

The major histocompatibility complex (MHC) in sheep, Ovar-Mhc, is poorly characterised, when compared to other domestic animals. However, its basic structure is similar to that of other mammals, comprising class I, II and III regions. Currently, there is evidence for the existence of four class I loci. The class II region is better characterised, with evidence of one DRA, four DRB (one coding and three non-coding), one DQA1, two DQA2, and one each of the DQB1, DQB2, DNA, DOB, DYA, DYB, DMA, and DMB genes in the region. The class III region is the least characterised, with the known presence of complement cascade (C4, C2 and Bf), TNFalpha and CYP21 genes. Products of the class I and II genes, MHC molecules, play a pivotal role in antigen presentation required for eliciting immune responses against invading pathogens. Several studies have focused on polymorphisms of Ovar-Mhc genes and their association with disease resistance. However, more research emphasis is needed on characterising the remaining Ovar-Mhc genes and developing simplified and cost-effective methods to score gene polymorphisms. Haplotype screening, employing multiple markers rather than single genes, would be more meaningful in MHC-disease association studies, as it is well known that most of the MHC loci are tightly linked, exhibiting very little recombination. This review summarises the current knowledge of the structure of Ovar-Mhc and polymorphisms of genes located in the complex.

Animals↗

PubMed2007

Local-scale genetic structure in the peatmoss Sphagnum fuscum.

Sphagnum (peatmoss) dominates huge areas of the Northern Hemisphere and acts as a significant carbon sink on a global scale, yet little is known about the genetic structure of Sphagnum populations. We investigated genetic structure within a population of the common peatmoss Sphagnum fuscum, to assess local patterns of genetic diversity and the spatial extent of clones. One hundred seventeen shoots were sampled from five transects in Fuglmyra, central Norway, and sequenced for three anonymous DNA regions. Five neighbourhood patches were marked along each transect, and from each patch, five stems were sampled for molecular analyses. Seventeen haplotypes could be distinguished and two major groups of haplotypes differed by 12 mutational steps. The two major haplotype groups differed significantly in microhabitat association along the distance to groundwater table and the pH gradients, indicating microhabitat differentiation. The haplotypes within these groups were all genetically similar, differing by one or two mutations. The most common haplotype occurred in four transects separated by 250-m distance. Most of the molecular variation in the population was found among transects, and within patches. Large dominating clones within each transect resulted in low variation explained by the among-patch-within-transect component of spatial structure. Mutation appears to account for a larger proportion of the population variation than recombination. Within the population, vegetative growth and asexual reproduction from gametophyte fragments dominate as the main reproductive mode.

Analysis of Variance↗

PubMed2004

Pleistocene glaciation is implicated in the phylogeographical structure of Potamopyrgus antipodarum, a New Zealand snail.

Pleistocene glaciation has been identified as an important factor shaping present-day patterns of phylogeographical structure in a diverse array of taxa. The purpose of this study was to use mitochondrial sequence data to address whether Pleistocene glaciation is also a major determinant of phylogeographical patterns in Potamopyrgus antipodarum, a freshwater snail native to New Zealand. We found that haplotypes were separated by no more than 3.7% sequence divergence, and major genetic divisions tended to occur on a north-south axis. These data fit the predictions of the hypothesis that isolation of P. antipodarum in glacial refugia at the northern and southern tip of the South Island of New Zealand during the Pleistocene glaciation underlies the present-day phylogeographical structure. Because sexual P. antipodarum occasionally produce asexual offspring, we also used these data to show that the appearance of asexuality is not phylogeographically constrained. This means that the maintenance of sex in P. antipodarum cannot be wholly due to limited contact between sexual and asexual lineages and must instead be linked to a selective advantage of sexual reproduction.

Analysis of Variance↗

PubMed1994

Structural and immunologic analysis of gene triplications in the Ig heavy chain constant region locus.

The Ig H chain C region is a multigene family often involved in genomic rearrangements leading to deleted and duplicated haplotypes, most probably through unequal crossing over between homologous regions within the locus. The frequency of these haplotypes in Italy is around 2.7% each. Using PFGE analysis in two unrelated Italian families we found an abnormal high m.w. band, inherited in a Mendelian fashion. To assess the extension of the haplotype we performed Southern blot analysis using several specific Ig H chain C probes. In both cases, the haplotype turned out to be triplicated, with three copies of the genes from A1 to E. In one family segregation of a duplication from EP to G4 was also observed. Analysis of polymorphic loci suggests that the two triplications are of independent origin. Serological detection of IgA2 allotypes demonstrated the functional activity of the genes at the 3' end of the triplicated locus, ruling out any major effect of these large genomic rearrangements on Ig class switching. Furthermore, the triplicated haplotype does not seem to give rise to any clinically significant immunological impairment or increase in Ig serum concentrations.

Gene Deletion↗

PubMed1996

T cell receptor germline gene segments and HLA haplotypes control the length of the CDR3 of human T cell receptor beta chains.

The third complementarity determining region (CDR3) is the most variable part of alpha beta T cell receptors (TCR) and represents the putative antigen contacting site. To identify parameters determining the structural diversity of the CDR3 region, the CDR3 length distributions of 66 BV-J combinations in peripheral CD4+ T cells (6 BV and ll BJ gene segments) of 12 unrelated individuals were analyzed. The median CDR3 length ranged from 8 to 12.5 amino acids and was partially determined by the usage of the BV and BJ gene segment. Beyond the influence of germline-encoded TCR gene segments, donors expressed an individual pattern of preferred CDR3 size classes. To identify mechanisms determining this individual pattern, 17 first-degree relatives from five families were studied. CDR3 length profiles were shared by some but not all relatives. Sharing of CDR3 length profiles correlated with the inheritance of both HLA-DR haplotypes. These data suggest that the length of the TCR beta chain is selected and that restrictions on the diversity of the CDR3 length are imposed by germline-encoded TCR gene segments as well as by major histocompatibility complex-dependent mechanisms.

Base Sequence↗