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Results for “Haplotype structures”

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PubMed2004

Nuclear-cytoplasmic male-sterility in diploid dandelions.

Male-sterility was found in diploid dandelions from two widely separated populations from France, and its inheritance was analysed by crossing a diploid male-sterile dandelion to diploid sexuals and triploid apomicts. Nuclear genetic variation, found in full-sib families, segregated for male-fertility, partial male-sterility, and full male-sterility, and also segregated for small-sized versus normally sized pollen. The crossing results are best explained by a cytoplasmic male-sterility factor in combination with two dominant restorer genes. Involvement of the cytoplasmic male-sterility factor was further investigated by chloroplast haplotyping. Male-sterility was exclusively associated with a rare chloroplast haplotype (designated 16b). This haplotype was found in seven male-sterile plants and one (apparently restored) male-fertile individual but does not occur in 110 co-existing male-fertile plants and not in several hundreds of individuals previously haplotyped. Apomicts with cytoplasmic male sterility were generated in some test crosses. This raises the question as to whether the male sterility found in natural dandelion apomicts, is of cytoplasmic or of nuclear genetic nature. As many breeding systems in Taraxacum are involved in shaping population structure, it will be difficult to predict the evolutionary consequences of nuclear-cytoplasmic male-sterility for this species complex.

Cell Nucleus↗

PubMed1999

Genetic homogeneity, high-resolution mapping, and mutation analysis of the urofacial (Ochoa) syndrome and exclusion of the glutamate oxaloacetate transaminase gene (GOT1) in the critical region as the disease gene.

The urofacial (Ochoa) syndrome (UFS) is a rare autosomal recessive disorder characterized by abnormal facial expression and urinary abnormalities. Previously, we mapped the gene to a genomic interval of approximately 1 cM on chromosome region 10q23-24, using families from Columbia. Here we demonstrate genetic homogeneity of the syndrome through homozygosity mapping in American patients with Irish heritage. We established a physical map and identified novel polymorphic markers in the UFS critical region. Haplotype analysis using the new markers mapped the UFS gene within one YAC clone of 1,410 kb. We also determined the precise location of the gene encoding for glutamate oxaloacetate transaminase (GOT1) within the new UFS critical region and determined its genomic structure. However, mutation analysis excluded GOT1 as a candidate for the UFS gene.

Abnormalities, Multiple↗

PubMed1997

The hemoglobin polymorphism of the Sardinian wild dwarf horse and the oxygen binding properties of the four different horse hemoglobins.

A study was made of the Hb phenotype of the Sardinian dwarfhorse (Equus caballus jara), one of the last surviving wild horse species in Europe. Hb haplotypes and their frequencies were found to be similar to those described in the Arabian horse (BI = 0.551, BII = 0.389, A = 0.036, V = 0.015), which suggests possible introduction onto the island from North Africa. The oxygen binding properties of the whole hemolysates and of the four different horse Hbs, separated by ion-exchange chromatography, were considered with regard to the effect of chloride, 2,3-bisphosphoglycerate and lactate. Results indicate that no differences exist in the four components that characterize horse Hb. The molecular basis of the intrinsically low oxygen affinity and of the weak interaction of horse Hb with 2,3-bisphosphoglycerate is discussed in the light of the primary structure of the molecule.

Animals↗

PubMed2000

Identification of fetal liver tyrosine kinase 3 (flt3) ligand domain required for receptor binding and function using naturally occurring ligand isoforms.

We used a comparative approach to identify the fetal liver tyrosine kinase 3 (flt3) ligand structure required for binding and function. Two conserved bovine flt3 ligand isoforms, which differ in a defined region within the extracellular domain, were identified and shown to be uniformly transcribed in individuals with diverse MHC haplotypes. Notably, at the amino acid level, the extracellular domain of the bovine flt3 ligand isoform 1 is 81 and 72% identical with the extracellular domains of the human and murine flt3 ligands, respectively, whereas isoform-2 has a deletion within this domain. Bovine flt3 ligand isoform 1, but not 2, bound the human flt3 receptor and stimulated murine pro B cells transfected with the murine flt3 receptor. This retention of binding and function allowed definition of key residues by identifying sequences conserved among species. We have shown that a highly conserved, 18 aa sequence within the flt3 ligand extracellular domain is required for flt3 receptor binding and function. However, a peptide representing this sequence is insufficient for receptor binding as demonstrated by its failure to inhibit the bovine flt3 ligand isoform 1 binding to the human flt3 receptor. The requirement for flanking structure was confirmed by testing bovine flt3 ligand isoform 1 constructs truncated at specific residues outside the 18 aa sequence. Overall, the flt3 ligand structure required for function is markedly similar to that of the related hemopoietic growth factors, CSF-1 and steel factor. This definition of the required flt3 ligand structure will facilitate development of agonists to enhance dendritic cell recruitment for vaccines and immunotherapy.

Amino Acid Sequence↗

PubMed2005

Spatial diversity in mitochondrial cytochrome c oxidase in house flies.

DNA sequence analysis at mitochondrial gene COI was surveyed in 293 house flies, Musca domestica Linneaus (Diptera: Muscidae), in 29 populations from North, Central and South America, Europe, Asia, Africa, and the Western Pacific. Nei's gene diversity index (H(S)) was 0.47, the chance that two randomly chosen flies have different COI haplotypes. Haplotype diversity was greater in the Old World (H(S) = 0.58) than the New World (H(S) = 0.31). The hierarchical partition of the total diversity indicated substantial differentiation at all levels (G(ST) = 0.30), and highly structured populations. All pairwise estimates of gene flow between zoogeographical regions were less than 0.70 reproducing females per generation. The results are compared to those of a similar study based on the single-strand conformation polymorphism method. Probable colonization scenarios for house flies into the New World are discussed and it is concluded that house flies are a recent addition to the fauna of the Western Hemisphere.

Animals↗

PubMed2005

Multiple testing in the context of haplotype analysis revisited: application to case-control data.

We have lately presented a testing procedure for family data which accounts for the multiple testing problem that is induced by the enormous number of different marker combinations that can be analyzed in a set of tightly linked markers. Most methods of haplotype based association analysis already require simulations to obtain an uncorrected P value for a specific marker combination. As shown before, it is nevertheless not necessary to carry out nested simulations to obtain a global P value that properly corrects for the multiple testing of different marker combinations without neglecting the dependency of the tests. We have now implemented this approach for case-control data in our program FAMHAP, as this data structure currently plays a dominant role in the field. We consider different ways to deal with phase ambiguities and two different statistical tests for the underlying single marker combinations to obtain uncorrected P values. One test statistic is chi-square based, the other is a haplotype trend regression. The performance of these different tests in the multiple testing situation is investigated in a large simulation study. We obtain a considerable gain in power with our global P values as opposed to Bonferroni corrected P values for all suggested test statistics. Good power was obtained both with the haplotype trend regression approach as well as with the simpler chi-square based test. Furthermore, we conclude that the better strategy to deal with phase ambiguities is to assign to each individual its list of weighted haplotype explanations, rather than to assign to each individual its most likely haplotype explanation. Finally, we demonstrate the usefulness of our approach by a real data example.

Algorithms↗

PubMed2005

Non-recombining chromosome Y haplogroups and centromeric HindIII RFLP in relation to blood pressure in 2,743 middle-aged Caucasian men from the UK.

Evidence from rodents and association analyses in humans suggest the presence on chromosome Y of one or more genes affecting blood pressure (BP). The HindIII centromeric alphoid polymorphism has been reported to be associated with BP in three independent human populations, although other studies reported null associations with this trait. Our objective was to test for association between BP and genetic variation of the Y chromosome. To this end, 2,743 unrelated Caucasian men recruited from nine UK practices were analysed for five SNPs (including the HindIII site) and two microsatellites spanning the non-recombining region of the Y chromosome. Systolic and diastolic BP were analysed both as quantitative traits and as categorical variables. Differences between locations were tested. Haplotypic and linkage disequilibrium (LD) analyses were also performed. Overall, no significant association was found between any of the loci analysed and BP, although post hoc analyses suggest a possible relation of specific Y haplogroups to BP. The HindIII polymorphism marks major structural differences in the Y centromere which could influence mitotic loss during ageing, or other somatic events. However, this study does not support a causal effect on BP, although association of one or more Y haplogroups cannot be excluded.

Blood Pressure↗

PubMed2003

Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration.

A primary feature of age-related macular degeneration (AMD) is the presence of extracellular deposits between the retinal pigment epithelium (RPE) and underlying Bruch's membrane, leading to RPE dysfunction, photoreceptor death and severe visual loss. AMD accounts for about 50% of blind registrations in Western countries and is a common, genetically complex disorder. Very little is known regarding its molecular basis. Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder with striking clinical and pathological similarity to AMD. Here we show that L-ORD is genetically heterogeneous and that a proposed founder mutation in the CTRP5 (C1QTNF5) gene, which encodes a novel short-chain collagen, changes a highly conserved serine to arginine (Ser163Arg) in 7/14 L-ORD families and 0/1000 control individuals. The mutation occurs in the gC1q domain of CTRP5 and results in abnormal high molecular weight aggregate formation which may alter its higher-order structure and interactions. These results indicate a novel disease mechanism involving abnormal adhesion between RPE and Bruch's membrane.

Age of Onset↗

PubMed2002

Possible migration routes into South America deduced from mitochondrial DNA studies in Colombian Amerindian populations.

Mitochondrial DNA haplotype studies have been useful in unraveling the origins of Native Americans. Such studies are based on restriction site and intergenic deletion/insertion polymorphisms, which define four main haplotype groups common to Asian and American populations. Several studies have characterized these lineages in North, Central, and South American Amerindian, as well as Na Dene and Aleutian populations. Siberian, Central Asian, and Southeast Asian populations have also been analyzed, in the hope of fully depicting the route(s) of migration between Asia and America. Colombia, a key route of migration between North and South America, has until now not been studied. To resolve the current lack of information about Colombian Amerindian populations, we have investigated the presence of the founder haplogroups in 25 different ethnic groups from all over the country. The present research is part of an interdisciplinary program, Expedición Humana, fostered by the Universidad Javeriana and Dr. J. E. Bernal V. The results show the presence of the four founder A-D Amerindian lineages, with varied distributions in the different populations, as well as the presence of other haplotypes in frequencies ranging from 3% to 26%. These include some unique or private polymorphisms, and also indicate the probable presence of other Asian and a few non-Amerindian lineages. A spatial structure is apparent for haplogroups A and D, and to a lesser extent for haplogroup C. While haplogroup A and D frequencies in Colombian populations from the northwestern side of the Andes resemble those seen in Central American Amerindians more than those seen in South American populations, their frequencies on the southeastern side more closely resemble the bulk of South American frequencies so far reported, raising the question as to whether they reflect more than one migration route into South America. High frequencies of the B lineage are also characteristic of some populations. Our observations may be explained by historical events during the pre-Columbian dispersion of the first settlers and, later, by disruptions caused by the European colonization.

Colombia↗

PubMed2005

A study of mutation rates and the characterisation of intermediate, null and duplicated alleles for 13 Y chromosome STRs.

Previously reported Y chromosome STR haplotype databases for three UK population groups, plus additionally analysed samples, have been scrutinised for the presence of non-standard (intermediate, null and duplicated) alleles. These alleles have been characterised by sequencing, some showing changes in the repeat structure, and the frequencies reported. Mutation rates for each of the 13 STRs have been calculated when analysis of father-son pairs has been possible. An example illustrating the use of non-standard alleles in a large family tree is outlined.

Chromosomes, Human, Y↗

PubMed1996

Analysis of allelic structures at the D7S21 (MS31A) locus in the Japanese, using minisatellite variant repeat mapping by PCR (MVR-PCR).

To sample the diversity of allelic structures at the D7821 (MS31 A) locus in the Japanese, allele-specific minisatellite variant repeat mapping using polymerase chain reaction (MVR-PCR) was performed on genomic DNA from a number of Japanese individuals. Three polymorphic positions in the MS31A 5' flanking DNA were typed from 214 un related Japanese, and the distribution of haplotypes was analysed. Allele-specific MVR-PCR using primers that discriminate between different alleles at these polymorphic positions in heterozygous individuals, allows single alleles to be mapped from genomic DNA in approximately 80% of Japanese. 149 Japanese alleles have been mapped to date and all of them, except for two pairs of indistinguishable alleles, have different internal structures. More than half of the mapped alleles showed similar regions of internal structure to other alleles and were classified into groups on this basis.

Alleles↗

PubMed2000

Context of maternal lineages in the Greater Southwest.

We present mitochondrial haplogroup characterizations of the prehistoric Anasazi of the United States (US) Southwest. These data are part of a long-term project to characterize ancient Great Basin and US Southwest samples for mitochondrial DNA (mtDNA) diversity. Three restriction site polymorphisms (RSPs) and one length polymorphism identify four common Native American matrilines (A, B, C, and D). The Anasazi (n = 27) are shown to have a moderate frequency of haplogroup A (22%), a high frequency of haplogroup B (56%), and a low frequency of C (15%). Haplogroup D has not yet been detected among the Anasazi. In comparison to modern Native American groups from the US Southwest, the Anasazi are shown to have a distribution of haplogroups similar to the frequency pattern exhibited by modern Pueblo groups. A principal component analysis also clusters the Anasazi with some modern (Pueblo) Southwestern populations, and away from other modern (Athapaskan speaking) Southwestern populations. The Anasazi are also shown to have a significantly different distribution of the four haplogroups as compared to the eastern Great Basin Great Salt Lake Fremont (n = 32), although both groups cluster together in a principal component analysis. The context of our data suggests substantial stability within the US Southwest, even in the face of the serious cultural and biological disruption caused by colonization of the region by European settlers. We conclude that although sample numbers are fairly low, ancient DNA (aDNA) data are useful for assessing long-term populational affinities and for discerning regional population structure.

DNA, Mitochondrial↗

PubMed2001

Phylogeography of the yucca moth Tegeticula maculata: the role of historical biogeography in reconciling high genetic structure with limited speciation.

Tegeticula maculata is one of the most ancient and morphologically variable lineages within the yucca moths, yet has apparently undergone little diversification in comparison with much younger yucca moth lineages that have rapidly diversified. A phylogeographic approach was used to determine the number of independent lineages within T. maculata and to examine whether these patterns corresponded with morphological differences between its subspecies maculata and extranea. Phylogenetic analysis of mitochondrial DNA sequence variation indicated that the two subspecies are in separate clades, but there was also an equally deep split within subspecies maculata. There was no evidence for gene flow among regions and there was considerable substructure within clades. The phylogeographic structure of moth populations among and within subspecies can be explained in part by historical biogeographic boundaries and increasingly patchy postglacial distribution of the exclusive host plant, Hesperoyucca whipplei. Local specialization and co-adaptation would be possible in the absence of apparent gene flow, yet gross morphological divergence is limited to the very old split between the subspecies. Sorting of ancient mitochondrial lineages followed by local genetic differentiation may explain the pattern of high genetic structure with limited speciation.

Animals↗

PubMedDate not supplied

A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information.

A general approach to family-based examinations of association between marker alleles and traits is proposed. The approach is based on computing p values by comparing test statistics for association to their conditional distributions given the minimal sufficient statistic under the null hypothesis for the genetic model, sampling plan and population admixture. The approach can be applied with any test statistic, so any kind of phenotype and multi-allelic markers may be examined, and covariates may be included in analyses. By virtue of the conditioning, the approach results in correct type I error probabilities regardless of population admixture, the true genetic model and the sampling strategy. An algorithm for computing the conditional distributions is described, and the results of the algorithm for configurations of nuclear families are presented. The algorithm is applicable with all pedigree structures and all patterns of missing marker allele information.

Algorithms↗

PubMed2004

Mitochondrial gene diversity in the common vole Microtus arvalis shaped by historical divergence and local adaptations.

The phylogeography of the common vole (Microtus arvalis) was examined by analysing mitochondrial DNA (mtDNA) sequence variation in 1044 base pairs (bp) of the cytochrome b (cytb) gene and in 322 bp of the control region (ctr) among 106 individuals from 58 locations. The geographical distribution of four previously recognized cytb evolutionary lineages in Europe was refined and a new lineage was found in southern Germany. All lineages were distributed allopatrically, except in one sample that was probably located in a contact zone. The occurrence of several lineages in the Alps is in keeping with their recent recolonization from distinct sources. The translation of 84 cytb DNA sequences produced 33 distinct proteins with relationships that differed from those of the DNA haplotypes, suggesting that the mtDNA lineages did not diverge in response to selection. In comparison with M. agrestis, a neutrality test detected no overall evidence for selection in the cytb gene, but a closer examination of a structural model showed that evolutionarily conserved and functionally important positions were often affected. A new phylogeographical test of random accumulation of nonsynonymous mutations generated significant results in three lineages. We therefore conclude that the molecular diversity of cytb in M. arvalis is overall the result of the demographic history of the populations, but that there have been several episodes of local adaptation to peculiar environments.

Adaptation, Biological↗

PubMed2004

The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis.

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon-Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early-onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 micro moles/mg/min vs. 1,678.7 +/- SD 527.2 micro moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS.

Adult↗

PubMed2002

Association of MHC class I and class II gene polymorphisms with vaccine or challenge response to Salmonella enteritidis in young chicks.

Salmonella enteritidis (SE) is a worldwide source of salmonellosis in humans, caused mainly by consumption of contaminated poultry products. The major histocompatibility complex (MHC) class I and class II molecules, which function as antigen-presentation structures, are involved in both macrophage and dendritic cell immune response to Salmonella and may, therefore, play an important role in host resistance to infections. The chicken MHC class I and class II were investigated as candidate genes for immune response to SE. We characterized the complete MHC class I cDNA sequences for an outbred broiler line and four diverse highly inbred lines: two MHC-congenic Leghorn (G-B2 and G-B1), one Egyptian Fayoumi (M15.2), and one Spanish (Sp21.1), to define the allelic sequences within these lines, so that we might study the association between particular MHC polymorphisms and response to SE. The F1 offspring of outbred broiler sires crossed with three inbred lines (G-B1, G-B2, and Fayoumi) were evaluated as young chicks for either bacterial load in spleen and cecum after pathogenic SE inoculation or antibody level after SE vaccination. Alleles defined by a Lys(148)-->Met(148) polymorphism in the MHC class I alpha(2) domain were associated with spleen bacterial load after SE challenge. These results suggest that particular MHC haplotypes may contribute to control of responses to SE, and that particular polymorphisms may serve as markers for genetic resistance to SE in the chicken.

Animals↗

PubMed2003

Mitochondrial DNA sequence-based population genetic structure of the firefly, Pyrocoelia rufa (Coleoptera: Lampyridae).

The genetic divergence, population genetic structure, and possible speciation of the Korean firefly, Pyrocoelia rufa, were investigated on the midsouthern Korean mainland, coastal islets, a remote offshore island, Jedu-do, and Tsushima Island in Japan. Analysis of DNA sequences from the mitochondrial COI protein-coding gene revealed 20 mtDNA-sequence-based haplotypes with a maximum divergence of 5.5%. Phylogenetic analyses using PAUP, PHYLIP, and networks subdivided the P. rufa into two clades (termed clade A and B) and the minimum nucleotide divergence between them was 3.7%. Clade A occurred throughout the Korean mainland and the coastal islets and Tsushima Island in Japan, whereas clade B was exclusively found on Jeju-do Island. In the analysis of the population genetic structure, clade B formed an independent phylogeographic group, but clade A was further subdivided into three groups: two covering western and eastern parts of the Korean peninsula, respectively, and the other occupying one eastern coastal islet and Japanese Tsushima Island. Considering both phylogeny and population structure of P. rufa, the Jeju-do Island population is obviously differentiated from other P. rufa populations, but the Tsushima Island population was a subset of the Korean coastal islet, Geoje. We interpreted the isolation of the Jeju-do population and the grouping of Tsushima Island with Korean coastal islets in terms of Late Pleistocene-Holocene events. The eastern-western subdivision on the Korean mainland was interpreted partially by the presence of a large major mountain range, which bisects the midpart of the Korean peninsula into western and eastern parts.

Animals↗