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Results for “Haplotype structures”

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PubMed1995

Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein.

Mannan-binding protein (MBP) is a serum lectin participating in the innate immune defense by opsonizing various microorganisms for phagocytosis. Opsonization defect due to MBP deficiency and low levels of the protein can partially be explained by the dominant effect of three different mutations in the structural part of the MBP gene. Large interracial differences in the frequencies of these variants have previously been described, but they cannot explain the large interindividual variation in MBP serum concentration. We describe the existence of additional polymorphisms at positions -550 (H/L variants) and -221 (X/Y variants) in the promoter region of the gene. The promoter haplotypes, HY, LY, and LX, show associations with high, medium, and low levels of MBP serum concentrations, respectively. Moreover, this represents a genetic system with additive effect of haplotypes in which a low producing LX haplotype in the homozygous state down-regulates the basal expression of MBP as effectively as a single structural variant. Populations of pure Eskimos, Caucasoids, and black Africans show marked interethnic differences in the frequencies of promoter haplotypes regulating the expression of the normal peptide, with the HY haplotype frequency varying from 0.83 in Eskimos via 0.33 in Caucasoids to 0.08 in Africans. The LY haplotype frequency varies from 0.04 in Eskimos via 0.39 in Caucasoids to 0.23 in Africans. The LX haplotype frequency varies from 0.03 in Eskimos via 0.24 in Caucasoids to 0.23 in Africans. The effect of the promoter variants can explain almost all of the ethnic differences not explainable by the structural variants alone.

Base Sequence↗

PubMed1987

Epitopes associated with MHC restriction site of T cells. III. I-J epitope on MHC-restricted T helper cells.

I-J epitopes were found to be associated with the functional site of the class II MHC-restricted helper T (Th) cells: Virtually all of the H-2k-restricted Th cell function of H-2kxbF1 T cells was inhibited by the anti-I-Jk mAb, leaving the H-2b-restricted function unaffected. The I-Jk epitope was inducible in Th cells of different genotype origin according to the environmental class II antigens present in the early ontogeny of T cells. Although above results suggested that I-J is the structure reflecting the inducible MHC restriction specificity, further studies revealed some interesting controversies: First, the I-J phenotype did not always correlate with the class II restriction specificity, e.g., I-Ab-restricted Th from 5R was I-Jk-positive, whereas I-Ak-restricted Th of 4R was not. Second, there was no trans expression of parental I-J phenotypes and restriction specificities in F1 Th, e.g., the I-J phenotype was detected only on I-Ab-restricted Th of (4R X 5R)F1, whereas it was absent on I-Ak-restricted Th. This strict linkage between the restriction specificity and I-J phenotype was also found on Th cells developed in bone marrow chimera constructed with intra-H-2-recombinant mice. The expression of I-Jk was always associated with the restriction specificity of the relevant host. Thus, the restriction specificity of Th cells followed the host type, and the I-J expression on Th was exactly the same as that expressed by the host haplotype. These results indicate that I-J is an isomorphic structure adaptively expressed on Th cells that is involved in the unidirectional regulatory cell interactions, and that the polymorphism cannot be explained merely by the restriction specificity of the conventional T cell receptor heterodimer.

Animals↗

PubMed2002

Distribution of TAP gene polymorphisms and extended MHC haplotypes in Mexican Mestizos and in Seri Indians from northwest Mexico.

The study of the genetic structure is very useful for investigating the biological significance of polymorphism and may provide clues to understand population origins. We present TAP1/TAP2 gene analysis in the Seri indians from Sonora, and in Mestizos from the highlands of Mexico. Thirty-two Seri and 89 Mestizos were studied. TAP genes were typed using the ARMS-PCR technique. The most frequent alleles in Seri were: TAP1*0101/02, (68.8%); TAP1*02011/02012, (31.2%); TAP2*0201, (38.7%) and TAP2*0101, (29.0%). TAP1*0301, TAP1*0401, TAP2*0102 TAP2*0103 and TAP2H were absent in them. For Mestizos, the prevalent alleles were: TAP1*0101/02 (75.8%); TAP1*02011/12 (20.3%); TAP2*0101 (45.4%) and TAP2*0201 (29.3%). These results are similar to those found in Kaingang and Caucasians from Brazil, four Mediterranean, other Caucasians, two Oriental and one African group. In Seri, the extended prevalent haplotypes are typically Amerindian, such as TAP1*0101/2-TAP2*0201-QBP3.21-DQB1*0302-QAP*3.1-DQA1*03011-DRB1*0407-B*3501-A*0201 (HF = 16.6%). Thirty-two extended haplotypes were found in Seri, although TAP contributed scarcely to diversity. Mestizos show Amerindian and Caucasian combinations. No difference was detected in the distribution of amino acids in the individual variable sites, between both groups. These findings are the basis for further anthropological studies and to explore the contribution of TAP genes to disease expression in Mexicans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study.

UNLABELLED: After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. CONCLUSIONS: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis.

Aged↗

PubMed1994

Low, but strongly structured mitochondrial DNA diversity in root knot nematodes (Meloidogyne).

Root-knot nematodes (genus Meloidogyne) have been the subject of recent and numerous studies of genetic variation because of the need to develop molecular diagnostics for the four globally distributed, parthenogenetic species that are significant agricultural pests. Our analysis of Meloidogyne mtDNA improves on previous studies: (i) by examining restriction site polymorphism among a large number of isolates also characterized for standard morphological, host range and allozyme phenotypes; (ii) by using higher resolution electrophoretic techniques; and (iii) by mapping variable restriction sites with reference to the complete nucleotide sequence. This revealed fivefold less sequence divergence (< 0.6%) between variants than estimated in previous restriction fragment length polymorphism (RFLP) studies, but perfect correspondence between mtDNA haplotype and allozyme (esterase) phenotypes. The mtDNA variation, although limited, is strongly structured with as much divergence between two lineages of Meloidogyne arenaria as between either of these and Meloidogyne javanica. The low diversity of mtDNAs suggests that these parthenogenetic lineages arose from distinct but closely related sexual females, a pattern seen in other parthenogenetic complexes. In contrast to the concordance between mtDNA and allozyme markers, there were several discrepancies between the traditional methods of identification. We suggest that further studies of these nematodes should focus on well defined genetic groups, whether or not these coincide with existing taxonomic units.

Animals↗

PubMed2006

Mitochondrial DNA analyses of the Cape hakes reveal an expanding, panmictic population for Merluccius capensis and population structuring for mature fish in Merluccius paradoxus.

The Cape hake species, Merluccius capensis and Merluccius paradoxus are the most important resource of the South African and Namibian demersal fishery, but it is unclear whether there is a single population of each shared by both countries. We analysed the population structure and evolutionary history of these two species using the variable 5' region of the mtDNA control region for 311 specimens of M. capensis and 333 specimens of M. paradoxus sampled between Lüderitz (southern Namibia) to south of Cape Point (South Africa). 107 haplotypes for M. capensis and eight haplotypes for M. paradoxus were recovered. AMOVA and pairwise Phi(st) analyses revealed no structure in M. capensis, however significant genetic differentiation between Namibian and South African 'populations' was detected for M. paradoxus. This was only restricted to mature fish older than 3 and 4 years and not for juvenile fish younger than 3 years. Analyses reveal that M. capensis has undergone population expansion (Fu's Fs=-26.65, P<0.001), possibly within the last 4500-23,000 years, whereas M. paradoxus has not. Our study highlights the utility of genetic markers to unravel the evolutionary history of sympatric species, as well as addressing management issues within regions where commercially valuable fish stocks are shared between nations.

Animals↗

PubMed2006

Molecular-based haplotype analysis of the beta 2-adrenergic receptor gene (ADRB2) in Japanese asthmatic and non-asthmatic subjects.

BACKGROUND: The beta2-adrenergic receptor gene (ADRB2) is a target molecule of beta2-agonists. Single nucleotide polymorphisms (SNPs) in the ADRB2 are related to the effectiveness of beta2-agonists. However, there are some discrepancies in the results of pharmacogenetic studies of ADRB2 among different ethnic groups. The aims of this study were to determine the ADRB2 haplotypes and diplotypes in Japanese asthmatic and non-asthmatic subjects and to examine their relation to asthma and to compare these results with previous studies done in other ethnic groups. METHODS: Complete sequences for 3 kb promoter and 1.2 kb structural regions of ADRB2 were analyzed in 48 Japanese asthmatics and 100 controls, and haplotypes and diplotypes of SNPs were analyzed. RESULTS: Fifteen SNPs including a novel one in -839 were observed. Allele frequencies for all SNPs were similar between asthmatics and controls. We also identified 42 haplotypes and 54 diplotypes of ADRB2 in a Japanese population. The frequencies were similar between the two groups. They were classified into 17 and 23 types, respectively, according to Drysdale's haplotype-organization system, and a significant ethnic difference was observed between the Japanese and Caucasian populations. CONCLUSIONS: The frequencies of SNPs and ADBR2 haplotypes in Japanese are different from those in Caucasians and African Americans. These divergences might imply the need for independent pharmacogenetic studies for ADBR2 in each ethnic group.

Black or African American↗

PubMed2005

Mitochondrial phylogeography and subspecific variation in the red panda (Ailurus fulgens): implications for conservation.

The red panda (Ailurus fulgens) is an endangered species and its present distribution is restricted to isolated mountain ranges in western China (Sichuan, Yunnan, and Tibet provinces) and the Himalayan Mountains chain of Nepal, India, Bhutan, and Burma. To examine the evolutionary history across its current range, and to assess the genetic divergence among current subspecies and population structure among different geographic locations, we sequenced mitochondrial DNA from the control region (CR) and cytochrome (cyt) b gene for 41 individuals in Sichuan, Yunnan, Tibet of China, and Burma. 25 CR haplotypes (10 for cyt b) were identified from 11 geographic locations. Only three haplotypes were shared among sample localities, including one among current subspecies. Nine haplotypes were shared with the study of Su et al. [Mol. Biol. Evol. 18 (2001) 1070]. CR haplotype diversity was high (0.95+/-0.02) and nucleotide diversity among all haplotypes was relatively low (0.018+/-0.009). Phylogenetic confirmed trees show a shallow pattern with very little structure or statistical robustness. The application of two coalescent-based tests for population growth allowed us to interpret this phylogeny as the result of a recent population expansion. Analysis of molecular variance and nested clade analysis failed to detect significant geographic structure in both data sets. The lack of significant differentiation between subspecies does not indicate the presence of evolutionary significant units. We suggest that the present population structure has resulted from habitat fragmentation and expansion from glacial refugia. Due to its habitat requirements it is likely that the red panda has undergone bottlenecks and population expansions several times in the recent past. The present population may exhibit a pattern reminiscent of a relatively recent population expansion.

Animals↗

PubMed1989

Quantitative variation of C4 variant proteins associated with many MHC haplotypes.

C4 protein variants were analyzed in 64 individuals, of which 51 were either homozygous or heterozygous for an extended major histocompatibility complex (MHC) haplotype (a fixed combination of MHC alleles). The relative amount of each C4 variant was measured by densitometric scanning of stained immunofixed electrophoretic patterns of neuraminidase- and carboxypeptidase-treated samples. The relative concentrations of C4 variants on any haplotype were stable and inherited in families. In five of the eight extended haplotypes investigated, the amount of one of the C4 variants relative to others in the same pattern was increased: [HLA-B8, SC01, DR3] and [HLA-B7, SC31, DR2] produced an approximately doubled amount of C4B1; [HLA-B18, S042, DR2] an increased amount of C4B2; and [HLA-B44, SC30, DR4] a double amount of C4A3. The extended haplotype [HLA-Bw57, SC61, DR7] gave rise to two to three times as much C4B1 as C4A6. In the extended haplotypes [HLA-B44, FC31, DR7] and [HLA-Bw62, SC33, DR4], the results did not clearly indicate differences in expression of the C4 isotypes. DNA analysis possibly supported an actual gene duplication only for the haplotype [HLA-B7, SC31, DR2]. The results suggest that, in addition to variation in the number of structural genes, other MHC-linked mechanisms may be involved in the regulation of the relative amounts of C4A or C4B protein specified by any haplotype.

Complement C4↗

PubMed1998

Structural motifs in rheumatoid T-cell receptors.

The linkage of rheumatoid arthritis (RA) to HLA-DR haplotypes, high levels of HLA-DR expression, and T-cell infiltration in the joints, indicate a central role for the interaction of T-cell receptors (TCR) with antigen (Ag) + major histocompatibility complex (MHC) complexes in pathogenesis. Receptor analysis in RA has uncovered a restricted heterogeneity of TCR transcripts, suggesting an antigen-driven response. We analyzed the sequence and structural features of RA-associated TCRs in light of the recently published TCR crystal structures. The surface-exposed residues of the third complementarity-determining region (CDR3s) showed preferential use of certain amino acid residues when sequences derived from synovial fluid or tissue were compared with those derived from peripheral blood, particularly for alpha chains. Sequence alignment of oligoclonal synovial TCR CDR3s revealed groupings with similar CDR3 lengths and amino acid compositions, which suggests shared antigen recognition. Given the limitations of analyzing TCR sequences without knowing their structures, we developed several in vivo-activated synovial-tissue Vbeta17 + RA T-cell clones. Two Vbeta17/V alpha7 clones with different CDR3 sequences were analyzed by molecular modeling. Although distinct topologic features were seen, a central patch of residues with similar chemical and geometric characteristics was present in both. Electrostatic maps revealed similar binding surfaces of both alpha domains and central patches, with differences in the beta domains. This suggests that an alpha-domain-focused binding trajectory would allow shared antigen recognition by these TCRs. These studies support recognition of a limited diversity of Ag + MHC complexes by synovial RA TCRs.

Amino Acid Sequence↗

PubMed2006

Doubly uniparental inheritance is associated with high polymorphism for rearranged and recombinant control region haplotypes in Baltic Mytilus trossulus.

Many bivalve species, including mussels of the genus Mytilus, are unusual in having two mtDNA genomes, one inherited maternally (the F genome) and the other inherited paternally (the M genome). The sequence differences between the genomes are usually great, indicating ancient divergence predating speciation events. However, in Mytilus trossulus from the Baltic, both genomes are similar to the F genome from the closely related M. edulis. This study analyzed the mtDNA control region structure in male and female Baltic M. trossulus mussels. We show that a great diversity of structural rearrangements is present in both sexes. Sperm samples are dominated by recombinant haplotypes with M. edulis M-like control region segments, some having large duplications. By contrast, the rearranged haplotypes that dominate in eggs lack segments from this M genome. The rearrangements can be explained by a combination of tandem duplication, deletion, and intermolecular recombination. An evolutionary pathway leading to the recombinant haplotypes is suggested. The data are also considered in relation to the hypothesis that the M. edulis M-like control region sequence is necessary to confer the paternal role on genomes that are otherwise F-like.

Animals↗

PubMedDate not supplied

Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheumatoid arthritis susceptibility.

OBJECTIVES: The CARD15/NOD2 gene product plays an important role in host response to bacterial lipopolysaccharides and bacterial muramyl dipeptide via activation of NF-kappaB in monocytes. Mutations in CARD15 are associated with Crohn's disease (CD), a chronic inflammatory bowel disease. In this study we sought to determine whether CD-associated mutations or any common variants of this gene might contribute to susceptibility to another chronic inflammatory disease, rheumatoid arthritis (RA). METHODS: We genotyped 376 Caucasian RA cases and 376 ethnically matched healthy controls for three CD-associated CARD15 mutations. We also genotyped these 752 individuals for 12 common CARD15 single nucleotide polymorphisms (SNPs), determined the linkage disequilibrium structure of the gene, and compared the frequencies of the common CARD15 haplotypes in the RA cases and controls. RESULTS: None of the CD-associated mutations or the CARD15 SNPs was associated with susceptibility to RA. We also found no significant difference in the frequencies of any of the common haplotypes of the CARD15 gene in RA patients and controls. Our haplotype analysis was consistent with earlier observations that all three CD-associated variants independently arose on the same ancestral haplotype. CONCLUSIONS: These data suggest that CARD15 variants are not associated with RA susceptibility.

Adolescent↗

PubMed2005

Population genetic structure in migratory sandhill cranes and the role of Pleistocene glaciations.

Previous studies of migratory sandhill cranes (Grus canadensis) have made significant progress explaining evolution of this group at the species scale, but have been unsuccessful in explaining the geographically partitioned variation in morphology seen on the population scale. The objectives of this study were to assess the population structure and gene flow patterns among migratory sandhill cranes using microsatellite DNA genotypes and mitochondrial DNA haplotypes of a large sample of individuals across three populations. In particular, we were interested in evaluating the roles of Pleistocene glaciation events and postglaciation gene flow in shaping the present-day population structure. Our results indicate substantial gene flow across regions of the Midcontinental population that are geographically adjacent, suggesting that gene flow for most of the region follows an isolation-by-distance model. Male-mediated gene flow and strong female philopatry may explain the differing patterns of nuclear and mitochondrial variation. Taken in context with precise geographical information on breeding locations, the morphologic and microsatellite DNA variation shows a gradation from the Arctic-nesting subspecies G. c. canadensis to the nonArctic subspecies G. c. tabida. Analogous to other Arctic-nesting birds, it is probable that the population structure seen in Midcontinental sandhill cranes reflects the result of postglacial secondary contact. Our data suggest that subspecies of migratory sandhills experience significant gene flow and therefore do not represent distinct and independent genetic entities.

Animal Migration↗

PubMed1995

Permissive recognition of a mycobacterial T-cell epitope: localization of overlapping epitope core sequences recognized in association with multiple major histocompatibility complex class II I-A molecules.

Most T-cell epitopes are recognized in the context of a single or limited number of major histocompatibility complex (MHC) class II molecules. We have shown previously, however, that the immunodominant p61-80 epitope from the Mycobacterium tuberculosis 19,000 MW protein is recognized in a genetically permissive manner. In this study, permissive recognition of p61-80 was analysed in three murine MHC haplotypes (H-2b,d and k) with respect to: (i) T-cell-epitope core structure; (ii) I-A/I-E class II MHC restriction; and (iii) the identification of critical amino acid residues within the core region. Overlapping epitope core sequences composed of 6 to 8 amino acids were identified for each of the three H-2 haplotypes by T-cell epitope scanning (PEPSCAN) using peptide-specific T-cell lines. The epitope core sequences recognized by peptide and 19,000 MW protein-specific T cells were similar. In all three haplotypes, responses to p61-80 were restricted by class II MHC I-A molecules. To identify residues within the epitope core critically required for recognition, single substitution (alanine or leucine) analogue peptides were tested for their capacity to stimulate p61-80-specific T-cell hybridomas. A heterogeneous pattern of reactivity was observed, even among individual hybridomas derived from the same H-2 haplotype. Although every core residue could be defined as critical for at least one hybridoma, only one critical substitution (74Val-->Ala) was common to all hybridomas. The identification and structural analysis of genetically permissive epitopes of mycobacteria may be a useful strategy for the rational design of peptide-based vaccines for tuberculosis.

Amino Acid Sequence↗

PubMed2005

Mitochondrial DNA variation in Chinese and Indian rhesus macaques (Macaca mulatta).

DNA was extracted from the buffy coats or serum of 212 rhesus macaques (Macaca mulatta) sampled throughout the species' geographic range. An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was amplified from each sample, sequenced, aligned, and used to estimate genetic distances from which phylogenetic trees were constructed. A tree that included sequences from rhesus macaques whose exact origins in China are known was used to determine the regional origin of clusters of haplotypes, or haplogroups, defined by the trees. Indian rhesus sequences formed one large homogeneous haplogroup with very low levels of nucleotide diversity and no geographic structure, and a second much smaller haplogroup apparently derived from Burma. The sequences from Burma and eastern and western China were quite divergent from those in the major haplogroup of India. Each of these sequences formed separate clusters of haplotypes that exhibited far greater nucleotide diversity and/or population structure. Correspondingly, sequences from Indian rhesus macaques that are considered to represent different subspecies (based on morphological differences) were intermingled in the tree, while those from China reflected some, but not all, aspects of subspecific taxonomy. Regional variation contributed 72% toward the paired differences between sequences in an analysis of molecular variance (AMOVA), and the average differences between the populations of eastern and western China were also statistically significant. These results suggest that Indian and Chinese rhesus macaques were reproductively isolated during most, if not all, of the Pleistocene, during which time Indian rhesus macaques experienced a severe genetic bottleneck, and that some gene flow westward into India was subsequently reestablished. Samples from breeding centers in three different provinces of China included sequences from rhesus macaques that originated in both eastern (or southern) and western China, confirming anecdotal reports that regional breeding centers in China exchange breeding stock. Genetic differences among rhesus macaques (even those acquired from the same regional breeding center) that originate in different geographic regions and are employed as subjects in biomedical experiments can contribute to phenotypic differences in the traits under study.

Animals↗

PubMed2006

Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants.

Flavin-containing monooxygenases (FMOs) are important for the disposition of many therapeutics, environmental toxicants, and nutrients. FMO3, the major adult hepatic FMO enzyme, exhibits significant interindividual variation. Eighteen FMO3 single-nucleotide polymorphism (SNP) frequencies were determined in 202 Hispanics (Mexican descent), 201 African Americans, and 200 non-Latino whites. Using expressed recombinant enzyme with methimazole, trimethylamine, sulindac, and ethylenethiourea, the novel structural variants FMO3 E24D and K416N were shown to cause modest changes in catalytic efficiency, whereas a third novel variant, FMO3 N61K, was essentially devoid of activity. The latter variant was present at an allelic frequency of 5.2% in non-Latino whites and 3.5% in African Americans, but it was absent in Hispanics. Inferring haplotypes using PHASE, version 2.1, the greatest haplotype diversity was observed in African Americans followed by non-Latino whites and Hispanics. Haplotype 2A and 2B, consisting of a hypermorphic promoter SNP cluster (-2650C>G, -2543T>A, and -2177G>C) in linkage with synonymous structural variants was inferred at a frequency of 27% in the Hispanic population, but only 5% in non-Latino whites and African Americans. This same promoter SNP cluster in linkage with one or more hypomorphic structural variant also was inferred in multiple haplotypes at a total frequency of 5.6% in the African-American study group but less than 1% in the other two groups. The sum frequencies of the hypomorphic haplotypes H3 [15,167G>A (E158K)], H5B [-2650C>G, 15,167G>A (E158K), 21,375C>T (N285N), 21,443A>G (E308G)], and H6 [15,167G>A (E158K), 21,375C>T (N285N)] was 28% in Hispanics, 23% in non-Latino whites, and 24% in African Americans.

Black or African American↗

PubMed2006

The D category VI type 4 allele is prevalent in the Spanish population.

BACKGROUND: The D category VI (DVI) is one of the clinically most important partial D. Three different molecular structures causing the DVI phenotype have been described. STUDY DESIGN AND METHODS: To determine the molecular basis of the DVI phenotype in the Spanish population, 20 DVI samples, previously detected in serologic screening, were examined by polymerase chain reaction with RHD exon-specific primers. Unexpected findings were further pursued by cDNA nucleotide sequencing. RESULTS: A novel pattern of RHD exon amplification was detected, which did not correspond to any of the previously described molecular structures. The cDNA sequence led to the identification of the new hybrid RHD-Ce(3-5)-D allele. The origin of exon 2 is undeterminable, because the 5' breakpoint was located within a region of RHD and RHCE identical sequence, which encompasses this exon. Sequencing of intron 5 allowed the 3' breakpoint to be mapped between the sixth and seventh polymorphic sites. Serologically, the hybrid protein has a D epitope expression pattern identical to the previously described DVI phenotypes and an antigen density slightly lower than DVI type 3. The new DVI variant is linked to the DCe haplotype and expresses the low-incidence BARC antigen. CONCLUSION: A novel structure causing the DVI phenotype, here named DVI type 4, has been characterized. This novel structure is the most frequent cause of DVI in Spain.

Base Sequence↗

PubMed2003

Evolution of the hominoid semenogelin genes, the major proteins of ejaculated semen.

The hominoid primates (apes and humans) exhibit remarkable diversity in their social and sexual behavioral systems. This is reflected in many ways in their anatomy and physiology. For example, the testes and seminal vesicles are relatively large in species with high sperm competition like the chimpanzee and small in species with low or no sperm competition like the gorilla. Additionally, the chimpanzee is the only hominoid primate known to produce a firm copulatory plug, which presumably functions in sperm competition by blocking insemination of subsequent males. Here we examine the molecular evolution of the semenogelin genes (SEMG1 and SEMG2), which code for the predominant structural proteins in human semen. High molecular weight complexes of these proteins are responsible for the viscous gelatinous consistency of human semen; their rodent homologs are responsible for the formation of a firm copulatory plug. Chimpanzees have an expanded SEMG1 gene caused by duplications of tandem repeats, each encoding 60 amino acids, resulting in a protein nearly twice as long as that of humans. In contrast, at both SEMG1 and SEMG2 we observed several gorilla haplotypes that contain at least one premature stop codon. We suggest that these structural changes in the semenogelin proteins that have arisen since the human-chimpanzee-gorilla split may be responsible for the physiological differences between these species ejaculated semen that correlate with their sociosexual behavior.

Animals↗