Alternative titles; symbols. Cytogenetic location: 1p Le Van Kim et al. They found that the predicted translation product is a amino acid protein of molecular mass 45, with a membrane organization of 13 bipolar-spanning domains similar to that of the polypeptide encoded by the CcEe gene. The D and CeEe polypeptides differ by 36 amino acids 8. The sequence homology supports the concept that the genes evolve by duplication of a common ancestral gene.
It is evident that the controversy between Wienerwho espoused the existence of a single gene with multiple epitopic sites, and the Fisher-Race school Race,which held to the existence of 2 closely linked genes, has now been resolved with the conclusion that each view was partially right and partially wrong.
None of the 3 researchers survived to see the definitive resolution of the issue. Arce et al. Smythe et al. Both c and E antigens were expressed after transduction of the test cells with a single cDNA, indicating that the c antigen does not arise by alternative splicing exon skipping of the product of the RHCE gene, as had been suggested.
By Southern blot analysis, Colin et al.
Alternative splicing of a primary transcript was considered the likely mechanism of the encoding of the Cc and Ee polypeptides by a single gene Le Van Kim et al.
The 3-prime ends of the genes face each other and are separated by about 30, bp that contain the SMP1 gene The breakpoints of the RHD deletion in the prevalent RHD-negative haplotypes are located in the 1,bp identity region of the Rhesus boxes.
Wagner and Flegel established technical procedures for specifically detecting the RHD gene deletion in the common RHD-negative haplotypes.
Bennett et al. An RhD-negative woman whose partner is heterozygous may have preexisting anti-RhD antibodies that may or may not affect a subsequent fetus, depending on whether it is heterozygous.
A safe method of determining fetal RhD type early in pregnancy would eliminate the risks to an RhD-negative fetus of fetal blood sampling or serial amniocenteses. In his review of the molecular genetics of the Rh blood group antigens, Cartron pointed out the desirability of an early and safe prenatal diagnosis of Rh status for use in pregnancies at risk of Rh alloimmunization. Such became possible when the structure and organization of the RH locus in RhD-positive and RhD-negative individuals was determined.
The general approach was based on the detection of D genomic sequences by PCR in fetal DNA samples from chorionic villus biopsy or amniocentesis. Huang et al. In chronically transfused patients, conventional blood group typing may be impossible because of mixed-field agglutination Spanos et al. Legler et al.Spirit halloween near me costumes
They found that serologic methods frequently led to false blood group results in mixed blood samples. Moreover, blood group determinations were frequently incomplete or doubtful.Image source: J.
The rhesus macaque is an Old World monkey. This primate model organism, while more distant from humans than chimpanzees or orangutans, is important for study of human disease due to its genetic, physiologic and metabolic similarity to humans.
Rhesus monkeys are used for essential research in neuroscience, behavioral biology, infectious diseases, reproductive physiology, endocrinology, cardiovascular studies, pharmacology and other areas.
The goals of the project were to produce a seven-fold WGS shotgun assembly, using small insert plasmids as well as large insert clone ends from BACs, Fosmids, and 50kb linking clones. There are finishing and BAC sequencing components of the project to investigate interesting regions for human diseases and to highlight primate evolution.
The project was compelling both because of the intense interest in this organism as a biomedical research model—including SIV and AIDS research—and because of its unique placement in the evolutionary tree relative to the human. The project was a 5x WGS draft assembly with additional finished regions up to Mb and an undefined BAC component, as needed to ensure overall quality. A BAC library from a male was available and the Genome Centre in Vancouver expressed interest in building a fingerprint map.
After sufficient data for 4x coverage, an "interim assembly" was generated by the HGSC to test overall fidelity of the work. After the WGS data was complete, independent assemblies were performed at each sequencing center using different approaches.Logic pro x price
A working group was convened to coordinate evaluation and comparison of each assembly and guide melding into a single assembly. The "melded assembly" used the fingerprint map and, at the very highest level i.
This assembly, released in Febwas used for gene predictions, and ongoing analysis. The BCM-HGSC is currently sequencing more than rhesus macaques from several different NIH-funded research colonies in order to identify and characterize genetic variation in this species. Southwest National Primate Research Center. Washington University rhesus site.
Y Chromosome Proposal. Rhesus macaque companion publications are found in ScienceApril 13, Skip to main content. Rhesus Monkey Genome Project. Origins and long-term patterns of copy-number variation in rhesus macaques. Mol Biol Evol. PLoS Genet. Reduced meiotic recombination in rhesus macaques and the origin of the human recombination landscape.Metrics details. G-protein coupled receptors GPCRs play an inordinately large role in human health.
Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms.
Recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes.
This work aims to extend those studies broadly across the roughly non-olfactory GPCRs. Initial efforts include resequencing 44 Indian-origin rhesus macaques Macaca mulatta20 Chinese-origin rhesus macaques, and 32 cynomolgus macaques M. Using the Agilent target enrichment system, capture baits were designed for GPCRs off the human and rhesus exonic sequence.
Using next generation sequencing technologies, nearly 25, SNPs were identified in coding sequences including over 14, non-synonymous and more than 9, synonymous protein-coding SNPs.
As expected, regions showing the least evolutionary constraint show greater rates of polymorphism and greater numbers of higher frequency polymorphisms.
While the vast majority of these SNPs are singletons, roughly 1, non-synonymous and 2, synonymous SNPs were found in multiple individuals. In all three populations, polymorphism and divergence is highly concentrated in N-terminal and C-terminal domains and the third intracellular loop region of GPCRs, regions critical to ligand-binding and signaling.Mastros fort lauderdale luxury hour
SNP frequencies in macaques follow a similar pattern of divergence from humans and new polymorphisms in primates have been identified that may parallel those seen in humans, helping to establish better non-human primate models of disease.
Animal research has provided the scientific community with extraordinary advances in medicine from the development of vaccines to the prevention and treatment of diseases. Reasons for these shortcomings include low patient recruitment, poor study design, and ineffective use of animal models[ 12 ].
Coupled with soaring drug development costs including both financial commitments and in years of labor, these shortfalls necessitate a biological and economic need for fundamental changes in the bench to bedside process.
Furthermore, with advances in genome sequencing technologies there is a growing awareness that animal models fall short in terms of predictive power.
Genome sequence and global sequence variation map with 5.5 million SNPs in Chinese rhesus macaque
A recent study comparing the genomic responses of human inflammatory diseases to mouse models, for example, suggested that mice poorly mimic the human genetic response[ 3 ]. Continued progress in the understanding of human disease pathologies and the development of safe and effective therapies demands a more comprehensive understanding of animals in preclinical research.
Although greater numbers of rodents are used in biomedical research, non-human primates are the gold standard of animal models in preclinical research offering advantages which include greater similarities in genome organization and sequence, behavior, and physiology[ 4 ]. The rhesus Macaca mulatta and cynomolgus M. Because of similarities in physiology and the central nervous system, non-human primates, for example, are crucial in stem cell-based regenerative medicine to ensure the efficacy and long-term safety of autologous cell therapies, which is not possible in rodents[ 7 ].
In industry settings, non-human primates are important to drug development and are commonly found in drug metabolism and toxicology studies[ 89 ]. Despite these distinct advantages, drawbacks to non-human primates include greater genetic heterogeneity and higher costs which tend to lead, in turn, to small samples sizes[ 4 ]. Ultimately these disadvantages contribute to the limited use of non-human primates in biomedical research, particularly in academic settings.
Performed the experiments: JF. Analyzed the data: JF. Wrote the paper: JF. Data compilation: JF. Rhesus factor polymorphism has been an evolutionary enigma since its discovery in Carriers of the rarer allele should be eliminated by selection against Rhesus positive children born to Rhesus negative mothers. Here I used an ecologic regression study to test the hypothesis that Rhesus factor polymorphism is stabilized by heterozygote advantage.
The study was performed in 65 countries for which the frequencies of RhD phenotypes and specific disease burden data were available. I performed multiple multivariate covariance analysis with five potential confounding variables: GDP, latitude distance from the equatorhumidity, medical care expenditure per capita and frequencies of smokers. The results showed that the burden associated with many diseases correlated with the frequencies of particular Rhesus genotypes in a country and that the direction of the relation was nearly always the opposite for the frequency of Rhesus negative homozygotes and that of Rhesus positive heterozygotes.
On the population level, a Rhesus-negativity-associated burden could be compensated for by the heterozygote advantage, but for Rhesus negative subjects this burden represents a serious problem.
Rhesus Monkey Genome Project
Before the introduction of prophylactic treatment inthe carriers of the rarer variant of the gene, namely Rhesus negative women in in a population of Rhesus positive subjects or Rhesus positive men in population of Rhesus negative subjects, had lower fitness.
This is because RhD-positive children born to pre-immunized RhD-negative mothers were at a higher risk of fetal and newborn death or health impairment from the haemolytic disease. Therefore, mutants or migrants with the rarer variant of the RHD gene could not invade the population and any already existing RhD polymorphism should be unstable.
It has been suggested that this polymorphism can be stabilized when the disadvantage of carriers of the locally rarer allele is counterbalanced by higher viability of their heterozygote children or by another form of frequency-dependent selection [ 6 ]. In the past seven years, several studies have demonstrated that Rhesus positive and Rhesus negative subjects differ in resistance to the adverse effects of parasitic infections, aging, fatigue and smoking [ 7 — 13 ].
A recently published cross sectional study performed on a cohort of on 3, subjects showed numerous associations between Rh negativity and incidence of many disorders. Within this subset, 31 significant associations with RhD negativity 21 positive and 10 negative were observed [ 14 ]. A study performed on blood donors has further shown that resistance to the effects of toxoplasmosis is higher in Rhesus positive heterozygotes than in Rhesus positive homozygotes and substantially higher than in Rhesus negative homozogotes [ 7 ].
This is the first direct evidence for the role of selection in favour of heterozygotes in stabilization of the RHD gene polymorphism in human populations. Such a mechanism is reminiscent of widely known situations with polymorphism in genes associated with sickle cell anaemia in geographic regions with endemic malaria [ 15 ]. RhD protein is a component of a membrane complex of which the function is not quite clear. It is most probably involved in NH 3 transport and possibly also in CO 2 transport [ 1617 ].
The complex is associated with spectrin-based cytoskeleton and therefore plays an important role in maintaining the typical shape biconcave discoid of human erythrocytes [ 18 ]. Therefore, no product of this allele is synthetized in the cells of RhD negative homozygotes and the RhD is most probably substituted in the corresponding molecular complex by the related protein RhCE. An important difference was also observed between erythrocytes of RhD positive homozygotes and heterozygotes.
About 33, and 17, D antigen sites were detected on the surfaces of an erythrocyte in RhD homozygotes and heterozygotes, respectively [ 18 ]. This suggests that the susceptibility of RhD positive homozygotes and RhD positive heterozygotes and even more so RhD negative homozygotes to various aberrant conditions, including various diseases, could differ dramatically.
Due to the general trade-off principle, heterozygotes could be more resistant to one disease and more prone to another disease while the opposite could be true for homozygotes. Such trade-offs could explain the heterozygote advantage hypothesis and all other observed phenomena.
The frequencies of Rhesus negative subjects and therefore also Rhesus positive heterozygotes as well as the incidences of particular diseases and disorders vary between countries. If the protective effect of Rhesus positivity or Rhesus heterozygosity is strong enough, then the relationship between the frequencies of Rhesus negative homozygotes and Rhesus positive heterozygotes should correlate with the incidences of specific diseases when important confounding variables are controlled.
This could be either because the incidences of particular disease influence the geographic distribution of RhD alleles, or because the differences in prevalence of particular phenotypes influence the incidences of particular diseases. Here, I have studied the correlation of disease burden estimates compiled by the WHO with the frequencies of Rhesus negative homozygotes and Rhesus positive heterozygotes in a set of 65 countries for which the data on the frequencies of Rhesus-negative individuals are available.
Hypothesis 1: The frequency of Rh negative homozygotes in particular countries correlates mostly positively with the incidence of some health disorder in these countries. Hypothesis 2: The frequency of Rh positive heterozygotes in particular countries correlates mostly negatively with the incidence of some health disorder in these countries.Metrics details.
Rhesus macaques serve a critical role in the study of human biomedical research.
While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus SIV infection. Single nucleotide polymorphisms SNPs can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis.
We surveyed the 3' end of 94 genes in 20 rhesus macaque animals. The study included 10 animals each of Indian and Chinese ancestry. We identified a total of SNPs, of which appeared exclusively in one or the other population. Seventy-nine additional animals were genotyped at 44 of the population-exclusive SNPs.
Of those, 38 SNPs were confirmed as being population-specific. This study demonstrates that the 3' end of genes is rich in sequence polymorphisms and is suitable for the efficient discovery of gene-linked SNPs. In addition, the results show that the genomic sequences of Indian and Chinese rhesus macaque are remarkably divergent, and include numerous population-specific SNPs.Communicationes archaeologicae hungariae 2017
These ancestral SNPs could be used for the rapid scanning of rhesus macaques, both to establish animal ancestry and to identify gene alleles that may contribute to the phenotypic differences observed in these populations. The rhesus macaque Macaca mulatta has served a critical role in the study of human disease for more than half a century. This macaque remains the animal of choice for much of biomedical research and is the primary model for the study of human immunodeficiency virus HIV and acquired immune deficiency syndrome AIDS [ 1 ].
Though Indian-origin rhesus were originally used in most research protocols, the ban on the export of primates from India resulted in reduced availability of these animals. Because the growing demand for rhesus macaques has exceeded the domestic supply, the U. In recent years, a variety of studies have investigated the relationship between Indian and Chinese rhesus macaques.
Studies of chromosomal microsatellite loci have also identified marked differences in allele frequencies between Indian and Chinese rhesus macaque populations [ 5 — 8 ]. Similarly, population-specific differences in the allele distributions within both Class I and II major histocompatibility complex MHC loci support the contention that the two populations have distinct genetic characteristics [ 910 ].The Rh blood group system is a human blood group system.
It contains proteins on the surface of red blood cells. It is the second most important blood group system, after the ABO blood group system. The Rh blood group system consists of 49 defined blood group antigens among which the five antigens D, C, c, E, and e are the most important.
There is no d antigen. Rh D status of an individual is normally described with a positive or negative suffix after the ABO type e. Antibodies to Rh antigens can be involved in hemolytic transfusion reactions and antibodies to the Rh D and Rh antigens confer significant risk of hemolytic disease of the fetus and newborn.
The Rh blood group system has two sets of nomenclatures: one developed by Ronald Fisher and R. Racethe other by Wiener. Both systems reflected alternative theories of inheritance. This system was based on the theory that a separate gene controls the product of each corresponding antigen e.Preferences translate in chinese
However, the d gene was hypothetical, not actual. The Wiener system used the Rh—Hr nomenclature. This system was based on the theory that there was one gene at a single locus on each of the 2 copies of chromosome 1, each contributing to production of multiple antigens.
Notations of the two theories are used interchangeably in blood banking e. Wiener's notation is more complex and cumbersome for routine use.
Because it is simpler to explain, the Fisher—Race theory has become more widely used. Thus, Wiener's postulate that a gene could have multiple specificities something many did not give credence to originally has been proved to be correct. On the other hand, Wiener's theory that there is only one gene has proved to be incorrect, as has the Fischer—Race theory that there are three genes, rather than the 2.
The proteins which carry the Rh antigens are transmembrane proteinswhose structure suggest that they are ion channels. Lowercase "d" indicates the absence of the D antigen the gene is usually deleted or otherwise nonfunctional. Rh phenotypes are readily identified through the presence or absence of the Rh surface antigens. As can be seen in the table below, most of the Rh phenotypes can be produced by several different Rh genotypes. The exact genotype of any individual can only be identified by DNA analysis.
Regarding patient treatment, only the phenotype is usually of any clinical significance to ensure a patient is not exposed to an antigen they are likely to develop antibodies against. A probable genotype may be speculated on, based on the statistical distributions of genotypes in the patient's place of origin. R 0 cDe or Dce is today most common in Africa. The allele was thus often assumed in early blood group analyses to have been typical of populations on the continent; particularly in areas below the Sahara.
Large-scale polymorphism discovery in macaque G-protein coupled receptors
Ottensooser et al. However, more recent studies have found R 0 frequencies as low as Rh antibodies are IgG antibodies which are acquired through exposure to Rh-positive blood generally either through pregnancy or transfusion of blood products.
The D antigen is the most immunogenic of all the non-ABO antigens.Metrics details. Rhesus macaque Macaca mulatta is the most widely used nonhuman primate animal in biomedical research. A global map of genetic variations in rhesus macaque is valuable for both evolutionary and functional studies.
Using next-generation sequencing technology, we sequenced a Chinese rhesus macaque genome with We further annotated 5, and nonsynonymous SNPs to the macaque orthologs of human disease and drug-target genes, respectively. Finally, we set up a genome-wide genetic variation database with the use of Gbrowse. Genome sequencing and construction of a global sequence variation map in Chinese rhesus macaque with the concomitant database provide applicable resources for evolutionary and biomedical research.
Rhesus macaque Macaca mulatta and human shared a most recent common ancestor about 25 million years ago [ 1 ] and their genome sequences share Due to the genetic and physiologic similarity between rhesus macaque and human, rhesus macaques are the most widely used nonhuman primate animals for biomedical research, for example, in vaccine development and as animal models for human diseases [ 3 — 7 ].
In research, rhesus macaque subspecies from India and China are the most commonly used, and the divergence between these was estimated to be aboutyears ago [ 8 ].
The observed genetic divergence, though shallow, is considered to underlie the observed phenotypic differences between them, such as with regard to immune responses and disease progression. The well-known example is that, compared with Indian rhesus macaques, simian immunodeficiency virus SIV pathogenesis in Chinese rhesus macaques is closer to HIV-1 infections in untreated adult humans [ 910 ].
Although previous studies have determined thousands of SNPs and hundreds of microsatellite polymorphisms [ 811 — 16 ], a genome-wide high-density genetic variation map of rhesus macaque could provide much more comprehensive information. Therefore, developing a global map of genetic variations within and between Indian- and Chinese-derived rhesus macaques has important implications for biomedical research and drug development.
Here we sequenced the genome of a male Chinese macaque and compared the data with the released reference genome of an Indian macaque rheMac2 [ 2 ]. We identified a total of 2. We also observeddeletions and other structural variations SVs by comparing Chinese with Indian macaques.
RHD Rh blood group D antigen [ (human)]
We have also integrated other valuable annotated information to enrich the CMSNP database, resulting in a comprehensive compilation of rhesus macaque genetic variations. We performed whole-genome sequencing of this macaque genomic DNA sample using the Illumina Genome Analyser, with span sizes of the three paired-end DNA libraries ranging from 44 to bp.
In total, 33 gigabases of high quality sequences with A summary of the resequencing data is shown in Table 1 and in Table S1 in Additional file 1. In general, For SNP identification, we utilized a statistical model based on Bayesian algorithms that has been used in human resequencing analysis [ 18 ]. After filtering, a total of 5. The remaining 2.
It has been shown that the total number of SNPs would reach saturation at a sequencing depth greater than ten-fold using the paired-end reads [ 20 ]. Therefore, with The observed ratio of heterozygous to homozygous SNPs is 1.
Additionally, our results suggest that these SNPs could efficiently distinguish Indian-derived from Chinese- derived rhesus macaques [ 15 ]. The chromosomal distribution of SNPs excluding sexual chromosomes per 1-Mb window is shown in Figure 1.
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